Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin
Evaluation of Bone Mineral Density and Bone Biomarkers in Patients With Type 2 Diabetes Treated With Canagliflozin
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DOI：
10.1210/jc.2015-1860
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发表时间：
2016-01-01
影响因子：
5.8
通讯作者：
Rosenthal, Norm
中科院分区：
文献类型：
--
作者：
Bilezikian, John P.;Watts, Nelson B.;Rosenthal, Norm
内容：Canagliflozin是一种钠葡萄糖协同转运蛋白2抑制剂，用于治疗2型糖尿病（T2 DM）。目的：我们的目的是描述Canagliflozin对T2 DM患者骨密度（BMD）和骨生物标志物的影响。设计：这是一项随机研究，包括26周、双盲、安慰剂对照期和78周、双盲、安慰剂对照扩展期。设置：本研究在17个国家的90个中心进行。患者：患者年龄为55-80岁（N = 716），其T2 DM在稳定的抗高血糖方案下控制不佳。干预措施：卡格列净100或300 mg或安慰剂每日一次给药。结果和测量：在第26、52和104周使用双能X射线吸收测定法评估BMD。在第52周使用定量计算机断层扫描和有限元分析评估骨强度。在第26周和第52周评估血清1型胶原β-羧基端肽、骨钙素和雌二醇。结果：卡格列净100和300 mg剂量与104周内全髋BMD降低相关（减去安慰剂的变化分别为：-0.9%和-1.2%），但在其他测量部位（股骨颈、腰椎或前臂远端）不相关。未观察到骨强度有意义的变化。在第52周，卡格列净与1型胶原蛋白β-羧基端肽的增加相关，而1型胶原蛋白β-羧基端肽的增加与体重减轻、骨钙素增加以及女性雌二醇减少显著相关。在老年T2 DM患者中，卡格列净显示全髋BMD小幅但显著降低，骨形成和吸收生物标志物增加，至少部分原因是体重减轻。
Context: Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).Objective: Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM.Design: This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension.Setting: This study was undertaken in 90 centers in 17 countries.Patients: Patients were aged 55-80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen.Interventions: Canagliflozin 100 or 300 mg or placebo were administered once daily.Outcome and Measures: BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 beta-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52.Results: Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: -0.9% and -1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 beta-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol.Conclusions: In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.