Collette J, Viethel P, Dethor M, Chevallier T, Micheletti M C, Foidart J M, Reginster J Y
Unité d'exploration du métabolisme osseux, CHU Brull, 45, quai Godefroid-Kurth, 4020 Liège, Belgique.
Gynecol Obstet Fertil. 2003 May;31(5):434-41. doi: 10.1016/s1297-9589(03)00118-8.
To compare changes in biochemical markers of bone turnover in postmenopausal women who received sequential discontinuous hormone replacement therapy (HRT) with either transdermal 17 beta-estradiol gel (group 1) or oral equine sulfoconjugated estrogen (group 2), plus nomegestrol acetate.
Prospective, open, randomized, controlled trial, conducted on 3 parallel groups of 106 postmenopausal women. All treated groups received estrogen therapy for 25 consecutive days every month. The estrogen used was either 1.5 mg/day of transdermal 17 beta-estradiol gel (group 1) [N = 42, average age (AA) = 51.6 years, average duration of menopause (ADM = 21.5 months)], or 0.625 mg/day of oral equine sulfoconjugated estrogen (group 2) [N = 39, AA = 51.3 years, ADM = 16.8 months]. In all cases nomegestrol acetate 5 mg/day was added for 12 consecutive days every month. The control group comprised 25 patients, [AA = 53.4 years, ADM = 33.7 months]. Two bone resorption markers: urinary cross-linked N-telopeptide and C-telopeptide of type I collagen (U-NTX/Cr, U-CTX/Cr), and a bone formation marker: serum bone specific alkaline phosphatase activity were measured before and 6 months after treatment start.
Significant decreases from baseline values were observed for the 3 biochemical markers in both treated groups compared with control (P < 0.001). There were no significant differences in changes between the 2 treated groups for the 3 biochemical markers. The mean percentage change in the 3 biochemical markers was: from -9.3 to -45.5% in group 1, from -20.5 to -39% in group 2, and from -3.3 to 2% in control group. In group 1, the mean percentage decreases in U-CTX reached optimal threshold of bone turnover change (-45%) which is considered by the International Osteoporosis Foundation as clinically relevant because it predicts an increase in BMD greater than 3% when treatment is maintained over a long term.
Both treated groups induced a significant comparable decrease of bone turnover markers after 6 months of intervention, compared with control. The group treated with cyclic administration of transdermal 17 beta-estradiol (1.5 mg/day) and nomegestrol acetate (5 mg/day) showed a bone resorption markers decrease corresponding to the threshold of clinical relevance described in the international literature and predictive of positive BMD response in long term.
比较接受序贯间断激素替代疗法（HRT）的绝经后女性，使用经皮17β-雌二醇凝胶（第1组）或口服马结合雌激素硫酸酯（第2组）加醋酸诺美孕酮后骨转换生化标志物的变化。
对3组各106名绝经后女性进行前瞻性、开放性、随机对照试验。所有治疗组每月连续25天接受雌激素治疗。使用的雌激素为每日1.5mg经皮17β-雌二醇凝胶（第1组）[N = 42，平均年龄（AA）= 51.6岁，平均绝经持续时间（ADM）= 21.5个月]，或每日0.625mg口服马结合雌激素硫酸酯（第2组）[N = 39，AA = 51.3岁，ADM = 16.8个月]。所有病例每月连续12天加用每日5mg醋酸诺美孕酮。对照组包括25名患者，[AA = 53.4岁，ADM = 33.7个月]。在治疗开始前及开始后6个月测量两种骨吸收标志物：尿I型胶原交联N-端肽和C-端肽（U-NTX/Cr，U-CTX/Cr），以及一种骨形成标志物：血清骨特异性碱性磷酸酶活性。
与对照组相比，两个治疗组的3种生化标志物均较基线值显著降低（P < 0.001）。两个治疗组的3种生化标志物变化无显著差异。3种生化标志物的平均百分比变化为：第1组从-9.3%至-45.5%，第2组从-20.5%至-39%，对照组从-3.3%至2%。在第1组中，U-CTX的平均百分比降低达到了骨转换变化的最佳阈值（-45%），国际骨质疏松基金会认为这具有临床相关性，因为长期维持治疗时它可预测骨密度增加大于3%。
与对照组相比，两个治疗组在干预6个月后均使骨转换标志物显著且相当程度地降低。经皮17β-雌二醇（每日1.5mg）和醋酸诺美孕酮（每日5mg）周期性给药治疗的组，骨吸收标志物降低至国际文献中描述的临床相关阈值，且可预测长期骨密度呈阳性反应。
