A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk

Summary We performed a systematic review on the effect of drug holidays (discontinuation) on bone mineral density (BMD) and fracture risk. Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3–5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation. Introduction We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk. Methods We searched PubMed, Embase, and Cochrane Library databases to locate controlled clinical trials and cohort studies evaluating the effect of drug holidays/discontinuation versus osteoporosis treatment continuation. We performed random-effects meta-analyses of hazard ratios of hip and any clinical osteoporotic fracture for individuals who discontinued bisphosphonates compared to persistent users. Results Thirteen records reporting results from eight different studies met inclusion criteria. The FLEX study found a reduced clinical vertebral fracture risk with 10 years of alendronate therapy compared to 5 (RR 0.45, 95% CI 0.24–0.85), and the HORIZON extension studies found a reduced risk of morphometric vertebral fracture with 6 years of zoledronic acid therapy compared to 3 (OR = 0.51, 95% CI 0.26–0.95); subgroup analyses showed that women with low hip BMD T-scores after the initial treatment period benefitted from continued treatment in terms of reduced vertebral fracture risk. Meta-analysis of adjusted hazard ratios of hip and any clinical osteoporotic fracture for women who discontinued bisphosphonates revealed no significant differences in the risk of hip fracture (summary estimate of HR 1.09, 95% CI 0.87–1.37) or any clinical fracture (summary estimate of HR 1.13, 95% CI 0.75–1.70) compared to persistent users. Conclusions Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3 to 5 years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.