Timing of the initiation of bisphosphonates after surgery for fracture healing: a systematic review and meta-analysis of randomized controlled trials

We performed a systematic review and meta-analysis of randomized clinical trials. Early administration of bisphosphonates (BPs) after surgery did not appear to delay fracture healing time either radiologically or clinically. Furthermore, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures. Bisphosphonates (BPs) are widely used in the prophylaxis and treatment of osteoporosis. However, early administration of BPs after surgical repair of a fracture may limit the reserve capacity of bone to heal. The aim of this review and meta-analysis was to analyze the benefits and adverse effects of early administration of BPs and give recommendations regarding when BPs should be utilized. We identified randomized controlled trials comparing the early administration of BPs to placebo, delayed BP treatment, or no therapy in adult patients after surgery. The search was performed in PubMed, the Cochrane Library, and Embase. Ten studies with 2888 patients were included. Four trials used alendronate, three trials used zoledronic, two trials used risedronate, and one trial used etidronate. Early administration of BPs was considered less than 3 months after surgery. Patients treated with BP therapy had no significant differences in radiological fracture healing times compared with patients in the control group (mean difference [MD] 0.47, 95 % confidence interval [CI] -2.75 to 3.69). There were also no significant differences in the rate of delay or nonunion of fracture healing (odds ratio [OR] 0.98, 95 % CI 0.64 to 1.50). However, the bone mineral density (BMD) of total hips did significantly improve after 12 months of treatment with BPs. And most bone turnover markers of patients in the study group were significantly decreased. Early administration of BPs after surgery did not appear to delay fracture healing time either radiologically or clinically. Furthermore, according to the changes in BMD and bone turnover markers, the anti-resorptive efficacy of BPs given immediately after surgical repair should positively affect the rate of subsequent fractures.