Abstract
The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO study included postmenopausal women with established osteoporosis, who had at least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral density (BMD) T-score ≤-1.5. Patients were treated with either s.c. daily teriparatide 20 μg or oral weekly risedronate 35 mg. As previously reported, the risk of new VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced with teriparatide compared with risedronate. Here we present the prospectively planned subgroup analyses of fracture data across subgroups, which were predefined by the following baseline characteristics: age, number and severity of prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before study entry, and baseline BMD. Heterogeneity of the treatment effect on the primary endpoint (new VFx), and the four key secondary endpoints (including clinical fractures and NVFFx) were investigated by logistic and Cox proportional hazards regression models. A total of 1360 women were randomized and treated (680 per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7 (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had a prior major NVFx, 43.2% were osteoporosis drug-naïve, 39.3% were recent bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone-equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of teriparatide versus risedronate did not significantly differ in any of the subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most subgroups mirroring results from the total study population. In conclusion, in postmenopausal women with severe osteoporosis, the antifracture efficacy of teriparatide compared with risedronate was consistent in a wide range of patient settings, including treatment-naïve and previously treated patients. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Highlights
The choice of the drug treatment for secondary prevention of fragility fractures in patients with osteoporosis is a controversial topic
We have recently reported the “VERtebral fracture treatment comparisons in Osteoporotic women” (VERO) trial,(1) the first active-controlled clinical trial adequately designed to show superiority in the incidence of new vertebral fractures (VFx) as the primary endpoint, comparing teriparatide with risedronate, an oral bisphosphonate that has shown significant antifracture efficacy results in postmenopausal women with low bone mass and prevalent VFx.[2,3,4,5] In the VERO trial, 24-month treatment with teriparatide significantly reduced the incidence of VFx and clinical fractures compared with risedronate by 56% and 52%, respectively, in postmenopausal women with established osteoporosis.[1]
Subgroup analyses of large clinical trials are useful because the beneficial treatment effects of osteoporosis drugs may vary across different categories of relevant risk factors, as has been found before in clinical trials with hip fracture as the study endpoint in patients treated with risedronate[5] or strontium ranelate.[16]. For instance, there is a lack of previous data from randomized clinical trials on fracture outcomes in patients receiving teriparatide who were pretreated with bisphosphonates
Summary
The choice of the drug treatment for secondary prevention of fragility fractures in patients with osteoporosis is a controversial topic. We have recently reported the “VERtebral fracture treatment comparisons in Osteoporotic women” (VERO) trial,(1) the first active-controlled clinical trial adequately designed to show superiority in the incidence of new vertebral fractures (VFx) as the primary endpoint, comparing teriparatide with risedronate, an oral bisphosphonate that has shown significant antifracture efficacy results in postmenopausal women with low bone mass and prevalent VFx.[2,3,4,5] In the VERO trial, 24-month treatment with teriparatide significantly reduced the incidence of VFx and clinical fractures (a composite of clinical VFx and nonvertebral fragility fractures [NVFFx]) compared with risedronate by 56% and 52%, respectively, in postmenopausal women with established osteoporosis.[1]. Similar subgroup analyses have been reported previously for alendronate,(9) risedronate,(4) zoledronic acid,(10) denosumab,(11) and abaloparatide[12] in the population of patients enrolled in the phase 3 trials but using placebo as the comparator, instead of an active comparator as utilized in the present study
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