Bartlow Christopher M, Oest Megan E, Mann Kenneth A, Zimmerman Nicholas D, Butt Bilal B, Damron Timothy A
Department of Orthopedic Surgery, Upstate Medical University, 750 East Adams Street, Syracuse, New York.
J Orthop Res. 2017 Aug;35(8):1707-1715. doi: 10.1002/jor.23442. Epub 2016 Oct 3.
Treatment of secondary pediatric osteoporosis-particularly that due to chronic diseases, immobilization, and necessary medical treatments-is currently limited by a poor understanding of the long-term efficacy and safety of skeletal metabolism modifying drugs. This study aimed to characterize longitudinal effects of representative anabolic (parathyroid hormone, PTH) and anti-catabolic (zoledronic acid, ZA) drugs on skeletal morphology, mechanical strength, and growth in juvenile mice. BALB/cJ mice aged 4 weeks were given PTH(1-34) or vehicle (control) daily for 8 weeks, or 4 weekly doses of ZA, and evaluated at time points 0-26 weeks after treatment initiation. There were no enduring differences in body length or mass between treatment groups. ZA increased femur size as early as week 0, including increased distal femur bone volume and diaphyseal cross-sectional area, persisting through week 26. PTH treatment only transiently increased bone size, including distal femur volume at weeks 4-12. ZA decreased diaphyseal cortical tissue mineral density (TMD) at 12-26 weeks versus controls; PTH decreased TMD only at 2 weeks (vs. controls). ZA increased bending strength at 0-12 weeks and flexural strength at week 4 (vs. controls), but decreased flexural strength and modulus at week 26. PTH treatment increased bending strength only at 4 weeks, and did not affect flexural strength. Overall, ZA rapidly and persistently increased femur strength and size, but compromised bone material quality long-term. In healthy juvenile mice, limited-duration PTH treatment did not exert a strong anabolic effect, and had no adverse effects on femur strength, morphology, or growth. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1707-1715, 2017.
目前，对于骨骼代谢调节药物的长期疗效和安全性了解不足，这限制了继发性小儿骨质疏松症的治疗，尤其是由慢性疾病、固定不动及必要的药物治疗引起的继发性小儿骨质疏松症。本研究旨在描述代表性的促合成代谢药物（甲状旁腺激素，PTH）和抗分解代谢药物（唑来膦酸，ZA）对幼年小鼠骨骼形态、机械强度和生长的纵向影响。4周龄的BALB/cJ小鼠每天接受PTH(1 - 34)或赋形剂（对照）治疗，持续8周，或接受4次每周剂量的ZA治疗，并在治疗开始后的0 - 26周时间点进行评估。各治疗组之间在体长或体重方面没有持久差异。ZA早在第0周就增加了股骨尺寸，包括增加了股骨远端骨体积和骨干横截面积，并持续到第26周。PTH治疗仅短暂增加了骨尺寸，包括在第4 - 12周时股骨远端体积增加。与对照组相比，ZA在12 - 26周时降低了骨干皮质组织矿物质密度（TMD）；PTH仅在第2周时降低了TMD（与对照组相比）。ZA在0 - 12周时增加了弯曲强度，在第4周时增加了挠曲强度（与对照组相比），但在第26周时降低了挠曲强度和模量。PTH治疗仅在第4周时增加了弯曲强度，且未影响挠曲强度。总体而言，ZA迅速且持续地增加了股骨强度和尺寸，但长期损害了骨材料质量。在健康的幼年小鼠中，有限疗程的PTH治疗并未产生强烈的促合成代谢作用，且对股骨强度、形态或生长没有不良影响。© 2016骨科研究协会。由威利期刊公司出版。《矫形外科学研究》35:1707 - 1715，2017年。
