HORMONAL REGULATION OF BONE GROWTH IN VIVO

超生理剂量的PTH和1，25（OH）2D 3已被用于尝试 骨质疏松症患者骨丢失的逆转， 主要影响老年人的疾病。 很少有人知道这些 激素调节骨细胞活性以增加骨量。 主要目的 研究钙对骨形成的调节作用 调节完整动物体内的激素。 我们已经在4-6周龄的大鼠上建立了增加骨生长的方案 通过正常钙量的hPTH 1-34给予12天， 矿化和刺激基质形成的高钙剂量的 1，25（OH）2D 3给药18天。 我们已经开发出了测量 骨量（Ca、Hyp、干重）变化股骨远端的变化 骨沉积率、骨形成表面和骨矿化率 大鼠胫骨干骺端和骨干。 为了研究 激素对体内骨形成的影响，我们正在开发一种新的方法， 使用Alzet对成熟家兔股骨进行动脉内激素输注 渗透微型泵 血清钙、磷、碱性磷酸酶、尿素的变化 氮和肌酐和全身生长的相关性进行了测试 骨骼的变化。 将通过单变量和 多元统计分析 这些方法将用于确定合成代谢剂量的早期影响 hPTH 1-34对骨形成和骨吸收的影响;以确定是否增加 骨量增加可能与骨沉积率增加相关，和/或 形成表面;以确定是否对骨骼的合成代谢作用也可以 通过将hPTH局部输注到股动脉循环中诱导， 可以研究局部骨生长因子， 联合PTH和1，25（OH）2D 3对骨生长协同作用可 使用年长的雌性大鼠在动物模型中复制。 我们将继续 我们研究了1，25（OH）2D 3对矿化的损害，以确定 如果矿化不足的基质在不再暴露于 1，25（OH）2D 3，如果是25（OH）D3或24，25（OH）2D 3，则与 1，25（OH）2D 3，将刺激受影响基质的矿化， 抑制1，25（OH）2D 3诱导的反应。

Supraphysiologic doses of PTH and 1,25(OH)2D3 have been used to attempt reversal of bone loss in patients with osteoporosis, a metabolic bone disease primarily affecting older people. Little is known of how these hormones regulate bone cell activity to increase bone mass. The main aim of this research is to study regulation of bone formation by calcium regulating hormones in intact animals. We have established protocols on rats, 4-6 wks old, to increase bone growth by normocalcemic doses of hPTH 1-34 given for 12 days, and to impair mineralization and stimulate matrix formation by hypercalcemic doses of 1,25(OH)2D3 given for 18 days. We have developed methods to measure the changes in bone mass (Ca, Hyp, dry wt.) of distal femurs and the changes in bone appositional rate and forming surfaces and in mineralization rate in rat tibia metaphysis and diaphysis. To study the localized effect of hormones on bone formation in vivo, we are developing a new method of intra-arterial hormone infusion of a femur in mature rabbits, using Alzet osmotic minipumps. Changes in serum Ca, Pi, alkaline phosphatase, urea nitrogen and creatinine and in systemic growth are tested for correlation with the changes in bone. Data will be evaluated by univariate and multivariate statistical analysis. These methods will be used to determine the early effects of anabolic doses of hPTH 1-34 on bone formation and resorption; to determine if the increase in bone mass can be correlated with increased bone apposition rate and/or forming surfaces; to determine if an anabolic effect on bone can also be induced by local infusion of hPTH into the femoral arterial circulation so that local bone growth factors can be investigated and to determine if the synergistic effect of combined PTH and 1,25(OH)2D3 on bone growth can be reproduced in an animal model using older female rats. We will continue our studies of the impairment of mineralization by 1,25(OH)2D3 to determine if the undermineralized matrix will mineralize when no longer exposed to 1,25(OH)2D3 and if 25(OH)D3 or 24,25(OH)2D3, in combination with 1,25(OH)2D3, will either stimulate mineralization of the affected matrix or inhibit the 1,25(OH)2D3-induced response.