Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial

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.

One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study

“…(32) This sequence of therapy-a bone-forming agent first, followed by an antiresorptive agent-may be particularly beneficial for patients at high risk for fracture. (20) Indeed, there is a growing body of literature suggesting that some high-risk patients may be at imminent risk of fracture (ie, in the next 1 to 2 years) on the basis of clinical characteristics such as recent fracture, older age, and lower BMD, (4)(5)(6)(7)(8)(9)(10)(11)(12) and these Fig. 3.…”

“…The consequences of osteoporosis, namely fractures, result in substantial clinical and economic burden among postmenopausal women . After a fracture, the risk of second fracture is five times higher in the next year, and recent fracture and other characteristics such as older age and low bone mineral density (BMD) can put patients at high risk for fracture both over a longer‐term horizon (eg, 10 years), as well as over shorter‐term horizons . However, even in patients in whom there is urgency to treat, there is a large treatment gap in osteoporosis, with only about 20% of patients receiving treatment following a fracture .…”

“…(1,2) After a fracture, the risk of second fracture is five times higher in the next year, (3) and recent fracture and other characteristics such as older age and low bone mineral density (BMD) can put patients at high risk for fracture both over a longer-term horizon (eg, 10 years), as well as over shorter-term horizons. (4)(5)(6)(7)(8)(9)(10)(11)(12) However, even in patients in whom there is urgency to treat, there is a large treatment gap in osteoporosis, with only about 20% of patients receiving treatment following a fracture. (13)(14)(15) Limited options for bone-forming therapy are currently available.…”

Advances and Unmet Needs in the Therapeutics of Bone Fragility

“…At 2 years, treatment with teriparatide resulted in a 56% (risk ratio 0.44, 95% CI 0.29–0.68) reduction in incident vertebral fractures with a reduction in non-vertebral fractures that did not achieve statistical significance; 25 (4.0%) in the teriparatide group vs. 38 (6.1%) in the risedronate group (hazard ratio (HR) 0.66, 95% CI 0.39–1.10, P = 0.10) ( 26 ). In a subgroup analyses, these changes were consistent across a range of characteristics of the participants ( 90 ).…”

Evidenz-basierte Prophylaxe, Diagnostik und Therapie der Osteoporose im Jahre 2019

“…B. zu, wenn schon proximale Femurfrakturen und Wirbelkörperfrakturen vorliegen oder wenn ein erhöhtes Risiko für Frakturen unter laufender oder geplanter Therapie mit Glukokortikoiden besteht. Deshalb sollte bei Patienten mit hohem Frakturrisiko Teriparatid den oralen Bisphosphonaten vorgezogen werden [22,23] Grundlage für die Entwicklung dieses Rechners waren große Populationsstudien aus den USA, Europa und Asien [8,9]. Allerdings sind im FRAX ® nur Faktoren aufgenommen worden, zu denen aus großen Studien valide Daten vorlagen.…”