ANABOLIC ACTIONS OF PTH IN OSTEOPOROTIC MEN AND WOMEN

描述：(摘自申请)：每天一次的PTH注射增加 骨质疏松症妇女和女性的骨量和强度高于其他治疗方法 男性，但很少治愈骨质疏松症。每天注射甲状旁腺素增加骨骼 吸收和形成，所以把它们和抗吸收药结合起来 药剂应加强对骨量的影响。在其他动物身上进行实验 人类未能证实这一预期，但他们的设计使 解释困难，所以我们正在治疗骨质疏松症的女性和男性 甲状旁腺素、阿伦磷酸钠或两者兼而有之，连续评估骨形成和吸收 多个部位的骨密度。这也测试了甲状旁腺激素是否必须增加骨骼 吸收以增加人类的骨形成和骨密度，或者 双膦酸盐干扰甲状旁腺激素介导的骨形成增加。在 实验结束后，我们将评估sc甲状旁腺素对骨骼和肾脏的反应， 对于12小时的甲状旁腺素静脉输注，停止甲状旁腺素，但不是阿伦磷酸钠，遵循 一年，然后重新评估骨密度和对sc和iv的急性反应。 PTH。这将测试对甲状旁腺素的急性肾脏和早期骨骼反应是否 在不服用甲状旁腺素的情况下每隔12个月恢复一次，以及骨密度是否 甲状旁腺激素停止后增加(因为骨改建减少)或(AS 在动物中)停止PTH后BMD迅速下降，除非抗吸收药物 代理已被管理。然后我们将为每位甲状旁腺功能亢进症患者治疗一年 (不改变任何阿伦磷酸钠治疗)，以测试每日sc甲状旁腺素 对骨转换的影响在不使用甲状旁腺素的情况下每隔12个月恢复一次 管理，随着骨密度的额外增加。在骨质疏松动物和 人类甲状旁腺激素？S的治疗效果受到甲状旁腺素抵抗的限制，即缓慢。 在每天长时间服用甲状旁腺素的过程中发展起来。我们将测试这是否 甲状旁腺素抵抗反映注射的多肽的血液水平下降，延迟 抗甲状旁腺素抗体的产生、甲状旁腺激素受体的下调和 受体介导的腺苷酸环化酶激活(在可及的甲状旁腺激素靶点 器官，肾脏)，还是甲状旁腺激素的减少？S早期对骨形成的影响(The 骨形成的抑制和骨吸收的刺激 甲状旁腺素静脉滴注12小时)。最后，我们将在一套新的 患者甲状旁腺激素抵抗能否通过连续增加 给予甲状旁腺素剂量。

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.