BONE FORMATION/RESORPTION COUPLING AND OSTEOPOROSIS

每日皮下注射甲状旁腺激素（PTH）或其 生物活性氨基末端片段，增加骨形成 戏剧性地，和“治愈”雌激素缺乏症小梁和皮质 大鼠骨质疏松症。甲状旁腺激素对骨形成的影响也是戏剧性的 但它对人体骨量的影响要小得多， 大鼠：皮质骨没有增加， 骨小梁不足以逆转慢性炎症的影响。 完全缺乏雌激素甲状旁腺素的合成代谢作用 在大鼠中，骨小梁和皮质骨呈线性剂量依赖性。PTH 用于人类的剂量远低于用于大鼠的剂量，因为PTH 对人体有更大的高钙作用。我们相信这个结果 从骨骼钙动员和骨- PTH的再吸收作用。通过给予抗吸收药物， 我们相信，通过治疗结核病， 增强甲状旁腺激素对骨骼的合成代谢作用实验性 动物，这种策略有可变的成功，随着物种或 抗骨吸收疗法为了测试抗吸收剂是否 增强PTH增加骨质疏松症患者骨量的能力 绝经后的妇女，我们会给他们外源性甲状旁腺激素， 长期连续测量他们的脊柱，臀部，手臂， 和全身用双能X线吸收法作为PTH 或者继续给药，补充阿仑膦酸盐， 改用阿仑膦酸钠或停药这样的实验提供了一个 研究骨吸收-形成偶联的不寻常机会， 人类新合成的生长因子的相对重要性，与 通过骨吸收局部释放的预形成生长因子转化为PTH 对人体骨骼合成代谢的影响尚不清楚。如果解放 预先形成的生长因子是不必要的骨骼合成代谢 我们假设PTH对人体的影响，然后伴随治疗 阻止骨吸收的药物不会降低PTH的能力， 刺激骨骼形成我们计划在年测试这一假设 绝经后骨质疏松症的妇女，用PTH治疗，直到他们 骨吸收增加，然后加入阿仑膦酸钠， 血清和尿I型胶原分泌指标的动态变化 和降解，以及示踪剂放射性的骨骼保留， 它们升高的骨吸收被抑制到控制水平， 添加阿仑膦酸钠。我们将进行平行观察， 适当控制患者。

Daily subcutaneous injections of parathyroid hormone (PTH), or its biologically-active amino-terminal fragments, increase bone formation dramatically, and "cure" estrogen-deficiency trabecular and cortical osteoporosis in rats. PTH's effects on bone formation are also dramatic in humans but its effects on bone mass are much smaller in humans than in rats: there is no increase in cortical bone and the increase in trabecular bone is not large enough to reverse the effects of chronic estrogen deficiency completely. The anabolic effects of PTH on trabecular and cortical bone are linearly dose-dependent in rats. PTH doses used in humans are much lower than those used in rats, because PTH has a greater hypercalcemic effect in humans. We believe this results from a species difference in the skeletal calcium-mobilizing and bone- resorbing effects of PTH. By administering an anti-resorptive drug to PTH-treated osteoporotic humans, we believe it will be possible to augment PTH's anabolic effects on their skeleton. In experimental animals, this strategy had variable success, varying with the species or the anti-resorptive regimen. To test whether an anti-resorptive agent enhances PTH's ability to increase bone mass in osteopenic postmenopausal women, we will give them exogenous parathyroid hormone chronically and serially measure their bone mass in the spine, hip, arm, and total body with dual-energy x-ray absorptiometry as PTH administration is either continued, supplemented with alendronate, switched to alendronate, or withdrawn. Such an experiment provides an unusual opportunity to investigate bone resorption-formation coupling in humans. The relative importance of newly-synthesized growth factors, vs. pre-formed growth factors released locally by bone resorption, to PTH's skeletal anabolic effects in humans is unclear. If the liberation of pre-formed growth factors is unnecessary for the skeletal anabolic effect of PTH in humans, as we hypothesize, then concomitant treatment with an agent that blocks bone resorption will not reduce PTH's ability to stimulate bone formation. We plan to test this hypothesis in postmenopausaI osteoporotic women by treating them with PTH until their bone resorption is increased and then adding alendronate and following serial changes in serum and urine indices of type I collagen secretion and degradation, and skeletal retention of tracer radioactivity, as their elevated bone resorption is suppressed to control levels by the addition of alendronate. We will make parallel observations in appropriate control patients.