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, 0.75; 95% confidence interval [CI], 0.61–0.92; p=0.0050) with significant reductions maintained at all subsequent timepoints. 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 year 2 and 3 slightly larger than in year 1 (p=0.097). This analysis shows that zoledronic acid offers significant protection from clinical fractures as early as 12 months. When administered annually, its beneficial effects persist for at least 3 years.

Risk of New Vertebral Fracture and Combination Therapy with Zoledronic Acid and Teriparatide in Diabetic Patients after Percutaneous Kyphoplasty

“…Anti-osteoporosis treatment would reduce the NVF risk. Zoledronic acid is an antiresorptive agent that plays an important role in the prevention of vertebral fractures because it has a short time-to-onset for reducing vertebral fractures and high patient compliance [14]. In the present study, for diabetes patients who have undergone PKP and were proven to be at high risk of NVF in several studies, the prevalence of NVF was 11.1% when zoledronic acid was administered, much lower than that reported previously.…”

Medication use to manage comorbidities for people with dementia: a systematic review

“…Current treatment for all people with osteoporosis is to provide treatment for a finite duration to reduce the risk of fracture . Bisphosphonates are documented to have an onset time for benefit to reduce fractures; bisphosphonates have been shown to have a reduction in fracture incidence after 2 years . The experimental study included in this literature review found that even in moderate dementia, mobile people continued to receive benefits from bisphosphonate treatment.…”

Unmet needs and current and future approaches for osteoporotic patients at high risk of hip fracture

“…The lack of evidence for hip fracture reduction in women aged 75 years and older in the two HORIZON studies, as evidenced by a pooled analysis, might raise the point that recurrent falls are the most prominent mechanism for hip fracture in this population [ 83 ]. Alternatively, that the level of hip bone fragility at that age cannot easily be reversed in just few years of pharmacological therapy.…”