Meta-analysis for the efficacy of bisphosphonates on hip fracture prevention
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ORIGINAL ARTICLE
Meta‑analysis for the efficacy of bisphosphonates on hip fracture prevention Takayuki Tsuda1 · Yoshichika Hashimoto1 · Yasunori Okamoto1 · Wataru Ando2 · Kosuke Ebina3 Received: 11 December 2019 / Accepted: 23 February 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract The aim of this study was to investigate the effect of bisphosphonates on preventing osteoporotic hip fracture in patients with or without prior major osteoporotic fracture. Randomized controlled trials (RCTs) and observational studies (OSs) based on electronic health records were used to assess bisphosphonate efficacy and were searched using PubMed, Scopus, and the Cochrane Library databases. Eight RCT studies and 14 OSs were extracted from the studies and quantitatively combined by random-effects meta-analysis. The odds ratio (OR) for all hip fractures in RCTs of 0.66, with a 95% confidence interval (CI) of 0.55–0.79, was lower than that in the OSs (OR 0.83; CI 0.74–0.94). The OR in patients with prior fracture was significantly reduced by bisphosphonates in both RCTs and OSs. Conversely, significant fracture reduction was not apparent in patients without prior fracture. A moderate relationship between prior major fracture rates and OR in hip fractures was defined. In patients with an average age of over 80 years, similar results were confirmed. In this meta-analysis, the efficacy of bisphosphonates was significant in patients with prior major fracture, recommending to prescribe for such patients. Their effect in patients without prior fracture, in contrast, remains unclear. Keywords Meta-analysis · Cross-design synthesis · Bisphosphonate · Hip fracture · Prior fracture
Introduction Nitrogen-containing bisphosphonates, such as alendronate, risedronate, and zoledronate, are widely prescribed and recommended as first-line drugs for osteoporotic therapy [1, 2]. They have proved effective in reducing the risk of vertebral and non-vertebral fractures. In addition, bisphosphonates are reported to prevent hip fractures in elderly osteoporotic patients [2, 3]. The early study conducted by McClung et al. showed a 40% relative reduction in the incidence of hip fracture in women with osteoporosis in their 70 s, whereas no significant change was observed in those ≥ 80 years of age * Takayuki Tsuda tsuda‑[email protected] 1
Department of Orthopaedic Surgery, Kansai Rosai Hospital, 3‑1‑69 Inabaso, Amagasaki, Hyogo 660‑8511, Japan
2
Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Yamada‑oka, Suita, Osaka 565‑0871, Japan
3
Department of Musculoskeletal Regenerative Medicine, Osaka University Graduate School of Medicine, Yamada‑oka, Suita, Osaka 565‑0871, Japan
with risk factors other than bone mineral density (BMD) [4]. This result differed considerably from those of the RCT showing a positive effect of zoledronate [3], and a metaanalysis which bisphosphonates can prevent recurrent hip fracture [5]. It has been
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