Okimoto N, Tsurukami H, Okazaki Y, Nishida S, Sakai A, Ohnishi H, Hori M, Yasukawa K, Nakamura T
Department of Orthopedic Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Bone. 1998 May;22(5):523-31. doi: 10.1016/s8756-3282(98)00024-6.
One hundred fifteen Wistar rats, 7 months of age, were ovariectomized (ovx) or sham-operated to evaluate the effects of a weekly injection of human parathyroid hormone (hPTH) and withdrawal on the bone mass, strength, and turnover in mature ovariectomized rats. At 3 months, ovx rats were given a weekly injection of hPTH(1-34) at the respective doses of 0 (vehicle), 10, and 90 microg/kg body weight (BW) for 3 months. Then, hPTH-treated rats were divided into two groups each: continuously treated groups, and the groups treated with vehicle only for another 3 months. Weekly hPTH injections at doses of 10 or 90 microg/kg BW maintained the lumbar BMD values and increased the values of the femoral cortical bone, increasing the bone formation rates in the trabecular, endocortical, and periosteal envelopes. Trabecular osteoclasts were increased in the 90 microg/kg dose group. Trabecular bone surface relative to the volume was decreased by hPTH. The compressive load of the lumbar bone and the bending moment of the midfemur were increased. The lumbar compressive load values, corrected for BMD and volume, and the moment of inertia of the midfemur were also increased. The intracortical porosity values were not increased by the treatment. After withdrawal of hPTH treatment, the BMD values in both the lumbar and the midfemur were reduced to ovx control levels. The bone mass stimulated by the 90 microg/kg dose was reduced faster than that by the 10 microg/kg dose. However, the parameters of bone strength were still larger than those of the ovx controls after cessation of the hPTH treatment. Thus, a weekly hPTH injection effectively stimulated the bone formation in both the trabecular and cortical bone, leading to positive effects on mass and structure of the bone. These data suggest the possibility of benefits of both a lower frequency of hPTH injections as well as high-frequency injections for human osteoporotics.
115只7月龄的Wistar大鼠接受卵巢切除术（ovx）或假手术，以评估每周注射人甲状旁腺激素（hPTH）及其撤药对成熟去卵巢大鼠骨量、骨强度和骨转换的影响。3个月时，对ovx大鼠分别按0（赋形剂）、10和90μg/kg体重（BW）的剂量每周注射hPTH(1-34)，持续3个月。然后，将接受hPTH治疗的大鼠每组再分为两组：持续治疗组和仅用赋形剂再治疗3个月的组。每周按10或90μg/kg BW的剂量注射hPTH可维持腰椎骨密度值，并增加股骨皮质骨的值，提高小梁、骨内膜和骨膜包膜的骨形成率。90μg/kg剂量组的小梁破骨细胞增加。hPTH使相对于体积的小梁骨表面减少。腰椎骨的压缩负荷和股骨中段的弯矩增加。校正骨密度和体积后的腰椎压缩负荷值以及股骨中段的转动惯量也增加。治疗未增加皮质内孔隙率值。撤去hPTH治疗后，腰椎和股骨中段的骨密度值均降至ovx对照组水平。90μg/kg剂量刺激的骨量比10μg/kg剂量的骨量减少得更快。然而，停止hPTH治疗后，骨强度参数仍高于ovx对照组。因此，每周注射hPTH可有效刺激小梁骨和皮质骨的骨形成，对骨量和骨结构产生积极影响。这些数据表明，较低频率和较高频率注射hPTH对人类骨质疏松症患者均可能有益。
