Abstract
Background Bisphosphonates typically are the first-line therapy for osteoporosis especially postmenopausal osteoporosis, but many reviews exist with conflicting conclusions about the safety of bisphosphonates. We performed an overview of reviews to systematically evaluate the risk of adverse events (AEs) of bisphosphonates used for the treatment of postmenopausal osteoporosis.
Methods We identified systematic reviews with meta-analyses published in English that evaluated the safety of bisphosphonates. Data sources used include the Cochrane library, Pubmed, the Web of Science and hand-searching of reference lists and clinical practice guidelines. The methodological quality of each systematic reviews was assessed by two reviewers using the assessment of multiple systematic reviews (AMSTAR) tool, and the quality of evidence for key outcomes (all adverse events (all AEs), gastrointestinal events (GI AEs), total cardiovascular events (total CV AEs), atrial
fibrillation (AF), serious atrial fibrillation (sAF), stroke, atypical fracture and fracture union) was assessed using the grading of recommendations, assessment, development and evaluation (GRADE) approach.
Results We identified 1362 potentially relevant citations of which only 16 systematic reviews with meta-analyses met the eligibility criteria. All the included reviews were published between 2009 and 2016, and documented the pooled estimates of effect size [relative risk (RR) or odds ratio (OR)] and their 95% confidence intervals [95% CI] for the incidence of adverse events. The median AMSTAR score was 8 (interquartile range, 7–10). Evidences of the key outcomes were mainly of low or moderate quality.
Conclusions Our overview provides a comprehensive assessment on the safety of bisphosphonates. This overview indicated that bisphosphonates significantly increased the risk of AF, sAF and stroke, but did not significantly increase the risk of atypical fracture or fracture union. It also showed that bisphosphonates could decrease the risk of total adverse CV events, CV death. In despite the vast number of systematic reviews published, high quality research and more complete inclusion criteria are needed.
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