This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Google Scholar Articles by Eastell, R. PubMed PubMed Citation Articles by Eastell, R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Hip Injuries and Disorders Hip Replacement Related Collections Calcium and Bone Metabolism

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

Academic Unit of Bone Metabolism (R.E.), University of Sheffield, Sheffield S5 7AU, United Kingdom; Department of Epidemiology and Biostatistics (D.M.B., L.P.), University of California at San Francisco, San Francisco, California 94107; Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine (S.B.), Katholieke Universiteit Leuven, 3000 Leuven, Belgium; Rheumatology Unit (S.A.), University of Verona, Ospedale Maggiore, 37126 Verona, Italy; Centre of Muscle and Bone Research (D.F.), Free University and Humboldt-University, 12203 Berlin, Germany; Osteoporosis Policlinic (K.L.), University Hospital and University of Bern, 3010 Bern, Switzerland; San Francisco Coordinating Center (S.R.C.), University of California, San Francisco, California 94107; Institut National de la Santé et de la Recherche Médicale Research Unit 831 and University of Lyon (P.D.D.), 69437 Lyon, France; Novartis Pharmaceuticals Corporation (P.M.), East Hanover, New Jersey 07936; and Department of Epidemiology (J.A.C.), University of Pittsburgh, Pittsburgh, Pennsylvania 15261

Address all correspondence and requests for reprints to: Richard Eastell, M.D., FRCP, FRCPath, FMedSci, Professor of Bone Metabolism, Head of the Academic Unit of Bone Metabolism, Metabolic Bone Centre, Sorby Wing, Northern General Hospital, Herries Road, Sheffield, South Yorkshire S5 7AU, United Kingdom. E-mail: r.eastell{at}sheffield.ac.uk.

Context: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly – Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk.

Objective: The aim of the study was to identify factors associated with greater efficacy during ZOL 5 mg treatment.

Design, Setting, and Patients: We conducted a subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis.

Intervention: A single infusion of ZOL 5 mg or placebo was administered at baseline, 12, and 24 months.

Main Outcome Measures: Primary endpoints were new vertebral fracture and hip fracture. Secondary endpoints were nonvertebral fracture and change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups were age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index, and concomitant osteoporosis medications.

Results: Greater ZOL induced effects on vertebral fracture risk were seen with younger age (treatment-by-subgroup interaction, P = 0.05), normal creatinine clearance (P = 0.04), and body mass index 25 kg/m² (P = 0.02). There were no significant treatment–factor interactions for hip or nonvertebral fracture or for change in BMD.

Conclusions: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women, and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.