ANABOLIC ACTIONS OF PTH IN OSTEOPOROTIC MEN AND WOMEN

描述：（摘自应用程序）：每日一次PTH注射增加 骨质量和强度高于其他治疗方法， 但很少治愈骨质疏松症。每天注射甲状旁腺素增加骨骼 吸收以及形成，所以将它们与抗吸收剂结合， 应加强对骨量的影响。其他动物实验 人类未能证实这一预期，但他们的设计使 很难解释，所以我们正在治疗患有糖尿病的女性和男性， 甲状旁腺激素、阿仑膦酸钠或两者，连续评估骨形成和吸收， 多个部位的BMD。这也测试了PTH是否必须增加骨骼 骨吸收，以增加骨形成和骨密度在人类，或是否 二膦酸盐干扰PTH介导的骨形成增加。在 本实验结束时，我们将评估骨骼和肾脏对皮下PTH的反应， 和12小时静脉PTH输注，停止PTH，但不阿仑膦酸钠，按照 患者一年，然后重新评估骨密度和对sc和iv的急性反应 PTH。这将测试是否急性肾脏和早期骨骼对PTH的反应， 恢复了12个月的时间间隔没有PTH管理，以及是否BMD 停止PTH后增加（因为骨重建减少）或是否（作为 在动物中）停止PTH后，BMD迅速下降，除非抗吸收剂 代理人被管理。然后我们会用PTH治疗每一个病人一年 (not改变任何阿仑膦酸钠治疗），以测试是否每天皮下PTH的 在没有PTH的情况下，对骨转换的影响在12个月的时间间隔内恢复 给药后，BMD增加。在哺乳动物中， 人类PTH的治疗效果受到PTH抵抗的限制， 在延长每日PTH给药期间发生。我们将测试这是否 PTH抵抗反映了注射肽的血液水平降低，延迟 抗PTH抗体的产生，PTH受体的下调， 受体介导的腺苷酸环化酶活化（在可接近的PTH靶点中 器官，肾脏），或减少PTH？对骨形成的早期影响（ 骨形成的抑制和骨吸收的刺激， 12-小时静脉内PTH输注）。最后，我们将在一组新的 患者PTH抵抗是否可以通过连续增加 给予PTH剂量。

DESCRIPTION: (Taken from the application): Once-daily PTH injections increase bone mass and strength more than other treatments in osteoporotic women and men, but rarely cure osteoporosis. Daily PTH injections increase bone resorption as well as formation, so combining them with an anti-resorptive agent should enhance the effect on bone mass. Experiments elsewhere in animals and humans failed to confirm this expectation, but their design made interpretation difficult, so we are treating osteoporotic women and men with PTH, alendronate, or both, serially assessing bone formation and resorption and BMD of multiple sites. This also tests whether PTH must increase bone resorption in order to increase bone formation and BMD in humans, or whether a bisphosphonate interferes with PTH-mediated increases in bone formation. At the end of this experiment we will evaluate skeletal and renal responses to sc PTH, and to a 12-hour iv PTH infusion, stop PTH but not alendronate, follow the patients for a year, and then re-evaluate BMD and acute responses to sc and iv PTH. This will test whether acute renal and early skeletal responses to PTH are restored by a 12 month interval without PTH administration, and whether BMD increases after stopping PTH (because bone remodeling decreases) or whether (as in animals) BMD decreases rapidly after stopping PTH, unless an anti-resorptive agent is administered. We will then treat every patient with PTH for a year (not changing any alendronate treatment), to test whether daily sc PTH's effects on bone turnover are restored by a 12 month interval without PTH administration, with additional increases in BMD. In osteoporotic animals and humans, PTH?s therapeutic effects are limited by a PTH resistance that slowly develops during prolonged daily PTH administration. We will test whether this PTH resistance reflects decreased blood levels of the injected peptide, delayed development of anti-PTH antibodies, down-regulation of PTH-receptors and receptor-mediated activation of adenylate cyclase (in an accessible PTH target organ, the kidney), or a decrease in PTH?s early effects on bone formation (the suppression of bone formation and stimulation of bone resorption seen during a 12-hour intravenous PTH infusion). Finally, we will test in a new set of patients whether PTH resistance can be overcome by serial increases in the administered PTH dose.