Health and adverse events associated with extended oral bisphosphonates among postmenopausal women: a systematic review

BACKGROUND: International guidelines recommend the use of oral bisphosphonates (oBP) for up to 5 years in the treatment of postmenopausal osteoporosis. However, benefits and risks of extending oBP therapy beyond this duration remain uncertain. AIM: To determine the health outcomes (bone mineral density [BMD], fracture risk) and adverse effects (atypical fracture, osteonecrosis of the jaw [ONJ]) of extended oBP therapy beyond 5 years among postmenopausal women. METHODOLOGY: A systematic search of Medline©, EMBASE©, and CINAHL© was conducted from inception to 15 March 2024. Interventional and observational studies published in English were included. Two authors independently performed screening, quality appraisal using the NIH Quality Appraisal tool, and data extraction. The review followed PRISMA guidelines and was registered on PROSPERO (CRD42024475332). High heterogeneity precluded meta-analysis. RESULTS: Eleven studies (4 controlled trials, 7 observational) were included: 3 rated as good quality, 7 as fair, and 1 as poor. Extended oBP therapy beyond 5 years increased BMD at the hip (3/3 studies), femoral neck (3/3 studies) and lumbar spine (5/5 studies). Prolonged oBP use reduced clinical vertebral fracture risk (1/6 studies) but increased the risk of atypical fractures (3/3 studies) and incomplete atypical femoral fractures (1/1 study). None of the included studies assessed or reported ONJ. CONCLUSION: Substantial heterogeneity and limited high-quality evidence preclude definitive conclusions regarding extended oBP use in postmenopausal women. While extended treatment may improve bone density and reduce vertebral fractures, it could also increase atypical fractures. Future high-quality studies are required to inform decisions regarding optimal treatment duration.