Hip and non-spine fracture risk reductions differ among antiresorptive agents: Evidence from randomised controlled trials

Biomedical Research Institute (BIOMED), Hasselt University, Hasselt, Flemish, Belgium
International Journal of Clinical Practice (Impact Factor: 2.57). 12/2006; 60(11):1394-400. DOI: 10.1111/j.1742-1241.2006.01148.x
Source: PubMed


A number of antiresorptive agents reduce the risk of vertebral fractures, but few have shown consistent effects on hip and other non-spine fractures. Meta-analysis provides a more precise estimate than individual trials when results are consistent across pooled trials. Earlier meta-analyses summarised the results for vertebral and non-spine fractures. New data have emerged for hormone therapy (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed recent reports of randomised, placebo-controlled trials with non-spine and/or hip fracture data, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. The magnitude of effect on hip fracture appears to be similar to that for non-spine fracture for each drug, but differs among drugs. Based on the current data, ALN reduces the risk of hip and non-spine fracture by 49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent evidence of an effect on these fractures for IBN, calcitonin and raloxifene.

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    • "At present, antiresorptive agents are still the major treatments. Besides the novel Denosumab, which is a human monoclonal antibody of receptor activator of NF-í µí¼…B ligand (RANKL) and potently suppresses osteoclastic bone resorption, alendronate (Aln), the most widely prescribed bisphosphonates, and raloxifene (Rlx), the only Food and Drug Administration approved selective estrogen receptor modulators (SERMs), are the most evident antiresorptive agents for prevention and treatment of postmenopausal osteoporosis [2] [3]. For deciding the therapeutic strategy, it is highly imperative to know an estimate of the difference in fracture risk reduction between Aln and Rlx [4] [5]. "
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    ABSTRACT: Purpose. The aim of this study was to directly compare the efficacy and the safety of the two agents for postmenopausal women. Methods/Principal Findings. Electronic databases were searched for relevant articles that met our predefined inclusion criteria. Seven randomized controlled trials (RCTs) involving 4054 women were identified and included. Although Aln was more effective than Rlx in increasing bone mineral density (BMD), no statistical differences were observed in reducing the risk of neither vertebral fractures (P = 0.45) nor nonvertebral fractures (P = 0.87) up to two-year followup. Aln reduced the risk of vasomotor (P = 0.006) but increased the risk of diarrhea compared to Rlx (P = 0.01). Our subgroup analysis further indicated the difference between Aln and Rlx in fracture risk and was not materially altered by the administration pattern, the age. The weekly strategy of Aln would further reduce the upper gastrointestinal (GI) disorders and might gain more bone mass increment at lumbar spine compared to its daily treatment. Conclusion. There was no evidence of difference of fracture risk reduction between Aln and Rlx. In addition, age did not obviously influence their relative antifracture efficacy. For Aln the weekly strategy would further reduce the upper GI disorders and gain more bone mass increment compared to the daily treatment. During clinical decision making, the patients' adherence and the related side-effects associated with both drugs should also be taken into account.
    International Journal of Endocrinology 01/2014; 2014(14):796510. DOI:10.1155/2014/796510 · 1.95 Impact Factor
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    • "There are current limitations to the use of DXA in monitoring osteoporosis therapies. The percent of fracture risk reduction attributable to changes in aBMD with different therapies varies from 5 % to 85 % [62–66]. HR-pQCT presents the potential to monitor other components of bone strength, with possibly greater discrimination between different osteoporosis therapies. "
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    ABSTRACT: Bone structure is an integral determinant of bone strength. The availability of high resolution peripheral quantitative computed tomography (HR-pQCT) has made it possible to measure three-dimensional bone microarchitecture and volumetric bone mineral density in vivo, with accuracy previously unachievable and with relatively low-dose radiation. Recent studies using this novel imaging tool have increased our understanding of age-related changes and sex differences in bone microarchitecture, as well as the effect of different pharmacological therapies. One advantage of this novel tool is the use of finite element analysis modelling to non-invasively estimate bone strength and predict fractures using reconstructed three-dimensional images. In this paper, we describe the strengths and limitations of HR-pQCT and review the clinical studies using this tool.
    Current Osteoporosis Reports 03/2013; 11(2). DOI:10.1007/s11914-013-0140-9
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    • "The efficacy of bisphosphonates in reducing the risk of vertebral and nonvertebral fractures has been clearly demonstrated [Hochberg, 2008], and although head-to-head trials have not been undertaken, analyses conducted using observational databases suggest that the common bisphosphonates (alendronate, risedronate, ibandronate, zoledronic acid) generally display similar vertebral antifracture efficacies , though differences have been observed at other skeletal sites (e.g. ibandronate has not been shown to be effective against hip fractures) [Harris et al. 2009; Pazianas et al. 2009; Silverman et al. 2007; Liberman et al. 2006]. "
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    ABSTRACT: Osteoporosis is a significant public health concern, particularly for postmenopausal women. Current treatment options may not be appropriate for all women. Selective estrogen-receptor modulators (SERMs) are a class of molecules with tissue-selective activity. Bazedoxifene is currently in clinical development for the prevention and treatment of postmenopausal osteoporosis. In a 2-year, phase III, osteoporosis prevention study (N = 1583), bazedoxifene 10, 20, and 40 mg was shown to preserve bone mineral density and decrease biochemical markers of bone turnover compared with placebo in postmenopausal women at risk for osteoporosis. In a pivotal 3-year, phase III, osteoporosis treatment study (N = 7492), bazedoxifene 20 and 40 mg significantly reduced the incidence of new vertebral fractures compared with placebo (p < 0.05 for both) in postmenopausal women with osteoporosis. In a post hoc subgroup analysis of women at higher risk for fracture (n = 1772), bazedoxifene 20 mg significantly reduced the risk of nonvertebral fractures versus placebo (p = 0.02) and raloxifene 60 mg (p = 0.05). Bazedoxifene 20 mg has demonstrated sustained efficacy in reducing the risk of vertebral fractures over 5 and 7 years. Overall, bazedoxifene was generally safe and well tolerated, with favorable endometrial and breast safety profiles. As with other SERMs, the rate of deep vein thrombosis was higher in the bazedoxifene groups compared with placebo at 3 and 5 years. Considering its demonstrated efficacy and safety, bazedoxifene may be an appropriate osteoporosis therapy for women who cannot take or are unwilling to take bisphosphonates because of safety or tolerability issues. Bazedoxifene may also be appropriate for younger women at increased fracture risk who are concerned about the effects of long-term bisphosphonate therapy. This article reviews the results of key clinical trials of bazedoxifene for the prevention and treatment of postmenopausal osteoporosis and describes its role in clinical practice.
    Therapeutic advances in musculoskeletal disease 02/2012; 4(1):21-34. DOI:10.1177/1759720X11422602
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