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Important Note: The following information
is provided for your education. It should not be relied upon for
personal diagnosis or treatment. If you believe that a
particular therapy applies to you or someone you care about, be
sure to consult a doctor before trying it.
Osteoporosis Research:
2002-2006
Spine J. 2006 Sep-Oct;6(5):479-87.
Osteoporotic compression fractures of the spine; current options
and considerations for treatment.
Kim DH, Vaccaro AR.
The Boston Spine Group, Department of Orthopaedic Surgery, Tufts University
Medical School, New England Baptist Hospital, 125 Parker Hill Avenue, Boston MA
02120, USA.
BACKGROUND CONTEXT: Vertebral compression fractures affect at least one-fourth
of all postmenopausal women. The most significant risk factor is osteoporosis,
most commonly seen among Caucasian women a decade or so after menopause.
Osteoporosis typically results from inadequate accumulation of bone mass during
childhood and early adulthood followed by rapid resorption after menopause.
Primary treatment of osteoporosis includes consideration of underlying metabolic
abnormalities and provision of supplemental calcium/vitamin D in conjunction
with bisphosphonates or calcitonin, or both. Routine hormone replacement therapy
has fallen out of favor because of concerns regarding adverse effects identified
in long-term follow-up studies. Acute osteoporotic vertebral compression
fracture management includes bracing, analgesics, and functional restoration.
Patients with chronic pain beyond 2 months may be appropriate candidates for
vertebral body augmentation, ie, vertebroplasty or balloon tamp reduction. Open
surgical management with decompression and stabilization should be reserved for
the rare patient with neural compression and progressive deformity with
neurologic deficits. PURPOSE: To review current principles in the evaluation and
treatment of osteoporotic compression fractures of the spine. STUDY
DESIGN/SETTING: A literature review on management of the osteoporotic spine.
METHODS: MEDLINE search of all English-language literature published between
1981 and 2005 on surgical and nonsurgical treatment of the osteoporotic spine.
The references selected for listing at the conclusion of this review are those
containing specific information cited within the text. RESULTS: Over 200
separate scientific and clinical studies addressing the epidemiology,
pathophysiology, diagnosis, and treatment of osteoporotic vertebral compression
fractures were reviewed. CONCLUSIONS: Osteoporotic vertebral compression
fractures are a common presenting complaint to spinal care specialists. Thorough
differential diagnosis should be considered before attributing fractures to
osteoporosis. Appropriate evaluation and medical treatment of underlying
osteoporosis should be recommended or instituted. Nonsurgical management of the
spinal fracture should focus on pain control and maximizing functional outcome.
The role of surgical treatment remains controversial and should be reserved for
patients who fail initial nonsurgical management options.
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Drugs Aging. 2006;23(8):617-25.
The problem of low levels of vitamin d and osteoporosis : use of
combination therapy with alendronic Acid and colecalciferol (vitamin d(3)).
Epstein S.
Doylestown Hospital, Doylestown, Pennsylvania, USA.
Osteoporosis and fragility fractures are common in the elderly population and
represent a large public health burden. Non-pharmacological recommendations for
the management of osteoporosis include modification of lifestyle behaviours,
increased weight-bearing exercise and consumption - through dietary or
supplement sources - of adequate amounts of calcium and vitamin D. Although
current guidelines include recommendations on calcium and vitamin D intake,
patients frequently do not take sufficient amounts, even when supplements are
provided free of charge. Vitamin D is essential for mineral metabolism, and low
levels are associated with impaired skeletal metabolism and neuromuscular
function. Nutritional sources of vitamin D are limited, and supplementation is
usually necessary. A high prevalence of low vitamin D levels has been reported
in a number of populations worldwide, including women being treated for
osteoporosis and those with fragility fractures. At present, bisphosphonates are
the most commonly prescribed pharmacological treatments for osteoporosis, and
alendronic acid is the most frequently prescribed bisphosphonate. A
nitrogen-containing bisphosphonate, alendronic acid has demonstrated
anti-fracture efficacy at vertebral and non-vertebral skeletal sites, including
the hip, in addition to long-term safety and efficacy. Weekly administration of
alendronic acid takes advantage of the pharmacokinetics of the drug and
osteoclast biology to optimise treatment, and may improve patient adherence.
Combining alendronic acid 70mg and colecalciferol (vitamin D(3)) 2800 IU in a
single, once-weekly tablet has the advantage of combining the proven efficacy of
an established bisphosphonate, alendronic acid, with the amount of vitamin D
currently recommended for osteoporosis management.
-----
Bone. 2006 Sep 4; [Epub ahead of print]
Weight-bearing exercise and bone mineral accrual in children and
adolescents: A review of controlled trials.
Hind K, Burrows M.
University of Leeds, Centre for Bone and Body Composition Research, Ground
Floor, Wellcome Wing, The General Infirmary, Leeds, LS1 3EX, UK.
INTRODUCTION: Osteoporosis is a serious skeletal disease and as there is
currently no cure, there is a large emphasis on its prevention, including the
optimisation of peak bone mass. There is increasing evidence that regular
weight-bearing exercise is an effective strategy for enhancing bone status
during growth. This systematic review evaluates randomised and non-randomised
controlled trials to date, on the effects of exercise on bone mineral accrual in
children and adolescents. METHODS: An online search of Medline and the Cochrane
database enabled the identification of studies. Those that met the inclusion
criteria were included in the review and graded according to risk for bias.
RESULTS: Twenty-two trials were reviewed. Nine were conducted in prepubertal
children (Tanner I), 8 in early pubertal (Tanner II-III) and 5 in pubertal
(Tanner IV-V). Sample sizes ranged from n=10 to 65 per group. Exercise
interventions included games, dance, resistance training and jumping exercises,
ranging in duration from 3 to 48 months. Approximately half of the trials (n=10)
included ground reaction force (GRF) data (2 to 9 times body weight). All trials
in early pubertal children, 6 in pre pubertal and 2 in pubertal children,
reported positive effects of exercise on bone (P<0.05). Mean increases in bone
parameters over 6 months were 0.9-4.9% in prepubertal, 1.1-5.5% in early
pubertal and 0.3-1.9% in pubertal exercisers compared to controls (P<0.05).
CONCLUSIONS: Although weight-bearing exercise appears to enhance bone mineral
accrual in children, particularly during early puberty; it remains unclear as to
what constitutes the optimal exercise programme. Many studies to date have a
high risk for bias and only a few have a low risk. Major limitations concerned
selection procedures, compliance rates and control of variables. More well
designed and controlled investigations are needed. Furthermore, the specific
exercise intervention that will provide the optimal stimulus for peak bone
mineral accretion is unclear. Future quantitative, dose-response studies using
larger sample sizes and interventions that vary in GRF and frequency may
characterise the most and least effective exercise programmes for bone mineral
accrual in this population. In addition, the measurement of bone quality
parameters and volumetric BMD would provide a greater insight into the
mechanisms implicated in the adaptation of bone to exercise.
-----
Drugs. 2006;66(12):1593-601.
Intravenous ibandronate : in the treatment of osteoporosis.
Croom KF, Scott LJ.
Adis International Limited, Auckland, New Zealand.
Ibandronate (ibandronic acid) is a potent nitrogen-containing bisphosphonate
that inhibits osteoclast-mediated bone resorption in women with postmenopausal
osteoporosis. Recently, an intravenous (IV) formulation of ibandronate for
intermittent injection, which circumvents the fasting and posture requirements
associated with administration of oral bisphosphonates, was approved for use in
this patient population.black triangle In initial placebo-controlled studies of
1 year's duration, IV ibandronate (</=2mg once every 3 months) increased lumbar
spine bone mineral density (BMD) and reduced levels of biochemical markers of
bone turnover in a dose-dependent manner. Dosages </=1mg every 3 months were
found to be suboptimal in terms of fracture prevention in a 3-year trial.black
triangle Subsequently, the large randomised, double-blind, noninferiority DIVA
trial showed that, in terms of increasing lumbar spine BMD (primary endpoint),
IV ibandronate 3mg once every 3 months and 2mg once every 2 months for 1 year
were noninferior and also superior to oral ibandronate 2.5mg once daily, a
regimen with proven antifracture efficacy. Median reductions from baseline in
biochemical markers of bone turnover were similar for the IV and oral
regimens.black triangle IV ibandronate was generally well tolerated in clinical
trials. Treatment-related adverse events included musculoskeletal events and
transient influenza-like symptoms, the latter mainly associated with the first
dose.
-----
Clin Calcium. 2006 Sep;16(9):1451-6.
[Treatment and management of severe osteoporosis.]
[Article in Japanese]
Okano T, Hagino H.
Tottori University, School of Medicine, Department of Orthopaedic Surgery.
Because there is an extremely high probability of new fractures occurring in
cases in which there are pre-existing fractures, it is easy for such patients to
develop severe osteoporosis. We therefore must correctly ascertain any existence
of either vertebral or hip fractures. High values of bone resorption markers
reflect the existence of microfractures, so it is necessary to be careful due to
the high risk of new fractures. Kinesitherapy for severe osteoporosis focuses on
therapeutic exercise, walking, balance drills, and so forth with the aim of
maintaining muscular strength and thus preventing falls. For severe osteoporosis
such as senile osteoporosis and glucocorticoid-induced osteoporosis,
bisphosphonates are currently the only medication that has been proven to be
effective for preventing fractures. For the treatment of disuse osteoporosis
stemming from paralysis, etc., the intravenous injection of bisphosphonates is
able to suppress the decline in bone mass, but there is still very little
evidence of its fracture prevention effect.
-----
Z Rheumatol. 2006 Sep 1; [Epub ahead of print]
[DVO Guideline 2006 : What changes have there been in the
diagnosis, prevention and treatment of osteoporosis?]
[Article in German]
Fassbender WJ, Stumpf UC.
Hospital zum Hl. Geist, Akademisches Lehrkrankenhaus der Heinrich-Heine-Universitat
Dusseldorf, Von-Broichhausen-Allee 1, 47906, Kempen/Niederrhein, Deutschland,
w.j.fassbender@krankenhaus-kempen.de.
The main changes in the updated DVO guideline 2006 on prevention, diagnosis and
treatment of osteoporosis in postmenopausal women and in older men concern the
evaluation of individual fracture risks and the selection of medicamentous
therapy by means of new thresholds. A 30% risk of osteoporotic vertebral or hip
fracture per decade is recommended as the threshold for implementation of
pharmacological therapy. Evaluation of the individual absolute fracture risk is
based on a combination of the results of densitometry at the lumbar spine and
femur, age, gender, and other risk factors that are specifically associated with
osteoporosis. Patient's mobility is assessed by carrying out special mobility
tests. Further changes seen in the 2006 update of the DVO guideline are therapy
proposals taking account of new pharmaceutical developments. New effective
medications are rh-PTH (1-34), or teriparatide, strontium ranelate, and
ibandronate (bisphosphonate) for monthly oral administration. Minimally invasive
operative techniques for use in vertebral fractures in combination with
medicamentous antiosteoporosis therapy are also included in the 2006 update of
the DVO guideline. Thus, in the 2006 update of the DVO-guideline we have a
practice-oriented S3 guideline that is adapted to individual fracture risk and
gives recommendations on the prevention, diagnosis and treatment of
osteoporosis.
-----
S D Med. 2006 Aug;59(8):343-5, 347.
Vertebral compression fractures: treatment and evaluation.
Babb A, Carlson WO.
Orthopedic Institute, Sioux Falls, SD, USA. acbabb@csbsju.edu
Vertebral compression fractures can occur secondary trauma, malignancies, or
most commonly osteoporosis. Osteoporosis causes almost 1.5 million fractures
throughout the United States every year and nearly 700,000 of these fractures
are vertebral compression fractures. These fractures are frequently seen in
elderly women; 40 percent of women older than 80 years old are affected by
vertebral compression fractures. These injuries can be treated both
conservatively and surgically. The conservative route includes bed rest, pain
control, bracing, and strength training. The surgical method includes
percutaneous vertebroplasty and kyphoplasty, both minimally invasive procedures.
This article provides a general introduction to vertebral compression fractures
and osteoporosis, the diagnostic methods used to identify vertebral compression
fractures, and the known treatments.
-----
Z Rheumatol. 2006 Aug 22; [Epub ahead of print]
[Physiotherapy strategies in osteoporosis - recommendations for
daily practice.]
[Article in German]
Uhlemann C, Lange U.
Kompetenzzentrum Naturheilverfahren, Klinik fur Innere Medizin II,
Friedrich-Schiller Universitat, Bachstrasse 18, 07740, Jena, christine.uhlemann@med.uni-jena.de.
Physiotherapy in osteoporosis essentially takes the form of stimulatory therapy
tailored to the findings and the pathomechanism. The choice of therapy and its
dosage depend on the desired result (prevention, cure, rehabilitation). Physical
therapy applied in osteoporosis includes electrical, thermic (hydrothermic, high
frequency thermic, light thermic) and mechanical (massage, physiotherapy)
stimuli, which can be applied regionally, locally or hoistically . To be
efficient, a pain therapy requires that the various painful states be
differentiated between:: whereas, for example, in the case of acute pain
physiotherapy fulfils the function of immediate therapy (normally rest and
"mild" cold applications), in chronic pain it has to fulfil the function of an
adaptive performance therapy of neuronal structures (formative-adaptive
physiotherapy, thermic therapy improving trophism, direct current,
transcutaneous electric nerve stimulation/TENS). It is necessary and extremely
important forday-to-day clinical practice that physiotherapy strategies that are
tailored to each patient's needs and also economically justifiable be
implemented. The article is intended to contribute to this.
-----
Nat Clin Pract Endocrinol Metab. 2006 Apr;2(4):211-9.
Drug insight: Bisphosphonates for postmenopausal osteoporosis.
Chapurlat RD, Delmas PD.
University Claude Bernard, Lyon, France.
Bisphosphonates are potent antiresorptive agents, which have largely been used
for the treatment of postmenopausal osteoporosis during the past 10 years. When
embedded in bone matrix, bisphosphonates are taken up by osteoclasts engaged in
bone resorption, leading--mainly by inhibition of farnesyl diphosphate synthase,
a key enzyme of the mevalonate pathway--to osteoclast apoptosis. Bone resorption
decreases, with consequent improvement in the mechanical properties of bone and
a reduced risk of fracture. Alendronate and risedronate are oral
nitrogen-containing bisphosphonates. Several randomized, placebo-controlled
trials have shown the ability of these bisphosphonates to halve the risk of
vertebral fracture when taken daily for 3 years. Nonvertebral fracture risk,
including that at the hip, was also significantly decreased. Weekly regimens
have simplified the administration of bisphosphonates and, probably, improved
adherence to treatment. A significant reduction in the risk of vertebral
fracture has also been demonstrated with an intermittent regimen of ibandronate,
which is a new, potent, nitrogen-containing bisphosphonate. Ibandronate was
recently marketed for use in an oral, once-monthly dose of 150 mg, with the goal
of improving compliance. Bisphosphonates are usually well tolerated in the long
term. Intravenous administration of bisphosphonates in women with osteoporosis,
which is currently under investigation, might be an interesting future option
for women who cannot tolerate oral regimens, and for enhancing compliance.
-----
Drugs Aging. 2006;23(7):569-78.
Importance of calcium co-medication in bisphosphonate therapy of
osteoporosis : an approach to improving correct intake and drug adherence.
Ringe JD, van der Geest SA, Moller G.
Medical Clinic 4, Klinikum Leverkusen, University of Cologne, Leverkusen,
Germany.
BACKGROUND AND OBJECTIVE: In all of the large, pivotal, multicentre trials of
bisphosphonate therapy, patients have received added calcium in amounts ranging
from 500 to 1000 mg/day above individual dietary intake. Accordingly, calcium
supplements or calcium/vitamin D combinations are currently recommended as
co-medication with anti-resorptive therapy in all recently published guidelines
on the treatment of osteoporosis. However, the consistent use or effectiveness
of calcium may be impaired by several factors in the individual patient,
including low prescription rate or lack of advice to purchase calcium, reduced
adherence because of the complexity of the regimen, and incorrect intake (e.g.
taking calcium with bisphosphonates at the same time). Patients with
osteoporosis who adhere to drug therapy experience a significantly lower
fracture rate. Therefore, there is a need to improve correct intake of
bisphosphonates together with calcium supplementation, which may enhance
adherence. The dosage regimen could be simplified by providing the two compounds
in an integrated pack. Such a pack, containing one tablet of risedronic acid and
six calcium carbonate tablets (Actonel((R)), Procter & Gamble Pharmaceuticals,
Weiterstadt, Germany), has been developed to facilitate correct intake. In this
study, the impact of this fixed-combination pack on patient understanding of
dosing instructions and on preference was tested by comparing the fixed
combination with separate risedronic acid and calcium packages. PATIENTS AND
METHODS: A new blister strip was developed containing one tablet of risedronic
acid 35mg and six tablets of calcium carbonate 1250mg (500mg elemental calcium),
representing 1 week of therapy; the control was the same medications in separate
packaging. The study was conducted in a cohort of 164 postmenopausal women (mean
age 69 years). Half of the participants were bisphosphonate users (n = 83). The
combined understanding of five instructions - risedronic acid intake in the
morning, only with water, without food, without other medication, and separate
from calcium - was tested in a crossover design. Participants were also asked to
state their preference for the combination packaging versus separate packs.
RESULTS: Understanding of the five instructions for the separate packaging was
70%. The combination pack significantly improved understanding of these
instructions to 80% (p < 0.05). Eighty-three percent of participants preferred
the combination pack over separate packs (p < 0.05). The most frequently given
reasons for preferring the combination pack were prefer one pack over two packs,
easy/convenient to use/practical/handy, easy to understand/less confusion, and
easier to remember/less likely to forget. CONCLUSIONS: The availability of a
fixed-combination pack of risedronic acid 35 mg/week and calcium tablets can
increase the likelihood that postmenopausal osteoporotic patients will receive
both a bisphosphonate and calcium, which in turn is likely to enhance the
correct intake of combination therapy.
-----
JNMA J Nepal Med Assoc. 2005 Apr-Jun;44(158):60-6.
Osteoporosis—an update.
Lamichhane AP.
TU Teaching Hospital, Maharajgunj, Kathmandu, Nepal. dr_ajun@yahoo.com
Osteoporosis is a systemic disease characterized by decrease in bone mass per
unit volume, compromised bone strength, which predisposes the affected bone to
fracture. This is currently one of the leading causes of morbidity and mortality
among elderly over the world. In general, osteoporosis is a silent and
progressive disorder that is often brought to attention of the patients or
physician only after a fracture. The aetiology of osteoporosis is multifactorial
and is related to two main processes: acquisition of peak bone density that
occurs at the end of the third decade and loss of bone at menopause, going on to
old age. The cardinal features of osteoporosis are pain, fracture and deformity.
Bone mineral density measurement is the most reliable diagnostic tool in the
early stage of osteoporosis. Management of osteoporosis involves prevention and
treatment. The best treatment for osteoporosis is prevention. The risk of
osteoporosis can be reduced by increasing peak bone mass or by decreasing the
bone loss. It needs to be emphasized that bone mineral density (BMD) peaks at
about age 35 and then begins to slowly decline with significant acceleration
after menopause.Therefore, the most logical and cost-effective preventive
strategies are to encourage young women to stop smoking and avoid excessive use
of alcohol. They should also be counseled to exercise regularly and consume
adequate amounts of calcium and vitamin D.
-----
Transplantation. 2006 Apr 27;81(8):1191-1195.
Comparison of Calcitonin versus Calcitonin + Resistance Exercise
as Prophylaxis for Osteoporosis in Heart Transplant Recipients.
Braith RW, Magyari PM, Fulton MN, Lisor CF, Vogel SE, Hill JA, Aranda JM Jr.
1 Center for Exercise Science, College of Health and Human Performance and the
College of Medicine, University of Florida, Gainesville, FL. 2 Division of
Exercise Physiology, Lynchburg College, Lynchburg, VA, 3 Medical Exercise
Associates, Daytona Beach, FL. 4 Spine Center, Orlando, FL.
BACKGROUND.: Rapid bone loss occurs early after heart transplantation. There is
no standard therapeutic intervention to prevent osteoporosis in heart transplant
recipients (HTR). The purpose of this study was to determine the effectiveness
of a regimen combining the antiresorptive properties of nasal calcitonin with
the osteogenic stimulus of resistance exercise. METHODS.: Eighteen candidates
for heart transplantation were randomly assigned either to a group that received
calcitonin and participated in 6 months of resistance exercise (n=10) or to a
group that received only calcitonin (n=8). Calcitonin therapy (200 IU daily for
8 months) was initiated 48 hr after transplantation. Resistance exercise was
initiated 2 months after transplantation. Bone mineral density (BMD) of the
total body, femur neck, and lumbar vertebra (L2-3) were assessed before, and at
2 and 8 months after transplantation. RESULTS.: Total body and femur neck BMD
did not decrease (P>/=0.05) below pretransplantation values at 2 months after
transplantation in either group. BMD of the lumbar spine was significantly
(P</=0.05) and comparably decreased at 2 months after transplantation in the
calcitonin (-10.1+/-1.8%) and calcitonin + training groups (-12.9+/-2.7%). At 8
months after transplantation lumbar BMD was -16.9% below pretransplant values in
the calcitonin group. In contrast, lumbar BMD was restored to within 5% of
pretransplant levels in the calcitonin + training group. CONCLUSIONS.:
Calcitonin attenuates BMD loss in the total body and femur neck but not in
trabecular bone of the lumbar vertebra. Mechanical loading, through progressive
resistance exercise, is an osteogenic stimulus in HTR.
-----
Unfallchirurg. 2006 Apr 26; [Epub ahead of print]
[Balloon kyphoplasty in the treatment of vertebral fractures.]
[Article in German]
Dafonseca K, Baier M, Grafe I, Libicher M, Noeldge G, Kasperk C, Meeder PJ.
Sektion Unfall- und Wiederherstellungschirurgie, Abteilung Chirurgie,
Ruprecht-Karls-Universitat, Im Neuenheimer Feld 110, 69120 , Heidelberg,
andrea.schatz@med.uni-heidelberg.de.
Approximately 500,000 vertebral fractures occur as a result of osteoporosis
every year in Europe. One third of the patients thus affected complain of severe
back pain and seek treatment. In the past, the treatment of such fractures was
limited to conservative methods, such as the use of braces and analgesics and
long-term immobilisation followed by physiotherapy. Since 1998 balloon
kyphoplasty, a minimally invasive procedure, has also been available for their
treatment. During balloon kyphoplasty a balloon system is introduced into the
fractured vertebral body to achieve bitranspedicular augmentation, after which
low-viscosity bone cement is injected into the vertebral body, where it sets
very quickly. In general the patient can be fully mobilized 24-48 h after the
procedure and in most cases the symptoms are then considerably attenuated; many
patients are actually free of pain. Published studies and our own experience
indicate that balloon kyphoplasty is a safe method of treating painful vertebral
compression fractures sustained in various ways and that complications are rare
with this procedure.
-----
J Clin Endocrinol Metab. 2006 Apr 24; [Epub ahead of print]
Comparison of Weekly Treatment of Postmenopausal Osteoporosis
with Alendronate versus Risedronate Over Two Years.
Bonnick S, Saag KG, Kiel DP, McClung M, Hochberg M, Burnett SA, Sebba A, Kagan
R, Chen E, Thompson DE, de Papp AE.
Clinical Research Center of North Texas, Denton, TX; Division of Clinical
Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham,
AL; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA;
Oregon Osteoporosis Center, Portland, OR; University of Maryland School of
Medicine, Baltimore, MD; Massachusetts General Hospital, Endocrine Unit, Boston,
MA; Arthritis Associates, Palm Harbor, FL; Foundation for Osteoporosis Research
and Education, Oakland, CA; Merck & Co., Inc., West Point, PA.
Full free text on: http://jcem.endojournals.org/cgi/rapidpdf/jc.2005-2602v1
Objective: A 1-year extension of the FOSAMAX((R)) ACTONEL((R)) Comparison Trial
(FACT) was completed to compare changes in bone mineral density (BMD), bone
turnover, and upper gastrointestinal tolerability over 2 yr of treatment.
Design: Randomized, double-blind extension conducted at 72 US sites. Patients
and Methods: Of the 1053 women who completed Year 1, 833 postmenopausal women
with low BMD entered the extension, continuing their same treatment allocation
(once-weekly (OW) alendronate 70 mg or OW risedronate 35 mg). Changes in BMD at
the hip trochanter, total hip, femoral neck, and lumbar spine and in markers of
bone turnover were compared at 24 months. Tolerability was assessed by adverse
experience reporting. Results: Alendronate produced greater increases from
baseline in BMD at 24 months than did risedronate at the trochanter (ALN, 4.6%;
RIS, 2.5%, P < 0.001), as well as at all other BMD sites. Significantly more
alendronate than risedronate patients had measured BMD increases of >/=0% and
>/=3% at all BMD sites (P < 0.001), and fewer alendronate patients had measured
decreases of >/=3% at all BMD sites. Significantly greater reductions in all
biochemical markers of bone turnover occurred with alendronate compared with
risedronate. No differences were seen in occurrence or discontinuations due to
upper gastrointestinal adverse experiences. Conclusions: Patients receiving OW
alendronate 70 mg had greater gains in BMD, were more likely to maintain or gain
BMD, and had greater reductions in bone turnover markers than patients receiving
OW risedronate 35 mg after 24 months, with no differences in upper
gastrointestinal tolerability.
-----
Cochrane Database Syst Rev. 2006 Apr 19;(2):CD005119.
Calcium supplementation for improving bone mineral density in
children.
Winzenberg T, Shaw K, Fryer J, Jones G.
BACKGROUND: Clinical trials have shown that calcium supplementation in children
can increase bone mineral density (BMD) although this effect may not be
maintained. There has been no quantitative systematic review of this
intervention. OBJECTIVES: .To determine the effectiveness of calcium
supplementation for improving BMD in children. .To determine if any effect
varies by sex, pubertal stage, ethnicity or level of physical activity, and if
any effect persists after supplementation is ceased. SEARCH STRATEGY: We
searched CENTRAL, (Cochrane Central Register of Controlled Trials) (Issue 3,
2005), MEDLINE (1966 to 1 April 2005), EMBASE (1980 to 1 April 2005), CINAHL
(1982 to 1 April 2005), AMED (1985 to 1 April 2005), MANTIS (1880 to 1 April
2005) ISI Web of Science (1945 to 1 April 2005), Food Science and Technology
Abstracts (1969 to 1 April 2005) and Human Nutrition (1982 to 1 April 2005).
Conference abstract books (Osteoporosis International, Journal of Bone and
Mineral Research) were hand-searched. SELECTION CRITERIA: Randomised controlled
trials of calcium supplementation (including by food sources) compared with
placebo, with a treatment period of at least 3 months in children without
co-existent medical conditions affecting bone metabolism. Outcomes had to
include areal or volumetric BMD, bone mineral content (BMC), or in the case of
studies using quantitative ultrasound, broadband ultrasound attenuation and
ultrasonic speed of sound, measured after at least 6 months of follow-up. DATA
COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and
extracted data including adverse events. We contacted study authors for
additional information. MAIN RESULTS: The 19 trials included 2859 participants,
of which 1367 were randomised to supplementation and 1426 to placebo. There was
no heterogeneity in the results of the main effects analyses to suggest that the
studies were not comparable. There was no effect of calcium supplementation on
femoral neck or lumbar spine BMD. There was a small effect on total body BMC (standardised
mean difference (SMD) +0.14, 95% CI+0.01, +0.27) and upper limb BMD (SMD +0.14,
95%CI +0.04, +0.24). Only the effect in the upper limb persisted after
supplementation ceased (SMD+0.14, 95%CI+0.01, +0.28). This effect is
approximately equivalent to a 1.7% greater increase in supplemented groups,
which at best would reduce absolute fracture risk in children by 0.1-0.2%per
annum. There was no evidence of effect modification by baseline calcium intake,
sex, ethnicity, physical activity or pubertal stage. Adverse events were
reported infrequently and were minor. AUTHORS' CONCLUSIONS: While there is a
small effect of calcium supplementation in the upper limb, the increase in BMD
which results is unlikely to result in a clinically significant decrease in
fracture risk. The results do not support the use of calcium supplementation in
healthy children as a public health intervention. These results cannot be
extrapolated to children with medical conditions affecting bone metabolism.
-----
Spine. 2006 Apr 15;31(8):915-9.
Cement leakage in percutaneous vertebroplasty: effect of
preinjection gelfoam embolization.
Bhatia C, Barzilay Y, Krishna M, Friesem T, Pollock R.
Department of Orthopaedics, University Hospital of North Tees, Hardwick,
Stockton on Tees, UK.
STUDY DESIGN: Prospective case series. OBJECTIVES: To determine the safety and
feasibility of routine preinjection of gelfoam embolization during percutaneous
vertebroplasty. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty has been
used effectively in pain relief for vertebral fractures resulting from
malignancy and osteoporosis. However, cement extrusion is a common problem and
can lead to complications. Gelfoam embolization of venous channels before cement
injection has not been widely used as a technique to prevent leakage. METHODS:
Thirty-one patients who met the inclusion-exclusion criteria for the study
underwent percutaneous vertebroplasty. Venography was first performed to
determine the flow pattern in the vertebrae and confirm needle placement. Next,
routine gelfoam embolization of venous channels was performed. This was followed
by low-pressure, minimal-volume cement injection. The outcome measure of cement
leakage was assessed after surgery using radiographs and CT scans. RESULTS:
There were no complications. In the 31 patients, 61 levels of vertebroplasty
were performed. Overall, there were 16 leaks out of 61 levels in 12 patients
(26.2%). In osteoporotic fractures, there were 11 leaks in 49 levels, giving a
leakage rate of 22.5%. There was only 1 epidural leak in this group (2%), and
this was asymptomatic. Seven leakages were into the adjacent disc, 2 into the
body, and 1 into the paravertebral tissues. In malignant fractures, there were 5
leakages out of 12 levels (41.7%). Of these, 2 were epidural leaks (16.7%),
which were asymptomatic. CONCLUSIONS: Complications resulting from leakage are
the most feared side effect of the procedure. This has resulted in only limited
application of vertebroplasty in the United Kingdom. Routine gelfoam
embolization together with careful technique has been shown to be a safe and
feasible method during vertebroplasty.
-----
Clin Rheumatol. 2006 Mar 25; [Epub ahead of print]
Comparison of the effect of alendronate on lumbar bone mineral
density and bone turnover in men and postmenopausal women with osteoporosis.
Iwamoto J, Takeda T, Sato Y, Uzawa M.
Department of Sports Medicine, Keio University School of Medicine, 35
Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan, jiwamoto@sc.itc.keio.ac.jp.
The purpose of the present study was to compare the effect of alendronate
treatment on lumbar bone mineral density (BMD) and bone turnover in men and
postmenopausal women with osteoporosis. Sixty men with primary or secondary
osteoporosis and 318 women with postmenopausal osteoporosis were treated with
alendronate. The primary end points were lumbar BMD and urinary cross-linked
N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase
(ALP) levels. The secondary end point was the incidence of vertebral and
nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could
complete the 12-month trial were analyzed. The mean ages of men and
postmenopausal women were 69.1 and 70.4 years, respectively. Both men and
postmenopausal women showed higher levels of urinary NTX as compared with normal
range of premenopausal women. Alendronate treatment decreased urinary NTX level
by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP
level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone
turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal
women, respectively, at 12 months. Reduction in urinary NTX level and increase
in lumbar BMD were smaller in men than in postmenopausal women. The incidence of
vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and
8.3 and 7.5%, respectively, in postmenopausal women, with no significant
difference in these incidences between them. These results suggested that
alendronate treatment effectively increased lumbar BMD from baseline in men with
primary or secondary osteoporosis following reduction in bone turnover, although
its efficacy did not appear to be greater than in postmenopausal women with
osteoporosis.
-----
Reumatismo. 2006 Jan-Mar;58(1):11-21.
[Glucocorticoid-induced osteoporosis and rheumatic diseases.
Pathogenesis, prevention and treatment.]
[Article in Italian]
Di Munno O, Delle Sedie A.
U.O. Reumatologia, Dipartimento di Medicina Interna, Universita di Pisa, Italia.
odimunno@int.med.unipi.it.
Glucocorticoids (GC) are diffusely used to treat a wide variety of inflammatory
and autoimmune disorders, including rheumatic diseases. GC-induced osteoporosis
(GIO) is the most common and serious side-effect for patients receiving GC. Loss
of bone mineral density (BMD) is greatest in the first few months of GC use;
fracture (Fx) risk is significantly increased at the spine and hip on doses even
as low as 2.5 mg of prednisolone daily; Fx risk increases rapidly from the onset
of therapy and, for a given BMD, is higher in GIO than in postmenopausal OP.
General measures to reduce bone loss include use of the lowest effective dose;
consideration of alternative routes of administration; adequate calcium and
vitamin D supplementation. Today, results from large randomised controlled
clinical trials provide evidence that bone loss and Fx may be prevented through
the use of bone sparing agents (hormone therapy, bisphosphonates, PTH 1-34).
Bisphosphonates (alendronate, risedronate) are first-choice therapy for the
prevention and treatment of GIO; patients at high risk for Fx, for example those
in post-menopausal status or aged >/=65 years and those with a prior fragility
Fx, should be advised to start bone-protective therapy at the time of starting
GC. Due to the prevalence of GC use, it is imperative that there be a greater
awareness of GIO and of therapies that may be offered to patients both for
prevention and treatment.
-----
Menopause. 2006 Jan-Feb;13(1):148-55.
Low-dose estrogen therapy for prevention of osteoporosis: working
our way back to monotherapy.
Richman S, Edusa V, Fadiel A, Naftolin F.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University,
New Haven, CT 06520, USA.
The risks of low bone mineral density, osteoporosis and fractures, are major
concerns in postmenopausal women. Although postmenopausal hormone therapy is
effective for reducing these risks, safety issues have been raised by the
results of studies such as the Women's Health Initiative. Although there are
scientifically valid reasons to be wary of the general applicability of the
Women's Health Initiative findings, the study has underscored the continuing
need for research into new forms of menopausal hormone therapy. Low-dose
transdermal estrogen monotherapy can preserve bone density while relieving
vasomotor symptoms. Transdermal administration may offer advantages, including
lack of first-pass liver metabolism, which permits the use of lower doses and
avoids a negative impact on the lipid profile. Moreover, a recently published
2-year study of ultra-low-dose transdermal estrogen monotherapy in an older
population similar to that of the WHI reported significant increases in bone
mineral density, accompanied by significant reductions in markers of bone
turnover, with no increased risk of endometrial hyperplasia or other side
effects. Additional studies are warranted to shed further light on the possible
benefits of low-dose estrogen monotherapy for the prevention of bone loss in
postmenopausal women.
-----
Clin J Pain. 2006 Feb;22(2):182-9.
Percutaneous cement injection into a created cavity for the
treatment of vertebral body fracture: preliminary results of a new
vertebroplasty technique.
Vallejo R, Benyamin R, Floyd B, Casto JM, Joseph NJ, Mekhail N.
>From the Millennium Pain Center, the Central Illinois Neuroscience Foundation,
Bloomington, IL; and the Department of Pain Management, Cleveland Clinic
Foundation, Cleveland, OH.
OBJECTIVES:: Vertebral body fractures (VBFs) are the most common complication of
osteoporosis. Minimally invasive placement of cement to stabilize VBFs results
in significant pain reduction and improved performance of daily activities. The
authors describe a modified percutaneous vertebroplasty (PV) procedure during
which a cavity is created manually in the VBF, allowing the cement to be
injected with less resistance. METHODS:: Data were gathered from a retrospective
chart review from 15 consecutive patients with acute compression VBFs who
underwent 33 PV procedures with the Cavity Creation System. Mean follow-up was
30 weeks. Oral opiate intake, quality of life improvement, and visual analog
pain scores (VAS) were measured before and 1 month after the procedure.
RESULTS:: All 15 patients exhibited a reduction in pain VAS (mean reduction 5.9
+/- 2.5). Improvement in quality of life was demonstrated by lower (improved)
FACIT scores in the General Activity, Enjoyment of Life, Mood, Normal Work
Routine, and Sleep subscales. In addition, opioid use decreased in 10 of the 12
(83%) patients who were taking opioids before surgery. In eight (67%) patients,
opioid use decreased by over 50%. Complications included extrusion of cement in
two patients (an incidence of 5.7% of the levels operated) and two patients with
intraoperative rib fractures. No postoperative neurologic deficits were noted.
CONCLUSIONS:: The Cavity Creation System is a safe, cost-effective treatment of
VBF resulting in good/excellent pain relief and an improved quality of life.
-----
J Bone Miner Res. 2006 Feb;21(2):283-91. Epub 2005 Oct 31.
Effect of Teriparatide [rhPTH(1-34)] on BMD When Given to
Postmenopausal Women Receiving Hormone Replacement Therapy.
Ste-Marie LG, Schwartz SL, Hossain A, Desaiah D, Gaich GA.
Centre de Recherche CHUM, Montreal, Canada.
The effects of teriparatide when given in combination with HRT were studied in
postmenopausal women with low bone mass or osteoporosis. The data provide
evidence that the adverse event profile for combination therapy with
teriparatide + HRT together is consistent with that expected for each treatment
alone and that the BMD response is greater than for HRT alone. INTRODUCTION:
Teriparatide [rhPTH(1-34)], given as a once-daily injection, activates new bone
formation in patients with osteoporosis. Hormone replacement therapy (HRT)
prevents osteoporosis by reducing bone resorption and formation. Combination
therapy with these two compounds, in small clinical trials, increased BMD and
reduced vertebral fracture burden. The purpose of this study was to determine
whether teriparatide provided additional effect on BMD when given in combination
with HRT. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled
study was conducted in postmenopausal women with either low bone mass or
osteoporosis. Patients were randomized to placebo subcutaneous plus HRT (n =
125) or teriparatide 40 mug/day (SC) plus HRT (TPTD40 + HRT; n = 122) for a
median treatment exposure of 13.8 months. Approximately one-half of the patients
in each group were pretreated with HRT for at least 12 months before
randomization. Patients received 1000 mg calcium and 400-1200 IU of vitamin D
daily as oral supplementation. BMD was measured by DXA. RESULTS: Compared with
HRT alone, TPTD40 + HRT produced significant (p < 0.001) increases in spine BMD
(14% versus 3%), total hip (5.2% versus 1.6%), and femoral neck (5.2% versus 2%)
at study endpoint. BMD, in whole body and ultradistal radius, was higher, and in
the one-third distal radius was lower, in the combination therapy but not in the
HRT group. Serum bone-specific alkaline phosphatase and urinary N-telopeptide/Cr
were increased significantly (p < 0.01) in the women receiving TPTD40 + HRT
compared with HRT. A similar profile of BMD and bone markers was evident in both
randomized patients as well as in subgroups of patients not pretreated or
pretreated with HRT. Patients tolerated both the treatments well. Nausea and leg
cramps were more frequently reported in the TPTD40 + HRT group. CONCLUSIONS:
Adding teriparatide, a bone formation agent, to HRT, an antiresorptive agent,
provides additional increases in BMD beyond that provided by HRT alone. The
adverse effects of teriparatide when added to HRT were similar to the adverse
effects described for teriparatide administered alone. Whether teriparatide was
initiated at the same time as HRT or after at least 1 year on HRT, the
incremental increases over HRT alone were similar.
-----
J Bone Miner Res. 2006 Jan;21(1):340-349. Epub 2005 Sep 6.
Anti-Hip Fracture Efficacy of Bisphosphonates:A Bayesian Analysis
of Clinical Trials.
Nguyen ND, Eisman JA, Nguyen TV.
Bone and Mineral Research Program, Garvan Institute of Medical Research, St
Vincent's Hospital; Faculty of Medicine, University of New South Wales, Sydney,
New South Wales, Australia.
In postmenopausal women, the efficacy of bisphosphonates on hip fracture risk is
not clear. This Bayesian meta-analysis quantitatively reviewed data from 12
randomized clinical trials with 18,667 patients and found that bisphosphonate
treatment was associated with a reduced risk for hip fracture by 42%.
INTRODUCTION: The efficacy of antiresorptive bisphosphonates therapy on reducing
hip fracture is not clear, because evidence from randomized clinical trials (RCTs)
is inconclusive. This study was undertaken to quantitatively assess the effect
of bisphosphonates on hip fracture using literature review and meta-analysis.
MATERIALS AND METHODS: Bayesian methods of meta-analysis were applied to
synthesize data from 12 RCTs available between 1990 and 2004. The trials
involved 18,667 postmenopausal women with low BMD or osteoporosis who have been
followed or treated for between 1 and 4 years. The medications used were
etidronate (two trials) alendronate (six trials), risedronate (three trials),
and clodronate (one trial). The primary endpoint was the incidence of hip
fracture. RESULTS: When data from all 12 studies were pooled, treatment with
bisphosphonates was associated with a reduced risk for hip fracture by 42%
(relative risk [RR], 0.58; 95% credible interval [CrI], 0.42-0.80). The absolute
rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4-110) for a
period of 3-year treatment. The probability that bisphosphonates are better than
placebo (in reducing hip fracture risk by at least 30%) was 0.90. CONCLUSIONS:
In postmenopausal women with osteoporosis or low BMD, bisphosphonate treatment
is associated with reduced risk of hip fracture.
-----
Hum Reprod. 2006 Jan 12; [Epub ahead of print]
A randomized clinical trial of the effects of isosorbide
mononitrate on bone formation and resorption in post-menopausal women: a pilot
study.
Nabhan AF.
Department of Obstetrics & Gynecology, Ain Shams University, Cairo, Egypt.
BACKGROUND: Nitric oxide (NO) stimulates bone formation and inhibits bone
resorption in vitro. NO donors (nitrates) are inexpensive and widely available,
but their value for post-menopausal osteoporosis has never been evaluated in a
randomized trial. The objective of this study was to compare the effects of 5
and 20 mg of isosorbide mononitrate (ISMO) on markers of bone turnover in
post-menopausal women. METHODS: A prospective randomized trial was carried out
in the Department of Obstetrics & Gynecology, Ain Shams University, Egypt. The
study included 50 healthy post-menopausal women with a hip bone mineral density
T score between 0 and -2.5. Participants were randomly assigned to 5 or 20
mg/day of ISMO for 12 weeks. Urine N-telopeptide (NTx), a marker of bone
resorption, and serum bone-specific alkaline phosphatase (BSALP), a marker of
bone formation, were measured. Markers were measured immediately before
randomization and after 12 weeks of treatment. The percent change in NTx and
BSALP for each of the treatment groups (5 mg ISMO and 20 mg ISMO) was
calculated. The main outcome measures were serum NTx and BSALP in the 5 and 20
mg ISMO groups after 12 weeks of treatment. RESULTS: Women adhering to 20 mg of
ISMO had a 42.03% (95% confidence interval (CI), 20.1-73.7) reduction in NTx and
a 29.05% (95% CI, 10.8-48.4) increase in BSALP, and women adhering to 5 mg of
ISMO had a 31.12% (95% CI, 8.3-68.2) reduction in NTx and a 28.4% (95% CI,
4.6-52.1) increase in BSALP. CONCLUSION: ISMO, as a NO donor, may be useful for
the prevention of post-menopausal osteoporosis.
-----
Geriatrics. 2006 Jan;61(1):24-30.
Osteoporosis in postmenopausal women. Therapy options across a
wide range of risk for fracture.
Miller RG.
Department of Medicine, The Johns Hopkins University School of Medicine,
Baltimore, MD, USA.
Osteoporosis is a highly prevalent skeletal disorder characterized by
compromised bone strength predisposing individuals to an increased risk of
fractures. Fractures related to osteoporosis are frequently associated with
chronic pain and decreased quality of life, as well as significant morbidity and
mortality. Postmenopausal women are at higher risk for developing osteoporosis
and osteoporosis-related fractures. Osteoporosis fractures are commonly
asymptomatic, necessitating a need for proactive screening, diagnostic testing,
and more importantly, therapeutic intervention that will rapidly reduce the risk
of fractures in at-risk patients. Current pharmacologic prevention and treatment
options for osteoporosis include antiresorptive therapies (alendronate,
risedronate, ibandronate, raloxifene, hormone therapy, and calcitonin) and the
anabolic agent teriparatide.
-----
Clin Calcium. 2006 Jan;16(1):167-74.
[Bisphosphonate or Raloxifene?:Which drug we can choose for
osteoporotic patients?]
[Article in Japanese]
Miki T, Saito S.
Geriatric Medicine, Postgraduate School of Medicine, Osaka City University
Medical School.
Raloxifene is preferred because of free from empty stomach and amelioration of
lipid metabolism in spite of the significant effect of bisphosphonate on BMD and
metabolic markers. As compliance is essential for the prevention of fracture,
physicians should discuss about the treatment with their patients. There are no
scientific evidences which drug is more suitable to osteoporotic patients.
Therefore, bisphosphonate is recommended to the patients with severe
osteoporosis, recognition of the disease, and/or expectation for the prevention
of hip fracture by the treatment, on the condition that patients are not vitamin
D deficiency. Raloxifene is recommended to the patients with mild osteoporosis,
poor recognition of the disease, and/or low risk of the new fracture (s). The
hyperlipidemic patients with osteoporosis are another candidates for raloxifene.
-----
Clin Calcium. 2006 Jan;16(1):96-101.
[The best physical therapy for osteoporosis.]
[Article in Japanese]
Koike T.
Rheumatosurgery, Osaka City University Medical School.
Osteoporosis and osteoporotic fractures have become an epidemic in the
industrialized world. Osteoporosis, low bone mass, is a silent condition with
microarchitectural deterioration of the bone structure leading to decreased bone
strength and osteoporotic fractures. Physical activity has been advocated as
offering a potential means to increase and maintain bone mineral density.
Previous cross-sectional studies showed that there is a strong association
between exercise and bone mineral density, especially in athletic individuals.
However, there might be a self-selection bias; i.e. individuals with larger
muscles and bones are more likely to choose an athletic lifestyle. Although
there is a report that physical activity is associated with a reduced risk for
hip fracture among older community-dwelling women, the effects of vigorous
exercises building bone mass is modest and considerably less than
bisphosphonates. The proper evaluation of exercise as a preventative therapy for
osteoporosis should focus on prevention of falls or osteoporotic fractures.
-----
Treat Endocrinol. 2006;5(1):15-23.
The treatment of severe postmenopausal osteoporosis : a review of
current and emerging therapeutic options.
Reginster JY, Sarlet N.
WHO Collaborating Center for Public Health Aspects of Rheumatic Diseases, Liege,
Belgium.
Several chemical entities have shown their ability to reduce axial and/or
appendicular fractures in patients with osteoporosis. Since patients who have
experienced a previous fracture are at high risk for subsequent vertebral or hip
fracture, it is of prime importance to treat such patients with medications that
have unequivocally demonstrated their ability to reduce fracture rates in
patients with prevalent fractures. Results obtained with calcium and vitamin D,
in this particular population, are not fully satisfactory and these medications
are probably better used in conjunction with other therapeutic regimens.
Bisphosphonates have shown their ability to reduce vertebral (alendronate,
risedronate, ibandronate) and non-vertebral (alendronate, risedronate) fractures
in patients with established osteoporosis. Raloxifene has also shown similar
properties, notwithstanding its effect on non-vertebral fractures, which has
only been derived from a post hoc analysis limited to patients with prevalent
severe vertebral fractures at baseline. This compound also has interesting
non-skeletal benefits, including effects on the breast and heart. Teriparatide,
a bone-forming agent, promptly reduces the rate of vertebral and all
non-vertebral fractures, without significant adverse effects. Strontium ranelate,
the first agent shown to concomitantly decrease bone resorption and stimulate
bone formation, has also shown its ability to reduce rates of vertebral and
non-vertebral fractures in patients with established osteoporosis. It
significantly reduces hip fractures in elderly individuals at high risk for such
events. Its safety profile is also excellent.
-----
J Pharm Pharmacol. 2006 Jan;58(1):3-18.
Statins and osteoporosis: new role for old drugs.
Jadhav SB, Jain GK.
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, P.O.
Box 173, Chattar Manzil Palace, Mahatma Gandhi Marg, Lucknow-226 001, India.
Osteoporosis is the most common bone disease, affecting millions of people
worldwide and leading to significant morbidity and high expenditure. Most of the
current therapies available for its treatment are limited to the prevention or
slowing down of bone loss rather than enhancing bone formation. Recent discovery
of statins (HMG-CoA reductase inhibitors) as bone anabolic agents has spurred a
great deal of interest among both basic and clinical bone researchers. In-vitro
and some animal studies suggest that statins increase the bone mass by enhancing
bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Although a
limited number of case-control studies suggest that statins may have the
potential to reduce the risk of fractures by increasing bone formation, other
studies have failed to show a benefit in fracture reduction. Randomized,
controlled clinical trials are needed to resolve this conflict. One possible
reason for the discrepancy in the results of preclinical, as well as clinical,
studies is the liver-specific nature of statins. Considering their high liver
specificity and low oral bioavailability, distribution of statins to the bone
microenvironment in optimum concentration is questionable. To unravel their
exact mechanism and confirm beneficial action on bone, statins should reach the
bone microenvironment in optimum concentration. Dose optimization and use of
novel controlled drug delivery systems may help in increasing the
bioavailability and distribution of statins to the bone microenvironment.
Discovery of bone-specific statins or their bone-targeted delivery offers great
potential in the treatment of osteoporosis. In this review, we have summarized
various preclinical and clinical studies of statins and their action on bone. We
have also discussed the possible mechanism of action of statins on bone.
Finally, the role of drug delivery systems in confirming and assessing the
actual potential of statins as anti-osteoporotic agents is highlighted.
-----
Curr Med Res Opin. 2006 Jan;22(1):131-7.
Prescribed vitamin D and calcium preparations in patients treated
with bone remodelling agents in primary care: a report of a pilot study.
Bayly JR, Hollands RD, Riordan-Jones SE, Yemm SJ, Brough-Williams I, Thatcher M,
Woodman NM, Dixon T.
Gloucestershire Primary and Community Care Audit Group, Gloucester, UK; Faculty
of Education Health and Sciences, University of Derby, Derby, UK.
BACKGROUND: Recent guidelines recommend that patients receiving treatment for
osteoporosis should also receive supplementation with calcium and vitamin D
unless they are calcium and vitamin D replete. Given that the majority of
elderly patients have inadequate levels of vitamin D and that determining
nutritional status is time-consuming and costly, it seems prudent to ensure that
the majority of patients aged over 65 and receiving medication for osteoporosis
should receive supplementation as a matter of course.OBJECTIVES: To determine
the level of co-prescription of calcium and vitamin D in patients receiving
treatment for osteoporosis with bisphosphonates, teriparatide, raloxifene or
strontium.Study design and methods: A pilot audit of nine general practices
covering a population of 61 202.RESULTS: Overall, 1.1% (n = 662) of patients
were receiving treatment for osteoporosis; of those, only 34.1% of patients were
co-prescribed calcium or calcium and vitamin D. Levels of co-prescription varied
considerably across practices from 74.0% to 12.2%.CONCLUSIONS: Despite national
guidelines, co-prescription of calcium and vitamin D with treatment for
osteoporosis remains sub-optimal with considerable variation between practices.
Strategies should be adopted to increase physician awareness of widespread
vitamin D inadequacy, the rationale for supplementation and poor compliance.
-----
J Bone Miner Res. 2005 Nov;20(11):1905-11. Epub 2005 Jul 18.
Combination teriparatide and raloxifene therapy for
postmenopausal osteoporosis: results from a 6-month double-blind
placebo-controlled trial.
Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, Glass EV, Myers SL,
Krege JH.
Cleveland Clinic Foundation, Cleveland, Ohio, USA.
We compared combination treatment with teriparatide plus raloxifene with
teriparatide alone in women with postmenopausal osteoporosis in a 6-month
double-blind, placebo-controlled trial that measured biochemical markers of bone
turnover and BMD. Markers of bone formation and spine BMD increased similarly
with teriparatide alone and combination therapy. However, combination therapy
induced a significantly smaller increase in bone resorption versus teriparatide
alone and significantly increased total hip BMD versus baseline. INTRODUCTION:
The effects of combining two approved treatments for osteoporosis with different
modes of action were examined by comparing teriparatide [rhPTH(1-34)]
monotherapy with combination teriparatide and raloxifene therapy. MATERIALS AND
METHODS: A 6-month randomized, double-blind trial comparing teriparatide plus
raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in
postmenopausal women with osteoporosis. RESULTS: Bone formation (N-terminal
propeptide of type 1 collagen [PINP]) increased similarly in both treatment
groups. However, the increase in bone resorption (serum C-terminal telopeptide
of type I collagen [CTx]) in the combination group was significantly smaller
than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly
increased 5.19 +/- 0.67% from baseline in the teriparatide-alone group. In the
combination group, lumbar spine (6.19 +/- 0.65%), femoral neck (2.23 +/- 0.64%),
and total hip (2.31 +/- 0.56%) BMD significantly increased from baseline to
study endpoint, and the increase in total hip BMD was significantly greater than
in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group,
mean serum calcium levels increased from baseline to endpoint (0.30 +/- 0.06
mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the
combination group, mean serum calcium was unchanged, and mean serum phosphate
decreased (-0.20 +/- 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes
in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly
different between treatment groups. The safety profile of combination therapy
was similar to teriparatide alone. CONCLUSIONS: Combination therapy increased
bone formation to a similar degree as teriparatide alone. However, the increase
in bone resorption was significantly less and total hip BMD significantly
increased for combination therapy compared with teriparatide alone. Combination
treatment with raloxifene may thus enhance the bone forming effects of
teriparatide. Further studies over longer treatment duration that include
fracture endpoints are necessary to fully ascertain the clinical significance of
combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.
-----
Osteoporos Int. 2005 Oct 14; [Epub ahead of print]
Effective and rapid treatment of painful localized transient
osteoporosis (bone marrow edema) with intravenous ibandronate.
Ringe JD, Dorst A, Faber H.
Medizinische Klinik IV, Klinikum Leverkusen, University of Cologne, 51375 ,
Leverkusen, Germany, ringe@klinikum-lev.de.
Localized transient osteoporosis (LTO; bone marrow edema syndrome) is a rare
disorder of generally unknown etiology that is characterized by acute onset of
disabling bone pain. Treatment options are currently limited and largely
ineffective. The locally increased bone turnover and low bone mineral density (BMD)
typical of LTO indicate a potential role for bisphosphonate therapy. Ibandronate,
a potent nitrogen-containing bisphosphonate, has proven efficacy in the
management of postmenopausal osteoporosis and corticosteroid-induced
osteoporosis when administered as a convenient intermittent intravenous (IV)
injection with a between-dose interval of 2 or 3 months. In a study of 12
patients with LTO, ibandronate was administered as an initial 4-mg IV dose with
a second, optional injection of 2 mg at 3 months. Daily calcium and vitamin D
supplements were provided. Pain was measured at baseline and at 1, 2, 3, and 6
months using a visual analog scale (VAS) of 1-10, and BMD was measured at
baseline and 6 months. IV ibandronate provided rapid and substantial pain
relief. The mean (SD) VAS score decreased from 8.4 (1.3) at baseline to 0.5
(0.7) at 6 months, at which time seven patients had achieved complete pain
relief. At 6 months, mean lumbar spine BMD had increased by 4.0% (range -0.8 to
7.7%) in the overall population. IV ibandronate injection affords advantages
over currently available oral and IV bisphosphonates and thus offers a promising
therapeutic advance in the treatment of LTO.
-----
Minerva Med. 2005 Oct;96(5):343-52.
Prevention and treatment of osteoporotic fractures.
Gardner MJ, Demetrakopoulos D, Shindle MK, Griffith MH, Lane JM.
Hospital for Special Surgery, New York, NY, USA.
With the aging international population, osteoporosis has become an epidemic.
This painless disease is characterized by a decreased bone mass, resulting in
decreased structural integrity of bone, and often goes undiagnosed. Typical
osteoporotic fractures include vertebrae, hip, and wrist fractures, and these
may have a dramatic impact on quality of life, even if the fracture is
successfully treated. Many antiresorptive agents have demonstrated the ability
to reduce the risk of osteoporotic fractures, and newer anabolic agents may
further reduce risk. Non-medical treatments, such as external hip protectors and
balance and low-impact strength training, are also very effective in preventing
fractures. Before specific treatments can be addressed, however, osteoporosis
must first be considered as a diagnosis in any patient with a low-energy
fracture. This requires continued public health initiatives involving patient
and physician education regarding the necessity for bone mass measurement and
the merits of antiresorptive therapy.
-----
Minerva Med. 2005 Oct;96(5):331-42.
The role of menopausal hormone therapy in preventing osteoporotic
fractures: a critical review of the clinical evidence.
Col NF, Bowlby LA, McGarry K.
Division of General Internal Medicine, Rhode Island Hospital, Brown University
Medical School, Providence, RI, USA.
Osteoporosis is a common disease resulting in millions of potentially
preventable fractures each year. Women are disproportionately affected by
osteoporosis compared to men, with loss of gonadal functioning and aging being
the 2 most important contributing factors to osteoporosis. For many decades,
menopausal hormone therapy (HT) has been the mainstay for the prevention and
treatment of osteoporosis among menopausal women. While recent randomized trial
data have confirmed findings from observational studies concerning HT's
protective effect on osteoporosis, they showed that HT increases the risks of
breast cancer, venous thromboses, stroke, and coronary heart disease. With a
strong body of evidence showing the benefit of HT in preventing osteoporotic
fractures, the challenge facing clinicians is not whether HT helps to prevent
osteoporotic fractures, but whether HT's fracture-prevention benefits outweigh
its risks. With several medications now available having efficacy comparable to
HT in preventing fractures, decisions about therapy for osteoporosis or
osteopenia should take into consideration bone mineral density, other risk
factors for osteoporotic fracture, and a careful examination of the benefits and
risks of each treatment option. After a brief discussion of the epidemiology and
pathophysiology of osteoporosis, we review the evidence from observational
studies and randomized studies examining the impact of menopausal hormone
therapy on osteoporosis. We focus on whether there are specific subgroups of
women that accrue greater or smaller benefit from HT in terms of osteoporotic
fracture reduction. We then expand our perspective to include clinical endpoints
other than osteoporosis, presenting a framework for factoring in the many risks
and benefits of HT. We conclude that all women should be informed of all
alternative treatment options and allowed to make an informed treatment decision
according to their personal risks, preferences, values, and willingness to
tolerate the risks of treatment.
-----
Paediatr Drugs. 2005;7(5):295-323.
Osteoporosis in children and adolescents : etiology and
management.
Baroncelli GI, Bertelloni S, Sodini F, Saggese G.
Department of Pediatrics, University of Pisa, Pisa, Italy.
Bone mass increases progressively during childhood, but mainly during
adolescence when approximately 40% of total bone mass is accumulated. Peak bone
mass is reached in late adolescence, and is a well recognised risk factor for
osteoporosis later in life. Thus, increasing peak bone mass can prevent
osteoporosis.The critical interpretation of bone mass measurements is a crucial
factor for the diagnosis of osteopenia/osteoporosis in children and adolescents.
To date, there are insufficient data to formally define osteopenia/osteoporosis
in this patient group, and the guidelines used for adult patients are not
applicable. In males and females aged <20 years the terminology 'low bone
density for chronologic age' may be used if the Z-score is less than -2. For
children and adolescents, this terminology is more appropriate than osteopenia/osteoporosis.
Moreover, the T-score should not be used in children and adolescents.Many
disorders, by various mechanisms, may affect the acquisition of bone mass during
childhood and adolescence. Indeed, the number of disorders that have been
identified as affecting bone mass in this age group is increasing as a
consequence of the wide use of bone mass measurements. The increased survival of
children and adolescents with chronic diseases or malignancies, as well as the
use of some treatment regimens has resulted in an increase in the incidence of
reduced bone mass in this age group.Experience in treating the various disorders
associated with osteoporosis in childhood is limited at present. The first
approach to osteoporosis management in children and adolescents should be aimed
at treating the underlying disease. The use of bisphosphonates in children and
adolescents with osteoporosis is increasing and their positive effect in
improving bone mineral density is encouraging. Osteoporosis prevention is a key
factor and it should begin in childhood. Pediatricians should have a fundamental
role in the prevention of osteoporosis, suggesting strategies to achieve an
optimal peak bone mass.
-----
Expert Opin Pharmacother. 2005 Oct;6(13):2301-13.
Oral ibandronate: a less frequently administered therapeutic
option for postmenopausal osteoporosis.
Reginster JY.
Unite d'Exploration du Metabolisme de l'Os et du Cartilage, CHU Centre Ville,
Liege, Belgium. jyreginster@ulg.ac.be
Osteoporosis is a severe condition, associated with significant disability as a
result of fragility fractures and increased mortality. Oral bisphosphonates
effectively reduce the risk of osteoporotic fracture and are generally well
tolerated. Unfortunately, patient outcomes are often compromised by suboptimal
therapeutic adherence. In other disease areas, reduced dosing frequency has been
shown to improve therapeutic adherence. A positive impact for adherence has been
observed with a reduction in the bisphosphonate dosing frequency from daily to
weekly. However, overall adherence remains suboptimal. Ibandronate is a potent
nitrogen-containing bisphosphonate specifically designed for less frequent than
weekly administration, without compromise for efficacy or tolerability. This
article reviews the pharmacology, efficacy and tolerability of oral ibandronate
when administered with extended dosing intervals in postmenopausal osteoporosis.
-----
J Rheumatol. 2005 Oct;32(10):1968-1974.
Safety and Tolerability of Oral Daily and Intermittent
Ibandronate Are Not Influenced by Age.
Ettinger MP, Felsenberg D, Harris ST, Wasnich R, Skag A, Hiltbrunner V, Wilson
K, Schimmer RC, Miller PD.
>From Radiant Research and Regional Osteoporosis Center of South Florida,
Stuart, Florida, USA; Universitatsklinikum Benjamin Franklin, Berlin, Germany;
University of California, San Francisco, California, USA; Radiant Research,
Honolulu, USA; Bergen Osteoporosesenter, Bergen, Norway; Roche Products Ltd.,
Welwyn Garden City, UK; F. Hoffmann-La Roche, Basel, Switzerland; and CCBR,
Lakewood, Colorado, USA.
OBJECTIVE:. The risk of osteoporosis increases exponentially with age. Elderly
patients, who are often frail, have declining functional status and take
multiple medications, and require osteoporosis therapies that are not only
effective, but also very well tolerated. Ibandronate is a potent
nitrogen-containing bisphosphonate that can be given intermittently with
extended between-dose intervals. Oral daily and intermittent ibandronate
(interval between doses > 2 mo) was found to significantly reduce the risk of
new morphometric vertebral fractures by 62% and 50%, respectively, compared with
calcium and vitamin D supplementation alone. We investigated the effect of age
on the safety profile of oral daily and intermittent ibandronate, with
particular emphasis on the upper gastrointestinal (GI) safety profile of
ibandronate. METHODS: A predefined subgroup analysis examined the tolerability
of oral ibandronate in women aged < 70 and >/= 70 years. RESULTS: The incidence
of adverse events in patients aged >/= 70 years receiving oral daily and
intermittent ibandronate was similar and comparable to placebo. The incidence of
upper GI adverse events, including dyspepsia and esophagitis, was also similar
between the 2 treatment groups and placebo. CONCLUSION: Older patients (>/= 70
yrs) receiving oral daily and intermittent ibandronate are at no greater risk of
adverse events than older patients receiving placebo. Older patients were at no
greater risk of upper GI adverse events than younger patients or patients
receiving placebo. As a result of the good efficacy and tolerability observed in
this trial, a once-monthly oral regimen of ibandronate is in late-stage clinical
development.
-----
Minerva Pediatr. 2005 Oct;57(5):203-11.
Idiopathic and secondary osteoporosis in childhood.
Rossi F, Perrotta S, Falcone E, Gimigliano F, Iodice M, Vetrella S, Iolascon G.
Dipartimento di Pediatria, Seconda Universita degli Studi di Napoli, Napoli,
Italy.
Osteoporosis is a common disease characterized by reduced bone mass, with a
consequent increase in bone fragility and susceptibility to fracture risk. Bone
mineral density (BMD) measurement is used to make the diagnosis of osteoporosis
prior to incident fracture, and to predict fracture risk. BMD is determined by
the peak bone mass achieved, and the rate and timing of subsequent bone loss.
Dual-energy X-ray absorptiometry (DEXA) is the most popular and effective method
utilized for osteoporosis screening. Bone disease is a side effect of concern
regarding chronic glucocorticoid (GC) administration. Most GC-treated patients
exhibit a process of bone loss, frequently leading to osteoporosis, with
increased fracture risk, especially in spinal vertebrae. Osteogenesis imperfecta
is an inherited and generalized connective tissue disorder characterized mainly
by bone fragility. Idiopathic osteoporosis of childhood or adolescence without
blue sclerae and other stigmata of osteogenesis imperfecta is occasionally
observed and sometimes more than one sib is affected. b-thalassemia major is
associated with significant bone disease. The etiology of the bone disease is
still debatable, many factors can adversely affect bone accretion in thalassemic
patients. These include delayed puberty, bone marrow expansion, the deleterious
effects of desferrioxamine, iron overload and genetic factors. Current treatment
alternatives of osteoporosis include bisphosphonates, calcitonin, and selective
estrogen receptor modulators.
-----
Nutr Rev. 2005 Aug;63(8):272-83.
Soybean foods and their benefits: potential mechanisms of action.
Omoni AO, Aluko RE.
Department of Human Nutritional Sciences, University of Manitoba, Winnipeg,
Manitoba, Canada.
Isoflavones have been proposed to be the active component responsible for the
beneficial effects of soybean foods, and appear to work in conjunction with the
proteins to protect against cancer, cardiovascular disease, and osteoporosis.
Most of the research activities on the benefits of soybean foods have focused on
the role these isoflavones play in disease prevention or treatment; however,
there is also some evidence that the benefits are attributable to certain
peptides or protein fractions from soybeans. This review will focus on some of
the potential mechanisms whereby soybeans exert their protective effects against
heart disease, cancer, and osteoporosis.
-----
Treat Endocrinol. 2005;4(5):263-77.
Antiresorptive therapy for the prevention of postmenopausal
osteoporosis : when should treatment begin?
Vestergaard P.
The Osteoporosis Clinic Aarhus Amtssygehus, Aarhus University Hospital, Aarhus,
Denmark.
Osteoporosis is a condition associated with decreased bone strength and an
increased fracture risk. It may be defined based on bone mineral density (BMD)
with a T-score at the hip or spine of less than -2.5 standard deviations in
young healthy individuals or from an osteoporotic fracture (i.e. a fracture
occurring after low-energy trauma or no apparent trauma).Risk factors
predisposing to fractures include: increasing age; female gender; low BMD; a
prior fragility fracture; a family history of fragility fractures; low
bodyweight; lack of estrogen in women (i.e. post menopause); corticosteroid use;
smoking; a number of diseases; deficiency in calcium and vitamin D; an increased
risk of falls (i.e. impaired vision); immobilization; and Caucasian race. The
more risk factors that are present the higher the risk of fractures over the
following 10 years. The need to initiate preventive therapy with anti-osteoporotic
treatment increases steeply with the absolute fracture risk.Indications for
referral for dual energy x-ray absorptiometry measurement of BMD include: age
>65 years; age <65 years in postmenopausal women with any of the risk factors
already mentioned; premature menopause (<45 years); prolonged amenorrhea (>1
year) in younger women; fragility fractures; and diseases or conditions known to
lead to osteoporosis.Antiresorptive therapies include calcium plus vitamin D,
bisphosphonates (alendronate, etidronate, risedronate, ibandronate), selective
estrogen receptor modulators (raloxifene), hormone replacement therapy, and
calcitonin.Guidelines from several countries on when to initiate antiresorptive
therapy state that therapy may be started in patients with a prior fragility
fracture (some guidelines state that in this situation no BMD measurements are
necessary) or in patients with a T-score of less than -2.5 (some guidelines
state that additional risk factors need to be present in this situation). Some
guidelines state that antiresorptive therapy may be initiated in patients with a
T-score in the osteopenic range (from -1 to -2.5, i.e. not frank osteoporosis)
in the presence of other risk factors.The cost effectiveness of antiresorptive
therapy increases with the absolute fracture risk. In some scenarios, treatment
with bisphosphonates may be cost effective in a 50-year-old woman with an
absolute hip fracture risk of >/=1.1% over the next 10 years.
-----
Crit Care Nurs Q. 2005 Jul-Sep;28(3):269-75.
The effects of weight loss on calcium and bone.
Hogan SL.
Performance Improvement Department, Allegheny General Hospital, Pittsburgh, Pa.
The article identifies 2 national healthcare problems that are occurring in the
United States. The first national healthcare problem is obesity and the second
is osteoporosis. What do these 2 healthcare problems have in common? They go
hand in hand in teenagers and adults who have undergone weight reduction
surgeries. These surgical procedures place a person at risk for osteoporosis
because of the surgical procedure causing malabsorption that comes from the
bypassing of the duodenum, which is the primary location for the absorption of
calcium. This new high-risk population needs to become educated regarding
osteoporosis and the treatment measures that can be instituted to prevent this
disease. Osteoporosis is a disease where the bones of the body become very
fragile and can easily break. Any bone can be affected by osteoporosis and
fracture. There is no cure for osteoporosis but this disease can be controlled
and prevented. This article discusses various treatment and prevention measures,
ranging from dietary changes to the addition of medications.
-----
Am J Health Syst Pharm. 2005 Aug 1;62(15):1574-81.
Vitamin K in the treatment and prevention of osteoporosis and
arterial calcification.
Adams J, Pepping J.
Castle Medical Center, Kailua, HI.
PURPOSE: The role of vitamin K in the prevention and treatment of osteoporosis
and arterial calcification is examined. SUMMARY: Vitamin K is essential for the
activation of vitamin K-dependent proteins, which are involved not only in blood
coagulation but in bone metabolism and the inhibition of arterial calcification.
In humans, vitamin K is primarily a cofactor in the enzymatic reaction that
converts glutamate residues into gamma-carboxyglutamate residues in vitamin
K-dependent proteins. Numerous studies have demonstrated the importance of
vitamin K in bone health. The results of recent studies have suggested that
concurrent use of menaquinone and vitamin D may substantially reduce bone loss.
Menaquinone was also found to have a synergistic effect when administered with
hormone therapy. Several epidemiologic and intervention studies have found that
vitamin K deficiency causes reductions in bone mineral density and increases the
risk of fractures. Arterial calcification is an active, cell-controlled process
that shares many similarities with bone metabolism. Concurrent arterial
calcification and osteoporosis have been called the "calcification paradox" and
occur frequently in postmenopausal women. The results of two dose-response
studies have indicated that the amount of vitamin K needed for optimal gamma-carboxylation
of osteocalcin is significantly higher than what is provided through diet alone
and that current dosage recommendations should be increased to optimize bone
mineralization. Few adverse effects have been reported from oral vitamin K.
CONCLUSION: Phytonadione and menaquinone may be effective for the prevention and
treatment of osteoporosis and arterial calcification.
-----
Liver Transpl. 2005 Aug;11(8):960-6.
Alendronate in combination with calcium and vitamin D prevents
bone loss after orthotopic liver transplantation: A prospective single-center
study.
Millonig G, Graziadei IW, Eichler D, Pfeiffer KP, Finkenstedt G, Muehllechner P,
Koenigsrainer A, Margreiter R, Vogel W.
Department of Gastroenterology and Hepatology, Innsbruck Medical University,
Innsbruck, Austria.
Bone loss is a common complication in patients before and after liver
transplantation (LT). The aim of this study was to investigate the efficacy of
prophylactic treatment with bisphosphonates after LT in preventing progressive
bone loss in LT patients. We included 136 patients with end-stage liver diseases
awaiting LT. Bone mineral density (BMD) (by dual X-ray absorptiometry) and
markers of bone metabolism were determined before, and 4, 12, 24, 36, and 48
months after LT. All patients received vitamin D and calcium supplementation
before and after LT, those with osteopenia or osteoporosis prior to LT were
additionally treated with alendronate following LT. Decreased BMD was seen in a
high percentage of patients undergoing LT (osteopenia 48.5%, osteoporosis
23.5%). Reduced BMD before LT was not related to gender, underlying liver
disease, or Child-Turcotte-Pugh classification. Body mass index (BMI) prior to
LT, however, correlated significantly with the fracture risk. Alendronate
prevented the ubiquitously observed bone loss after LT in patients with
osteoporosis and osteopenia and, in addition, led to an increase in BMD in
patients with osteoporosis within 24 months after LT. In conclusion, our study
suggests that alendronate is efficacious in preventing the natural course of
bone loss associated with LT. (Liver Transpl 2005;11:960-966.).
-----
Drug Saf. 2005;28(8):721-30.
Benefit-risk assessment of raloxifene in postmenopausal
osteoporosis.
Cranney A, Adachi JD.
Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Raloxifene, a nonsteroidal benzothiophene, is a second-generation selective
estrogen receptor modulator (SERM) that is an antiresorptive agent. Raloxifene
is a non-hormonal agent that binds to the estrogen receptor and results in
estrogen agonist effects on bone and the cardiovascular system and estrogen
antagonist effects on endometrial and breast tissue. Raloxifene has diverse
pharmacodynamic properties due to its differential interactions with the
estrogen receptor and tissue selectivity. Raloxifene was the first SERM to be
approved for the prevention and treatment of postmenopausal osteoporosis. In
this review, we conducted a systematic search of the literature for trials that
evaluated the following outcomes: bone density, fractures, quality of life,
cardiovascular outcomes, safety and adverse events. Raloxifene at the approved
dosage of 60 mg/day increased lumbar spine bone density by 2.5% relative to
control after 2 years of therapy. A large fracture prevention trial confirmed
that treatment with raloxifene 60 mg/day for 3 years decreased the relative risk
of incident vertebral fractures by 30-50% in women with prevalent fractures or
osteoporosis. Extraskeletal effects of raloxifene include a reduction in total
cholesterol and low density lipoprotein cholesterol levels. Assessment of the
safety profile revealed that raloxifene was not associated with endometrial
hyperplasia and that there was a 72% reduction in the incidence of invasive
breast cancer in raloxifene-treated postmenopausal women with osteoporosis.
Adverse events associated with raloxifene included an increase in the absolute
risk of venous thromboembolism and an increase in the risk of hot flashes and
leg cramps. In comparison to other osteoporosis therapies, raloxifene has a
lesser impact on bone mineral density, a similar effect on the occurrence of
vertebral fractures, but no effect on the frequency of non-vertebral fractures.
Raloxifene can be recommended for the prevention of vertebral fractures in women
with osteopenia/osteoporosis who are not at high risk of non-vertebral fractures
and who do not have a past history of venous thromboembolism.
-----
Cochrane Database Syst Rev. 2005 Jul 20;(3):CD000227.
Vitamin D and vitamin D analogues for preventing fractures
associated with involutional and post-menopausal osteoporosis.
Avenell A, Gillespie W, Gillespie L, O'connell D.
Health Services Research Unit, University of Aberdeen, Polwarth Building,
Foresterhill, Aberdeen, Scotland, UK, AB25 2ZD.
BACKGROUND: Vitamin D and related compounds have been used to prevent fractures.
OBJECTIVES: To determine the effects of vitamin D or analogues, with or without
calcium, in the prevention of fractures in older people. SEARCH STRATEGY: We
searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the
Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1,
2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent
search: March 2005. SELECTION CRITERIA: Randomised or quasi-randomised trials
comparing vitamin D or an analogue, alone or with calcium, against placebo, no
intervention, or calcium, reporting fracture outcomes, in older people. DATA
COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and
extracted data. Data were pooled, where admissible, using the fixed-effect
model, or random-effects model if the relative risks were heterogeneous. MAIN
RESULTS: Vitamin D alone showed no statistically significant effect on hip
fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41),
vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13,
95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR
0.99, 95% CI 0.91 to 1.09).Vitamin D with calcium marginally reduced hip
fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96),
non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78
to 0.97), but there was no evidence of effect of vitamin D with calcium on
vertebral fractures. The effect appeared to be restricted to those living in
institutional care.Hypercalcaemia was more common when vitamin D or its
analogues was given compared with placebo or calcium (14 trials, 8035
participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with
calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61).
There was no evidence that vitamin D increased gastro-intestinal symptoms (seven
trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or
renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87).
AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain
fewer hip and other non-vertebral fractures if given vitamin D with calcium
supplements. Effectiveness of vitamin D alone in fracture prevention is unclear.
There is no evidence of advantage of analogues of vitamin D compared with
vitamin D. Calcitriol may be associated with an increased incidence of adverse
effects. Dose, frequency, and route of administration of vitamin D in older
people require further investigation.
-----
Ann Med. 2005;37(4):303-10.
Non-pharmacological means to prevent fractures among older
adults.
Kannus P, Uusi-Rasi K, Palvanen M, Parkkari J.
Accident & Trauma Research Center, UKK Institute for Health Promotion Research,
Tampere, Finland. pekka.kannus@uta.fi
Bone fractures affecting elderly people are a true public health burden, because
they represent one of the most important causes of long-standing pain,
functional impairment, disability, and death among this population. Compromised
bone strength (osteoporosis) and falling, alone, or more frequently in
combination, are the two independent and immediate risk factors of elderly
people's fractures through which all the other, more distant risk factors, such
as aging, inactivity, poor nutrition, smoking, use of alcohol, diseases,
medications, functional impairments, and disabilities, operate. Of these two,
falling, not osteoporosis, is the strongest single risk factor for a fracture.
The most usual occurrence resulting in a fracture of an older adult is a
'simple' fall from standing height or less. Although in general terms this type
of trauma is mild or moderate only (compared with, for example, motor vehicle
collisions), to the specific injury site these traumas are high-impact injuries
often creating forces clearly exceeding the breaking strength of the bone.
Therefore, fractures affecting elderly people should be called 'fall-induced
high-impact injuries' instead of the commonly used, partly misleading terms of
osteoporotic fractures or minimal-trauma fractures. Prevention of elderly
people's fractures consists of prevention of osteoporosis and of falling, and
prevention of fractures using injury-site protection. Concerning osteoporosis,
maximizing peak bone mass and preventing bone loss by regular exercise, calcium,
and vitamin D, and, treatment of established osteoporosis with bone-specific
drugs, have a strong scientific basis. In fall prevention, regular strength and
balance training, reducing psychotropic medication, and diet supplementation
with vitamin D and calcium have been shown to be effective. The multifaceted
risk factor-assessing and modifying interventions have also been successful in
preventing falls among the older adults by simultaneously affecting many of the
risk factors of falling. Finally, concerning injury-site protection, padded
strong-shield hip protectors whose effectiveness is scientifically proven seem
to be a promising option in preventing hip fractures.
-----
Ann Med. 2005;37(4):286-94.
Osteoporosis in chronically ill children.
Sochett EB, Makitie O.
The Hospital for Sick Children, Division of Endocrinology, University of
Toronto, Canada. etienne.sochett@sickkids.ca
Gains in bone mass are very rapid during adolescence and peak bone mass, the
most important determinant of osteoporosis, is attained by early adulthood.
Glucocorticoids, widely used in children with chronic illness, are known to
impact bone mass and quality. In addition, disease and treatment-related
factors, nutrient and hormone deficiencies and decreased physical activity may
all negatively affect bone mass accrual. Although decreased bone density is
increasingly recognized in chronically ill children, current knowledge of the
epidemiology, diagnosis and optimal treatment of pediatric secondary
osteoporosis is limited. In addition to bone densitometry, biochemical and
radiographic tests should be used in the diagnosis of osteoporosis. Bone
histomorphometry may be needed in selected situations. At risk children should
be advised to ensure sufficient calcium and vitamin D intake and weight bearing
physical activity. Growth and pubertal development require careful assessment
because of their close correlation with bone formation. Given limited experience
with bisphosphonates, it seems prudent to target antiresorptive therapy to those
children who have developed symptomatic disease. Ideally this should be done in
controlled settings. Early identification and adequate intervention, in selected
cases with bisphosphonates, is needed in order to prevent deleterious skeletal
complications of osteoporosis in chronically ill children.
-----
Ann Med. 2005;37(4):278-85.
The role of vitamin D in the prevention of osteoporosis.
Vieth R.
Department of Nutritional Sciences, Laboratory Medicine and Pathology,
University of Toronto, Ontario, Canada. rvieth@mtsinai.on.ca
The need for vitamin D to prevent rickets was the drive for selection of lighter
skin color in temperate climates. Anthropologists also know that as human
populations developed more sedentary lifestyles, this coincided with a decline
in bone quantity, quality, and fracture resistance. Since osteoporosis occurs
after the reproductive years, there is no way that natural selection could have
adapted our biology to prevent it. However, osteoporosis can be largely
prevented by optimizing physical activity, and the vitamin D-related factors of
environment, and nutrition. The role of vitamin D3 in osteoporosis is
conclusively established from a very simple meta-analysis of the four
randomized, placebo-controlled clinical trials into the effect of 20 microg (800
IU) per day. These have all demonstrated that this dose prevents approximately
30% of hip or non-vertebral fractures compared to placebo, in adults older than
65 years. Intakes less than this have never been found effective. The lowest
average serum 25-hydroxyvitamin D concentration in any study demonstrating
fracture reduction was 74 nmol/L. Thus, 25-hydroxyvitamin D levels in older
adults should exceed this amount. The role of vitamin D supplementation is to
provide humans with the nutrient in an amount closer to our species' biological
norm. This amount of vitamin D results in the optimal function of many aspects
of health, including balance and muscle strength that lessen the risk of
fracture beyond what is possible via the quality and quantity of bone itself.
-----
Mol Aspects Med. 2005 Jun;26(3):203-19.
Vitamin D in the aging musculoskeletal system: An authentic
strength preserving hormone.
Montero-Odasso M, Duque G.
Geriatric Medicine Program, Hospital Italiano de Buenos Aires, Buenos Aires,
Argentina; Centre Bloomfield for Research in Aging, McGill University, Montreal,
QC, Canada.
Until recently, vitamin D was only considered as one of the calciotrophic
hormones without major significance in other metabolic processes in the body.
Several recent findings have demonstrated that vitamin D plays also a role as a
factor for cell differentiation, function and survival. Two organs, muscle and
bone, are significantly affected by the presence, or absence, of vitamin D. In
bone, vitamin D stimulates bone turnover while protecting osteoblasts of dying
by apoptosis whereas in muscle vitamin D maintains the function of type II
fibers preserving muscle strength and preventing falls. Furthermore, two major
changes associated to aging: osteoporosis and sarcopenia, have been also linked
to the development of frailty in elderly patients. In both cases vitamin D plays
an important role since the low levels of this vitamin seen in senior people may
be associated to a deficit in bone formation and muscle function. In this
review, the interaction between vitamin D and the musculoskeletal components of
frailty are considered from the basic mechanisms to the potential therapeutic
approach. We expect that these new considerations about the importance of
vitamin D in the elderly will stimulate an innovative approach to the problem of
falls and fractures which constitutes a significant burden to public health
budgets worldwide.
-----
Joint Bone Spine. 2005 May;72(3):202-206.
Androgens and bone metabolism.
Alexandre C.
Research Unit Inserm U366, Service de Rhumatologie, St-Etienne University,
Hopital Bellevue, CHU de St-Etienne, Boulevard Pasteur, 42055 St Etienne,
France.
The gradual reductions in bone mass and skeletal calcium density seen throughout
adulthood occur in parallel with changes in the production of bioactive sex
hormones in both men and women. The long-held belief that osteoporosis is
dependent on androgens in men and estrogens in women has been challenged by
recent reports of osteoporosis in young men with normal testosterone levels but
extremely low estrogen levels. A review of the literature indicates that
estrogens have a far greater influence on bone mass than do androgens. This may
suggest new approaches to the treatment of male osteoporosis. Furthermore,
osteoporosis induced by prostate cancer treatment should receive greater medical
attention.
-----
Eur Spine J. 2005 Apr 15; [Epub ahead of print]
Does raloxifene treatment influence back pain and disability
among postmenopausal women with osteoporosis?
Papadokostakis G, Katonis P, Damilakis J, Hadjipavlou A.
Department of Orthopaedic Surgery and Traumatology, University General Hospital,
Heraklio, Crete, Greece.
Clinical studies have suggested that postmenopausal women on estrogen
replacement treatment are more likely to experience back pain and related
disability compared to women who do not take estrogens. Raloxifene, a selective
estrogen receptor modulator has estrogen-like effects on bone tissue, and
antagonize the action of estrogens on endometrium and breast tissue. It is
unknown if the treatment of osteoporosis with raloxifene has estrogen-like or
opposite effects on back pain and functional capacity among postmenopausal women
with osteoporosis. A total of 120 postmenopausal women with osteoporosis and
chronic back pain were randomized to receive raloxifene 60 mg with 1,000 mg
calcium, and 800 IU vitamin D daily or 1,000 mg calcium and 800 IU vitamin D
daily. Pain intensity and pain-related disability were measured before treatment
at 6 months and after 1 year. Repeated measures of ANOVA, did not reveal
statistically significant differences over time, on pain intensity and
disability scores, between groups studied. There was a trend in pain intensity
changes during the follow-up period, but the differences between the groups were
not statistically significant. It seems that treatment with raloxifene does not
influence back pain and disability among postmenopausal women with osteoporosis.
Raloxifene may have estrogenic agonist effects on nociceptive processing in the
central nervous system.
-----
Clin Calcium. 2005 Apr;15(4):666-72.
[The role of nutrition in the treatment of osteoporosis.]
[Article in Japanese]
Tanaka K, Nakanishi Y, Kido S.
Kyoto Women's University, Department of Food and Nutrition.
Calcium intake was reported to be associated with peak bone mass. Vitamin D
insufficiency, which is less severe than deficiency, is prevalent in the elderly
and known to cause osteoporosis. Protein malnutrition increases the fracture
risk due to decreased bone mineral density and muscle weakness. Other nutrients
have also been reported to be associated with osteoporosis. Thus nutritional
aspect of osteoporosis should be interpreted from the broader perspectives.
Since nutritional status greatly varies from one nation to another, we must add
our original evidence in Japan to the report from WHO.
-----
Presse Med. 2005 Mar 12;34(5):379-84.
[Osteoporosis and hormone replacement therapy]
[Article in French]
Roux C.
Service de rhumatologie, Universite Rene Descartes, Hopital Cochin, 27, rue du
Faubourg, St Jacques, 75014 Paris. christian.roux@cch.ap-hop-paris.fr
Hormone replacement therapy prevents bone loss and the increase in bone
resorption due to the hormone deficiency in oestrogen in postmenopausal women.
The WHI (Women's Health Initiative) randomised, double-blind study against
placebo, demonstrated that which all the epidemiological trials had already
suggested: replacement therapy can reducing by around 30% the risk of fractures
in postmenopausal women. Administration of hormone replacement therapy requires
account being taken of (in view of the uncertainties regarding the anti-fracture
effect of low dose therapy): the duration (in view of the absence of remnant
effect of the product on bone loss and on the risk of fracture) and the
benefit/risk ration (in view of the benefits demonstrated on climacteric
disorders, but the increase in risk of breast cancer). The menopause is the
occasion to assess individual risks, notably vascular and of fractures, taking
into account the clinical risk factors and measurement of bone density.
-----
Expert Opin Investig Drugs. 2005 Mar;14(3):265-78.
Emerging and potential therapies for osteoporosis.
Grey A, Reid IR.
Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz
Osteoporotic fractures are an important public health problem, contributing
substantially to morbidity and mortality in an ageing world population and
consuming considerable health resources. Currently available pharmacological
therapies for prevention of fragility fractures are limited in scope, efficacy
and acceptability to patients. Considerable efforts are being made to develop
new, more effective treatments for osteoporosis and to refine/optimise existing
therapies. These novel treatments include an expanding array of drugs that
primarily inhibit osteoclastic bone resorption; oestrogenic compounds,
bisphosphonates, inhibitors of receptor activator of nuclear factor-kappaB
ligand signalling, cathepsin K inhibitors, c-src kinase inhibitors, integrin
inhibitors and chloride channel inhibitors. The advent of intermittent para-thyroid
hormone (PTH) therapy has provided proof-of-principle that osteo-blast-targeted
(anabolic) agents can effectively prevent osteoporotic fractures, and is likely
to be followed by the introduction of other therapies based upon PTH, such as
orally active PTH analogues, antagonists of the calcium sensing receptor, PTH-related
peptide analogues, and/or agents that induce osteoblast anabolism via pathways
involving key, recently identified, molecular targets (wnt low-density
lipoprotein receptor-related protein-5 signalling, sclerostin and matrix
extracellular phosphoglycoprotein).
-----
Clin Calcium. 2005;15(4):655-660.
[Active vitamin D metalolite and prevention of falls.]
[Article in Japanese]
Hayashi Y.
Tokyo Metropolitan geriatric Hospital / Director.
Recently, vitamin D metabolites have been internationally recognized to be
effective for osteoporosis. The beneficial trend of the drugs for osteoporosis
has been more in the prevention of fracture than in the increase of bone mineral
density, and more in the prevention of fractures of four extremities compared to
spinal fractures. The reason to reduce the fracture frequency of four
extremities is due to increase the muscle power, the decrease of body sway and
the reduction of falls by the action of the vitamin D. In the study of Japanese,
it was declared that administration of active vitamin D significantly reduced
the frequency of femoral neck fracture.
-----
Clin Breast Cancer. 2005 Feb;5 Suppl 2:S63-70.
Strategies to prevent chemotherapy-induced bone loss in women
with breast cancer.
Theriault RL.
Department of Breast Medical Oncology, Box 424, M. D. Anderson Cancer Center,
1515 Holcombe Blvd, Houston, TX 77030; e-mail: rtheriau@mdanderson.org.
Treatment-induced osteoporosis is an increasing problem for women diagnosed with
breast cancer. As more women receive adjuvant endocrine therapy and
chemotherapy, and breast cancer survival improves, the impact of cancer
treatment on bone health and the morbidity associated with chemotherapy-induced
bone loss becomes more of a significant medical concern. Endocrine agents like
aromatase inhibitors and luteinizing hormone-releasing hormone agonists decrease
the production of ovarian and adrenal estrogens and are widely used in the
adjuvant and metastatic settings for treatment of women with hormone
receptor-positive breast cancer. Estrogen is important for bone health. It
stimulates osteoblasts and maintains bone integrity. As bone density decreases,
the risk of fracture increases. This can include fractures of the wrist, femur,
and vertebrae. Several potent bisphosphonates have been developed to prevent or
treat cancer treatment-induced bone loss.
-----
Eur Radiol. 2005 Feb;15(2):360-7. Epub 2004 Nov 25.
Percutaneous vertebroplasty immediately relieves pain of
osteoporotic vertebral compression fractures and prevents prolonged
immobilization of patients.
Kobayashi K, Shimoyama K, Nakamura K, Murata K.
Department of Radiology, Kyoto Renaiss Hospital, 1-38 Suehiro-cho, Fukuchiyama,
Kyoto, 620-0054, Japan, radiology@renaiss.jp.
To assess the immediate efficacy of percutaneous vertebroplasty (PVP) in relief
of pain and improving mobility of patients with vertebral compression fractures
(VCF) secondary to osteoporosis, 205 cases (175 patients) underwent 250
percutaneous injections of polymethylmethacrylate (PMMA; unilateral, 247 levels;
bilateral, 3 levels) into vertebrae under CT and fluoroscopic guidance for 34
months. Patients were prospectively asked to quantify their pain on a visual
analog scale (VAS) before and a day after PVP. The interval to mobilization was
recorded in those who were immobilized because of pain and/or bed-rest therapy
(115 cases). PVP was technically successful in all patients, with three cases of
minimal complications. The mean VAS score available for 196 cases was improved
from 7.22+/-1.89 (range, 3-10) to 2.07+/-1.19 (range, 0-10) by PVP. Ninety-four
of 115 immobilized cases (81.7%) were mobile by 24 h after PVP, and the mean
value was 1.9+/-2.8 days. The incidence of recurrent and new fractures was 15.6%
in 4-25 months (mean, 15.3 months). PVP is a safe and effective treatment for
relieving the pain associated with osteoporotic VCF and strengthening the
vertebrae, avoiding refractures. This therapy leads to early mobilization and
avoidance of the dangers of conservative therapy of bed-rest.
-----
Maturitas. 2005 Feb 14;50(2):78-85.
Levonorgestrel and 17beta-estradiol given transdermally for the
prevention of postmenopausal osteoporosis.
Warming L, Ravn P, Christiansen C.
Center for Clinical and Basic Research A/S, Ballerup Byvej 222, DK-2750 Ballerup,
Denmark.
Aim: To evaluate the efficacy and safety of a new transdermal continuous
combined hormone replacement therapy (HRT) for the prevention of postmenopausal
osteoporosis. Methods: 212 osteopenic (lumbar spine and/or hip (femoral neck)
bone mineral density (BMD) between -1.0 and -2.5 S.D. of the premenopausal mean
value) postmenopausal women aged 45-65 years participated in a 2-year
prospective study. Treatments were 45mug 17beta-estradiol combined with 30 (n =
69) or 40mug (n = 72) levonorgestrel daily or placebo (n = 71) given as a 7-day
patch. All received a daily supplement of 500mg calcium. BMD at lumbar spine
(L2-L4), hip and total body, as well as blood and urinary biochemical markers of
bone turnover (serum osteocalcin (sOC), serum bone-specific alkaline phosphatase
(sBSAP), urinary calcium (uCa) and urinary CrossLaps (uCTX)) were measured
regularly. Results: BMD at the lumbar spine, hip and total body increased by 8,
6 and 3% (P < 0.001), respectively, in the hormone groups versus placebo. The
bone markers all decreased accordingly (sOC: 37%, sBSAP: 34% and uCTX: 65% from
baseline (all P < 0.001)), except for uCa that did not change significantly. No
significant dose-related effect of levonorgestrel was found. Vaginal
bleeding/spotting decreased from 48 to 25% of the HRT-treated women during the
study period. Skin tolerance was good in 84% of the women with no difference
between the study groups. No incidences of endometrial hyperplasia, uterine or
mammary cancer occurred. Conclusion: The transdermal combination of
17beta-estradiol and levonorgestrel has a positive effect on BMD in an
osteopenic postmenopausal population. Furthermore, a high safety profile was
observed.
-----
Ann Rheum Dis. 2005 Feb;64(2):176-8.
How to prevent steroid induced osteoporosis.
Sambrook PN.
Royal North Shore Hospital, St Leonards, Sydney, Australia 2065. sambrook@med.usyd.ed.au.
The first choice for prevention of corticosteroid osteoporosis is a potent oral
bisphosphonate-for example, alendronate or risedronate. Intravenous
bisphosphonates should be considered for patients intolerant of the oral route.
For patients receiving chronic low dose corticosteroids treatment with calcium
and vitamin D may prevent further bone loss. Use of parathyroid hormone is
promising.
-----
Bone. 2005 Jan;36(1):47-51. Epub 2004 Nov 25.
The effect of intranasal salmon calcitonin therapy on bone
mineral density in idiopathic male osteoporosis without vertebral fractures-An
open label study.
Toth E, Csupor E, Meszaros S, Ferencz V, Nemeth L, McCloskey EV, Horvath C.
Department of Rheumatology, Flor Ferenc Country Hospital, Kistarcsa, H-2143,
Hungary.
The aim of this study was to examine the effect of intranasal salmon calcitonin
therapy on bone mineral density (BMD) in idiopathic male osteoporosis without
vertebral fractures. We conducted a randomized, open label, controlled trial in
71 male patients (mean age 59 +/- 6 years) suffering from idiopathic
osteoporosis (femoral neck T-score <-2.5) without vertebral deformity. Patients
in the control group (n = 31) received 400 IU Vitamin D + 1000 mg elemental
calcium daily while the treatment group (n = 40) received 400 IU Vitamin D, 1000
mg elemental calcium plus 200 IU calcitonin nasal spray daily during alternate
months. The study period was 18 months. Compared to controls, nasal calcitonin
was associated with significant increases in bone mineral density at the lumbar
spine (+3.5 +/- -4.3% vs. +0.83 +/- 6.4%, P = 0.04) and the femoral neck (+3.2
+/- 3.9% vs. +0.68 +/- 5.7%, P = 0.004). No significant difference was observed
at the radius between the treatment groups (+1.4 +/- 8.8% vs. +1.4 +/- 10.9%, P
= 0.98). Treatment was well tolerated with no premature discontinuations or
significant side effects compared to the control group. We conclude that 200 IU
salmon calcitonin nasal spray used daily, intermittently proved to be an
effective and safe therapy in male idiopathic osteoporosis.
-----
Rheumatol Int. 2005 Jan 20; [Epub ahead of print]
Comparison of cyclic and continuous calcitonin regimens in the
treatment of postmenopausal osteoporosis.
Tekeoglu I, Adak B, Budancamanak M, Demirel A, Ediz L.
Yuzuncu Yil University PMR and Rheumatology, Van, Turkey.
We aimed to compare and evaluate the efficacies of a continuous regimen of
intranasal salmon calcitonin (SCT) and two cyclic regimens (different cyclic
regimens from previous studies) based on alternating 15 days or on 10 days
consecutively per month for 1 year in the treatment of postmenopausal
osteoporosis. We performed an open-label, prospective, randomized clinical
trial. A total of 120 postmenopausal osteoporotic participants between 50 and 65
years old were randomly assigned to one of three treatment groups. Patients in
group 1 (n=40) received continuously SCT nasal spray at a dose of 200 IU/day,
plus continuously 500 mg/day elementary calcium and 0.25 mug/day 1-alpha
hydroxyvitamin D3, for 1 year. Patients in group 2 (n=40) received cyclically
SCT nasal spray at a dose of 200 IU/day on alternating 15 days per month, plus
continuously 500 mg/day elementary calcium and 0.25 mug/day 1-alpha
hydroxyvitamin D3, for 1 year. Patients in group 3 (n=40) received cyclically
SCT nasal spray on 10 days consecutively per month (20 days/month rest), plus
continuously 500 mg/day elementary calcium and 0.25 mug/day 1-alpha
hydroxyvitamin D3, for 1 year. Data was evaluated by repeated analysis of
variance (ANOVA). In addition, statistical differences between groups were
assessed by the two-tailed Student's t test. After 1 year of the study, seven
patients from group 1, eight patients from group 2 and five patients from group
3 withdrew from the study. No patient discontinued the study because of adverse
drug effects. There was a statistically-significant improvement in pain
intensity VAS scores at the end of the year to baseline scores in all three
groups (p<0.001). There was no significant difference in pain intensity VAS
scores between groups at the end of the year (p>0.05). Lumbar and femur neck BMD
scores improved significantly at the end of treatment in all three groups
(p<0.05). There was no statistically-significant difference in BMD scores
between groups at final (p>0.05). Urinary DPD/Cre levels decreased significantly
in all three groups by the end of the year (p<0.05). There was no
statistically-significant difference in urinary DPD/Cre final levels between
groups (p>0.05). According to the results of the present study, consecutive 10
days therapy with SCT, which is the first in the literature to our knowledge, is
as effective as the other two regimens in the treatmnent of osteoporosis. Both
cyclic regimens in our study (alternating 15 days and 10 consecutive days each
month for 1 year) do appear to offer some advantages, especially economically
and clinically, as compared to continuous treatment.
-----
Osteoporos Int. 2005 Jan 15; [Epub ahead of print]
Bone response to treatment with lower doses of conjugated
estrogens with and without medroxyprogesterone acetate in early postmenopausal
women.
Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH.
Helen Hayes Hospital, Route 9 W, West Haverstraw, NY, 10993, USA, lindsayr@helenhayeshosp.org.
Lower doses of conjugated estrogens (CE) alone or combined with lower doses of
medroxyprogesterone acetate (MPA) increase mean bone mineral density (BMD) from
baseline at the spine and hip in early postmenopausal women. However, not all
women on therapy gain BMD. The incidence of continued bone loss (defined as a
loss of BMD of >2% from baseline) among women using lower doses of CE and CE/MPA
is unknown. This randomized, double-blind, placebo-controlled, multicenter
substudy of the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE)
trial investigated the incidence of continued bone loss with lower-dose CE and
CE/MPA. Eight hundred twenty-two healthy postmenopausal women with intact uteri
received CE 0.625, CE 0.625/MPA 2.5, CE 0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5,
CE 0.3, CE 0.3/MPA 1.5 (all doses in mg/day), or placebo for 2 years along with
600 mg/day of calcium. Changes from baseline in spine and total hip BMD were
compared among treatment groups in an intent-to-treat analysis. At 12 months,
<10% of women on active treatment lost >2% of spinal BMD (except CE 0.3/MPA 1.5
[15.6%]), compared with 41.2% of women on placebo. At 24 months, the percentages
of women on active treatment who lost >2% of spine BMD ranged from 4.5% with CE
0.45/MPA 1.5-15.6% with CE 0.3/MPA 1.5, compared with 55.2% of women taking
placebo. More than 85% of women on active treatment did not experience continued
BMD loss at the hip at 12 months and 24 months, in contrast to 30.6% of women on
placebo at 12 months and 36.5% at 24 months. Women receiving active treatment
who lost >2% of spine or hip BMD also had a lesser reduction in biochemical
markers of bone turnover. In summary, continued bone loss among early
postmenopausal women treated with lower doses of CE or CE/MPA is uncommon.
-----
Clin Rheumatol. 2005 Jan 13; [Epub ahead of print]
Effect of intermittent administration of 200 IU intranasal salmon
calcitonin and low doses of 1alpha(OH) vitamin D(3) on bone mineral density of
the lumbar spine and hip region and biochemical bone markers in women with
postmenopausal osteoporosis: a pilot study.
Kaskani E, Lyritis GP, Kosmidis C, Galanos A, Andypas G, Chorianopoulos K,
Giagiosis A, Iliadou K, Karagianis A, Katsimichas K, Koskinas A, Matsouka K.
Laboratory for the Research of the Musculoskeletal System (LRMS), KAT Hospital,
Kifisia, Greece, lyritis@lrms.edu.gr.
A 1-year prospective, open, randomized, controlled trial was conducted as a
pilot study to examine the effect of intermittent administration of 200 IU
intranasal salmon calcitonin and 1alpha(OH) vitamin D(3) [1alpha(OH)D(3)] on
bone mineral density (BMD) of the lumbar spine and hip as well as on the markers
of bone metabolism in women with postmenopausal osteoporosis. A total of 102
randomly recruited women received either 200 IU intranasal salmon calcitonin (Miacalcic
nasal 200, Novartis, Basel, Switzerland) daily, 1 month on-1 month off, 0.25 mug
1alpha(OH)D(3), and 500 mg elemental calcium continuously (n=57 women) or only
0.25 mug 1alpha(OH)D(3) and 500 mg calcium (n=45 women) for a period of 1 year.
BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca)
metabolism and bone turnover [serum Ca, serum phosphorus, intact parathormone (iPTH),
total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary
Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio]
were measured at the beginning of the study before treatment and after 6 and 12
months of treatment. Baseline characteristics of participants, including age,
body mass index, lumbar and hip BMD, and biochemical markers were similar
between the two groups. A total of 91 patients completed the study (50 in the
salmon calcitonin nasal spray group and 41 in the other group). Lumbar BMD
increased significantly in the salmon calcitonin group from baseline (3.0%,
p=0.005) and in comparison to the non-calcitonin-treated group (p=0.009). The
salmon calcitonin group also had a significant increase in femoral neck BMD
compared with baseline values (3.1%, p=0.0005) and in comparison to the non-calcitonin-treated
group (p=0.0005) in Ward's triangle BMD (2.9% from baseline values, p=0.009) and
in comparison to the non-calcitonin-treated group (p=0.005) in trochanteric BMD
(3.4% from baseline values, p=0.007) and in comparison to the non-calcitonin-treated
group (P=0.01). Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were
significantly decreased from baseline in the salmon calcitonin-treated group
(-6.1 and -6.3%, respectively, p=0.001). Bone-specific alkaline phosphatase
levels were also significantly decreased from baseline in the salmon calcitonin-treated
group (-3.6%, p=0.003). In the same group, a significant decrease in iPTH serum
levels compared to baseline values (-2.5%, p=0.005) and in comparison to the
non-calcitonin-treated group (p=0.005) was noted. In conclusion, in this pilot
study, 1-year intermittent treatment with 200 IU intranasal salmon calcitonin
and low doses of 1alpha(OH)D(3) produced a significant effect on bone turnover
and BMD in postmenopausal women with osteoporosis.
-----
Rev Med Liege. 2004 Nov;59(11):633-47.
[Treatment of postmenopausal osteoporosis]
[Article in French]
Reginster JY, Devogelaer JP.
Centre Collaborateur de l'Institut Mondial de la Sante pour les Aspects de Sante
Publique des Maladies Rhumatismales, Liege, Belgique. jyreginster@ulg.ac.be
Major improvements have been observed, during the last ten years, in the
management of postmenopausal osteoporosis. The most significant benefits have
been obtained through the availability of new medications which have
demonstrated their anti-fracture efficacy in the course of well conducted,
scientifically sound studies. Due to the pharmacological properties of these new
medications, treatment of osteoporosis can now be tailored to the needs of each
and every single postmenopausal woman. Calcium supplementation (500 mg/day)
should be offered to all post menopausal women unless dietary records show a
sufficient intake. On the grounds of the high prevalence of low serum vitamin D
levels in the ederly Belgian population, the systematic use of a calcium-vitamin
D combination, after the age of 65 years, appears to be justified. Raloxifene is
an interesting option for women with low mineral density or prevalent vertebral
fractures. This molecule has demonstrated unequivocal anti-fracture efficacy at
the level of the spine and is also caracterized by a beneficial effect on
non-spinal fractures, in high risk women. Bisphosphonates (alendronate and
risedronate) have shown the anti-fracture efficacy at the level of the axial and
appendicular skeleton. The availability of a weekly formulation improves their
compliance, notwithstanding the constrains related to the potential upper
gastro-intestinal toxicity of these compounds. Bisphosphonates appear to be the
first-line choice for patients with more severe osteoporosis and high risk to
develop hip fractures. Teriparatide (1-34 Fragment of parathyroid hormone) is a
new pharmacological option, oriented, mainly if not exclusively because of its
parenteral administration and high cost, to patients with severe osteoporosis
(low bone density and prevalent vertebral fracture(s). Strontium ranelate offers
an anti-fracture efficacy at all skeleton sites and an oustanding overall
tolerance and may play a main role in the future management of osteoporosis.
-----
Drugs Today (Barc). 2004 Nov;40(11):935-48.
Teriparatide: A bone formation treatment for osteoporosis.
Eriksen EF, Robins DA.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
eriksen_erik_f@lilly.com.
Teriparatide is the recombinant human N-terminal fragment (1-34) of endogenous
human parathyroid hormone, and it is the first bone anabolic agent for the
treatment of osteoporosis. When given as once-daily subcutaneous injections,
teriparatide can reverse the course of osteoporosis by stimulating formation of
new bone and restoring lost architecture. Teriparatide (20 microg) treatment of
osteoporosis in postmenopausal women rapidly increased markers of bone formation
and reduced the incidence of vertebral fractures by 65% and of nonvertebral
fragility fractures by 53%. In addition, treatment with this compound increased
spine bone mineral density by 10% and hip bone mineral density by 3% at study
endpoint. Teriparatide is well tolerated and is not associated with any serious
side effects. The compound has been approved in Europe and in the US for the
treatment of osteoporosis. Duration of treatment is 18-24 months and the dose
does not need to be adjusted for age or gender. (c) 2004 Prous Science. All
rights reserved.
-----
Pharmacol Res. 2004 Dec;50(6):637-41.
Effect of supplementation of calcium and Vitamin D on bone
mineral density and bone mineral content in peri- and post-menopause women; A
double-blind, randomized, controlled trial.
Daniele ND, Carbonelli MG, Candeloro N, Iacopino L, De Lorenzo A, Andreoli A.
Human Nutrition Unit, Via Montpellier 1, University of Rome, "Tor Vergata",
00173 Rome, Italy.
Background: Osteoporosis is a serious global health problem for the future, that
is why improving diagnostic methods and prevention of this disease could be
helpful. Objectives: To assess the effects of calcium supplementations combined
with Vitamin D on bone mineral density (BMD) and bone mineral content (BMC) in a
representative sample of peri- and post-menopausal women in a double-blind, a
randomized, controlled trial was untaken. Design: A total of 120 women aged over
45 were included in a randomised placebo-controlled, double-blind trial on the
effect of a daily dietary supplementation of calcium and Vitamin D on bone
mineral density and bone mineral content; over a 30-month period. Methods:
Dietary intake assessment; dual-energy X-ray absorptiometry to measure total
body and segmental bone mineral density and bone mineral content at beginning of
the study and every 15 months were undertaken. Results: There was no significant
change in dietary calcium or Vitamin D intakes in either of the treatment groups
during the 30-month intervention period. The change in total BMD in the calcium
group was significantly different from that in the placebo group (P < 0.005).
The placebo group lost a total BMD at a rate of about 0.4% per year. There was
an inverse correlation between BMD and age. Conclusions: The effect of calcium
and Vitamin D supplementation on bone mineral density of calcium has been
demonstrated in this group of young adult women. Our results showed the positive
effect of calcium and Vitamin D supplementation in women both peri- and
post-menopausal status; for this reason a supplementation of calcium and Vitamin
D should be recommended as a strategic option in helping to prevent early
postmenopausal bone loss.
-----
J Am Geriatr Soc. 2004 Nov;52(11):1832-9.
Safety and efficacy of risedronate in reducing fracture risk in
osteoporotic women aged 80 and older: implications for the use of antiresorptive
agents in the old and oldest old.
Boonen S, McClung MR, Eastell R, El-Hajj Fuleihan G, Barton IP, Delmas P.
Leuven University Center for Metabolic Bone Diseases and Division of Geriatric
Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Objectives: To determine the efficacy of risedronate in reducing vertebral
fracture risk in women aged 80 and older with osteoporosis. Design: Pooled
analysis of data from three randomized, double-blind, controlled,
3-year-fracture-endpoint trials conducted from November 1993 to April 1998: Hip
Intervention Program (HIP), Vertebral Efficacy with Risedronate
Therapy-Multinational (VERT-MN), and VERT-North America (NA). Setting:
Office-based practices, research centers, and osteoporosis clinics in Europe,
North America, and Australia. Participants: Osteoporotic (femoral neck bone
mineral density T-score < -2.5 standard deviations or at least one prevalent
vertebral fracture) women aged 80 and older. Intervention: Patients received
placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients
received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d
vitamin D. Measurements: Cumulative incidence of new vertebral fractures.
Results: After 1 year, the risk of new vertebral fractures in the risedronate
group was 81% lower than with placebo (95% confidence interval=60-91%; P<.001).
The number of women who needed to be treated to prevent one new vertebral
fracture after 1 year was 12. This early onset of efficacy was consistent across
the clinical programs, and antifracture efficacy was confirmed over 3 years.
Risedronate was well tolerated, with a safety profile comparable with that of
placebo. Conclusion: These findings provide the first evidence that, even in the
very old, reducing bone resorption rate remains an effective treatment strategy
for osteoporosis. Because each therapeutic agent used for the treatment of
osteoporosis may have unique characteristics, the observations made in this
study should not be assumed to apply to other bisphosphonates.
-----
J Clin Endocrinol Metab. 2004 Oct 13 [Epub ahead of print]
Controlled substitution of soy protein for meat protein: effects
on calcium retention, bone and cardiovascular health indices in postmenopausal
women1-4.
Roughead ZK, Hunt JR, Johnson LK, Badger TM, Lykken GI.
From the US Department of Agriculture, Agricultural Research Service, Grand
Forks Human Nutrition Research Center, PO Box 9034, Grand Forks, ND 58202-9034;
Arkansas Children's Nutrition Center, Department of Pediatrics and Physiology,
University of Arkansas for Medical Sciences, Little Rock, Arkansas; Physics
Department, University of North Dakota, Grand Forks, ND.
In a controlled feeding study, the effects of substituting 25 g of soy protein
for meat on calcium retention and bone biomarkers were determined.
Postmenopausal women (n = 13) ate two diets which were similar, except that in
one diet 25 g of high-isoflavone soy protein (SOY) was substituted for an
equivalent amount of meat protein (CONTROL), for 7 wk each in a randomized
crossover design. After 3 wk of equilibration, calcium retention was measured by
labeling the 2-d menu with (47)Ca, followed by whole body counting for 28 d.
Urinary calcium and renal acid excretion were measured at wk 3, 5 and 7.
Biomarkers of bone and cardiovascular health were measured at the beginning and
end of each diet. Calcium was similarly retained during the CONTROL and SOY
diets (d 28, % dose, mean +/- pooled SD: 14.1 and 14.0 +/- 1.6, respectively).
Despite a 15-20% lower renal acid excretion during the SOY diet, urinary calcium
loss was unaffected by diet. Diet also did not affect any of the indicators of
bone or cardiovascular health. Substitution of 25 g of high isoflavone soy
protein for meat, in presence of typical calcium intakes, did not improve or
impair calcium retention or indicators of bone and cardiovascular health in
postmenopausal women. Key Words: calcium, absorption, meat, soy, protein, IGF-1,
bone, postmenopausal, human, radiotracer, osteoporosis, calciuria, lipid,
cholesterol, homocysteine, isoflavones.
-----
Osteoporos Int. 2004 Oct 12 [Epub ahead of print]
Prevention of vertebral fractures by strontium ranelate in
postmenopausal women with osteoporosis.
Compston J.
Department of Medicine, Box 157, Addenbrooke's Hospital, Hills Road, CB2 2QQ,
Cambridge, UK.
The antifracture efficacy of strontium ranelate, a compound with a novel
mechanism of action on bone, has been assessed in two large, randomized,
controlled trials conducted in postmenopausal women. Strontium ranelate was
given at a daily dose of 2 g, and all women received calcium and vitamin D
supplements. In women with established osteoporosis there was a 41% reduction in
vertebral fractures over 3 years' treatment [relative risk (RR) 0.59; 95%
confidence interval (CI) 0.48-0.73; P<0.001]; significant reductions were also
seen after only 1 year of treatment. The beneficial effect was also seen for
clinical vertebral fractures: over 3 years there was a significant reduction in
new clinical vertebral fractures (RR 0.62; 95% CI 0.47-0.83; P<0.001); this
reduction was also observed during the first year of treatment (RR 0.48; 95% CI
0.29-0.80; P=0.003). Over the 3-year treatment period significantly fewer
patients had height loss and fewer patients reported new or worsening back pain
in the treated group than in the control group. These results demonstrate that
strontium ranelate is a new therapeutic option in the prevention of osteoporotic
vertebral fractures in postmenopausal women.
-----
Calcif Tissue Int. 2004 Oct 14 [Epub ahead of print]
Five Years of Treatment with Risedronate and its Effects on Bone
Safety in Women with Postmenopausal Osteoporosis.
Ste-Marie LG, Sod E, Johnson T, Chines A.
Centre de Recherche du CHUM Hospital, Saint-Luc Montreal, Quebec, Canada.
We have recently reported that risedronate preserves normal bone formation and
decreases bone remodeling in women with postmenopausal osteoporosis after 3
years of treatment. We report now the results of a 2-year extension study. The
primary objective of this study was to determine the effect of 5 years of
risedronate treatment (5 mg daily) on bone quality and bone remodeling based on
paired transiliac bone biopsies. There were additional measurements that
included bone turnover markers and bone mineral density (BMD). Histologic
evaluation of biopsy sections (placebo, n = 21; risedronate, n = 27) yielded no
pathologic findings after 5 years in either treatment group. Histomorphometric
assessment of paired biopsy specimens after 5 years (placebo, n =12; risedronate,
n = 13) found no statistically significant differences between treatment groups
in structural or resorption parameters. There was a significant reduction in
osteoid (-27%) and mineralizing surfaces (-49%) from baseline values in the
risedronate group that were also significantly different from placebo at 5
years. Similarly, activation frequency decreased significantly (-77%) in the
risedronate group, although it was not significantly different from placebo at 5
years (0.09 vs. 0.21, respectively). Double tetracycline labels were identified
in all biopsy specimens indicating continuous bone turnover. After 5 years of
risedronate treatment, serum bone-specific alkaline phosphatase (bone ALP) and
N-telopeptide (NTX) decreased significantly from baseline by 33.3% and 47.5%,
respectively. In the placebo group, bone ALP decreased by 3.9% ( P = NS),
whereas NTX decreased by 27.0% ( P < 0.005). Lumbar spine BMD increased
significantly in the risedronate group (9.2%), whereas no significant change was
seen in the placebo group (-0.26%). Risedronate was overall well tolerated;
during the 2-year study extension nonvertebral fractures occurred in 7 patients
in placebo and 2 patients in risedronate groups. The findings from this study
are consistent with the antiremodeling effect of risedronate and support
long-term bone safety and antifracture efficacy of risedronate treatment.
-----
J Clin Endocrinol Metab. 2004 Oct;89(10):4879-85.
Prevention of postmenopausal bone loss: six-year results from the
early postmenopausal intervention cohort study.
McClung MR, Wasnich RD, Hosking DJ, Christiansen C, Ravn P, Wu M, Mantz AM,
Yates J, Ross PD, Santora AC 2nd.
Oregon Osteoporosis Center, 5050 Northeast Hoyt, Suite 651, Portland, Oregon
97213. mmcclung@orost.com.
We report the effect of continuous treatment with alendronate for 6 yr vs.
placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609
healthy, early postmenopausal women were recruited; we describe results for the
585 women who received continuous placebo or alendronate (2.5 or 5 mg) daily for
6 yr. Bone mineral density (BMD) was evaluated at the lumbar spine, hip,
forearm, and total body at baseline and annually thereafter. Bone turnover
markers were measured every 6 months from baseline to yr 2 and annually
thereafter. Adverse experiences, including upper gastrointestinal events and
fractures, were recorded throughout the study. Women receiving placebo
experienced progressive decreases in BMD at all skeletal sites. Patients
receiving alendronate experienced significant gains in spine and hip BMD that
were maintained through yr 6. Significantly greater, dose-related decreases in
bone turnover markers in the alendronate groups vs. placebo occurred within the
first year and were sustained through yr 6. Women receiving alendronate had
adverse experience incidences similar to those receiving placebo. Fractures
occurred in 11.5, 10.3, and 8.9% of women taking placebo, 2.5 mg alendronate, or
5 mg alendronate daily, respectively. Therapy with alendronate is an effective
and promising strategy for the prevention of postmenopausal osteoporosis.
-----
Am J Health Syst Pharm. 2004 Sep 1;61(17):1801-11.
Current approaches to the management of osteoporosis in men.
Vondracek SF, Hansen LB.
Department of Clinical Pharmacy, School of Pharmacy, University of Colorado
Health Sciences Center, Denver 80262, USA. sheryl.vondracek@uchsc.edu
PURPOSE: The epidemiology, pathophysiology, diagnosis, and management of
osteoporosis in men are reviewed. SUMMARY: Men with osteoporosis account for
approximately one fifth of all patients with osteoporosis, and their morbidity
and mortality rates from this disease are higher than in other patients.
Guidelines specifically addressing the management of osteoporosis in men are not
available. Lifestyle modifications, including smoking cessation, limited alcohol
consumption, routine exercise, and fall prevention strategies, are beneficial to
maintain bone health. Appropriate calcium and vitamin D intakes are critical
components of any osteoporosis management strategy. Drug therapy should be
initiated in all men at high risk for fracture. Alendronate is indicated for the
treatment of osteoporosis. It is considered first-line therapy because of its
efficacy and safety profiles. Teriparatide is indicated for the management of
osteoporosis in high-risk men, but the drug's cost, complex administration
schedule, and potential risks have caused it to be restricted to a second-line
therapy. Other options reserved for select patients include calcitonin and
testosterone. Further studies are needed to better understand the distinctive
features and management strategies for men with osteoporosis. CONCLUSION: While
the rate of osteoporosis in men is lower than in women, the consequences are
possibly more devastating. Evaluation of secondary causes, especially
hypogonadism, is important, as they can play a significant role in the
development of osteoporosis in men. All men should be educated to improve
modifiable risk factors and maintain recommended daily intakes of calcium and
vitamin D. Bone mineral density should be evaluated in high-risk men using
central dual energy x-ray absorptiometry, and drug treatment should be
considered in those with a history of low-trauma fracture or significant bone
loss.
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J Hum Nutr Diet. 2004 Aug;17(4):359-64.
Is dietary counselling effective in increasing dietary calcium,
protein and energy intake in patients with osteoporotic fractures? A randomized
controlled clinical trial.
Wong SY, Lau EM, Lau WW, Lynn HS.
Department of Community and Family Medicine, The Chinese University of Hong
Kong, Hong Kong.
Abstract To determine the feasibility of increasing the calcium, protein and
calorie intake of osteoporotic fracture patients by repeated dietary counselling
delivered by a dietitian, a randomized controlled trial was conducted. Among 189
patients presenting with osteoporotic fractures to an Orthopaedics and
Traumatology Department of a large regional hospital, 98 patients were
randomized to the intervention group and 91 were randomized to the control group
(with usual care). Intervention group received three sessions of dietary
counselling with tailored made recommendations over a period of 4 months, while
the control group only received dietary assessment and pamphlets on the
prevention of osteoporosis. Almost all subjects in both intervention and control
groups had calcium intake below the recommended level of 1000 mg at baseline.
Half and 60% of subjects in both groups had total energy and protein intake
below recommended levels respectively. The mean weights of control and
intervention groups at baseline were 51.5 and 50.9 kg respectively, while the
body mass index (BMI) were 22.6 (kg m(-2)) and 22.6 (kg m(-2)) respectively.
After dietary intervention, significant increase of intake was seen in calcium
intake (P = 0.0095 by t-test) in the intervention group. No significant increase
was seen in protein or calorie intake. No significant change was observed in the
body weight or BMI although there was a positive trend in the intervention group
for all these parameters. We concluded that there was general malnutrition in
Chinese elderly who presented with osteoporotic fractures. Dietary calcium could
be increased by repeated professional dietary counselling. Future studies with
longer duration and more objective clinical outcomes will be helpful to further
demonstrate the long-term effects of dietary intervention on osteoporosis and
other chronic diseases.
-----
J Bone Miner Res. 2004 Aug;19(8):1270-5.
Risk-Benefit Profile for Raloxifene: 4-Year Data From the
Multiple Outcomes of Raloxifene Evaluation (MORE) Randomized Trial.
Barrett-Connor E, Cauley JA, Kulkarni PM, Sashegyi A, Cox DA, Geiger MJ.
Division of Epidemiology, Department of Family and Preventive Medicine,
University of California at San Diego, La Jolla, California, USA.
Posthoc analysis of the MORE osteoporosis treatment trial assessed risk-benefit
profile of raloxifene in 7705 postmenopausal women. A major disease outcomes
global index resulted in annual rates of 1.39% and 1.83% in the raloxifene and
placebo groups, respectively (HR, 0.75; 95% CI, 0.62-0.92), compatible with a
favorable risk-benefit profile for raloxifene for treating postmenopausal
osteoporosis. INTRODUCTION: The Women's Health Initiative (WHI) trial reported
overall risks that exceeded benefits from use of estrogen-progestin in healthy
postmenopausal women. The objective of this posthoc analysis of the Multiple
Outcomes of Raloxifene Evaluation (MORE) trial was to assess the safety profile
of raloxifene, a selective estrogen receptor modulator indicated for the
prevention and treatment of osteoporosis, using the global index method from the
WHI trial. MATERIALS AND METHODS: A total of 7705 postmenopausal women (mean
age, 67 years) were enrolled in the MORE osteoporosis treatment trial and
randomly assigned to receive placebo or one of two doses of raloxifene (60 or
120 mg/day) for 4 years. A global index of clinical outcomes, defined as
described for the WHI trial (the earliest occurrence of coronary heart disease,
stroke, pulmonary embolism, invasive breast cancer, endometrial cancer,
colorectal cancer, hip fracture, or death because of other causes) was applied
to the MORE trial data. Physicians blinded to treatment assignment adjudicated
events. Intention-to-treat survival analysis of time-to-first-event was
performed using a proportional hazards model. RESULTS AND CONCLUSIONS: The
annualized rate of global index events was 1.83% in the placebo group and 1.39%
in the combined raloxifene dose groups (hazard ratio [HR], 0.75; 95% CI,
0.62-0.92). Analyzing individual dose groups separately yielded the same results
(HR for 60 mg/day, 0.75; 95% CI, 0.60-0.96: HR for 120 mg/day, 0.75; 95% CI,
0.59-0.95). Subgroup analyses showed no significant interactions between age or
hysterectomy status and the effect of raloxifene on the global index
(interaction p > 0.1), whereas the global index risk reduction seemed to be
greater in obese women compared with nonobese women (interaction p = 0.03). The
significant 25% reduction in global index is compatible with a favorable
risk-benefit safety profile when raloxifene is used for osteoporosis treatment
in postmenopausal women. These results require confirmation in ongoing clinical
trials.
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J Bone Miner Res. 2004 Aug;19(8):1241-9.
Effects of oral ibandronate administered daily or intermittently
on fracture risk in postmenopausal osteoporosis.
Chesnut III CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A,
Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD.
Osteoporosis Research Group, University of Washington, Seattle, Washington, USA.
Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2
months), delivering a similar cumulative exposure, were evaluated in 2946
osteoporotic women with prevalent vertebral fracture. Significant reduction in
incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3
years. This is the first study to prospectively show antifracture efficacy for
the intermittent administration of a bisphosphonate. INTRODUCTION:
Bisphosphonates are important therapeutics in postmenopausal osteoporosis.
However, they are currently associated with stringent dosing instructions that
may impair patient compliance and hence therapeutic efficacy. Less frequent,
intermittent administration may help to overcome these deficiencies. This study
assessed the efficacy and safety of oral ibandronate administered either daily
or intermittently with a dose-free interval of >2 months. MATERIALS AND METHODS:
This randomized, double-blind, placebo-controlled, parallel-group study enrolled
2946 postmenopausal women with a BMD T score </= -2.0 at the lumbar spine in at
least one vertebra (L(1)-L(4)) and one to four prevalent vertebral fractures
(T(4)-L(4)). Patients received placebo or oral ibandronate administered either
daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3
months). RESULTS AND CONCLUSIONS: After 3 years, the rate of new vertebral
fractures was significantly reduced in patients receiving oral daily (4.7%) and
intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and
intermittent oral ibandronate significantly reduced the risk of new morphometric
vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively,
versus placebo. Both treatment groups also produced a statistically significant
relative risk reduction in clinical vertebral fractures (49% and 48% for daily
and intermittent ibandronate, respectively). Significant and progressive
increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate,
intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD,
normalization of bone turnover, and significantly less height loss than in the
placebo group were also observed for both ibandronate regimens. The overall
population was at low risk for osteoporotic fractures. Consequently, the
incidence of nonvertebral fractures was similar between the ibandronate and
placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent,
and placebo groups, respectively; difference between arms not significant).
However, findings from a posthoc analysis showed that the daily regimen reduces
the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup
(femoral neck BMD T score < -3.0). In addition, oral ibandronate was well
tolerated. Oral ibandronate, whether administered daily or intermittently with
an extended between-dose interval of >2 months, is highly effective in reducing
the incidence of osteoporotic fractures in postmenopausal women. This is the
first time that significant fracture efficacy has been prospectively shown with
an intermittently administered bisphosphonate in the overall study population of
a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as
an effective and convenient alternative to current bisphosphonate therapies.
-----
J Bone Miner Res. 2004 Aug;19(8):1208-14.
Musculoskeletal rehabilitation in osteoporosis: a review.
Pfeifer M, Sinaki M, Geusens P, Boonen S, Preisinger E, Minne HW.
Institute of Clinical Osteology, Clinic "DER FURSTENHOF,".
Measures of musculoskeletal rehabilitation play an integral part in the
management of patients with increased fracture risk because of osteoporosis or
extraskeletal risk factors. This article delineates current scientific evidence
concerning nonpharmacologic approaches that are used in conjunction with
pharmacotherapy for prevention and management of osteoporosis. Fractures caused
by osteoporotic fragility may be prevented with multidisciplinary intervention
programs, including education, environmental modifications, aids, and
implementation of individually tailored exercise programs, which are proved to
reduce falls and fall-related injuries. In addition, strengthening of the
paraspinal muscles may not only maintain BMD but also reduce the risk of
vertebral fractures. Given the strong interaction between osteoporosis and
falls, selection of patients for prevention of fracture should be based on
bone-related factors and on risk factors for falls. Rehabilitation after
vertebral fracture includes proprioceptive dynamic posture training, which
decreases kyphotic posturing through recruitment of back extensors and thus
reduces pain, improves mobility, and leads to a better quality of life. A newly
developed orthosis increases back extensor strength and decreases body sway as a
risk factor for falls and fall-related fractures. Hip fractures may be prevented
by hip protectors, and exercise programs can improve strength and mobility in
patients with hip fracture. So far, there is no conclusive evidence that
coordinated multidisciplinary inpatient rehabilitation is more effective than
conventional hospital care with no rehabilitation professionals involved for
older patients with hip fracture. Further studies are needed to evaluate the
effect of combined bone- and fall-directed strategies in patients with
osteoporosis and an increased propensity to falls.
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Menopause. 2004;11(4):405-415.
Once-weekly alendronate 70 mg and raloxifene 60 mg daily in the
treatment of postmenopausal osteoporosis.
Luckey M, Kagan R, Greenspan S, Bone H, Kiel RD, Simon J, Sackarowitz J,
Palmisano J, Chen E, Petruschke RA, De Papp AE.
St. Barnabas Osteoporosis & Metabolic Bone Disease Center, Livingston, NJ;
Foundation for Osteoporosis Research and Education, Oakland, CA; Osteoporosis
Prevention and Treatment Center, Pittsburgh, PA; Michigan Bone & Mineral Clinic,
Detroit, MI; Beth Israel Deaconess Medical Center and Hebrew Rehabilitation
Center for Aged, Boston, MA; George Washington University, Washington, DC; and
Merck & Co., Inc., West Point, PA.
OBJECTIVE:: To compare the efficacy and tolerability of once-weekly (OW)
alendronate (ALN) 70 mg and raloxifene (RLX) 60 mg daily in the treatment of
postmenopausal osteoporosis. DESIGN:: This 12-month, randomized, double-blind
study enrolled 456 postmenopausal women with osteoporosis (223 ALN, 233 RLX) at
52 sites in the United States. Efficacy measurements included lumbar spine (LS),
total hip, and trochanter bone mineral density (BMD) at 6 and 12 months,
biochemical markers of bone turnover, and percent of women who maintained or
gained BMD in response to treatment. The primary endpoint was percent change
from baseline in LS BMD at 12 months. Adverse experiences were recorded to
assess treatment safety and tolerability. RESULTS:: Over 12 months, OW ALN
produced a significantly greater increase in LS BMD (4.4%, P < 0.001) than RLX
(1.9%). The percentage of women with >/= 0% increase in LS BMD (ALN, 94%; RLX,
75%; P < 0.001) and >/= 3% increase in LS BMD (ALN, 66%; RLX, 38%; P < 0.001)
were significantly greater with ALN than RLX. Total hip and trochanter BMD
increases were also significantly greater (P </=0.001) with ALN. Greater (P <
0.001) reductions in N-telopeptide of type I collagen and bone-specific alkaline
phosphatase were achieved with ALN compared with RLX at 6 and 12 months. No
significant differences in the incidence of upper gastrointestinal or vasomotor
adverse experiences were seen. CONCLUSION:: ALN 70 mg OW produced significantly
greater increases in spine and hip BMD and greater reductions in markers of bone
turnover than RLX over 12 months. A greater percentage of women maintained or
gained BMD on ALN than RLX. Both medications had similar safety and tolerability
profiles.
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J Rheumatol. 2004 Jul;31(7):1305-9.
Effect of low dose methotrexate on bone density in women with
rheumatoid arthritis: results from a multicenter cross-sectional study.
di Munno O, Mazzantini M, Sinigaglia L, Bianchi G, Minisola G, Muratore
M, la Corte R, di Matteo L, Canesi B, Caminiti M, Broggini M, Adami S.
Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa,
Italy. o.dimunno@int.med.unipi.it
OBJECTIVE: To analyze the influence of low dose methotrexate (MTX) on bone using
data from a large multicenter, cross-sectional study on bone mineral density (BMD)
in women with rheumatoid arthritis (RA). METHODS: We selected 731 female
patients with RA divided into 2 groups on the basis of MTX use: never MTX users
(n = 485) and MTX users for at least 6 months (n = 246). Demographic, disease,
and treatment related variables were collected for each patient. BMD was
measured at lumbar spine and proximal femur by dual energy x-ray absorptiometry.
Osteoporosis was defined as BMD < -2.5 T-score. RESULTS: The frequency of
osteoporosis among never MTX users and MTX users was 29.1% and 28.3% (p = NS)
for lumbar spine, and 34.8% and 37.8% (p = NS) for femoral neck, respectively.
Mean T-score values at lumbar spine and femoral neck were comparable in the 2
groups, even after adjusting for age, menopausal status, body mass index (BMI),
Health Assessment Questionnaire (HAQ) score, and steroid use. The generalized
linear model showed that age, menopause, BMI, HAQ score, and steroid use were
significant independent predictors of BMD at lumbar or at femoral level, whereas
MTX use was not. Logistic procedure showed that only age, HAQ score, and BMI
were significantly associated with the risk of osteoporosis. CONCLUSION: We
found no negative effect of low dose MTX on BMD in women with RA.
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Clin Mol Allergy. 2004 Jul 14;2(1):9.
Management of osteoporosis.
Lewiecki EM.
Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in
1.5 million fragility fractures per year. The consequences of these fractures
include pain, disability, depression, loss of independence, and increased
mortality. The burden to the healthcare system, in terms of cost and resources,
is tremendous, with an estimated direct annual USA healthcare expenditure of
about $17 billion. With longer life expectancy and the aging of the baby-boomer
generation, the number of men and women with osteoporosis or low bone density is
expected to rise to over 61 million by 2020. Osteoporosis is a silent disease
that causes no symptoms until a fracture occurs. Any fragility fracture greatly
increases the risk of future fractures. Most patients with osteoporosis are not
being diagnosed or treated. Even those with previous fractures, who are at
extremely high risk of future fractures, are often not being treated. It is
preferable to diagnose osteoporosis by bone density testing of high risk
individuals before the first fracture occurs. If osteoporosis or low bone
density is identified, evaluation for contributing factors should be considered.
Patients on long-term glucocorticoid therapy are at especially high risk for
developing osteoporosis, and may sustain fractures at a lower bone density than
those not taking glucocorticoids. All patients should be counseled on the
importance of regular weight-bearing exercise and adequate daily intake of
calcium and vitamin D. Exposure to medications that cause drowsiness or
hypotension should be minimized. Non-pharmacologic therapy to reduce the
non-skeletal risk factors for fracture should be considered. These include fall
prevention through balance training and muscle strengthening, removal of fall
hazards at home, and wearing hip protectors if the risk of falling remains high.
Pharmacologic therapy can stabilize or increase bone density in most patients,
and reduce fracture risk by about 50%. By selecting high risk patients for bone
density testing it is possible to diagnose this disease before the first
fracture occurs, and initiate appropriate treatment to reduce the risk of future
fractures.
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Trends Endocrinol Metab. 2004 Jul;15(5):229-33.
What's new with PTH in osteoporosis: where are we and where are
we headed?
Rosen CJ.
Maine Center for Osteoporosis Research and Education, St Joseph Hospital, 900
Broadway, Bldg 2, Bangor, Maine 04401, USA.
A new era in osteoporosis management began with the recent approval of
parathyroid hormone (PTH) for postmenopausal and idiopathic osteoporosis
treatment. Intermittent PTH dramatically increases spine bone mineral density
and significantly reduces fragility fractures. However, the skeletal response to
PTH varies greatly and there are few large scale, randomized, placebo-controlled
trials in conditions such as glucocorticoid-induced osteoporosis. Moreover, the
mechanisms of PTH action are complex, involving multiple pathways linked to
common signaling peptides regulating osteoblast gene transcription. In addition,
important interactions between osteoclasts and osteoblasts are activated by PTH.
This review presents recent findings on PTH signaling in bone and discusses how
they could be used to design randomized trials and establish clinical practice
guidelines for this novel anabolic peptide.
-----
Arch Phys Med Rehabil. 2004 Jul;85(6 Suppl):31-42.
Benefits of exercise for community-dwelling older adults.
Bean JF, Vora A, Frontera WR.
This focused review highlights the benefits of exercise and physical activity
for community-dwelling older adults. It is part of the study guide on geriatric
rehabilitation in the Self-Directed Physiatric Education Program for
practitioners and trainees in physical medicine and rehabilitation. This article
specifically focuses on the benefits of physical activity and exercise for older
adults with regard to morbidity, mortality, and disability. It discusses the
appropriate preexercise screening and evaluation procedures for older adults
contemplating exercise. Last, it reviews the current literature on the benefits
of varying modes of exercise to modify the most prevalent chronic medical
conditions of late life, including arthritis, heart disease, diabetes, stroke,
pulmonary disease, and osteoporosis. Overall article objective To summarize the
current knowledge regarding the therapeutic benefits of exercise for
community-dwelling older adults.
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Diabetes Care. 2004 Jul;27(7):1547-53.
Effect of alendronate on bone mineral density and biochemical
markers of bone turnover in type 2 diabetic women: the fracture intervention
trial.
Keegan TH, Schwartz AV, Bauer DC, Sellmeyer DE, Kelsey JL.
Department of Health ResearchPolicy, Division of Epidemiology, HRP Redwood
Building, T224, Stanford University School of Medicine, Stanford, CA 94305-5405.
tkeegan@nccc.org
OBJECTIVE-Alendronate sodium (ALN) increases bone mineral density (BMD) in
heterogeneous populations of postmenopausal women, but its effect is unknown in
women with type 2 diabetes. The objective of this project was to compare changes
in BMD during 3 years of ALN treatment versus placebo in diabetic women.
RESEARCH DESIGN AND METHODS-We used data from the Fracture Intervention Trial, a
randomized blinded placebo-controlled trial conducted at 11 centers in which
6,458 women aged 54-81 years with a femoral neck BMD of </=0.68 g/cm(2) were
randomly assigned to either placebo or 5 mg/day ALN for 2 years, followed by 10
mg/day for the remainder of the trial. BMD was measured by dual-energy X-ray
absorptiometry. Type 2 diabetes (n = 297) was defined by self-report, use of
insulin or other hypoglycemic agents, or a random nonfasting glucose value
>/=200 mg/dl. RESULTS-In diabetic women, 3 years of ALN treatment was associated
with increased BMD at all sites studied, including 6.6% at the lumbar spine and
2.4% at the hip, whereas women in the placebo group experienced a decrease in
BMD at all sites except the lumbar spine. The safety/tolerability of ALN was
similar to placebo, except for abdominal pain, which was more likely in the ALN
group. CONCLUSIONS-ALN increased BMD relative to placebo in older women with
type 2 diabetes and was generally well tolerated as a treatment for
osteoporosis. Increases in BMD with ALN therapy compared with placebo were
similar between women with and without diabetes.
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Expert Opin Investig Drugs. 2004 Jul;13(7):857-64.
Strontium ranelate: a new paradigm in the treatment of
osteoporosis.
Reginster JY, Lecart MP, Deroisy R, Lousberg C.
Bone and Cartilage Metabolism Research Unit, CHU Centre'Ville, Policliniques
Lucien Brull, Quai Godefroid Kurth 45 (9eme etage), 4020 Liege, Belgium.
jyreginster@ulg.ac.be
In vitro, strontium ranelate increases collagen and non-collagenic protein
synthesis by mature osteoblast-enriched cells. The effects of strontium ranelate
on bone formation were confirmed as the drug enhanced preosteoblastic cell
replication. In the isolated osteoclast, a preincubation of bone slices with
strontium ranelate induced a dose-dependent inhibition of the bone resorbing
activity of treated rat osteoclast. Strontium ranelate dose-dependently
inhibited preosteoclast differentiation. The drug was administered in 160 early
postmenopausal women, in a 24-month, double-blind, placebo-controlled,
prospective randomised study. At the conclusion of the study, the percentage
variation of lumbar bone mineral density (BMD) from baseline was significantly
different in the group receiving strontium ranelate 1000 mg/day as compared with
placebo (+5.53 versus -0.75%, respectively). Increase in total hip and neck BMD
averages were 3.2 and 2.5%, respectively. The effect of strontium ranelate in
postmenopausal women with established osteoporosis was assessed during a
multinational, prospective, double-blind, randomised, placebo-controlled trial.
Strontium ranelate (500, 1000, 2000 mg/day) or placebo were given to 353
Caucasian women with prevalent vertebral osteoporosis. At the conclusion of this
2-year study, the annual increase in lumbar BMD of the group receiving strontium
ranelate 2000 mg was 7.3% (p < 0.001). A significant increase in bone alkaline
phophatase (p = 0.002) over a 6-month period and a significant decrease in N-telopeptide
crosslinks (p = 0.004) throughout the 2-year period were seen in the group
receiving 2000 mg of strontium ranelate. During the second year of treatment,
the dose of 2000 mg was associated with a 44% reduction in the number of
patients experiencing a new vertebral deformity. Bone histomorphometry showed no
mineralisation defects. The primary analysis of the SOTI study, evaluating the
effect of strontium ranelate 2000 mg on vertebral fracture rates, revealed a 41%
reduction in the relative risk of patients experiencing a first new vertebral
fracture with strontium ranelate throughout the 3-year study. The TROPOS study
showed a significant reduction in the risk of experiencing a first non-vertebral
fracture in the group treated with strontium ranelate throughout the 3-year
study. A reduction in the risk of experiencing a hip fracture was also
demonstrated in the patients treated for >/= 18 months.
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Expert Opin Pharmacother. 2004 Jul;5(7):1635-8.
Recent important clinical trials of drugs in osteoporosis.
Doggrell SA.
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New
Zealand. s_doggrell@yahoo.com
The antiresorptive therapies (raloxifene, bisphosphonates) commonly used to
treat postmenopausal osteoporotic women, reduce the rate of bone remodeling and
lowers the fracture rate, but do not increase bone mass. Strontium ranelate has
the advantage of also stimulating bone formation. In the Spinal Osteoporosis
Intervention study, at the end of 1 year, there was a lower incidence of
fractures in the strontium ranelate group than the placebo group (12.2 and 6.4%,
placebo and strontium, respectively) and this difference was maintained over the
3 years (32.8 and 20.9%, placebo and strontium, respectively). With the demise
of oestrogen treatment for postmenopausal osteoporosis, it is useful that
strontium ranelate is emerging as a promising drug in this condition. Secondary
osteoporosis (e.g., due to glucocorticoid treatment after cardiac
transplantation) tends to be more severe than primary osteoporosis. In a recent
trial comparing calcitriol to alendronate after cardiac transplantation, both
showed similar abilities to prevent bone loss. As hypercalcaemia is a relatively
common adverse effect with calcitriol in the treatment of secondary
osteoporosis, requiring monitoring of calcium levels, alendronate is the easier
agent to use.
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Maturitas. 2004 Jul 15;48(3):179-92.
Postmenopausal osteoporosis and alendronate.
Perez-Lopez FR.
Department of Obstetrics and Gynaecology, University of Zaragoza Faculty of
Medicine, Hospital Clinico de Zaragoza, San Juan Bosco 15, Zaragoza 50010,
Spain.
Osteoporosis is a systemic metabolic disorder associated with a decreased bone
mass and resistance. Bisphosphonates suppress bone resorption and bone turnover
by a mechanism that depends on their structure. They are characterized by low
gastrointestinal absorption. In postmenopausal women, alendronate (ALN) reduces
bone resorption markers and increases bone mineral density (BMD) in the lumbar
spine, femoral neck, and total body. Individuals receiving ALN have been studied
for up to 10 years with an apparent linear increase in BMD over that time period
estimated at 13.7% at the lumbar spine. Treatment with ALN reduced the risk of
both vertebral and non-vertebral fractures, including hip fractures, in
postmenopausal women with osteoporosis. Direct comparisons of the results
obtained with different antiresortive agents is difficult, because the designs
of the respective studies, populations and other factors. However, the
meta-analysis of available publications seems to indicate that ALN reduces the
relative risk of vertebral fractures in a greater proportion than any other
agent. Furthermore, ALN prevents the reduction in BMD after hormone replacement
therapy discontinuation.
-----
J Bone Miner Metab. 2004;22(4):352-9.
Alfacalcidol reduces accelerated bone turnover in elderly women
with osteoporosis.
Shiraki M, Fukuchi M, Kiriyama T, Okamoto S, Ueno T, Sakamoto H, Nagai T.
Research Institute and Practice for Involutional Diseases, 1610-1 Meisei,
Misatomura, Minamiazumigun, 399-8101, Nagano, Japan. ripid@fc4.so.net.ne.jp
To evaluate the effects of alfacalcidol on bone turnover in elderly women with
osteoporosis, an open-label, prospective, calcium-controlled study was
conducted. A total of 80 patients with osteoporosis were divided into two
groups: the control group, group C (mean age, 78.0 years), in which patients
were given calcium, and group D (mean age, 77.4 years), in which the patients
were given alfacalcidol 1 micro g/day together with calcium for 6 months.
Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone
turnover were assessed. A significant increase in urinary calcium/creatinine
ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months;
P = 0.0091) and a significant decrease in serum parathyroid hormone (30%
decrease from baseline at 6 months; P < 0.0001) was observed in group D compared
with the corresponding changes in group C. Significant decreases of bone
resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15%
decrease from the baseline values) were observed in group D compared with the
corresponding changes in group C. The changes in bone formation markers
(bone-derived alkaline phosphatase and osteocalcin) in group D were
significantly different at 6 months (-21.5%; P = 0.0047 and -13.4%; P = 0.0032,
respectively) from the values in group C. The magnitudes of the decrease in bone
turnover markers were highly correlated with the corresponding baseline values,
suggesting that alfacalcidol treatment effectively reduces bone turnover in
patients with high bone turnover rates. The LBMD in group D increased by 1.7%
and that in group C decreased by 1.6% ( P = 0.0384). The changes in calcium
metabolism and LBMD were in good agreement with those in previous reports.
Although the changes in bone turnover markers in group D were slight,
significant reduction in bone turnover with alfacalcidol treatment, together
with the change in calcium metabolism, may account for the effects of
alfacalcidol on BMD and on fracture prevention reported previously. In
conclusion, alfacalcidol reduces bone turnover in elderly women with
high-bone-turnover osteoporosis, and it may have beneficial effects on bone.
-----
Osteoporos Int. 2004 Jun 17 [Epub ahead of print]
Effects of high-impact exercise on bone mineral density: a
randomized controlled trial in premenopausal women.
Vainionpaa A, Korpelainen R, Leppaluoto J, Jamsa T.
Department of Medical Technology, University of Oulu, PO Box 5000, 90014, Oulu,
Finland.
Introduction: The purpose of this randomized controlled study was to assess the
effects of high-impact exercise on the bone mineral density (BMD) of
premenopausal women at the population level. Materials and methods: The study
population consisted of a random population-based sample of 120 women from a
cohort of 5,161 women, aged 35 to 40 years. They were randomly assigned to
either an exercise or control group. The exercise regimen consisted of
supervised, progressive high-impact exercises three times per week and an
additional home program for 12 months. BMD was measured on the lumbar spine
(L1-L4), proximal femur, and distal forearm, by dual-energy X-ray absorptiometry
at baseline and after 12 months. Calcaneal bone was measured using quantitative
ultrasound. Results: Thirty-nine women (65%) in the exercise group and 41 women
(68%) in the control group completed the study. The exercise group demonstrated
significant change compared with the control group in femoral neck BMD (1.1% vs
-0.4%; p=0.003), intertrochanteric BMD (0.8% vs -0.2%; p=0.029), and total
femoral BMD (0.1% vs -0.3%; p=0.006). No exercise-induced effects were found in
the total lumbar BMD or in the lumbar vertebrae L2-L4. Instead, L1 BMD (2.2% vs
-0.4%; p=0.002) increased significantly more in the exercise group than in the
control group. Calcaneal broadband ultrasound attenuation showed also a
significant change in the exercise group compared with the control group (7.3%
vs -0.6%; p=0.015). The changes were also significant within the exercise group,
but not within the control group. There were no significant differences between
or within the groups in the distal forearm. Conclusions: This study indicates
that high-impact exercise is effective in improving bone mineral density in the
lumbar spine and upper femur in premenopausal women, and the results of the
study may be generalized at the population level. This type of training may be
an efficient, safe, and inexpensive way to prevent osteoporosis later in life.
-----
J Br Menopause Soc. 2004 Jun;10(2):70-4.
Physical activity and postmenopausal health.
Beitz R, Doren M.
Charite - Universitatsmedizin Berlin, Campus Benjamin Franklin, Klinisches
Forschungszentrum Frauengesundbeit, Hindenburgdamm 30 D-12200 Berlin, Germany.
Physical activity leads to a 30-50 % reduction in cardiovascular disease in
women. Moderate activities such as walking, gardening or light sports appear to
have beneficial effects. Additional exercise training may enhance these effects.
Moderate-intensity activities constitute a key recommendation for primary
prevention. Vigorous intensity activity may render additional benefits. Recent
recommendations suggest an increase to at least 60 minutes of cumulative daily
physical activity. Practical recommendations for the prevention of osteoporosis
are less clear. There is a relative abundance of randomised controlled trials
assessing bone mineral density at various sites. Meta-analyses of these studies
indicate a beneficial health effect of physical activity on prevention of bone
loss. However, the effects seen appear to be relatively small. Two recent
end-point studies examining hip and fragility fractures show stronger evidence
for the protective potential of physical activity in bone health. Exercise
throughout life, particularly weight-bearing, is assumed to be beneficial for
bone health. Older people at risk of falling are advised to participate in
tailored exercise programmes to improve strength and balance, since physical
training might contribute to fracture prophylaxis by increasing mobility and
general activity of ageing people. Beyond the promotion of regular physical
activity, primary disease prevention requires the adoption of healthy life
habits including dietary patterns, weight control, and avoiding smoking. In the
light of the failure of postmenopausal hormone use to protect against heart
disease, rethinking the role of exercise in maintaining postmenopausal health is
of increasing importance.
-----
Clin Ther. 2004 Jun;26(6):841-54.
Teriparatide: A review.
Quattrocchi E, Kourlas H.
Pharmacy Practice Department, Arnold and Marie Schwartz College of Pharmacy and
Health Sciences, Long Island University, Brooklyn, New York, USA.
Background: Traditionally, the management of osteoporosis in men and women has
included the use of antiresorptive agents in combination with calcium and
vitamin D supplementation. The mechanism of action of teriparatide is unique in
that it possesses anabolic properties and therefore builds bone. Since the
approval of teriparatide in the United States in 2002, a great deal of interest
regarding its use in osteoporosis has developed. Objectives: This article
reviews the information available on the new recombinant human parathyroid
hormone teriparatide (hPTH [1-34]), including its clinical pharmacology,
mechanism of action, pharmacokinetic properties, clinical efficacy, safety
profile, potential drug interactions, contraindications and warnings, dosage and
administration, and pharmacoeconomics. Methods: The articles included in this
review were identified through searches of PubMed and MEDLINE (1966-December
2003) and International Pharmaceutical Abstracts (1970-December 2003). Search
terms included teriparatide, Forteo, recombinant human parathyroid hormone
(1-34), and osteoporosis. The references of the identified articles were
reviewed for additional publications. Specific product information was also
obtained from the manufacturer of teriparatide. Results: Teriparatide has been
studied in postmenopausal women with osteoporosis, drug-induced osteoporosis
(specifically, corticosteroid-induced osteoporosis), and men with osteoporosis.
The data available from various clinical trials have shown an increase in both
bone mineral density (BMD) and bone mineral content (BMC) with the use of
teriparatide compared with placebo. One study found that women treated with the
20-microg dose and the 40-microg dose were 35% and 40%, respectively, less
likely to have one or more new nonvertebral fractures compared with placebo (
[Formula: see text] ). Another study compared the use of daily teriparatide
40-microg injections versus oral daily alendronate. Results showed that the
incidence of nonvertebral fractures was significantly lower in the teriparatide
group than the alendronate group ( [Formula: see text] ). A study using 20- and
40-microg daily injections of teriparatide was performed in men with
osteoporosis. There was a statisticatly significant increase in lumbar spine BMD
of 5.9% in the 20-microg group and 9.0% in the 40-microg group (both, [Formula:
see text] ). In the femoral neck, a 1.5% increase in BMD occurred in the
20-microg group ( [Formula: see text] ) and a 0.9% increase in the 40-microg
group ( [Formula: see text] ). A limited number of studies are available
assessing the combination of antiresorptive medications and teriparatide;
however, the available data suggest that the effects of teriperatide do not
require prior stimulation of bone resorption. Conclusions: Teriparatide has been
shown clinically to improve BMD and BMC in postmenopausal women and in men.
Because of its anabolic capabilities, teriparatide can be used as an alternative
to the traditional therapies that are currently available for the treatment of
osteoporosis, with scheduled monitoring for adverse effects such as
hypercalcemia and urinary calcium excretion. In 1 study, mild hypercalcemia was
seen most often 4 to 6 hours after SC injection of teriparatide before returning
to normal. Urinary calcium was observed to increase by 30 mg/d (0.75 mmol/d)
with teriparatide.
-----
Altern Med Rev. 2004 Jun;9(2):136-156.
Therapeutic applications of whey protein.
Marshall K.
Master of Science, Social and Preventive Medicine, State University of New York
at Buffalo; Graduate, National College of Naturopathic Medicine. Private
practice, Sandpoint, Idaho Correspondence address: 515 Pine Street, Suite H,
Sandpoint, ID 83864 Email: mackaynd@aol.com
Whey, a protein complex derived from milk, is being touted as a functional food
with a number of health benefits. The biological components of whey, including
lactoferrin, beta-lactoglobulin, alpha-lactalbumin, glycomacropeptide, and
immunoglobulins, demonstrate a range of immune-enhancing properties. In
addition, whey has the ability to act as an antioxidant, antihypertensive,
antitumor, hypolipidemic, antiviral, antibacterial, and chelating agent. The
primary mechanism by which whey is thought to exert its effects is by
intracellular conversion of the amino acid cysteine to glutathione, a potent
intracellular antioxidant. A number of clinical trials have successfully been
performed using whey in the treatment of cancer, HIV, hepatitis B,
cardiovascular disease, osteoporosis, and as an antimicrobial agent. Whey
protein has also exhibited benefit in the arena of exercise performance and
enhancement.
-----
Rheumatol Int. 2004 Jun 30 [Epub ahead of print]
Prevention and therapy of osteoporosis: the roles of plain
vitamin D and alfacalcidol.
Ringe JD, Schacht E.
Rheumatologie/Osteologie, Medizinisches Klinik 4, Klinikum Leverkusen,
Akademisches Lehrkrankenhaus der Universitat zu Koln, 51375, Leverkusen,
Germany.
Severe vitamin D deficiency was identified only in the first decades of the last
century as the most common aetiology of rickets in children and osteomalacia in
adults. It was later shown that vitamin D is not, as had been supposed, the
biologically active principle for healing bone disease but must be hydroxylated
in the liver and then finally in the kidney to become
1alpha,25-dihydroxy-cholecalciferol, a biologically highly active renal hormone.
This study reviews the various principles, mechanisms, and approaches to the
treatment of different forms of osteoporosis using vitamin D, alfacalcidol, and
calcitriol therapy regimens.
-----
Osteoporos Int. 2004 Jun 3 [Epub ahead of print]
The importance of bisphosphonate therapy in maintaining bone mass
in men after therapy with teriparatide [human parathyroid hormone(1-34)].
Kurland ES, Heller SL, Diamond B, McMahon DJ, Cosman F, Bilezikian JP.
Department of Medicine, Columbia University College of Physicians and Surgeons,
630 West 168th Street, PH 8 West 864, NY 10032, New York, USA.
Teriparatide, the active fragment of human parathyroid hormone (hPTH 1-34), is
an anabolic agent for the treatment of osteoporosis. Important questions remain
regarding management strategy beyond the recommended 18- to 24-month course of
teriparatide treatment. We followed 21 men for up to 2 years after discontinuing
teriparatide. Twelve men (57%) chose treatment with bisphosphonate immediately
after teriparatide withdrawal, while 9 (43%) opted for no pharmacologic agent.
At the end of 1 year lumbar spine bone density increased an additional
5.1+/-1.0% in the bisphosphonate group, while it declined by 3.7+/-1.7% in those
on no medication ( P<0.002). In six men who delayed initiation of bisphosphonate
until 1 year after teriparatide withdrawal, their subsequent gains in the second
year, 2.6+/-1.7%, still placed them below the peak gains they achieved on
teriparatide. In contrast, the 12 men who began bisphosphonates immediately and
continued treatment for the entire 2-year post-PTH period had continued gains at
the lumbar spine, 8.9+/-1.5% above their post-PTH values ( P=0.002). For the
4-year period, including 2 years of teriparatide and 2 years of bisphosphonate,
the total gains at the lumbar spine were 23.6+/-2.9%. Men, who received
bisphosphonate in only the 2nd year post-teriparatide, had cumulative gains of
11.1+/-3.4%. Three men who did not receive any bisphosphonate at any time during
the post-PTH period had cumulative gains of only 5.5+/-3.7%. These findings
suggest that the use of bisphosphonates following teriparatide is an important
component of any strategy utilizing this anabolic drug for osteoporosis in men.
The immediate use of bisphosphonates after teriparatide withdrawal may help to
optimize gains in bone density at the lumbar spine.
-----
Menopause. 2004 May-Jun;11(3):337-42.
Trimegestone in a low-dose, continuous-combined hormone therapy
regimen prevents bone loss in osteopenic postmenopausal women.
Warming L, Ravn P, Spielman D, Delmas P, Christiansen C.
Center for Clinical and Basic Research, Ballerup, Denmark, Wyeth CR&D, USA. lw@ccbr.dk
OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg
17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal
osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with
osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of
the premenopausal mean value] were enrolled in a 2-year prospective, randomized
study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg
trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All
received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD
measurements at the lumbar spine, total hip, and femoral neck as well as blood
and urinary biochemical markers of bone turnover (serum osteocalcin), serum
bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took
place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and
3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P <
0.001). The biochemical markers of bone turnover were suppressed accordingly.
Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%,
respectively, whereas serum osteocalcin and serum bone-specific alkaline
phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of
the women receiving hormone therapy, 75% had amenorrhea from the first cycle,
and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This
new estrogen + progestogen therapy is efficient in increasing BMD in an
osteopenic postmenopausal population. Furthermore, it is well tolerated, with
few adverse events and an early bleeding control, which is likely to improve
compliance to the treatment over the long term.
-----
J Gynecol Obstet Biol Reprod (Paris). 2004 May;33(3):195-209.
[Alternatives to hormone replacement therapy for menopause: an
epidemiological evaluation]
[Article in French]
Ringa V.
INSERM U 149, Unite de Recherches Epidemiologiques en Sante Perinatale et Sante
des Femmes, Hopital Paul-Brousse, 16 avenue Paul-Vaillant-Couturier, 94807
Villejuif Cedex, France. ringa@vjf.inserm.fr
OBJECTIVE: Recent results put into question the risks/benefits ratio of hormone
replacement therapy and emphasize the importance of precise knowledge of the
effects of other treatments that exist for postmenopausal symptoms or diseases.
Our aim is to analyze their effect. METHODS: A review of randomized trials or
epidemiological studies was undertaken. RESULTS: Bisphophonates, calcitonin,
parathormone, strontium ranelate, calcium and vitamin D have specific effects on
bone. The efficacy of bisphophonates for prevention and treatment of
osteoporosis has been proven and parathormone and strontium ranelate seem
promising. These treatments are useful for women at high risk of osteoporosis
who do not suffer from menopausal symptoms. Tibolone, SERMs and phytoestrogens
exert effects on various tissues. SERMs are very promising, but they do not
improve climacteric symptoms and their long term effects are still unknown.
Tibolone has beneficial effects on climacteric symptoms and on bone loss, but
recent results concerning its effects on the risk of breast cancer call into
question its interest. The beneficial effects of phytoestrogens on bone and on
vasomotor symptoms need to be confirmed. CONCLUSION: At this time, none of the
existing treatments for postmenopausal symptoms or diseases is ideal. The
existence of several options for treatments of symptoms or diseases of the
postmenopause is helpful as it affords several choices for physicians and for
women who sometimes need to be treated for many years. However several questions
remain unanswered concerning the long term effects of these treatments.
-----
Maturitas. 2004 May 28;48(1):19-25.
Climacteric medicine: European Menopause And Andropause Society (EMAS)
statements on postmenopausal hormonal therapy.
Skouby SO.
Frederiksberg Hospital, Ob/Gyn, Ndr Fasanvej, 2000 F Copenhagen, Denmark.
Hormonal therapy (HT) is one of the most frequently prescribed drug regimens for
women after the age of 50 years. HT has been developed progressively since the
1960s to provide estrogen to those women (a) who require relief of symptoms
which have resulted from reduced circulating estrogen or (b) to act as an anti-resorptive
agent to counteract the effect of the increased bone turnover which occurs with
falling menopausal estrogen levels and which results in loss of bone mass
leading to postmenopausal osteoporosis. However, a large number of women pass
through the menopausal transition without experiencing distress as a result of
the natural fall in estrogen hormone levels and since the introduction HT has
been thought to be associated with a number of health benefits that have been
tested in clinical trials but not substantiated. In women experiencing
distressing climacteric symptoms double-blind randomised controlled clinical
trials with a variety of HT regimens have shown that HT of any type provides
symptom relief with no alternative treatment of similar effect. The dose and
regimen of HT need to be individualised and in general the appropriate dose is
dependent on the menopausal age. Women experiencing urogenital estrogen
deficiency symptoms require long-term treatment which is most easily achieved
with local estrogen. With the perspective provided by the most recent
epidemiological findings not least from the estrogen only arm of the Women's
Health Initiative Study (WHI) EMAS supports research activities generating HT
with new compositions including lower doses and a wider range of progestins in
order to positively affect the balance of clinical benefit and risk. Currently,
however, individualized and appropriate prescription of the available HT
products together with life-style management will sustain possibilities for
beneficial effects on climacteric symptoms, quality of life and degenerative
diseases after the menopause.
-----
J Nutr Sci Vitaminol (Tokyo). 2004 Apr;50(2):114-20.
Promotion of bone formation by fermented soybean (Natto) intake
in premenopausal women.
Katsuyama H, Ideguchi S, Fukunaga M, Fukunaga T, Saijoh K, Sunami S.
Department of Public Health, Kawasaki Medical School, Kurashiki 701-0192, Japan.
katsu@med.kawasaki-m.ac.jp
A therapeutic agent of vitamin K2 is approved for the treatment of osteoporosis
in Japan. However, little is known about the efficacy of dietary intake of
vitamin K2 for bone health. We compared the effects of various levels of
fermented soybeans (Natto) intake, which contains plenty of vitamin K2, on bone
stiffness and bone turnover markers in healthy premenopausal women.
Seventy-three healthy premenopausal women were randomly divided into four groups
matched for age and parity categories. Natto was supplied as follows: Group 1
(no intake), Group 2 (once per month), Group 3 (once per week) and Group 4
(three times per week). Subjects took Natto at a lunch for 1 y, and the
stiffness index by quantitative ultrasound and bone turnover markers were
assessed at baseline, 6 mo and 1 y. There was no statistical difference in the
stiffness index during the 1 y observation. However, bone specific alkaline
phosphatase (BAP) in Group 4 was higher than that in Group 3 at 1 y and
undercarboxylated osteocalcin (Glu) in Group 4 was significantly lower than
those in Groups 1, 2 and 3 at 6 mo. Logistic regression analysis showed that the
risk of reduction of bone formation markers declined to 0.07 in Group 4 based on
that in Group 1. In premenopausal women who had to keep the stiffness index as
high as possible before menopause, Natto intake may have contributed to the
promotion of bone formation.
-----
Endocr Pract. 2004 Mar-Apr;10(2):139-48.
Clinical use of teriparatide in the real world: initial insights.
Miller PD, Bilezikian JP, Deal C, Harris ST, Ci RP.
Colorado Center for Bone Research, Lakewood, Colorado.
Objective: To summarize expert opinion regarding clinical application of the
recently introduced anabolic agent teriparatide [human parathyroid hormone
(1-34)] in treatment of postmenopausal osteoporosis in women, and osteoporosis
in men. Summary: The anabolic agent teriparatide was approved for clinical use
by the Food and Drug Administration (FDA) on November 26, 2002. Since the launch
of teriparatide, many more questions about clinical use of this exciting agent
have emerged than there are answers provided by clinical trials or FDA-approved
product labeling. A group of physicians with a broad range of experience in
research and clinical applications of teriparatide met recently to address
practical issues related to its use. This manuscript is a compendium of the
consensus opinions of the authors that attempts to provide practical answers to
many real-world questions being asked about teriparatide therapy since its
approval by the FDA. (Endocr Pract. 2004;10:139-148)
-----
Climacteric. 2004 Mar;7(1):103-11.
Safety and efficacy of drospirenone used in a continuous
combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.
Warming L, Ravn P, Nielsen T, Christiansen C.
Center for Clinical and Basic Research A/S, Ballerup, Denmark.
OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous
drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total
of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year
prospective study. Bone mineral density (BMD) at lumbar spine, hip and total
body as well as endometrial thickness, markers of bone turnover and serum lipids
were measured regularly. Treatment groups were given placebo or 1 mg
17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at
the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in
all hormone groups versus placebo (all p < 0.001). Bone markers all decreased
accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase
36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p <
0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by
8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol
and triglycerides remained unchanged. No significant dose-related effects were
found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone
group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol
and drospirenone has a positive effect on BMD and a potentially beneficial
effect on lipids. Although endometrial thickness increased slightly, the safety
of the endometrium was assured, as no cases of hyperplasia or cancer occurred.
-----
Gac Med Mex. 2004 Mar-Apr;140(2):235-40.
[A guide for osteoporosis management]
[Article in Spanish]
Zarate A, Saucedo R, Basurto L.
Unidad de Investigacion Medica de Enfermedades Endocrinas, Hospital de
Especialidades, Centro Medico Nacional IMSS. zaratre@att.net.mx
Osteoporosis has to be considered only as a risk factor for bone fractures and
its measurement by the bone mass index has some limitations. The aim of
treatment of osteoporosis is to reduce the frequency of fractures (especially at
the vertebral and the hip) which are responsible for morbidity and mortality
with the osteoporosis. It has been demonstrated that antiresorptive drugs (bisphosphonates,
estrogens, raloxifen) as well as anabolic agents (synthetic parathormone) are
useful for preventing fractures. Calcium and vitamin D supplementation is not
sufficient to treat persons with osteoporosis. Choice of treatment depends of
age, the presence or absence of prevalent fractures, and the degree of bone
mineral density measured at the spine and hip. The main inconvenient for the
adherence of treatment is the high cost of the medicaments and agents as well as
the poor information given to the patients.
-----
Intern Med J. 2004 Mar;34(3):129-32.
Secondary prevention of fractures in older people:
evaluation of a protocol for the investigation and treatment of
osteoporosis.
Sidwell AI, Wilkinson TJ, Hanger HC.
Older Persons Health, Princess Margaret Hospital, Christchurch,
New Zealand.
Abstract It has been found previously that the investigation
and treatment of osteoporosis following a fracture is poor, with
only 9% of older people after a fracture being on effective osteoporosis
treatment. To improve this aspect of post-fracture care in older
people, a protocol has been instituted on an orthogeriatric rehabilitation
ward in Christchurch, New Zealand. An audit was performed to assess
the efficacy of this protocol in improving the investigation and
treatment of osteoporosis (n = 193). Compliance with the investigation
protocol was assessed and the pharmacological therapy initiated
was requested from the general practitioner. All recommended blood-test
investigations were requested in 62.8% of cases. Compared to a
pre-protocol population, there was a marked increase in the measurement
of bone mineral density (BMD; 93 vs 11%, P < 0.01) and vitamin
D (95 vs 12%, P < 0.01). Vitamin D levels were low/-borderline
in 95.6% of cases. BMD was performed in 77.7% of cases and showed
osteoporosis and osteopenia to be present in 78.6 and 14.0%, respectively.
For the 60 patients with BMD-confirmed osteoporosis whose therapy
was obtained, 13.3% had no pharmacological therapy prescribed.
Calcium, vitamin D or both were prescribed in 85.0%, bisphosphonates
in 50.0% and hormone replacement therapy in 1.7% of patients.
Vitamin D deficiency and osteoporosis on the basis of the BMD
result are very common. The institution of a protocol has shown
a significant improvement in the management of osteoporosis following
a fracture. Some of the multifactorial barriers to full implementation
of the guidelines are described. (Intern Med J 2004; 34: 129-132)
-----
J Obstet Gynecol Neonatal Nurs. 2004 Jan-Feb;33(1):21-33.
Calcium in women: healthy bones and much more.
Kass-Wolff JH.
The University of Texas at Austin School of Nursing, USA jane.kass-wolff@utsouthwestern.edu
Osteoporosis is one of the leading health problems of women
today, and the expectation is that more than 41 million women
worldwide will be affected within the next 20 years if current
trends are not reversed. Prevention of osteoporosis must be a
focus for nurses, rather than merely the treatment of the problem.
The majority of bone mass is developed during the adolescent and
young adulthood years, with nearly 90% of skeletal mass accumulated
by age 18. Current research has demonstrated that young women's
intake of calcium is significantly below the recommended dietary
intake. This article reviews the role and functions of calcium,
how it is transported, and factors that may significantly increase
or impair the absorption of this macronutrient. Strategies are
described that will assist nurses in assessing the patient's diet
and making appropriate recommendations regarding the intake of
calcium and other micronutrients. A more in-depth and thorough
understanding of this important mineral will enable nurses to
strengthen their knowledge and confidence in helping patients
and themselves change the focus from treating the disease to the
improvement and maintenance of healthy bones and the prevention
of other health conditions in women.
-----
Mayo Clin Proc. 2004 Jan;79(1):91-7.
Phosphorus nutrition and the treatment of osteoporosis.
Heaney RP.
Creighton University Medical Center, Omaha, Neb 68131, USA. rheaney@creighton.edu
Bone mineral consists of calcium phosphate, and phosphorus
is as important as calcium in supporting bone augmentation and
maintenance. Although typical adult diets contain abundant phosphorus,
10% to 15% of older women have intakes of less than 70% of the
recommended daily allowance. When these women take high-dose calcium
supplements that consist of the carbonate or citrate salts, all
their food phosphorus may be bound and hence unavailable for absorption.
Current-generation anabolic agents for treating osteoporosis require
positive phosphorus balances of up to 90 mg/d. Attention to the
nutritional adequacy of the diets of such patients is essential
if they are to realize the full potential of such therapies. A
calcium phosphate supplement may be preferable to the usual carbonate
or citrate salts because its phosphate serves to spare food phosphorus.
-----
South Med J. 2003 May;96(5):469-76.
Selective estrogen receptor modulators.
Haskell SG.
Section of General Internal Medicine, Yale University School of
Medicine, New Haven, CT, USA. haskell.sally@west-haven.va.gov
Because of recent concerns about the long-term risks of estrogen
replacement therapy in postmenopausal women, there is growing
interest in a group of compounds known as selective estrogen receptor
modulators (SERMs). The SERMs bind to estrogen receptors and have
tissue-specific effects that allow them to function as estrogen
agonists in some tissues and estrogen antagonists in other tissues.
There are four SERMs currently marketed in the United States.
These include the triphenylethylenes--clomiphene citrate (Clomid),
tamoxifen, and toremifene--and the benzothiophene, raloxifene.
Clomid is used primarily in the treatment of infertility. Tamoxifen
is indicated for the treatment and prevention of breast cancer.
It has an estrogen antagonist effect on breast tissue, but an
estrogen-like effect on lipids, bone, and the endometrium. Toremifene
has an antagonist/agonist profile similar to that of tamoxifen.
Raloxifene is approved for the prevention of osteoporosis in postmenopausal
women. It is thought to be an estrogen antagonist on the uterus
and breast tissues and an estrogen agonist with respect to bone
and serum lipids.
-----
Cleve Clin J Med. 2003 Jul;70(7):585-6, 589-90, 592-4 passim.
Recombinant human PTH 1-34 (Forteo): an anabolic
drug for osteoporosis.
Deal C, Gideon J.
Center for Osteoporosis and Metabolic Bone Disease, Department
of Rheumatic and Immunologic Disease, The Cleveland Clinic Foundation,
OH 44195, USA.
Forteo (teriparatide of rDNA origin), a genetically engineered
fragment of parathyroid hormone, is the first of a new class of
drugs to treat osteoporosis. The drug's anabolic action increases
bone turnover, stimulating osteoblasts to a greater extent than
osteoclasts, and reducing both vertebral and nonvertebral fractures.
However, a number of issues about its use remain unanswered.
-----
Best Pract Res Clin Endocrinol Metab. 2003 Mar;17(1):1-16.
Medical choices available for management of menopause.
Farrell E.
Menopause Unit, Monash Medical Centre, Clayton, Australia. elizabethfarrell@ozemail.com.au
The indications for hormone therapy (HT) have changed markedly
since the 1980s; they now include the treatment of menopausal
symptoms and the prevention and treatment of osteoporosis in the
short term. Long-term therapy is discouraged because of the small
increase in risk of breast cancer after 5 years of therapy. Careful
assessment of the midlife woman allows for individualized risk-benefit
analysis with the formulation of a specific health management
plan. Lifestyle advice and modification form the cornerstone of
management-followed by therapeutic options if appropriate indications
exist. In some industrialized countries alternative therapies
are preferred despite little scientific evidence of their efficacy.
The choices of hormonal products have increased, with the introduction
of new formulations and routes of administration allowing for
more optimal treatment of the menopause, especially in the presence
of concurrent medical conditions, for example, diabetes, breast
cancer or fibroids.
-----
Med Pediatr Oncol. 2003 Sep;41(3):222-7.
Management of osteoporosis due to ovarian failure.
Eastell R.
University of Sheffield, Sheffield, United Kingdom. r.eastell@sheffield.ac.uk
The management of oestrogen deficiency bone loss needs to include
general measures to protect against osteoporosis, the identification
and treatment of other reversible causes of bone loss, and the
use of proven agents for the treatment of osteoporosis. The general
measures include improved physical activity, adequate diet (paying
particular attention to calcium and vitamin D), and avoidance
of behaviours that promote bone loss, such as smoking and alcohol
abuse. The diseases that should be identified, other than estrogen-deficiency,
include primary hyperparathyroidism, thyrotoxicosis and celiac
disease. The treatments that are proven to prevent fractures in
women with estrogen deficiency, include hormone replacement therapy,
raloxifene, nasal calcitonin, bisphosphonates, (alendronate and
risedronate) and parathyroid hormone. The most appropriate therapy
in the younger woman is HRT, although the trial-based evidence
that HRT prevents fractures is not strong. There is a wide choice
of preparations and the use of continuous combined preparations
avoids regular menstrual periods, one of the limitations to the
use of HRT. Raloxifene has less effect on bone mineral density
than HRT, but a similar effect on vertebral fractures and does
not result in menstrual bleeding or increased risk of breast cancer.
There is recent evidence suggesting that the beneficial effects
on lipids translate into reduced risk of cardiovascular disease.
Bisphosphonates are the standard treatment for the older woman
with osteoporosis. Alendronate has been found to reduce the risk
of spine, hip, and wrist fractures and has approval for a once
weekly regimen, an approach that appears to prevent GI side effects.
Risedronate reduces the risk of spine and non-vertebral fractures
within the first year of treatment and has been shown to reduce
the risk of hip fracture. It has not been associated with an excess
of GI side effects. Parathyroid hormone therapy results in increases
in BMD that are even greater than estrogen and the bisphosphonates
and to an even greater reduction in the risk of fractures, particularly
non-vertebral fractures. It works by stimulation of bone formation
rather than by inhibition of bone resorption. However, it has
to be given by daily injection. Thus, we have a wide choice of
therapies for the woman with osteoporosis due to ovarian failure.
Copyright 2003 Wiley-Liss, Inc.
-----
Keio J Med. 2003 Jun;52(2):113-9.
Early response to alendronate after treatment
with etidronate in postmenopausal women with osteoporosis.
Iwamoto J, Takeda T, Ichimura S, Uzawa M.
Department of Sports Medicine, Keio University School of Medicine,
Tokyo, Japan. jiwamoto@sc.itc.keio.ac.jp
The purpose of the present study was to examine the early response
of lumbar bone mineral density (BMD), bone resorption, and back
pain to alendronate after treatment with cyclical etidronate in
postmenopausal women with osteoporosis. Forty postmenopausal women
with osteoporosis, 60-83 years of age, without any vertebral fractures
in the lumbar spine, were randomly divided into two groups with
20 patients in each group: 18 months of cyclical etidronate (200
mg daily for 2 weeks every 3 months) group and 12 months of cyclical
etidronate followed by 6 months of alendronate (5 mg daily) group.
BMD of the lumbar spine (L1-L4) measured by DXA, urinary cross-linked
N-terminal telopeptides of type I collagen (NTX) level measured
by enzyme-linked immunosorbent assay, and back pain evaluated
by face scale score were assessed at baseline and every 6 months.
There were no significant differences in baseline characteristics
including age, body mass index, years since menopause, lumbar
BMD, urinary NTX level, and face scale score between the two groups.
Cyclical etidronate significantly reduced urinary NTx level and
face scale score over 12 months, but did not significantly increase
lumbar BMD. After 12 months of treatment, the switch to alendronate
significantly reduced urinary NTX level and face scale score,
and significantly increased lumbar BMD, while continued cyclical
etidronate did not significantly alter these parameters. These
results suggest that switching to alendronate after treatment
with cyclical etidronate produces a greater response of lumbar
BMD, bone resorption, and back pain than continued cyclical etidronate
in postmenopausal women with osteoporosis.
-----
Int J Clin Pract. 2003 Jun;57(5):417-22.
Ibandronate: a potent new bisphosphonate in the
management of postmenopausal osteoporosis.
Papapoulos SE.
Department of Endocrinology and Metabolic Diseases, Leiden University
Medical Centre, Leiden, The Netherlands.
Osteoporosis is a serious, common skeletal disease. Oral bisphosphonates
are among the most effective therapeutics available to manage
this condition. Currently, bisphosphonates are administered orally
either daily or once weekly. Less frequent dosing, while retaining
efficacy, may provide greater convenience, thereby promoting long-term
adherence to treatment and maximising therapeutic outcomes. Ibandronate
is a highly potent nitrogen-containing bisphosphonate that has
been given orally or intravenously at variable dosing intervals
for the prevention and treatment of osteoporosis. Recent studies
with oral ibandronate, given daily or intermittently with a between-dose
interval longer than two months to women with postmenopausal osteoporosis,
demonstrated significant and sustained antifracture efficacy.
Additional studies showed that ibandronate given as a convenient
intravenous injection every three months induces significant increases
in bone mineral density and suppression of bone turnover. Ongoing
studies aim to determine the optimal therapeutic regimen of this
promising new bisphosphonate in clinical practice.
-----
J Am Geriatr Soc. 2003 Jul;51(7):985-90.
Effects of exercise training added to ongoing
hormone replacement therapy on bone mineral density in frail elderly
women.
Villareal DT, Binder EF, Yarasheski KE, Williams DB, Brown
M, Sinacore DR, Kohrt WM.
Washington University Claude Pepper Older Americans Independence
Center, USA. dvillare@im.wustl.edu
OBJECTIVES: To determine whether exercise training added to
ongoing hormone replacement therapy (HRT) increases bone mineral
density (BMD) in physically frail elderly women. DESIGN: Prospective
controlled trial. SETTING: University-based research center. PARTICIPANTS:
Twenty-eight women on HRT, aged 75 and older with physical frailty.
INTERVENTIONS: Participants were assigned to 9 months of supervised
(EXER) or home (HOME) exercise. The EXER program started with
physical therapy and gradually incorporated resistance and endurance
training. The HOME program consisted of flexibility exercises.
MEASUREMENTS: Changes in BMD and body composition. RESULTS: There
were larger increases in lumbar spine BMD in response to EXER
than with HOME (3.5% vs 1.5%, P =.048), with a trend for larger
increases in total body BMD (1.5% vs 0.2%, P =.058). There were
no significant between-group differences in hip BMD. The EXER
group had decreases in weight (-2.2 +/- 0.3 kg, P =.010) and fat
mass (-2.7 +/- 0.4 kg, P =.018) and increases in muscle strength
(9-30%, P <.05). CONCLUSION: In physically frail elderly women
on HRT, relatively vigorous exercise training significantly increased
lumbar spine BMD. The improved BMD and strength in response to
exercise could reduce fracture risk in frail women already on
HRT.
-----
Lakartidningen. 2003 May 15;100(20):1790-7.
[After the early termination of the Women's Health
Initiative study. New American recommendations for postmenopausal
hormone therapy]
[Article in Swedish]
Stjernquist M; North American Menopause Society (NAMS) Advisory
Panel.
Institutionen for obstetrik och gynekologi, Malmo, Lunds universitet,
kvinnokliniken, Universitetssjukhuset MAS, Malmo. martin.stjernquist@obst.mas.lu.se
One treatment-arm of the Women's Health Initiative (WHI) study
was recently terminated because the overall risks of hormone treatment
were considered to outweigh the benefits. The main findings were
an increased risk of venous thromboembolism and a decreased risk
of osteoporotic fractures with treatment. No beneficial effects
on cardiovascular disease could be detected. The North American
Menopause Society (NAMS) Advisory Panel has given the following
recommendations concerning hormone therapy: The primary indications
are vasomotor and urogenital symptoms. The only indication for
progesterone treatment is for endometrial protection. Hormones
should not be prescribed for primary or secondary prevention of
coronary heart disease. Alternative therapies should also be considered
for the prevention of osteoporosis. A short duration of therapy
and lower-than-standard doses are preferable. Establishing an
individual risk profile is essential. The author of this article
also emphasizes a restrictive attitude for patients with increased
risk of thromboembolic disease.
-----
J Pediatr Endocrinol Metab. 2003 Apr-May;16(4):529-36.
Bisphosphonates, a new treatment for glucocorticoid-induced
osteoporosis in children.
Noguera A, Ros JB, Pavia C, Alcover E, Valls C, Villaronga
M, Gonzalez E.
Pediatrics Department, Unitat Integrada Hospital Sant Joan de
Deu-Hospital Clinic, Universitat de Barcelona, Barcelona, Spain.
BACKGROUND: Long-term corticoids used as a treatment for rheumatic
diseases are the most frequent cause of osteoporosis in the pediatric
population. Bisphosphonates have been proved to be useful in treating
osteoporosis. OBJECTIVE: To investigate the efficacy of pamidronate
in corticoid-induced osteoporosis in children. PATIENTS AND METHODS:
Ten children affected with rheumatic diseases and osteoporosis
underwent biannual cycles of intravenous pamidronate (4 to 12
cycles). Complete clinical, radiological, biochemical and densitometric
follow-up was performed at every treatment cycle. RESULTS: Good
clinical and radiological evolution was observed in most of our
patients; no new vertebral fractures were reported. Good densitometric
evolution has been linked to the onset of puberty (rise in IGF-I
levels) and low values for inflammatory activity markers (ESR
and CRP). Self-limited hyperthermia and mild abdominal pain were
observed during pamidronate infusion, but no other side effects
were reported. CONCLUSIONS: Pamidronate is a safe and useful treatment
for corticoid-induced osteoporosis in the pediatric population.
-----
Ann Endocrinol (Paris). 2003 Apr;64(2):141-7.
[Osteoporosis in the elderly man]
[Article in French]
Kaufman JM.
Departement d'Endocrinologie et Unite d'Osteoporose et Metabolisme
Osseux, Hopital Universitaire de Gand, De Pintelaan 185 B-9000
Gand, Belgique.
Elderly men are at substantial risk for fracture. Morbidity
after osteoporotic fractures appears to be more serious and mortality
more common in men than in women. Risk factors for osteoporotic
fractures in men appear to be qualitatively similar to those in
women. Low bone mineral density (BMD) is an important risk factor
for fracture in men; however, further clarification of the relationship
between BMD, bone geometry and fracture risk is needed. Our understanding
of the mechanisms underlying senile bone loss and the pathogenesis
of senile osteoporosis in men remains fragmentary with, in particular,
the need for further clarification regarding the precise impact
of hormonal status in elderly men on skeletal homeostasis. Nevertheless,
the available evidence indicates a role for both testosterone
and estrogens in the regulation of bone metabolism in elderly
men. Recommendations concerning prevention and treatment of senile
osteoporosis in men should focus on the minimization of known
risk factors for bone loss and falls. Testosterone treatment may
be useful only in those men with initially low serum testosterone.
As to other pharmacological treatment modalities, prospective
trials specifically in elderly men, and preferably with fracture
incidence as the primary clinical endpoint, are required.
-----
Am J Health Syst Pharm. 2003 May 1;60(9):883-901; quiz 903-4.
Current approaches to the prevention and treatment
of postmenopausal osteoporosis.
Follin SL, Hansen LB.
Department of Pharmacy Practice and Family Medicine, University
of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Box
C238, Denver, CO 80262, USA. sheryl.follin@uchsc.edu
Current approaches to the prevention, detection, treatment,
and monitoring of postmenopausal osteoporosis are discussed. In
the United States, 44 million men and women ages 50 years or older
have low bone mass or osteoporosis. The most devastating consequence
of this disease is fractures. The assessment of osteoporosis risk
includes determining risk factors, conducting laboratory and physical
examinations, and measuring bone density and bone-turnover markers.
Once risk has been established, nonpharmacologic strategies, such
as exercise, appropriate dietary habits, and discontinuing tobacco
and alcohol use, are helpful. Fall prevention and adequate intake
of calcium and vitamin D are critical. When pharmacologic therapy
is warranted, bisphosphonates have shown the greatest benefit
in preventing bone loss and lowering fracture rates. Selective
estrogen-receptor modulators and calcitonin are also options for
prevention or treatment of osteoporosis. Estrogen should not be
used for the sole purpose of osteoporosis prevention; however,
short-term use is acceptable for women with vasomotor symptoms
or in whom the benefits outweigh the risks. Parathyroid hormone
may offer another treatment alternative. A variety of pharmacologic
options are available for patients with osteoporosis in whom lifestyle
modifications have proven insufficient. Bisphosphonates are the
mainstay of drug therapy.
-----
J Womens Health (Larchmt). 2003 Mar;12(2):151-6.
Vitamin D and bone health in postmenopausal women.
Malabanan AO, Holick MF.
Section of Endocrinology, Diabetes and Nutrition, Department of
Medicine, Boston University School of Medicine, Boston, Massachusetts,
USA. alan.malabanan@bmc.org
Osteoporosis, a disease of increased skeletal fragility, is
becoming increasingly common as the U.S. population ages. Adequate
vitamin D and calcium intake is the cornerstone of osteoporosis
prevention and treatment. Age-related changes in vitamin D and
calcium metabolism increase the risk of vitamin D insufficiency
and secondary hyperparathyroidism. Although longitudinal data
have suggested a role of vitamin D intake in modulating bone loss
in perimenopausal women, studies of vitamin D and calcium supplementation
have failed to support a significant effect of vitamin D and calcium
during early menopause. There is a clearer benefit in vitamin
D and calcium supplementation in older postmenopausal women. Vitamin
D intake between 500 and 800 IU daily, with or without calcium
supplementation, has been shown to increase bone mineral density
(BMD) in women with a mean age of approximately 63 years. In women
older than 65, there is even more benefit with vitamin D intakes
of between 800 and 900 IU daily and 1200-1300 mg of calcium daily,
with increased bone density, decreased bone turnover, and decreased
nonvertebral fractures. The decreases in nonvertebral fractures
may also be influenced by vitamin D-mediated decreases in body
sway and fall risk. There are insufficient available data supporting
a benefit from vitamin D supplementation alone, without calcium,
to prevent osteoporotic fracture in postmenopausal women.
-----
Curr Womens Health Rep. 2003 Jun;3(3):181-6.
Long-term estrogen and hormone replacement therapy
for the prevention and treatment of osteoporosis.
Levine JP.
Department of Family Medicine, UMDNJ-Robert Wood Johnson Medical
School, One Robert Wood Johnson Place CN19, New Brunswick, NJ
08903-0019, USA. jeffzoo@aol.com
Recent studies have called into question whether the risks
of hormone replacement therapy (HRT) outweigh its long-term benefits.
There is a clear causal relationship between estrogen deficiency
and osteoporosis. Postmenopausal status or estrogen-deficiency
at any age significantly increases a patient's risk for osteoporosis
and subsequent fragility fractures. Estrogen, in various formulations,
is currently FDA-indicated for the prevention of osteoporosis.
However, estrogen is not FDA-approved for the treatment of osteoporosis.
Recent randomized clinical trials have demonstrated that estrogen
significantly reduces fractures among osteoporotic postmenopausal
women. Most postmenopausal women choose to use estrogen for relief
of vasomotor symptoms and urogenital atrophy. HRT should be limited
to osteoporosis prevention in women with significant ongoing vasomotor
symptoms who are not at an increased risk for cardiovascular disease.
An annual, individualized, risk/benefit reassessment should be
performed on these patients. Further research is needed to assess
the potential risks and benefits of various formulations, combinations,
doses, and delivery routes of estrogen for postmenopausal women.
-----
Am Fam Physician. 2003 Apr 1;67(7):1521-6.
Osteoporosis in men.
Campion JM, Maricic MJ.
Department of Medicine, University of Arizona Health Sciences
Center, Tucson, Arizona 85724-5069, USA.
Osteoporosis in men is now recognized as an increasingly important
public health issue. About 30 percent of hip fractures occur in
men, and one in eight men older than 50 years will have an osteoporotic
fracture. Because of their greater peak bone mass, men usually
present with hip, vertebral body, or distal wrist fractures 10
years later than women. Hip fractures in men, however, result
in a 31 percent mortality rate at one year after fracture versus
a rate of 17 percent in women. Major risk factors for osteoporosis
in men are glucocorticoid use for longer than six months, osteopenia
seen on plain radiographs, a history of nontraumatic fracture,
hypogonadism, and advancing age. Bisphosphonates and teriparatide
(recombinant parathyhroid hormone) have recently been approved
for use in men and should be considered along with supplemental
calcium and vitamin D. Increased awareness by physicians of risk
factors for male osteoporosis--and early diagnosis and treatment--are
needed to decrease the morbidity and mortality resulting from
osteoporotic fractures.
-----
Eur J Clin Invest. 2003 May;33(5):412-9.
Effect of electrical stimulation-induced cycling
on bone mineral density in spinal cord-injured patients.
Eser P, de Bruin ED, Telley I, Lechner HE, Knecht H, Stussi
E.
Swiss Paraplegic Centre, Nottwil, Swiss Federal Institute of Technology,
Schlieren, Switzerland. prisca.eser@paranet.ch
BACKGROUND: Bone atrophy in spinal cord-injured people (SCI)
is, among other factors, caused by immobilization and is initiated
shortly after the injury. The present study measured the effect
of an functional electrical stimulation (FES)-cycling intervention
on bone mineral density (BMD) of the tibia in recently injured
SCI people. METHODS: As soon as possible after the injury (mean
4.5 weeks), para- and tetraplegic patients were recruited into
an intervention and control group comparable with regard to gender,
age, and lesion level. The intervention consisted of 30-min functional
electrical stimulation-cycling three times a week for the duration
of their primary rehabilitation (mean = 6 months). Computed tomography
(CT) scans of the right tibia diaphysis were taken at the beginning
and at the end of the intervention. Bone mineral density of cortical
bone was calculated from the CT scans. RESULTS: A total of 38
subjects (19 in each group) were included in the study. Both groups
showed a reduction in tibial cortical BMD of 0-10% of initial
values within 3-10 months. The mean decrease in BMD was 0.3% (+/-
0.6) per month in the intervention group and 0.7% (+/- 0.8) in
the control group. This difference did not reach statistical significance.
Decrease of BMD was linearly correlated to initial BMD and age
in the pooled data of both groups; subjects who had a high initial
BMD and/or were older lost more bone. In neither group was bone
loss associated with duration of immobilization nor lesion level.
CONCLUSIONS: Functional electrical stimulation-cycling applied
shortly after SCI did not significantly attenuate bone loss.
-----
Minerva Ginecol. 2003 Apr;55(2):107-16.
Hormone replacement therapy. Current controversies.
Burkman RT.
Department of Obstetrics and Gynecology, Baystate Medical Center,
Springfield, MA, USA. RTB@bhs.org
Hormone replacement therapy has had a controversial history
since its introduction for medical use several decades ago. Current
evidence indicates that users of hormone replacement therapy have
an increased risk of venous thromboembolism, stroke, and coronary
heart disease compared to non-users. Among users, the risk of
breast cancer is modestly increased. This effect becomes apparent
after 4 to 5 years use and primarily with use of combination estrogen
plus progestin products. The risk of colorectal cancer is decreased
with use of hormone replacement therapy. In addition, the risk
of osteopenia and osteoporosis is decreased as is the risk of
osteoporotic fracture.
-----
Ann Pharmacother. 2003 May;37(5):711-24.
Comparing therapies for postmenopausal osteoporosis
prevention and treatment.
Eichner SF, Lloyd KB, Timpe EM.
College of Pharmacy, University of Tennessee, Memphis, TN, USA.
seichner@utmem.edu
OBJECTIVE: To review the literature concerning the efficacy
of calcium, hormone replacement therapy (HRT), bisphosphonates,
selective estrogen receptor modulators, and calcitonin in the
prevention and treatment of postmenopausal osteoporosis. DATA
SOURCES: Articles were identified through searches of the MEDLINE
(1966-July 2002), EMBASE (1980-July 2002), and International Pharmaceutical
Abstracts (1970-July 2002) databases using the key words osteoporosis,
postmenopausal, fracture, calcium, vitamin D, hormone replacement
therapy, bisphosphonates, alendronate, risedronate, raloxifene,
and calcitonin. Additional references were located through review
of the bibliographies of the articles cited. Searches were not
limited by time restriction, language, or human subject. STUDY
SELECTION AND DATA EXTRACTION: Experimental and observational
studies of the use of calcium and antiresorptive therapies for
the prevention and treatment of postmenopausal osteoporosis were
selected. Articles evaluating bone mineral density (BMD) or fracture
efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates,
raloxifene, and calcitonin have demonstrated stabilization of
and improvement in BMD. Randomized clinical trials have shown
fracture risk reduction with bisphosphonates, raloxifene, HRT,
calcium, and calcitonin. The largest risk reductions have been
reported with use of bisphosphonates in several trials. CONCLUSIONS:
Several therapeutic options with well-documented improvements
in BMD and reductions in fracture risk are available to women
for the prevention and treatment of postmenopausal osteoporosis.
-----
Drugs Today (Barc). 2003 Feb;39(2):89-101.
Strontium ranelate: a new paradigm in the treatment
of osteoporosis.
Reginster JY, Deroisy R, Jupsin I.
WHO Collaborating Center for Public Health Aspects of Rheumatic
Diseases, Liege, Belgium. jyreginster@ulg.ac.be
Not one of the currently available medications has, so far,
unequivocally demonstrated its ability to fully prevent the occurrence
of new vertebral or peripheral osteoporotic fractures once osteoporosis
is established. Therefore, several new therapies are currently
under development to optimize the risk/benefit ratio of osteoporosis
treatment. Strontium ranelate is composed of an organic moiety
(ranelic acid) and of two atoms of stable nonradioactive strontium.
In vitro, strontium ranelate increases collagen and noncollagenic
proteins synthesis by mature osteoblast enriched cells. The effects
of strontium ranelate on bone formation were confirmed as strontium
ranelate enhanced pre-osteoblastic cell replication. The stimulation
by strontium ranelate of the replication of osteoprogenitor cell
and collagen, as well as noncollagenic protein synthesis in osteoblasts,
provides substantial evidence to categorize strontium ranelate
as a bone-forming agent. In the isolated rat osteoclast assay,
a pre-incubation of bone slices with strontium ranelate induced
a dose- dependent inhibition of the bone resorbing activity of
treated rat osteoclast. Strontium ranelate also dose-dependently
inhibited, in a chicken bone marrow culture, the expression of
both carbonic anhydrase II and the alpha-subunit of the vitronectin
receptor. These effects showing that strontium ranelate significantly
affects bone resorption due to a direct and/or matrix-mediated
inhibition of osteoclast activity and also inhibits osteoclasts
differentiation, are compatible with the profile of an anti-resorptive
drug. In normal rats, administration of strontium ranelate induces
an improvement in the mechanical properties of the humerus and/or
the lumbar vertebra associated with a commensurate increase in
bone dimension, shaft and volume. Strontium ranelate was administered
in 160 early postmenopausal women, in a 24-month, double-blind,
placebo-controlled, prospective randomized study. Daily oral dose
of 125 mg, 500 mg and 1 g of strontium ranelate were compared
with a placebo. At the conclusion of the study, the percent variation
of lumbar-adjusted bone mineral density from baseline was significantly
different in the group receiving 1 g/day of strontium ranelate
compared with placebo (+1.41% vs. -0.98%, respectively). Increase
in total hip and neck bone mineral density averages, respectively,
3.2% and 2.5%. Strontium ranelate does not induce any significant
adverse reaction compared with those observed in women receiving
a placebo for the same duration. In a phase II study, the effect
of strontium ranelate in postmenopausal women with vertebral osteoporotic
fractures was assessed during a double-blind, placebo-controlled
trial. Doses of 500 mg, 1 g and 2 g daily of strontium ranelate
or placebo were given to 353 Caucasian women with prevalent osteoporosis.
At the conclusion of this 2-year study, the annual increase in
lumbar-adjusted bone mineral density of the group receiving 2
g of strontium ranelate was + 2.97%. This result was significantly
different compared with placebo. A significant increase in bone
alkaline phosphatase and, over a 6-month period, a significant
decrease in urinary-pyridium crosslinks (NTX) were evidenced.
During the second year of treatment, the dose of 2 g was associated
with a 44% reduction in the number of patients experiencing a
new vertebral deformity. Bone histomorphometry showed no mineralization
defects. The same percentage of withdrawals following an adverse
effect was observed for patients receiving placebo and for those
receiving 2 g of strontium ranelate. The compound was further
investigated in a large phase III program that included two extensive
trials for the treatment of severe osteoporosis, one assessing
the effects of strontium ranelate on the risk of vertebral fractures
(SOTI) and one evaluating its effects on peripheral (nonspinal)
fractures (TROPOS). The primary analysis of the SOTI study, evaluating
the effect of 2 g of strontium ranelate on vertebral fracture
rates, revealed a 41% reduction in the relative risk of expein
the relative risk of experiencing a first new vertebral fracture
with strontium ranelate, throughout the 3-year study, compared
with placebo. The TROPOS study, showed a significant (p = 0.05)
reduction in the relative risk of experiencing a first non-vertebral
fracture in the group treated with strontium ranelate throughout
the 3-year study compared with placebo in the intention-to-treat
population. A 41% reduction in the relative risk of experiencing
a hip fracture was demonstrated in the per protocol population.
All these results imply that strontium ranelate is a new, effective
and safe treatment for vertebral and nonvertebral osteoporosis,
with a unique mode of action. Copyright 2003 Prous Science. All
rights reserved.
-----
Postgrad Med J. 2003 Mar;79(929):133-8.
What is osteoporosis?
Christodoulou C, Cooper C.
MRC Environmental Epidemiology Unit, University of Southampton,
Southampton General Hospital, Southampton.
Osteoporosis is a very common disorder, which results in an
increase in fracture risk. The annual cost attributable to hip,
vertebral, and wrist fractures in England and Wales is pound 1.7
billion. Significant mortality and morbidity are associated with
osteoporotic fractures. The method that is most widely used for
the diagnosis of osteoporosis is dual energy x-ray absorptiometry.
The aim of prevention and treatment of osteoporosis is to prevent
the occurrence of future fractures. Lifestyle changes should be
encouraged in high risk patients. Pharmacological treatments include
the bisphosphonates, hormone replacement therapy, selective oestrogen
receptor modulators, calcitonin, the 1-34 fragment of parathyroid
hormone, calcium and vitamin D supplements, and calcitriol.
-----
Instr Course Lect. 2003;52:785-9.
Medical management of osteoporosis.
Lane JM, Garfin SR, Sherman PJ, Poynton AR.
Hospital for Special Surgery, New York, New York, USA.
Osteoporosis is characterized by low-energy fractures resulting
from inadequate bone mass and compromised microarchicture. Bone
mass is maximized by adequate nutrition and calcium intake, normal
menstrual cycles, and appropriate exercises. Low bone density,
as determined by dual-energy x-ray absorptiometry, and high bone
turnover, as characterized by elevated bone collagen breakdown
products, are the primary indicators of bone fragility. Prevention
and treatment of osteoporosis should emphasize adequate calcium
and vitamin D intake and exercise. In addition, estrogen supplementation
and selective estrogen receptor modulators (estrogen antagonists)
can enhance bone mass and decrease the risk of spinal fractures,
oral and intravenous bisphosphonates can significantly decrease
the incidence of both spinal and hip fractures, and antiosteoporotic
agents can help rebuild healthy bone.
-----
Clin Exp Rheumatol. 2003 Jan-Feb;21(1):19-26.
Calcium, vitamin D and etidronate for the prevention
and treatment of corticosteroid-induced osteoporosis in patients
with rheumatic diseases.
Loddenkemper K, Grauer A, Burmester GR, Buttgereit F.
Department of Rheumatology and Clinical Immunology, Charite University
Hospital, Humboldt University of Berlin, Berlin, Germany. konstanze.loddenkemper@charite.de
INTRODUCTION: Long-term glucocorticoid therapy, a major risk
factor for the development of osteoporosis, is often necessary
in chronically ill patients. At present there are no generally
accepted guidelines for the prevention or treatment of steroid-induced
osteoporosis. METHODS: In an open prospective study we investigated
99 patients with chronic rheumatic diseases receiving > or
= 5 mg/day of prednisolone or the equivalent for at least one
year. The objective was to identify osteoporosis risk factors
in addition to glucocorticoid therapy and to evaluate the efficacy
of prevention with calcium/vitamin D (group 1--patients with osteopenia)
and treatment with cyclical etidronate (group 2--patients with
osteoporosis). Biochemical markers of bone turnover, clinical
parameters and bone mineral density (BMD) were measured. RESULTS:
Increasing age and postmenopausal status were associated with
more advanced manifestations of steroid-induced osteoporosis (p
< 0.05). One year after the start of therapy parameters of
bone metabolism increased significantly in group 1, while BMD
did not change. In group 2, lumbar spine BMD increased significantly
(p < 0.05) whereas femoral neck BMD and bone metabolism parameters
remained constant. The intensity of back pain decreased in both
groups (p < 0.05). There were fewer new fractures in group
2 than in group 1. CONCLUSION: Treatment with etidronate is effective
in patients with glucocorticoid-induced osteoporosis.
-----
Nippon Rinsho. 2003 Feb;61(2):235-9.
[Risedronate]
[Article in Japanese]
Fukunaga M.
Department of Nuclear Medicine, Kawasaki Medical School.
Risedronate (RSD) containing nitrogen, the third generation
of bisphosphonate, has a powerful antiresorptive activity, without
a stronger inhibition of mineralization. RSD is available for
the treatment of osteoporosis. In Japanese the effective dose
is 2.5 mg given orally daily, while in Caucasians it is 5 mg.
This difference of dose suggests that RSD may be absorbed more
efficiently in Japanese than in Caucasians. RSD administered orally
at 2.5 mg per day for 48 weeks induced a 5% increase of bone mineral
density in the lumbar spines in osteoporotic women. RSD, 5 mg
daily, decreases vertebral and non-vertebral, especially hip fractures
in elderly osteoporotic women. Thus, RSD is an important agent
for the treatment of osteoporosis.
-----
Nippon Rinsho. 2003 Feb;61(2):231-4.
[Clinical trials of alendronate]
[Article in Japanese]
Okano T, Teshima R.
Department of Orthopaedic Surgery, Faculty of Medicine, Tottori
University.
A number of large scale double-blind controlled studies with
alendronate were carried out to evaluate therapeutic efficacy
for osteoporotics. Alendronate administered orally at 5 mg per
day for 7 years induced an average 8.2% increase of bone mineral
density in the spine and 2.6% in the hip. Alendronate given orally
for 4 years decreased significantly by 44% the occurrence of vertebral
and non-vertebral fractures in patients with low bone mineral
density and at least one fracture. In patients without any fracture,
the results were significant for non-vertebral fractures when
initial BMD was low. In histomorphometry with iliac bone biopsies,
mineralization was normal, and trabecular bone turnover markedly
decreased in patients receiving long-term dosing with alendronate.
Alendronate is expected to have a potency to inhibit bone fracture
occurrence in Japanese osteoporotics safely.
-----
Nippon Rinsho. 2003 Feb;61(2):226-30.
[Etidronate]
[Article in Japanese]
Inui K, Takaoka K.
Department of Orthopaedic Surgery, Osaka City University Medical
School.
Intermittent cyclical therapy with etidronate increases bone
mineral density in spine and hip, and reduces the incidence of
new vertebral fractures in women with postmenopausal osteoporosis,
as well as steroid-induced osteoporosis. Seven years treatment
with etidronate was reported to be safe, effective and well-tolerated.
And additive effects of etidronate were documented in bone mineral
density when hormone replacement therapy was combined. Recently
many bisphosphonates have been commercially available in clinics.
Although the potency of etidronate to inhibit bone resorption
is relatively weak among those bisphosphonates, equal effects
for others in osteoporosis can be obtained with the intermittent
therapy, which is easy to be complied for the patients with less
adverse events. In conclusion cyclical etidronate therapy is still
important for osteoporosis therapy.
-----
Expert Opin Pharmacother. 2003 Apr;4(4):567-80.
Zoledronic acid: an advance in tumour bone disease
therapy and a new hope for osteoporosis.
Body JJ.
Supportive Care Clinic, Clinic of Endocrinology and Bone Diseases
and Laboratory of Endocrinology and Breast Cancer Research, Dept
of Medicine, Institut J Bordet, 1 rue Heger-Bordet, Univ. Libre
de Bruxelles, Brussels, Belgium. jj.body@bordet.be
The two main therapeutic applications of bisphosphonates are
tumour bone disease and osteoporosis. They constitute the standard
treatment for cancer hypercalcaemia, and placebo-controlled trials
have shown that the prolonged administration of bisphosphonates,
such as pamidronate or clodronate, can reduce the frequency of
complications from tumour bone disease due to metastatic breast
cancer or myeloma by a quarter to one-half. The results obtained
with the intravenous route appear to be more impressive and more
rapidly obtained than with oral compounds. Both agents can reduce
the risk of vertebral, wrist and hip fractures by 30 - 50%, whereas
other antiresorptive agents, such as raloxifene (Eli Lilly &
Co.) or calcitonin (Unigene Laboratories Inc.), have only been
demonstrated to reduce the incidence of vertebral fractures. The
short infusion time (4 mg over 15 min) offers a convenient therapy
and constitutes the most evident advantage of zoledronic acid,
which will improve patients' quality of life. Zoledronic acid
has the potential to change the treatment of osteoporosis dramatically.
-----
Expert Opin Drug Saf. 2002 May;1(1):93-107.
Pharmacotherapy of osteoporosis in postmenopausal
women: focus on safety.
Reid IR.
Department of Medicine, University of Auckland, Private Bag 92019,
Auckland, New Zealand. i.reid@auckland.ac.nz
The therapy of osteoporosis has made enormous strides in the
last decade. There is now a range of interventions, each with
its pros and cons. Calcium and vitamin D supplementation remain
the foundation and have few safety issues. Bisphosphonates are
widely used, though gastrointestinal tolerance is a problem with
some oral preparations. Intravenous administration may circumvent
this, although this introduces the smaller problem of acute phase
reactions. The side effect profile of hormone replacement therapy
(HRT) is still being delineated after 40 years of use, with substantial
new information expected in the next few years. This will clarify
its place in the medical management of the menopause. Raloxifene
appears to have a superior safety profile to HRT, though its efficacy
on bone may be less. While none of these options is suitable for
everyone, the range of available therapies does mean that most
patients can find an intervention that is effective and acceptable.
-----
Clin Cornerstone. 2002;4(6):31-41.
Prevention and treatment of osteoporosis.
Prestwood KM, Raisz LG.
Division of Geriatrics, University of Connecticut Center on Aging,
University of Connecticut Health Center, Farmington, Connecticut,
USA.
Osteoporosis develops in older adults when the normal processes
of bone formation and resorption become uncoupled or unbalanced,
resulting in bone loss. Fractures are the result of decreased
bone mass and strength and, in the case of wrist and hip fractures,
usually involve a fall. Osteoporosis prevention and treatment
programs should then focus on strategies that minimize bone resorption
and maximize bone formation as well as on strategies that reduce
falls. Optimal treatment and prevention of osteoporosis require
modification of risk factors, particularly smoking cessation,
adequate physical activity, and attention to diet, in addition
to pharmacologic intervention. A number of pharmacologic options
are now available to health care providers. This article focuses
on US Food and Drug Administration-approved medications for osteoporosis
and emphasizes the importance of using these agents as part of
a comprehensive program that includes nonpharmacologic measures,
complete diagnostic evaluation, and adequate follow-up with bone
mineral density measurement.
-----
Przegl Lek. 2002;59(12):987-92.
[Developmental age idiopathic osteoporosis--diagnostics
and rehabilitation]
[Article in Polish]
Dobosiewicz K, Jedrzejewska A, Durmala J, Dyner-Jama I, Jendrzejek
H, Czernicki K, Flak M, Szota M.
Katedra i Klinika Rehabilitacji GCM Slaskiej AM 40-635 Katowice-Ochojec,
ul. Ziolowa 45/47.
Developmental age idiopathic osteoporosis is a rare metabolic
disease, which pathomechanism is different from involutional osteoporosis.
Its etiology still remains unknown. An onset of the disease is
rapid, affecting previously healthy children of both sexes aged
3.5-15. A rapid loss of bone mass is especially remarkable. Clinical
picture of the disease includes pain localised initially in feet,
then in thoraco-lumbar section of the vertebral column, gradually
progressive deformation of the longitudinal axes of limbs, gait
pathology and progressive depletion of a lower limb muscle strength.
The onset of the disease is non-specific. Diagnosis is possible
on the basis of roentgen imaging depicting rarefaction of cancellous
layer of the bone, numerous infractions of long bones and typical
for osteoporotic deformation of vertebral shafts with reduction
of their vertical dimension. Current research presents two-staged
method of rehabilitation applied in developmental age osteoporosis.
The main principle of treatment is based on increasing axial load
of lower limbs in antigravitational position causing joint surfaces
to be pushed together. Final stage of rehabilitation includes
interval training on a moving track.
-----
Pol Merkuriusz Lek. 2002 Dec;13(78):473-6.
[Influence of diet and physical activity on the
course and therapy of osteoporosis]
[Article in Polish]
Owecki M, Horst-Sikorska W, Baszko-Blaszyk D, Sowinski J.
Katedra i Klinika Endokrynologii, Przemiany Materii i Chorob Wewnetrznych
AM, Poznaniu.
Osteoporosis is a disease, the course of which is dependent
among others on diet and physical activity. The aim of study was
to find correlation between these factors and changes in bone
density measured in lumbar spine. The project comprised 82 women
with primary postmenopausal or senile osteoporosis treated with
calcitonin, hormone replacement therapy and vitamin D. Bone density
was measured by DEXA method before and after 12 month therapy.
The patients were divided into four groups depending upon amount
of ingested calcium and time of physical activity performed daily.
RESULTS: Only in the group of women (n = 32) who were physically
active and presented high dietary calcium intake (over 500 mg
daily) statistically significant improvement in bone density was
found: T-score increased by +0.23 (p = 0.010449). No statistically
significant difference of bone density in other subgroups was
found. CONCLUSIONS: Daily dietary calcium intake over 500 mg and
physical activity performed for over 45 minutes every day provides
higher bone density increase during pharmacotherapy of osteoporosis
compared to pharmacotherapy alone or pharmacotherapy associated
with only one of the above mentioned elements.
-----
J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):157-65.
Pros and cons of existing treatment modalities
in osteoporosis: a comparison between tibolone, SERMs and estrogen
(+/-progestogen) treatments.
Kloosterboer HJ, Ederveen AG.
Research and Development Laboratories, N.V. Organon, P.O. Box
20, 5340 BH Oss, The Netherlands. lenus.kloosterboer@organon.com
Tibolone, selective estrogen receptor modulators (SERMs) like
tamoxifen and raloxifene, and estrogen (+/-progestogen) treatments
prevent bone loss in postmenopausal women. They exert their effects
on bone via the estrogen receptor (ER) and the increase in bone
mass is due to resorption inhibition. The effect of SERMs on bone
mineral density is less than that with the other treatments, but
the SERM raloxifene still has a positive effect on vertebral fractures.
In contrast to tibolone and estrogens (+/-progestogen), SERMs
do not treat climacteric complaints, whilst estrogen plus progestogen
treatments cause a high incidence of bleeding. Estrogen plus progestogen
combinations have compromising effects on the breast. Tibolone
and SERMs do not stimulate the breast or endometrium. Unlike SERMs,
tibolone does not possess antagonistic biological effects via
the ER in these tissues. Estrogenic stimulation in these tissues
is prevented by local metabolism and inhibition of steroid metabolizing
enzymes by tibolone and its metabolites. SERMs and estrogen (+/-progestogen)
treatments increase the risk of venous thromboembolism (VTE),
whilst estrogen (+/-progestogen) combinations have unwanted effects
on cardiovascular events. So far, no detrimental effects of tibolone
have been observed with respect to VTE or cardiovascular events.
The clinical profile of tibolone therefore has advantages over
those of other treatment modalities. It is also clear that tibolone
is a unique compound with a specific mode of action and that it
belongs to a separate class of compounds that can best be described
as selective, tissue estrogenic activity regulators (STEARs).
-----
J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):133-47.
Phytoestrogens for hormone replacement therapy?
Wuttke W, Jarry H, Westphalen S, Christoffel V, Seidlova-Wuttke
D.
Department of Clinical and Experimental Endocrinology, University
of Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.
ufkendo@med.uni-goettingen.de
Due to some severe side effects "classical" hormone
replacement therapy (HRT) is currently being challenged by a therapy
with phytoestrogens. Particularly soy and red clover derived isoflavones
are advertised as selective estrogen receptor modulators (SERMs)
with only desired and no undesired estrogenic effects. Evidence
that this is the case however is scarce. Most studies investigating
climacteric complaints did not find beneficial effects. A proposed
beneficial effect on mammary cancer is unproven. The majority
of studies however indicate an antiosteoporotic effect of isoflavones,
while putative beneficial effects in the cardiovascular system
are questionable due to the fact that estradiol which--like isoflavones--increase
HDL and decrease LDL concentrations appear not to prevent arteriosclerosis
in the human. In the urogenital tract, including the vagina, soy
and red clover derived isoflavones are without effects. Cimicifuga
racemosa extracts are traditionally used for the treatment of
climacteric complaints. Evidence is now available that the yet
unknown compounds in Cimicifuga racemosa extracts prevent climacteric
complaints and may also have antiosteoporotic effects.
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