EFFICACY AND SAFETY OF ZOLEDRONIC ACID 5 MG IN PREVENTING FRACTURES IN MEN AND WOMEN AFTER HIP FRACTURE

Abstract

Fracture prevention has so far been studied in patients included on the basis of low bone density, and not after a fracture. In this study the inclusion criteria was a new hip fracture irrespective of bone density. An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (HORIZON-RFT) studied whether the bisphosphonate, zoledronic acid (ZOL) 5 mg, reduced subsequent clinical fractures in men and women ≥50 yrs after a hip fracture.

Methods: Patients with hip fracture were included. They received daily vitamin D3 and calcium supplements. Of 2127 randomized, 2111 were treated with once-yearly IV infusions of ZOL 5 mg (n=1054) or placebo (PBO; n=1057) and followed until 211 experienced new clinical fractures (the primary efficacy endpoint).

Results: Baseline characteristics were similar. Median age was 76 yrs (range, 50–98); 76% were women. Clinical fractures occurred in 92 ZOL and 139 PBO patients. 2-year cumulative event rates were 8.59% and 13.88%, respectively (Kaplan-Meier); relative risk reduction was 35% (HR=0.65; 95% CI: 0.50–0.84; P=.0012). ZOL reduced risk for clinical vertebral and nonvertebral fractures vs. PBO by 46% (HR=0.54; 95% CI: 0.32–0.92; P=.0210) and 27% (HR=0.73; 95% CI: 0.55–0.98; P=.0338), respectively. ZOL reduced risk of hip fractures by 30% vs. PBO (HR=0.70; 95% CI: 0.41–1.19; P=NS). AEs and SAEs were comparable between groups. There were no significant differences in cardiovascular parameters or long-term renal function. No cases of ONJ were reported. Death occurred in 9.58% of ZOL patients vs 13.34% PBO, a 28% lower mortality risk (HR=0.72; 95% CI: 0.56–0.93, P=.0117).

Conclusions: Subjects with a new hip fracture treated with annual IV ZOL infusions experienced significantly fewer clinical fractures vs. placebo. ZOL was well tolerated with a favorable safety profile. This is the first trial demonstrating a mortality benefit for an antiresorptive agent.