Ejersted C, Oxlund H, Andreassen T T
Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C. Denmark.
Calcif Tissue Int. 1998 Apr;62(4):316-22. doi: 10.1007/s002239900438.
This study was designed to determine the fate of new parathyroid hormone (PTH)-induced cortical bone after withdrawal of PTH treatment, and to evaluate whether subsequent treatment with a bisphosphonate would influence this. Six groups of 21-month-old rats were used: a baseline group killed at the beginning of the experiment, three groups injected with human PTH (1-34) (62 mug/kg) daily for 8 weeks (day 1-56), then one group was killed and the other two groups were injected for another 8 weeks (day 57-112) with either saline or bisphosphonate (risedronate 5 mug/kg twice a week). Two control groups were injected with vehicle for the first 8 weeks, then one group was killed and the other group injected with saline the next 8 weeks. All animals were labeled with tetracycline and calcein on day 35 and day 49 of the experiment, respectively. PTH increased periosteal (35%) and in particular endosteal mineralizing surfaces (188%), mineral appositional rates, and bone formation rates at the femur diaphysis, leading to an increase in cortical cross-sectional area of 31%. Withdrawal of PTH induced a fast and pronounced endosteal bone resorption whereas risedronate prevented this resorption. No differences were seen in apparent density of dry defatted bone and ash among the groups. PTH increased the mechanical strength of the femur diaphysis; ultimate load increased by 64% and ultimate stress by 25%. A pronounced decrease in mechanical strength and competence was found after withdrawal of PTH: ultimate load decreased by 31% and ultimate stress by 21%. Risedronate, however, prevented this decrease in mechanical strength and competence in these 2-year-old rats.
本研究旨在确定甲状旁腺激素（PTH）治疗停止后新形成的皮质骨的转归，并评估随后使用双膦酸盐治疗是否会对此产生影响。使用了六组21月龄大鼠：一组为在实验开始时处死的基线组，三组每天注射人PTH（1-34）（62μg/kg），持续8周（第1天至56天），然后一组处死，另外两组再注射8周（第57天至112天），分别注射生理盐水或双膦酸盐（利塞膦酸盐5μg/kg，每周两次）。两个对照组在前8周注射赋形剂，然后一组处死，另一组在接下来的8周注射生理盐水。在实验的第35天和第49天，所有动物分别用四环素和钙黄绿素进行标记。PTH增加了股骨骨干的骨膜（35%），特别是内膜矿化表面（188%）、矿物质沉积率和骨形成率，导致皮质横截面积增加31%。停止PTH治疗后诱导了快速且明显的内膜骨吸收，而利塞膦酸盐可防止这种吸收。各组之间脱脂干骨和灰分的表观密度未见差异。PTH增加了股骨骨干的机械强度；极限载荷增加了64%，极限应力增加了25%。停止PTH治疗后发现机械强度和性能明显下降：极限载荷下降了31%，极限应力下降了21%。然而，利塞膦酸盐可防止这些2岁大鼠的机械强度和性能下降。
