Liu C C, Kalu D N
Research Service, American Lake Veterans Administration Medical Center, Tacoma, WA 98493.
J Bone Miner Res. 1990 Sep;5(9):973-82. doi: 10.1002/jbmr.5650050911.
A group of 3-month-old Sprague-Dawley rats were sham operated or ovariectomized and given daily injections of human PTH-(1-34) (8 or 16 micrograms per 100 g body weight) for 5 weeks. At the termination of the study histomorphometric techniques were used to examine changes in cortical and cancellous bone in the diaphysis and proximal metaphysis of the tibia. Ovariectomy resulted in a 50% decrease in cancellous bone that was accompanied by a 41 and 120% increase in osteoclasts and osteoblasts, respectively. In contrast, in the ovariectomized animals treated with PTH, the metaphyseal cancellous bone increased by over 300% to a level in excess of that present in the sham-operated control animals. The increase in cancellous bone induced by PTH was associated with an over 70% increase in osteoblasts and tetracycline-labeled area and an unexpected decrease in trabecular osteoclasts. In the tibial diaphysis PTH also decreased endosteal osteoclasts and at the same time increased osteoblast size and number as well as endosteal and periosteal bone formation; ovariectomy increased only periosteal bone formation. Our findings demonstrate that intermittent administration of PTH prevents ovariectomy-induced bone loss and augments cancellous and cortical bone formation in sexually mature ovariectomized rats. Although the basis of the bone anabolic action of PTH remains elusive, our data indicate that it may involve the uncoupling of bone formation and resorption such that the latter is inhibited as bone formation is enhanced. Our findings are also compatible with the view that intermittent administration of PTH increases bone mass, in part by stimulating the proliferation and differentiation of osteoblast progenitors while inhibiting osteoclast proliferation.
一组3个月大的Sprague-Dawley大鼠接受假手术或卵巢切除，并每天注射人甲状旁腺激素（1-34）（每100克体重8或16微克），持续5周。在研究结束时，使用组织形态计量学技术检查胫骨骨干和近端干骺端皮质骨和松质骨的变化。卵巢切除导致松质骨减少50%，同时破骨细胞和成骨细胞分别增加41%和120%。相比之下，在用甲状旁腺激素治疗的卵巢切除动物中，干骺端松质骨增加超过300%，达到超过假手术对照动物的水平。甲状旁腺激素诱导的松质骨增加与成骨细胞增加超过70%、四环素标记面积增加以及小梁破骨细胞意外减少有关。在胫骨骨干，甲状旁腺激素还减少了骨内膜破骨细胞，同时增加了成骨细胞大小和数量以及骨内膜和骨膜骨形成；卵巢切除仅增加了骨膜骨形成。我们的研究结果表明，间歇性给予甲状旁腺激素可预防卵巢切除诱导的骨质流失，并增强性成熟卵巢切除大鼠的松质骨和皮质骨形成。尽管甲状旁腺激素的骨合成作用的基础仍然难以捉摸，但我们的数据表明，它可能涉及骨形成和吸收的解偶联，使得随着骨形成增强，后者受到抑制。我们的研究结果也与以下观点一致，即间歇性给予甲状旁腺激素可增加骨量，部分原因是刺激成骨祖细胞的增殖和分化，同时抑制破骨细胞增殖。
