title: Time to onset of antifracture efficacy and year-by-year persistence of effect of zoledronic acid in women with osteoporosis.
abstract: Oral bisphosphonates reduce fracture risk in osteoporotic patients but are often associated with poor compliance, which may impair their antifracture effects. This post hoc analysis assessed the time to onset and persistence of the antifracture effect of zoledronic acid, a once-yearly bisphosphonate infusion, in women with osteoporosis. Data from 9355 women who were randomized in two placebo-controlled pivotal trials were included. Endpoints included reduction in the rate of any clinical fracture at 6, 12, 18, 24, and 36 months in the zoledronic acid group compared with placebo, and the year-by-year incidence of all clinical fractures over 3 years. Cox proportional hazards regression was used to determine the timing of onset of antifracture efficacy. A generalized estimating equation model was used to assess fracture reduction for the 3 consecutive years of treatment, thereby evaluating persistence of effect. Safety results from women in the two studies were collated. Zoledronic acid reduced the risk of all clinical fractures at 12 months (hazard ratio [HR] = 0.75, 95% confidence interval [CI] 0.61-0.92, p = 0.0050) with significant reductions maintained at all subsequent time points. Year-by-year analysis showed that zoledronic acid reduced the risk for all clinical fractures compared with the placebo group in each of the 3 years (year 1: odds ratio [OR] = 0.74, 95% CI 0.60-0.91, p = 0.0044; year 2: OR = 0.53, 95% CI 0.42-0.66, p < 0.0001; year 3: OR = 0.61, 95% CI 0.48-0.77, p < 0.0001). This antifracture effect was persistent over 3 years, with the reductions in years 2 and 3 slightly larger than in year 1 (p = 0.097). This analysis shows that zoledronic acid offered significant protection from clinical fractures as early as 12 months. When administered annually, its beneficial effects persisted for at least 3 years.
authors.affiliation: University of Leuven, Leuven, Belgium. steven.boonen@uz.kuleuven.ac.be
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Guoqin
authors.initials: G
authors.lastname: Su
authors.forename: Peter
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: Felicia
authors.initials: F
authors.lastname: Cosman
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.forename: Frank
authors.initials: F
authors.lastname: Claessens
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Lyles
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D058866:Osteoporotic Fractures / Q000517:prevention & control; D010919:Placebos; D016016:Proportional Hazards Models; D012306:Risk; D013997:Time Factors; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D010919:Placebos; D000077211:Zoledronic Acid