Palacios S, Kalouche-Khalil L, Rizzoli R, Zapalowski C, Resch H, Adachi J D, Gallagher J C, Feldman R G, Kendler D L, Wang A, Wagman R B, Adami S
a * Institute of Women's Health , Madrid , Spain.
b Amgen (Europe) GmbH , Zug , Switzerland.
Climacteric. 2015;18(6):805-12. doi: 10.3109/13697137.2015.1045484. Epub 2015 Sep 28.
A history of prior fracture is one of the strongest predictors of a future fragility fracture. In FREEDOM, denosumab significantly reduced the risk of new vertebral, non-vertebral, and hip fractures. We carried out a post-hoc analysis of FREEDOM to characterize the efficacy of denosumab in preventing secondary fragility fractures in subjects with a prior fracture.
A total of 7808 women aged 60-90 years with a bone mineral density T-score of less than - 2.5 but not less than - 4.0 at either the lumbar spine or total hip were randomized to subcutaneous denosumab 60 mg or placebo every 6 months for 36 months. The anti-fracture efficacy of denosumab was analyzed by prior fracture status, to assess secondary fragility fracture, and by subject age, prior fracture site and history of prior osteoporosis medication use.
A prior fragility fracture was reported for 45% of the overall study population. Compared with placebo, denosumab significantly reduced the risk of a secondary fragility fracture by 39% (incidence, 17.3% vs. 10.5%; p < 0.0001). Similar results were observed regardless of age or prior fracture site. In the overall population, denosumab significantly reduced the risk of a fragility fracture by 40% (13.3% vs. 8.0%; p < 0.0001), with similar results observed regardless of history of prior osteoporotic medication use.
Denosumab reduced the risk of fragility fractures to a similar degree in all risk subgroups examined, including those with prior fragility fractures. Identifying and treating high-risk individuals could help to close the current care gap in secondary fracture prevention.
既往骨折史是未来发生脆性骨折的最强预测因素之一。在FREEDOM研究中，地诺单抗显著降低了新发椎体、非椎体和髋部骨折的风险。我们对FREEDOM研究进行了事后分析，以确定地诺单抗在预防既往有骨折的受试者继发性脆性骨折方面的疗效。
共有7808名年龄在60 - 90岁之间、腰椎或全髋部骨密度T值小于-2.5但不低于-4.0的女性被随机分组，每6个月皮下注射60mg地诺单抗或安慰剂，为期36个月。根据地诺单抗的既往骨折状态分析其抗骨折疗效，以评估继发性脆性骨折，并按受试者年龄、既往骨折部位和既往骨质疏松药物使用史进行分析。
在整个研究人群中，45%的人有既往脆性骨折史。与安慰剂相比，地诺单抗显著降低了39%的继发性脆性骨折风险（发生率分别为17.3%和10.5%；p < 0.0001）。无论年龄或既往骨折部位如何，均观察到类似结果。在总体人群中，地诺单抗显著降低了40%的脆性骨折风险（分别为13.3%和8.0%；p < 0.0001），无论既往是否使用过骨质疏松药物，结果相似。
在所有检查的风险亚组中，包括既往有脆性骨折的亚组，地诺单抗降低脆性骨折风险的程度相似。识别和治疗高危个体有助于缩小目前二级骨折预防中的护理差距。
