Kleerekoper Michael, Greenspan Susan L, Lewiecki E Michael, Miller Paul D, Kendler David L, Maricic Michael, Keaveny Tony M, Kopperdahl David L, Ruff Valerie A, Wan Xiaohai, Janos Boris, Krohn Kelly
Division of Endocrinology, Department of Medicine, University of Toledo, 3000 Arlington Avenue, Toledo, OH 43614. E-mail address:
Osteoporosis Treatment and Prevention Center, University of Pittsburgh, 3459 Fifth Avenue, 4th Floor, Pittsburgh, PA 15213.
J Bone Joint Surg Am. 2014 Jun 4;96(11):e90. doi: 10.2106/JBJS.L.01757.
To gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.
In this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.
Thirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.
High-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
为深入了解特立帕肽如何影响各种骨骼健康参数，我们使用标准双能X线吸收法（DXA）技术以及两种较新的技术，即高分辨率磁共振成像（MRI）和定量计算机断层扫描（CT）扫描的有限元分析，评估了特立帕肽治疗的效果。
在这项4期开放标签研究中，重度骨质疏松的绝经后女性接受每日20μg特立帕肽治疗。评估内容包括：（1）DXA测量的桡骨、脊柱和髋部的面积骨密度（BMD）（单位：g/cm²）变化；（2）定量CT扫描测量的脊柱和髋部的体积骨密度（单位：mg/cm³）变化；（3）高分辨率MRI测量的桡骨骨微结构变化；（4）根据定量CT扫描的有限元分析估算的脊柱和髋部强度变化；（5）血清中骨转换标志物的变化；（6）安全性。
共纳入35名受试者；30名完成了18个月的治疗，25名完成了为期6个月的可选延长期治疗。主要结局指标，即桡骨远端的高分辨率MRI，未观察到显著变化。在第18个月时，脊柱总体积骨密度较基线的最小二乘平均百分比变化为10.05%（95%置信区间[CI]，6.83%至13.26%；p<0.001），估算的脊柱强度增加了17.43%（95%CI，12.09%至22.76%；p<0.001）。髋部总体积骨密度增加了2.22%（95%CI，0.37%至4.06%；p=0.021），估算的髋部强度增加了2.54%（95%CI，0.06%至5.01%；p=0.045）。腰椎和股骨颈的面积骨密度增加，全髋和桡骨最远端的面积骨密度无变化，腕关节与肘关节之间三分之一处的面积骨密度降低。骨转换标志物在第3个月、第6个月和第24个月时升高（均p<0.05）。未观察到意外不良事件。
高分辨率MRI未能发现桡骨远端（一个非负重部位，可能不适于评估骨合成代谢药物的效果）的骨微结构变化。特立帕肽增加了脊柱和股骨颈的面积骨密度以及脊柱和髋部的体积骨密度。估算的椎体和股骨强度也增加。这些发现以及至第24个月时骨转换标志物的升高与特立帕肽已知的骨合成代谢作用一致。
治疗性IV级。有关证据水平的完整描述，请参阅《作者须知》。
