Antifracture Efficacy and Reduction of Mortality in Relation to Timing of the First Dose of Zoledronic Acid After Hip Fracture


  • Dr. Eriksen has been an employee of and owns stock in Novartis. Dr. Lyles receives research grants from Novartis, the Alliance for Better Bone Health (Sanofi-Aventis and Procter & Gamble), and Amgen, consults for Novartis, Procter & Gamble, Merck, Amgen, GTx, GlaxoSmithKline, Eli Lilly, and Bone Medical, and holds patents. Dr. Colón-Emeric consults for Novartis and receives research grants from Novartis and the Alliance for Better Bone Health. Dr. Pieper receives research grants from Novartis. Dr. Magaziner receives research grants from Novartis and Merck, consults for Amgen, Merck, Aventis, and GTx, and speaks for Merck and Pfizer. Dr. Adachi receives research grants from Amgen, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Procter & Gamble, and Roche and consults for Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, and Servier. Dr. Hyldstrup receives research grants from Eli Lilly, Novartis, Pfizer, Nycomed, Roche, and GlaxoSmithKline, consults for Novartis, Eli Lilly, and Nycomed, and speaks for Merck, Eli Lilly, Nycomed, Novartis, Novo Nordisk, and Servier. Dr. Recknor receives research grants from Procter & Gamble, consults for Procter& Gamble, Roche, and Eli Lilly, and speaks for Procter & Gamble, Eli Lilly, Roche, GlaxoSmithKline, Merck, and Aventis. Dr. Nordsletten receives research grants from Biomet, consults for Novartis and DePuy, and speaks for Wyeth. Ms. Lavecchia is an employee of and owns stock in Novartis. Dr. Hu is an employee of Novartis. Dr. Boonen receives research grants from Amgen, Eli Lilly, Novartis, Pfizer, Procter & Gamble, Sanofi-Aventis, and Roche–GlaxoSmithKline and consults or speaks for Amgen, Eli Lilly, Merck, Novartis, Procter & Gamble, Sanofi-Aventis, and Servier. Dr. Mesenbrink is an employee of and owns stock, restricted stock, exercisable options, and tradable options in Novartis

  • Published online on February 16, 2009


Annual infusions of zoledronic acid (5 mg) significantly reduced the risk of vertebral, hip, and nonvertebral fractures in a study of postmenopausal women with osteoporosis and significantly reduced clinical fractures and all-cause mortality in another study of women and men who had recently undergone surgical repair of hip fracture. In this analysis, we examined whether timing of the first infusion of zoledronic acid study drug after hip fracture repair influenced the antifracture efficacy and mortality benefit observed in the study. A total of 2127 patients (1065 on active treatment and 1062 on placebo; mean age, 75 yr; 76% women and 24% men) were administered zoledronic acid or placebo within 90 days after surgical repair of an osteoporotic hip fracture and annually thereafter, with a median follow-up time of 1.9 yr. Median time to first dose after the incident hip fracture surgery was ∼6 wk. Posthoc analyses were performed by dividing the study population into 2-wk intervals (calculated from time of first infusion in relation to surgical repair) to examine effects on BMD, fracture, and mortality. Analysis by 2-wk intervals showed a significant total hip BMD response and a consistent reduction of overall clinical fractures and mortality in patients receiving the first dose 2-wk or later after surgical repair. Clinical fracture subgroups (vertebral, nonvertebral, and hip) were also reduced, albeit with more variation and 95% CIs crossing 1 at most time points. We concluded that administration of zoledronic acid to patients suffering a low-trauma hip fracture 2 wk or later after surgical repair increases hip BMD, induces significant reductions in the risk of subsequent clinical vertebral, nonvertebral, and hip fractures, and reduces mortality.