Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).
Effect of treatment for 6 months with human parathyroid hormone (1-34) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).
复制标题
人甲状旁腺激素 (1-34) 肽治疗 6 个月对切除卵巢的食蟹猴（食蟹猴）的效果。
DOI：
10.1016/s8756-3282(99)00166-0
复制
发表时间：
1999
期刊：
影响因子：
4.1
通讯作者：
Mosekilde,L
中科院分区：
文献类型：
--
作者：
Jerome,CP;Johnson,CS;Vafai,HT;Kaplan,KC;Bailey,J;Capwell,B;Fraser,F;Hansen,L;Ramsay,H;Shadoan,M;Lees,CJ;Thomsen,JS;Mosekilde,L
间歇性甲状旁腺激素（PTH）治疗骨质疏松症的潜在副作用是皮质骨丢失伴松质骨质量增加。我们通过研究甲状旁腺素对哈氏皮质骨重建动物模型全身、轴向和骨外骨量的影响来解决这个问题。将切除卵巢的年轻成年雌性食蟹猴分配至安慰剂组（n = 9）或PTH组（n = 10）。PTH组通过皮下注射接受10 μg/kg合成人PTH（1-34）肽，每周3天，持续6个月，安慰剂组接受媒介物。评估了轴骨和骨外骨骼的骨量、强度和转换的多个终点，包括双能X线吸收测定法（DEXA）、定量计算机断层扫描（qCT）、血清（钙、磷、碱性磷酸酶、骨钙素和抗酒石酸酸性磷酸酶）和尿液（钙和肌酐）生物标志物分析、组织形态计量学和生物力学测试。与安慰剂治疗的动物相比，PTH治疗的猴子全身骨量没有变化，但观察到脊髓区域骨矿物质密度（aBMD）增加6.7%。通过qCT测量的骨关节部位的皮质骨质量不受PTH治疗的影响，但胫骨近端的松质骨质量显著增加，桡骨远端的趋势相似。观察到血清和尿钙的小幅一过性增加，但对其他生化终点无给药相关影响。桡骨中段和股骨中段的骨形成率（BFR/BV）增加，同时股骨中段孔隙率无显著增加。椎体松质骨体积（BV/TV）增加与骨小梁和间质厚度增加相关，对壁厚度无影响。在轴向（椎骨最大应力和骨折载荷）和非轴向（股骨颈骨折载荷）骨骼中均观察到骨强度增加。总之，这些结果表明，食蟹猴的甲状旁腺激素治疗导致脊柱和阑尾松质骨质量净增加，对皮质骨没有不良影响。
A potential negative side effect of intermittent parathyroid hormone (PTH) therapy to treat osteoporosis is the loss of cortical bone concomitant with increased cancellous bone mass. We addressed this issue by studying the effects of PTH on whole-body, axial, and appendicular bone mass in an animal model with haversian cortical bone remodeling. Ovariectomized, young adult female cynomolgus monkeys were assigned to placebo (n = 9) or PTH groups (n = 10). The PTH group received 10 μg/kg synthetic human PTH(1-34) peptide by subcutaneous injection, 3 days/week for 6 months, and the placebo group received vehicle. Multiple endpoints of bone mass, strength, and turnover in the axial and appendicular skeleton were assessed, including dual-energy X-ray absorptiometry (DEXA), quantitative computed tomography (qCT), analysis of serum (calcium, phosphorus, alkaline phosphatase, osteocalcin, and tartrate-resistant acid phosphatase) and urinary (calcium and creatinine) biomarkers, histomorphometry, and biomechanical testing. Compared with placebo-treated animals, PTH-treated monkeys had no change in whole-body bone mass, but a 6.7% increase in spinal areal bone mineral density (aBMD) was observed. Cortical bone mass measured by qCT at appendicular sites was not affected by PTH treatment, but there were significant increases in cancellous bone mass in the proximal tibia, and a similar trend in the distal radius. Small, transient increases in serum and urinary calcium were observed, but there were no treatment-related effects on other biochemical endpoints. Increased bone formation rate (BFR/BV) in the midradius and midfemur was accompanied by a nonsignificant increase in midfemur porosity. Increased vertebral cancellous bone volume (BV/TV) was associated with greater trabecular and interstitial thickness with no effect on wall thickness. Increases in bone strength were observed in both axial (vertebral maximum stress and load at fracture) and appendicular (femoral neck fracture load) skeleton. Together, these results indicate that PTH therapy in the cynomolgus monkey results in a net gain of spinal and appendicular cancellous bone mass with no adverse effect on cortical bone.