甲状旁腺激素（1-34）和生长激素预防大鼠废用性骨质疏松和肌少症。

PTH (1-34) and growth hormone in prevention of disuse osteopenia and sarcopenia in rats.

机构信息

Department of Biomedicine, Aarhus University, Denmark.

出版信息

Bone. 2018 May;110:244-253. doi: 10.1016/j.bone.2018.02.017. Epub 2018 Feb 20.

DOI:10.1016/j.bone.2018.02.017

Abstract

Osteopenia and sarcopenia develops rapidly during disuse. The study investigated whether intermittent parathyroid hormone (1-34) (PTH) and growth hormone (GH) administered alone or in combination could prevent or mitigate disuse osteopenia and sarcopenia in rats. Disuse was achieved by injecting 4IU botulinum toxin A (BTX) into the right hindlimb musculature of 12-14-week-old female Wistar rats. Seventy-two rats were divided into six groups: 1. Baseline; 2. Ctrl; 3. BTX; 4. BTX+GH; 5. BTX+PTH; 6. BTX+PTH+GH. PTH (1-34) (60μg/kg/day) and GH (5mg/kg/day). The animals were sacrificed after 6weeks of treatment. Sarcopenia was established by histomorphometry, while the skeletal properties were determined using DXA, μCT, mechanical testing, and dynamic bone histomorphometry. Disuse resulted in lower muscle mass (-63%, p<0.05), trabecular BV/TV (-28%, p<0.05), Tb.Th (-11%, p<0.05), lower diaphyseal cortical thickness (-10%, p<0.001), and lower bone strength at the distal femoral metaphysis (-27%, p<0.001) compared to Ctrl animals. PTH fully counteracted the immobilization-induced lower BV/TV, Tb.Th, and distal femoral metaphyseal strength. GH increased muscle mass (+17%, p<0.05) compared to BTX, but did not prevent the immobilization-induced loss of bone strength, BV/TV, and cortical trabecular thickness. Combination of PTH and GH increased distal femoral metaphyseal bone strength (+45%, p<0.001), BV/TV (+50%, p<0.05), Tb.Th (+40%, p<0.05), and whole femoral aBMD (+15%, p<0.001) compared to BTX and muscle mass (+21%, p<0.05) compared to BTX+PTH. In conclusion, PTH and GH in combination is more efficient at preventing the disuse-related deterioration of bone strength, density, and micro-architecture than either PTH or GH given as monotherapy. Furthermore, GH, either alone or in combination with PTH, attenuated disuse-induced loss of muscle mass. The combination of PTH and GH resulted in a more effective treatment than PTH and GH as monotherapy.

摘要

废用会导致骨质疏松症和肌肉减少症迅速发展。本研究旨在探讨单独或联合使用甲状旁腺激素（1-34）（PTH）和生长激素（GH）是否可以预防或减轻大鼠的废用性骨质疏松症和肌肉减少症。通过向 12-14 周龄雌性 Wistar 大鼠的右后肢肌肉注射 4IU 肉毒杆菌毒素 A（BTX）来实现废用。72 只大鼠分为六组：1. 基线；2. Ctrl；3. BTX；4. BTX+GH；5. BTX+PTH；6. BTX+PTH+GH。PTH（1-34）（60μg/kg/天）和 GH（5mg/kg/天）。治疗 6 周后处死动物。通过组织形态计量学来确定肌肉减少症，而骨骼特性则通过 DXA、μCT、力学测试和动态骨组织形态计量学来确定。与对照动物相比，废用导致肌肉质量降低（-63%，p<0.05）、小梁骨体积/总体积（BV/TV）降低（-28%，p<0.05）、骨小梁厚度（Tb.Th）降低（-11%，p<0.05）、骨干皮质厚度降低（-10%，p<0.001）和股骨远端骺骨强度降低（-27%，p<0.001）。PTH 完全抵消了固定引起的 BV/TV、Tb.Th 和股骨远端骺骨强度降低。GH 与 BTX 相比增加了肌肉质量（+17%，p<0.05），但不能预防骨强度、BV/TV 和皮质小梁厚度的固定诱导丢失。与 BTX 相比，PTH 和 GH 的联合使用增加了股骨远端骺骨强度（+45%，p<0.001）、BV/TV（+50%，p<0.05）、Tb.Th（+40%，p<0.05）和全股骨 aBMD（+15%，p<0.001），与 BTX 相比，肌肉质量也增加了（+21%，p<0.05）。综上所述，与单独使用 PTH 或 GH 相比，PTH 和 GH 联合使用在预防与废用相关的骨强度、密度和微观结构恶化方面更有效。此外，GH 无论是单独使用还是与 PTH 联合使用，都能减轻废用引起的肌肉质量减少。PTH 和 GH 的联合使用比单独使用 PTH 和 GH 更有效。