Anti-Hip Fracture Efficacy of Bisphosphonates: A Bayesian Analysis of Clinical Trials

Bone and Mineral Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, University of New South Wales, Sydney, Australia.
Journal of Bone and Mineral Research (Impact Factor: 6.83). 03/2006; 21(2):340-9. DOI: 10.1359/JBMR.050903
Source: PubMed


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%.
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.
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.
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.
In postmenopausal women with osteoporosis or low BMD, bisphosphonate treatment is associated with reduced risk of hip fracture.

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    ABSTRACT: We have developed clinical nomograms for predicting 5-year and 10-year fracture risks for any elderly man or woman. The nomograms used age and information concerning fracture history, fall history, and BMD T-score or body weight. Introduction Although many fracture risk factors have been identified, the translation of these risk factors into a prognostic model that can be used in primary care setting has not been well realized. The present study sought to develop a nomogram that incorporates non-invasive risk factors to predict 5-year and 10-year absolute fracture risks for an individual man and woman. Methods The Dubbo Osteoporosis Epidemiology Study was designed as a community-based prospective study, with 1358 women and 858 men aged 60+ years as at 1989. Baseline measurements included femoral neck bone mineral density (FNBMD), prior fracture, a history of falls and body weight. Between 1989 and 2004, 426 women and 149 men had sustained a low-trauma fracture (not including morphometric vertebral fractures). Two prognostic models based on the Cox’s proportional hazards analysis were considered: model I included age, BMD, prior fracture and falls; and model II included age, weight, prior fracture and fall. Results Analysis of the area under the receiver operating characteristic curve (AUC) suggested that model I (AUC = 0.75 for both sexes) performed better than model II (AUC = 0.72 for women and 0.74 for men). Using the models’ estimates, we constructred various nomograms for individualizing the risk of fracture for men and women. If the 5-year risk of 10% or greater is considered “high risk”, then virtually all 80-year-old men with BMD T-scores <-1.0 or 80-year-old women with T-scores <-2.0 were predicted to be in the high risk group. A 60-year-old woman’s risk was considered high risk only if her BMD T-scores ≤-2.5 and with a prior fracture; however, no 60-year-old men would be in the high risk regardless of their BMD and risk profile. Conclusion These data suggest that the assessment of fracture risk for an individual cannot be based on BMD alone, since there are clearly various combinations of factors that could substantially elevate an individual’s risk of fracture. The nomograms presented here can be useful for individualizing the short- and intermediate-term risk of fracture and identifying high-risk individuals for intervention to reduce the burden of fracture in the general population.
    Full-text · Article · Nov 2007 · Osteoporosis International

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