Register T C, Jayo M J, Jerome C P
Department of Comparative Medicine, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157-1040, USA.
Osteoporos Int. 1997;7(4):348-53. doi: 10.1007/BF01623776.
The purpose of the present study was to determine the effects of oral contraceptive therapy on bone density and serum markers of bone metabolism in a prospective, longitudinal study of young adult female cynomolgus monkeys. Two hundred and seven intact cynomolgus monkeys were randomized to two groups, and fed an atherogenic diet containing either no drug (Control) or a triphasic oral contraceptive regimen (Contraceptive). Measurements of bone density were carried out by dual-energy X-ray absorptiometry at 10-month intervals (0, 10, and 20 months) and serum bone biomarkers were determined at 5-month intervals over the 20-month time course. No significant differences in these variables were observed prior to treatment. Both groups of animals gained bone mineral during the study, indicating that peak bone mass had not been reached at baseline. Contraceptive-treated animals gained less spinal (lumbar vertebrae 2-4) bone mineral content and density and less whole-body bone mineral content than Controls over the course of the study. Significant depressive effects of contraceptive treatment on gains in BMC and BMD were observed during each 10-month interval of the study. Bone metabolism was inhibited in the Contraceptive group, as reflected by marked reductions (approximately 40%) in serum osteocalcin and alkaline phosphatase levels along with moderate reductions in serum acid phosphatase and calcium. The results suggest that triphasic oral contraceptive treatment of young adult female monkeys that have not reached peak bone mass inhibits net bone accretion and/or growth by reducing bone metabolism. Thus, prolonged continuous oral contraceptive use in skeletally immature females may lead to a lower peak bone mass--an effect which could increase the risk of fractures in later life.
本研究的目的是通过对年轻成年雌性食蟹猴进行前瞻性纵向研究，确定口服避孕药治疗对骨密度和骨代谢血清标志物的影响。207只未生育的食蟹猴被随机分为两组，分别喂食不含药物的致动脉粥样化饮食（对照组）或三相口服避孕药方案（避孕药组）。每隔10个月（0、10和20个月）通过双能X线吸收法测量骨密度，并在20个月的时间内每隔5个月测定血清骨生物标志物。治疗前这些变量未观察到显著差异。两组动物在研究期间均获得了骨矿物质，表明基线时未达到峰值骨量。在研究过程中，接受避孕药治疗的动物腰椎（第2 - 4腰椎）的骨矿物质含量和密度以及全身骨矿物质含量的增加均少于对照组。在研究的每个10个月间隔期间，均观察到避孕药治疗对骨矿物质含量（BMC）和骨密度（BMD）增加有显著的抑制作用。避孕药组的骨代谢受到抑制，表现为血清骨钙素和碱性磷酸酶水平显著降低（约40%），同时血清酸性磷酸酶和钙也有中度降低。结果表明，对尚未达到峰值骨量的年轻成年雌性猴子进行三相口服避孕药治疗会通过降低骨代谢来抑制净骨量增加和/或生长。因此，在骨骼未成熟的女性中长时间持续使用口服避孕药可能会导致峰值骨量降低，这种影响可能会增加晚年骨折的风险。
