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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.
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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).
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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.
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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.
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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.
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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 B |
