Thiébaud D, Bigler J M, Renteria S, Pache T, Welti H J, Landry M, Burckhardt P
Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Climacteric. 1998 Sep;1(3):202-10. doi: 10.3109/13697139809085542.
The aim of this study was to investigate the effects of tibolone in the prevention of postmenopausal bone loss over 3 years, and to compare these with the effects of sequential hormone replacement therapy. Forty early postmenopausal women were randomized to a 21-day regimen of conjugated equine estrogens (CEE, Premarin) plus sequential medroxyprogesterone acetate (MPA, Prodafem), or tibolone (Livial) daily. In total, 36 women completed 12 months and were considered for the intent-to-treat analysis, 34 completed 24 months and 23 completed 36 months. Main drop-out reasons were: lost to follow-up (n = 9) and minor side-effects (n = 4). Bone mineral density was measured at baseline and after 6, 12, 24 and 36 months, using dual-energy X-ray absorptiometry at the lumbar spine and the upper femur (neck, trochanter, total hip). In both groups, bone loss was prevented. Treatment with tibolone demonstrated significant increases in bone density at the spine (+4.6%; p < 0.01), at the total hip (+3.2%; p < 0.01) and at the trochanter (+4.5%; p < 0.01), whereas the CEE/MPA group showed a non-significant increase of bone mineral density at the lumbar spine (+2.6%) but no increases at the hip. Between-group differences in bone mineral density changes were significant (p < 0.05) for the total hip and the trochanter at 36 months. This increase of bone mineral density was not accompanied by changes in insulin-like growth factor-I (IGF-I) or insulin-like growth factor binding protein-3 (IGFBP-3) in either group. Osteocalcin, alkaline phosphatase and urinary ratios of hydroxyproline/creatinine and calcium/creatinine significantly decreased in both groups. In conclusion, sequential CEE/MPA prevented cortical and trabecular bone loss, with a transient increase of bone mineral density only during the first 6 months. Tibolone not only prevented cortical and trabecular bone loss, but further increased bone mineral density at the lumbar spine and at the hip throughout the 3 years of treatment, suggesting a sustained positive effect on bone mass.
本研究旨在调查替勃龙预防绝经后3年内骨质流失的效果，并将其与序贯激素替代疗法的效果进行比较。40名绝经早期女性被随机分为两组，一组采用21天的结合马雌激素（CEE，倍美力）加序贯醋酸甲羟孕酮（MPA，普维拉）方案，另一组每日服用替勃龙（利维爱）。共有36名女性完成了12个月的治疗，并纳入意向性分析，34名完成了24个月的治疗，23名完成了36个月的治疗。主要退出原因是：失访（n = 9）和轻微副作用（n = 4）。在基线以及6、12、24和36个月后，使用双能X线吸收法测量腰椎和股骨上段（颈部、大转子、全髋）的骨密度。两组均预防了骨质流失。替勃龙治疗组的脊柱骨密度显著增加（+4.6%；p < 0.01）、全髋骨密度显著增加（+3.2%；p < 0.01）、大转子骨密度显著增加（+4.5%；p < 0.01），而CEE/MPA组腰椎骨矿物质密度有不显著的增加（+2.6%），但髋部无增加。在36个月时，两组间全髋和大转子骨矿物质密度变化的差异具有显著性（p < 0.05）。两组骨矿物质密度的增加均未伴随胰岛素样生长因子-I（IGF-I）或胰岛素样生长因子结合蛋白-3（IGFBP-3）的变化。两组的骨钙素、碱性磷酸酶以及尿羟脯氨酸/肌酐和钙/肌酐比值均显著降低。总之，序贯CEE/MPA预防了皮质骨和小梁骨的流失，仅在最初6个月骨矿物质密度有短暂增加。替勃龙不仅预防了皮质骨和小梁骨的流失，而且在整个3年的治疗期间进一步增加了腰椎和髋部的骨矿物质密度，表明对骨量有持续的积极作用。
