Samuels A, Perry M J, Gibson R, Tobias J H
University of Bristol Division of Medicine, UK.
Calcif Tissue Int. 2001 Sep;69(3):164-70. doi: 10.1007/s002230020026.
Parathyroid hormone (PTH) is thought to increase trabecular bone mass in postmenopausal women by stimulating osteoblast function. A similar action may contribute to estrogen's protective effect on the skeleton, which we have explored in female mice, in which estrogen induces an exaggerated osteogenic response. In the present investigation, we used this model to determine whether an interaction exists between stimulatory effects of PTH and estrogen on osteoblast function in cancellous bone. An initial dose response study was performed where PTH (hPTH, 1-38) was administered to ten-week-old intact female mice by daily sc injection for 28 days, at doses of 1, 10, 100 microg/kg. In a subsequent study, intact female mice were given PTH and/or 17beta-estradiol (E2) 10 and 40 microg/kg/day respectively. Femoral BMD was assessed by peripheral DXA (PIXImus), and histomorphometry was performed to analyse changes in cancellous and cortical bone. PTH caused a small gain in femoral BMD, and increased the extent of periosteal bone formation surfaces, but had relatively little effect on other skeletal parameters when given alone. As previously found, E2 produced a large increase in femoral BMD, stimulated cancellous and endocortical bone formation, but inhibited periosteal bone formation. In mice treated with combination therapy, a greater increase in femoral BMD was observed compared to that following treatment with either agent alone. No differences in indices of cancellous bone were found between animals treated with E2 compared to the combination group. However, cortical area and periosteal bone formation rate were significantly greater in the latter group. We conclude that PTH and E2 exert an additive effect on bone mass in long bones of female mice, possibly reflecting an ability of PTH to oppose E2-induced suppression of periosteal bone formation.
甲状旁腺激素（PTH）被认为可通过刺激成骨细胞功能来增加绝经后女性的小梁骨量。类似的作用可能有助于雌激素对骨骼的保护作用，我们已在雌性小鼠中对此进行了研究，在这些小鼠中雌激素会诱导过度的成骨反应。在本研究中，我们使用该模型来确定PTH和雌激素对松质骨中成骨细胞功能的刺激作用之间是否存在相互作用。进行了一项初始剂量反应研究，将PTH（hPTH，1 - 38）以1、10、100微克/千克的剂量通过每日皮下注射给予10周龄的完整雌性小鼠，持续28天。在随后的研究中，完整雌性小鼠分别给予PTH和/或17β - 雌二醇（E2），剂量分别为10和40微克/千克/天。通过外周双能X线吸收仪（PIXImus）评估股骨骨密度，并进行组织形态计量学分析以分析松质骨和皮质骨的变化。单独给予PTH时，股骨骨密度有小幅增加，并增加了骨膜骨形成表面的范围，但对其他骨骼参数的影响相对较小。如先前发现的那样，E2使股骨骨密度大幅增加，刺激了松质骨和内皮质骨形成，但抑制了骨膜骨形成。在联合治疗的小鼠中，与单独使用任何一种药物治疗相比，观察到股骨骨密度有更大的增加。与联合治疗组相比，接受E2治疗的动物的松质骨指标没有差异。然而，后一组的皮质面积和骨膜骨形成率明显更高。我们得出结论，PTH和E2对雌性小鼠长骨的骨量发挥相加作用，这可能反映了PTH对抗E2诱导的骨膜骨形成抑制的能力。
