Effect of osteoporosis treatments on ris of non-vertebral fractures: Review and meta-analysis of intent-to-treat studies

Division of Geriatric Medicine, Center for Metabolic Bone Diseases, Catholic University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
Osteoporosis International (Impact Factor: 4.17). 10/2005; 16(10):1291-8. DOI: 10.1007/s00198-005-1945-x
Source: PubMed


Most osteoporosis treatments have proven efficacy in reducing the risk of vertebral fractures, whereas evidence is less straightforward for prevention of non-vertebral fractures. Conclusions as to the efficacy of a treatment should be based primarily on analyses of the intention to treat (ITT) population rather than on exploratory subgroup analyses; however, non-vertebral anti-fracture efficacy has been largely derived by post-hoc subgroup analyses. This review and meta-analysis was performed to assess non-vertebral anti-fracture efficacy of several osteoporosis therapies, including a more stringent assessment of the ITT populations. Data on non-vertebral anti-fracture efficacy, a defined endpoint of the ITT analyses and confirmed by radiographs, were obtained from randomized, placebo-controlled, phase III clinical trials of at least 3-year duration. Meta-analyses were performed for the two bisphosphonates, alendronate and risedronate. Relative risks (RR), 95% confidence intervals (CI) and statistical significance for active treatment compared with placebo were calculated. Eleven clinical trials met the criteria for review, three of which showed statistically significant ( P < or =0.05) non-vertebral anti-fracture efficacy in the ITT population: two trials with risedronate and one trial with strontium. A meta-analysis showed significant reductions in the relative risk of non-vertebral fracture for both alendronate (RR=0.86; 95% CI: 0.76-0.97, P =0.012) and risedronate (RR=0.81; 95% CI: 0.71-0.92, P =0.001). Risedronate and strontium ranelate were the only treatments to show non-vertebral anti-fracture efficacy in this robust assessment of anti-fracture efficacy of osteoporosis therapy using ITT populations in trials of 3 years or more in duration. Risedronate was the only agent shown to demonstrate efficacy in more than one trial. Meta-analysis showed that both alendronate and risedronate provide non-vertebral anti-fracture efficacy.

4 Reads
  • Source
    • "Perhaps most important, they are at high risk of further vertebral7 and other osteoporotic fractures.8 However, if these undiagnosed women were prescribed appropriate osteoporosis medications, then expected further fractures could be reduced by between 20% and 50%.9, 10 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 12% of postmenopausal women have osteoporotic vertebral fractures (VFs); these are associated with excess morbidity and mortality and a high risk of future osteoporotic fractures. Despite this, less than one-third come to clinical attention, partly due to lack of clear clinical triggers for referral for spinal radiographs. The aim of this study was to investigate whether a novel primary care-based screening tool could be used to identify postmenopausal women with osteoporotic VFs and increase appropriate management of osteoporosis. A randomized controlled trial was undertaken in 15 general practices within the Bristol area of the UK. A total of 3200 women aged 65 to 80 years were enrolled, with no exclusion criteria. A simple screening tool was carried out by a nurse in primary care to identify women at high risk of osteoporotic VFs. All identified high-risk women were offered a diagnostic thoracolumbar radiograph. Radiographs were reported using standard National Health Service (NHS) reporting, with results sent back to each participant's general practitioner (GP). Participants in the control arm did not receive the screening tool or radiographs. The main outcome measure was self-reported prescription of medication for osteoporosis at 6 months with a random 5% subsample verified against electronic GP records. Secondary outcome was self-reported incidence of new fractures. Results showed that allocation to screening increased prescription of osteoporosis medications by 124% (odds ratio [OR] for prescription 2.24 at 6 months; 95% confidence interval [CI], 1.16 to 4.33). Allocation to screening also reduced fracture incidence at 12-month follow-up (OR for new fracture 0.60; 95% CI, 0.35-1.03; p = 0.063), although this did not reach statistical significance. This study supports the use of a simple screening tool administered in primary care to increase appropriate prescription of medications for osteoporosis in postmenopausal women in the UK.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2012; 27(3):664-71. DOI:10.1002/jbmr.1478 · 6.83 Impact Factor
  • Source
    • "Bisphosphonate therapy results in modest gains in BMD and clinically relevant reductions in vertebral fracture rates [4-13]. Effects on hip and non-vertebral fracture risk, however, have been variable [12,13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Increased osteoclast activity is a pivotal finding in osteoporosis. This increase is mediated via the mevalonate-to-cholesterol pathway, which is involved in producing the intermediates required for osteoclast activity. D-003, a mixture of high molecular weight sugarcane wax acids, has been shown to inhibit cholesterol synthesis prior to mevalonate production, resulting in a reduction of bone loss and resorption in ovariectomized rats. Moreover, previous studies have demonstrated that short-term D-003 treatment reduces urinary excretion of deoxypyridinoline/creatinine in postmenopausal women. We performed a double-blinded, placebo-controlled study to investigate the effects of D-003 (10 mg/day) treatment for 3 years on bone mineral density (BMD) in 83 postmenopausal women with low BMD. Over 3 years, D-003 treatment increased lumbar spine BMD (5.1%, p < 0.01) and improved osteoporosis-related quality of life scores as compared with placebo-treated controls. D-003 was also well tolerated; the frequency of adverse events in the bone, joints, or muscle with D-003 treatment (p < 0.05) was lower than in the placebo group. D-003 treatment (10 mg/day) for 3 years increased lumbar spine BMD and produced clinical improvements in postmenopausal women with low BMD. Further studies, however, will be required to confirm these results.
    The Korean Journal of Internal Medicine 06/2011; 26(2):168-78. DOI:10.3904/kjim.2011.26.2.168 · 1.43 Impact Factor
  • Source
    • "P = .001). Risedronate and strontium ranelate further evinced clinically relevant non-vertebral anti-fracture efficacy in the context of this research synthesis [89]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research attributes these outcomes in part at least to the ART, PI, and HAART therapies endured by these patients. We review and discuss these lines of evidence from the perspective of translational clinically relevant complex systematic reviews for comparative effectiveness analysis and evidence-based intervention on a global scale.
    Pathology Research International 05/2011; 2011:359242. DOI:10.4061/2011/359242
Show more

Preview (2 Sources)

4 Reads
Available from