Effect of Once-Yearly Zoledronic Acid Five Milligrams on Fracture Risk and Change in Femoral Neck Bone Mineral Density

Abstract

The HORIZON-PFT (Health Outcomes and Reduced Incidence with Zoledronic Acid Once-Yearly–Pivotal Fracture Trial) was a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis. The results demonstrated that a once-yearly intravenous infusion of zoledronic acid (ZOL) 5 mg over a period of 3 years significantly reduced the risk of vertebral, hip, and other fractures. Several risk factors for fracture in postmenopausal women have been identified. Some investigators have suggested that ZOL may be more effective across individual categories of risk factors, and that there may be an interaction between these factors and treatment. This study investigated the possible association of individual baseline risk factors with greater treatment efficacy during ZOL 5 mg treatment in patients from HORIZON-PFT. The study subjects received a single intravenous infusion of ZOL 5 mg (treatment group, [n = 2822]) or placebo (control group, [n = 2853]) at baseline, 12 and 24 months. The primary study outcomes were new vertebral fracture and hip fracture. Secondary outcomes included nonvertebral fracture and change in femoral neck bone mineral density (BMD). Evaluated baseline risk factors were age, BMD, race and geographic region, body mass index (BMI), renal impairment (creatinine clearance), concomitant osteoporosis medications, and previous bisphosphonate therapy. The data were adjusted using logistic regression analysis. ZOL treatment was associated with greater reduction in the risk of vertebral fracture (significant treatment-factor interactions) in younger women (<70 years) (P = 0.05), women who were overweight or obese (BMI >30 gm/cm2) (P = 0.02), and those with normal creatinine clearance (P = 0.04). Treatment-factor interactions were not significant for hip or nonvertebral fracture or for change in BMD. These findings show that once-a-year therapy with ZOL for postmenopausal osteoporosis is more effective in preventing vertebral fracture in younger women, and those with higher BMI or normal renal function.