Objectives and methods: The HORIZON-PFT is a multinational, 3-year, randomized, double-blind, placebo-controlled trial evaluating the potential of once-yearly zoledronic acid (ZOL) 5 mg, infused over 15 minutes, to decrease risk of fracture in 7736 postmenopausal osteoporotic women 6589 years of age.
Results: Treatment with ZOL 5 mg resulted in significant relative risk reductions in morphometric vertebral fracture of 70% vs PBO (3.8% vs 12.8%; 95% CI [62%, 76%]) and in hip fracture of 41% vs PBO (1.4% vs 2.5%; 95% CI [17%, 58%]). Secondary endpoints, non-vertebral (excluding finger, toe, and facial), clinical vertebral, and any clinical fracture (including non-vertebral, hip, and clinical vertebral), were significantly reduced by 25%, 77%, and 33% (all P<.001), respectively. Bone mineral density increased significantly in ZOL vs PBO at total hip (6.0%), lumbar spine (6.9%) and femoral neck (5.0%) (P<.0001). While transient increases in serum creatinine ≥0.5 mg/dL over pre-infusion levels were seen in a small fraction (1.3%) of patients in the ZOL 5 mg group; no cumulative impact on renal function was demonstrable. Hypocalcemia (serum calcium <2.075 mmol/L) was observed in 2.3% of patients. Virtually all events occurred after the first infusion of ZOL, and all cases were asymptomatic and transient. Adverse events occurring ≤3 days after infusion were more frequent after first infusion (44.7% ZOL vs 14.7% PBO) but declined markedly on subsequent infusions. There were more atrial fibrillation serious adverse events in ZOL vs PBO (1.3% vs 0.5%). Two cases of osteonecrosis of the jaw (1 in PBO, 1 in ZOL) were confirmed with adjudication; both cases resolved with antibiotic therapy and limited debridement.
Conclusions: Once-yearly infusion of ZOL 5 mg over 3 years achieves a highly significant decrease in vertebral, hip, and other fracture risk and is generally safe and well tolerated.