ABSTRACT: 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.