Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis.
Dissociation of bone formation from resorption during 2-week treatment with human parathyroid hormone-related peptide-(1-36) in humans: potential as an anabolic therapy for osteoporosis.
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DOI：
10.1210/jcem.83.8.5047
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发表时间：
1998-08
期刊：
影响因子：
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通讯作者：
H. Plotkin;C. Gundberg;M. Mitnick;A. F. Stewart;A. F. Stewart
中科院分区：
文献类型：
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作者：
H. Plotkin;C. Gundberg;M. Mitnick;A. F. Stewart;A. F. Stewart
甲状旁腺素给药增加啮齿动物和人类的骨量。PTH相关蛋白（PTHrP）与骨骼PTH受体结合并通过其发出信号。PTHrP每日一次给药可增加大鼠的骨矿物质含量。在人类中，PTHrP-（1-36）与PTH-（1-34）是等效的，并且当皮下施用时是有活性的。这些发现表明PTHrP可能在骨质疏松症的治疗中具有治疗益处。在这项研究中，13名绝经后雌激素缺乏的妇女每天接受一次皮下注射。PTHrP-（1-36）的剂量持续14天，以确定PTHrP-（1-36）1）是否可以以不改变全身矿物质稳态但增加骨转换标志物的剂量给予;和2）是否耐受而无副作用。每日皮下注射PTHrP-（1-36）给药不会导致血清钙或磷浓度、钙排泄分数、肾小管最大磷浓度、钙排泄分数或血浆1，25-二羟维生素D浓度发生显着变化。肾源性cAMP和内源性PTH-（1-84）下降。重要的是，骨形成标志物呈上升趋势，如接受PTH治疗的受试者所报告。与PTH治疗受试者的结果形成鲜明对比，在PTHrP治疗受试者中，骨吸收标记物以高度显著的方式下降。这些观察结果表明，PTHrP-（1-36）处理使骨形成与再吸收分离，有利于骨形成。如果这种解偶联持续较长时间，则PTHrP-（1-36）可能是骨质疏松症的有效合成代谢治疗剂。
PTH administration increases bone mass in rodents and in humans. PTH-related protein (PTHrP) binds to and signals via the skeletal PTH receptor. Administration of PTHrP on a once daily basis increases bone mineral content in rats. In humans, PTHrP-(1-36) is equipotent to PTH-(1-34) and is active when administered s.c. These findings suggest that PTHrP might have therapeutic benefit in the treatment of osteoporosis. In this study, 13 postmenopausal estrogen-deficient women received a single daily s.c. dose of PTHrP-(1-36) for a 14-day period to determine whether PTHrP-(1-36) 1) could be given in doses that do not alter systemic mineral homeostasis, but increase markers of bone turnover; and 2) is tolerated without adverse effects. Daily s.c. PTHrP-(1-36) administration caused no significant changes in serum calcium or phosphorus concentrations, fractional calcium excretion, the tubular maximum for phosphorus, fractional calcium excretion, or plasma 1,25-dihydroxyvitamin D concentrations. Nephrogenous cAMP and endogenous PTH-(1-84) declined. Importantly, markers of bone formation trended upward, as reported in subjects treated with PTH. In marked contrast to findings in PTH-treated subjects, in PTHrP-treated subjects, markers of bone resorption declined in a highly significant fashion. These observations indicate that PTHrP-(1-36) treatment uncouples bone formation from resorption, in favor of formation. This uncoupling, if it were to continue over the longer term, would predict that PTHrP-(1-36) might be a potent anabolic therapeutic agent for osteoporosis.