Maastricht University Medical Center, Maastricht, The Netherlands.
Lilly Research Center Europe, Madrid, Spain.
J Bone Miner Res. 2018 May;33(5):783-794. doi: 10.1002/jbmr.3384. Epub 2018 Feb 9.
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.
这项为期 2 年、随机、双盲、阳性药物对照的骨折终点 VERO 研究纳入了绝经后骨质疏松症女性患者，这些患者至少有 2 处中度或 1 处严重基线椎体骨折（VFx），且骨密度（BMD）T 评分≤-1.5。患者接受每日皮下注射特立帕肽 20μg 或每周口服利塞膦酸钠 35mg 治疗。如既往报道，与利塞膦酸钠相比，特立帕肽可显著降低新椎体骨折（VFx）和临床骨折（临床 VFx 和非椎体脆性骨折[NVFFx]的复合）风险。在此，我们根据以下基线特征预先设定的亚组分析了骨折数据：年龄、既往 VFx 数量和严重程度、既往非椎体骨折（NVFx）、糖皮质激素使用、既往骨质疏松症药物、近期双膦酸盐使用、研究入组前 1 年的临床 VFx 和基线 BMD。通过逻辑回归和 Cox 比例风险回归模型，对主要终点（新发 VFx）和四个关键次要终点（包括临床骨折和 NVFFx）的治疗效果进行了异质性分析。共纳入 1360 名女性患者，随机分组并接受治疗（每组 680 名）。平均年龄为 72.1 岁，平均（SD）既往 VFx 数量为 2.7（2.1）处，55.4%患者的 BMD T 评分<-2.5，36.5%患者近期有临床 VFx，28.3%患者有既往主要的 NVFx，43.2%患者为骨质疏松症药物初治患者，39.3%为近期双膦酸盐使用者，9.3%患者服用糖皮质激素的泼尼松等效剂量>5mg/d。对于大多数骨折终点，特立帕肽与利塞膦酸钠相比，风险降低在分析的大多数亚组中无显著差异（治疗-亚组交互作用 p>0.1），大多数亚组与总研究人群的结果一致。综上，在严重骨质疏松症的绝经后女性中，与利塞膦酸钠相比，特立帕肽的抗骨折疗效在广泛的患者人群中一致，包括初治和既往治疗患者。
