Elraiyah Tarig, Ahmed Adil H, Wang Zhen, Farr Joshua N, Murad Mohammad H, Drake Matthew T
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States; Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, United States.
Wichita Falls Family Practice Residency Program (WFFRP), North Central Texas Medical Foundation, Wichita Falls, TX, United States.
Bone Rep. 2015 Nov 17;4:17-22. doi: 10.1016/j.bonr.2015.11.001. eCollection 2016 Jun.
While teriparatide is the only skeletal anabolic agent approved in the United States, treatment failure is a major concern which complicates its clinical utility. We sought to identify factors that predict response failure in patients with low bone mass.
We performed a retrospective study of adults with osteopenia or osteoporosis (T-scores < - 1.0 and - 2.5 SD below normal, respectively, at the total hip or lumbar spine) treated with teriparatide at the Mayo Clinic (Rochester, Minnesota) between November 2002-December 2012. Trained study investigators blinded to patient outcomes collected electronic medical record data. Potential response failure predictors were identified using univariate analysis. Multivariable logistic regression modeling was used to identify independent predictors of treatment failure based on either osteoporotic fragility fracture or BMD response.
During the 10-year period, 494 patients received teriparatide treatment and met eligibility criteria. Thirty-five patients had osteoporotic fractures, while 172 did not achieve a ≥ 3% BMD increase. Among predictors as defined by BMD change, both prior bisphosphonate treatment [odds ratio (95% confidence interval), 1.50 (1.01-2.24)] and vitamin D therapy [1.50 (1.01-2.22)] were significantly (P < 0.05) associated with teriparatide treatment failure. By contrast, no predictors were associated with treatment failure when fracture was the endpoint.
These data suggest that prior bisphosphonate or vitamin D exposure may predict response failure to teriparatide therapy. Although these findings may, in part, reflect increased severity or longer duration of disease, this knowledge should help guide clinicians and patients when therapy choices are made.
虽然特立帕肽是美国唯一获批的骨骼合成代谢药物，但治疗失败是一个主要问题，这使其临床应用变得复杂。我们试图确定预测低骨量患者治疗反应失败的因素。
我们对2002年11月至2012年12月在梅奥诊所（明尼苏达州罗切斯特）接受特立帕肽治疗的骨质疏松症或骨质减少症成人患者（全髋或腰椎的T值分别低于正常水平1.0和2.5个标准差）进行了一项回顾性研究。经过培训的研究人员在对患者结局不知情的情况下收集电子病历数据。使用单因素分析确定潜在的反应失败预测因素。多变量逻辑回归模型用于根据骨质疏松性脆性骨折或骨密度反应确定治疗失败的独立预测因素。
在这10年期间，494例患者接受了特立帕肽治疗并符合纳入标准。35例患者发生骨质疏松性骨折，而172例患者骨密度未增加≥3%。在由骨密度变化定义的预测因素中，既往双膦酸盐治疗[比值比（95%置信区间），1.50（1.01 - 2.24）]和维生素D治疗[1.50（1.01 - 2.22）]均与特立帕肽治疗失败显著相关（P < 0.05）。相比之下，以骨折为终点时，没有预测因素与治疗失败相关。
这些数据表明，既往双膦酸盐或维生素D暴露可能预测特立帕肽治疗反应失败。尽管这些发现可能部分反映了疾病的严重程度增加或病程延长，但这些知识应有助于在做出治疗选择时指导临床医生和患者。
