Increased cortical porosity is associated with daily, not weekly, administration of equivalent doses of teriparatide
Increased cortical porosity is associated with daily, not weekly, administration of equivalent doses of teriparatide
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DOI：
10.1016/j.bone.2017.03.042
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发表时间：
2017-06-01
期刊：
影响因子：
4.1
通讯作者：
Seeman, Ego
中科院分区：
文献类型：
--
作者：
Zebaze, Roger;Takao-Kawabata, Ryoko;Seeman, Ego
简介：甲状旁腺激素 (PTH) 的药代动力学特征决定了其对骨吸收和形成的影响。与连续治疗相比，间歇给药时，合成代谢效果更佳。在间歇治疗方案中，较低的给药频率可能对骨重塑的效果较低。因此，我们假设每周施用特立帕肽比每日治疗所产生的皮质内重塑和孔隙率增加要少。 方法：我们用特立帕肽[人 PTH(1-34)] 治疗 17 只 6 个月大的雌性新西兰白兔，为期 1 个月，如下。 (i) 媒介物处理对照 (n = 4)； (ii) 每日 20 微克/公斤（n = 3）； (iii) 每日 40 微克/公斤（n = 3）； (iv) 每周 140 微克/公斤（n = 3）； (v) 每周 280 微克/公斤 (n = 4)。使用微型 CT (Scanco Viva CT-40) 以 15 μm 体素大小对近端股骨进行离体成像。使用 StrAx1.0 对从中轴开始的 10 毫米长感兴趣区域 (ROI) 中的总致密皮层 (CC) 和过渡区的面积、孔径和孔隙率进行分析。 结果：与对照相比，每天 20 μ g/kg 与过渡区孔隙率高出 3.0% 相关 (p = 0.09)，而每天 40 μ g/kg 与较高孔隙率相关。皮层（8.7%；p = 0.04）和过渡区（5.7%；p = 0.007）。由于孔隙 > 15 μ m(2)，每日治疗方案也与较大比例的孔隙率相关；特别是在过渡区，每天 20 和 40 μg/kg 的孔隙率相对于对照分别增加了 2 倍（p = 0.06）和 5 倍（p = 0.04）。每周140和280μg/kg与孔隙率的增加无关。各组之间的总横截面积、致密区横截面积或过渡区横截面积没有差异。结论：间歇性特立帕肽的效果取决于给药剂量和频率。每日给药，尤其是较高剂量，但不是每周给药，会增加皮质孔隙度。需要开展工作来研究这些方案对骨形成的影响。 2017 年作者。由爱思唯尔公司出版
Introduction: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment.Methods: We treated 17 female New Zealand white rabbits aged 6 months for I month with teriparatide [human PTH(1-34)] as follows. (i) Vehicle-treated Control (n = 4); (ii) 20 mu g/kg daily (n = 3); (iii) 40 mu g/kg daily (n = 3); (iv) 140 mu g/kg weekly (n = 3); (v) 280 mu g/kg weekly (n = 4). Proximal femurs were imaged ex vivo using micro CT (Scanco Viva CT-40) at 15 mu m voxel size. Areas, pore size, and porosity were analyzed on the total, compact cortex (CC), and transitional zones in a 10 mm length region of interest (ROI) starting at the midshaft using StrAx1.0.Results: Compared to controls, the 20 mu g/kg daily was associated with 3.0% higher porosity in the transitional zone (p = 0.09) while the 40 mu g/kg daily was associated with a higher porosity in the cortex (8.7%; p = 0.04) and in the transitional zone (5.7%; p = 0.007). The daily regimens were also associated with a greater proportion of porosity due to pores > 15 mu m(2); particularly in the transitional zone where 20 and 40 mu g/kg daily increased porosity 2 fold (p = 0.06) and 5 fold (p = 0.04) relative controls respectively. The 140 and 280 mu g/kg weekly were not associated with an increase in porosity. There was no difference in total, compact or transitional zone cross sectional areas between the groups.Conclusion: Effects of intermittent teriparatide depend on the dose and frequency of administration. Daily dosing, particularly the higher dose, but not weekly dosing, increased cortical porosity. Work is needed to investigate the effects of the regimens on bone formation. 2017 The Authors. Published by Elsevier Inc.