Association between timing of zoledronic acid infusion and hip fracture healing

Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. Introduction Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. Methods In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL (n=1,065) or placebo (n=1,062). Clinical symptoms of delayed hip fracture healing were sought at randomization, 6 months and 12 months after fracture; if present, a central adjudication committee blinded to treatment assignment reviewed radiographs and clinical records. Median follow-up was 1.9 years. Results The overall incidence of delayed healing was 3.2% (ZOL) and 2.7% (placebo; odds ratio [OR], 1.17; 95% confidence interval [CI], 0.72-1.90; p=0.61). Logistic regression models revealed no association between ZOL and delayed healing even after adjusting for other risk factors (OR, 1.21; 95% CI, 0.74-1.99; p=0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49-4.39; p<0.001). Conclusions ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period.