Effect of Administration of h-PTH and Estrogen in Experimental Osteoporosis

（目的）研究间歇给药h-PTH对去卵巢大鼠（OVX）和链脲佐菌素（STZ）诱导的糖尿病（DM）大鼠骨变化的影响。（材料与方法）选用7 ~ 8月龄Wistar大鼠。双侧卵巢切除术和腹腔注射STZ建立的糖尿病诱导骨质疏松症。对照组为给药组。h-PTH给药剂量分为低剂量（0.6mug/kg）和高剂量（60.0 mug/kg）。从OVX和STZ给药后9周开始，每周皮下注射h-PTH或载体6次，持续4周。腹腔注射盐酸四环素2次，双标。组织学上，h- pth给药大鼠可见许多长而粗的骨小梁，并有广泛的类骨覆盖。在荧光显微镜下，观察到四环素标记表面的范围在h- pth给药的大鼠中明显增加。h- pth给药大鼠抗酒石酸酸性磷酸酶（TRAP）阳性表面降低。b.1的骨矿物质密度和矿物质含量显著降低。对照组和载药组均大于假手术组。pth给药组的数值高于对照组和对照组。骨组织形态学测量显示，STZ组骨体积和骨形成均明显减少。给予h- pth的大鼠骨体积和骨形成相关参数均增加。TRAP阳性面积减少，破骨细胞数量减少。与载药组相比，h-PTH组骨形成明显被激活，骨吸收略有减少，但不明显。因此，骨体积的增加是由于活化骨形成的加速，如类骨表面、矿物质附着率和骨形成率的增加，超过骨吸收率。

(purpose)We investigated the effects of intermittent administration o h-PTH on bone changes in ovariectomized rats (OVX) and streptozotocin (STZ) -induced diabetes mellitus (DM) rats.(Materials and Methods)Wistar rats, 7-8 months old, were used. Osteoporosis was induced by bilateral ovariectomy and diabetes mellitus which was established by an intraperitoneal injection of STZ.Vehicle-administered groups were used by control. Dose of administration of h-PTH is low (0.6mug/kg) or high dose (60.0 mug/kg). h-PTH or vehicle was injected subcutaneously six times a week for 4 weeks from 9 weeks after OVX and STZ administration. Tetracycline hydrochloride was injected intraperitoneally twice for double labeling. Histologically, the h-PTH-administered rats showed many long and thick trabeculae with extensive osteoid covering. By fluorescence microscopy, the extent of tetracycline-labeled surfaces was observed to be markedly increased in the h-PTH-administered rats. Tartrate-resistant acid phosphatase (TRAP) positive surface decreased in the h-PTH-administered rats. Bone mineral density and mineral contents were significantly lower in the b.1.control and vehicle groups than in the sham group. The PTH-administered groups showed the higher values compared with both vehicle and b.l.control groups. In bone histomorphometry, both bone volume and bone formation in the STZ group were marked reduced. The h-PTH-administered rats showed an increase in both bone volume and bone formation-related parameters. While the TRAP positive area and the number of osteoclasts decreased. In the h-PTH groups, bone formation was markedly activated, while bone resorption was slightly but not significantly reduced compared with in the with in the vehicle group. Accordingly the increase in bone volume was due to the acceleration of activated bone formation, as demonstrated by increases in osteoid surface, mineral apposition rate and bone formation rate, over the rate of bone resorption.