Source
Duke University Medical Center (K.W.L., C.S.C.-E., C.F.P., K.A.M., P.K.H.) and the Geriatrics Research Education and Clinical Center, Veterans Affairs Medical Center (K.W.L.) - both in Durham, NC; the University of Maryland, Baltimore (J.S.M.); McMaster University, Hamilton, ON, Canada (J.D.A.); Centro de Osteopatías Médicas, Buenos Aires (C.M.); Hvidovre Hospital, Hvidovre, Denmark (L.H.); United Osteoporosis Centers, Gainesville, GA (C.R.); Ullevål University Hospital, Oslo (L.N.); Novartis Pharmaceuticals, East Hanover, NJ (C.L., J.Z., P.M., K.A., J.J.O.); Savient Pharmaceuticals, East Brunswick, NJ (Z.H.); Novartis Pharma AG, Basel, Switzerland (E.F.E.); and Katholieke Universiteit Leuven, Leuven, Belgium (S.B.).
Abstract
BACKGROUND:
Mortality is increased after a hip fracture, and strategies that improve outcomes are needed.
METHODS:
In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture.
RESULTS:
The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction (P = 0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P = 0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P = 0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 1057 patients in the placebo group (13.3%) died, a reduction of 28% in deaths from any cause in the zoledronic-acid group (P = 0.01). The most frequent adverse events in patients receiving zoledronic acid were pyrexia, myalgia, and bone and musculoskeletal pain. No cases of osteonecrosis of the jaw were reported, and no adverse effects on the healing of fractures were noted. The rates of renal and cardiovascular adverse events, including atrial fibrillation and stroke, were similar in the two groups.
CONCLUSIONS:
An annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with a reduction in the rate of new clinical fractures and improved survival. (ClinicalTrials.gov number, NCT00046254.).