Tseng Li-Nien, Sheu Wayne Huey-Herng, Ho Esther Shih-Chu, Lan Howard Haw-Chang, Hu Chung-Chieh, Kao Chia-Hung
Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 407, Republic of China.
Metabolism. 2006 Jun;55(6):741-7. doi: 10.1016/j.metabol.2006.01.008.
To evaluate the effect of alendronate combined with hormone replacement therapy (HRT) on postmenopausal osteoporotic Chinese women living in Taiwan, we treated 151 women (age range, 47-70 years; mean, 61 years) with conjugated equine estrogen (0.625 mg), medroxyprogesterone 5 mg, and elemental calcium 500 mg daily with either alendronate 10 mg (n = 79) or placebo (n = 72), and measured their bone mineral density (BMD) at the lumbar spine and hip every 6 months for 3 years. Urine N-telopeptide of type I collagen corrected by concentration of urine creatinine (NTx/Cr) and serum osteocalcin (OC) concentration was also measured at weeks 2, 4, and every 3 months from month 3 for 2 years. Significantly higher percentage increases in BMD at the lumbar spine (P < .0001, 2-way analysis of variance) throughout the 36-month treatment period were found in the alendronate plus HRT group than in the HRT-only group. However, there was no difference in BMD at the femoral neck and trochanter between these 2 groups. Treatment with alendronate plus HRT resulted in a 10.1% increase at the L-spine BMD and a 7.7% increase at the trochanter BMD at the end of the 3-year study period (P < .01, compared with baseline at both sites). A significant decline in urine NTx/Cr was observed at week 4 in the alendronate plus HRT group, whereas in the HRT-only group, a significant decline in urine NTx/Cr occurred at month 9. By the end of 24 months, urine NTx/Cr decreased by 49.7% in the alendronate plus HRT group (P = .001 compared with a 20.4% increase in the HRT group). A significant decline in serum OC level occurred at month 3 in the alendronate plus HRT group, whereas a similar decline was observed at month 6 in the HRT-only group. By the end of 24 months, serum OC decreased by 52.2% in the alendronate plus HRT group (P < .001 compared with a 1.5% increase in the HRT-only group). Subjects treated with alendronate plus HRT had a significantly greater percentage decrease in urine NTx/Cr (P = .0001) and serum OC (P = .0007) than subjects treated with HRT only throughout the 24-month treatment period by 2-way analysis of variance comparison. There was no difference in upper gastrointestinal or drug-related side effects between groups. In conclusion, our data suggest that the use of alendronate combined with HRT for 3 years was well tolerated and it significantly increased BMD at the L-spine and hip in postmenopausal Chinese women with osteoporosis. This regimen is safe and can be used in subjects who have no satisfactory response to a single agent or who have very low BMD with multiple risks. However, this study does not indicate whether HRT plus alendronate has any greater effect on BMD than alendronate alone.
为评估阿仑膦酸钠联合激素替代疗法（HRT）对居住在台湾的绝经后骨质疏松中国女性的疗效，我们对151名女性（年龄范围47 - 70岁，平均61岁）进行治疗，她们每日服用结合马雌激素（0.625毫克）、甲羟孕酮5毫克和元素钙500毫克，其中79人加用阿仑膦酸钠10毫克，72人服用安慰剂。在3年时间里，每6个月测量她们腰椎和髋部的骨密度（BMD）。在第2周、第4周以及从第3个月开始每3个月测量一次尿I型胶原N - 端肽经尿肌酐浓度校正值（NTx/Cr）和血清骨钙素（OC）浓度，持续2年。在整个36个月的治疗期内，阿仑膦酸钠加HRT组腰椎BMD的百分比增加值显著高于单纯HRT组（P <.０００１，双向方差分析）。然而，两组在股骨颈和大转子处的BMD无差异。在3年研究期结束时，阿仑膦酸钠加HRT治疗使腰椎BMD增加10.1%，大转子BMD增加7.7%（与两个部位的基线相比，P <.０１）。阿仑膦酸钠加HRT组在第4周时尿NTx/Cr显著下降，而单纯HRT组在第9个月时尿NTx/Cr显著下降。到24个月结束时，阿仑膦酸钠加HRT组尿NTx/Cr下降了49.7%（与HRT组增加20.4%相比，P =.００１）。阿仑膦酸钠加HRT组在第3个月时血清OC水平显著下降，而单纯HRT组在第6个月时出现类似下降。到24个月结束时，阿仑膦酸钠加HRT组血清OC下降了52.2%（与单纯HRT组增加1.5%相比，P <.００１）。通过双向方差分析比较，在整个24个月的治疗期内，阿仑膦酸钠加HRT治疗的受试者尿NTx/Cr（P =.０００１）和血清OC（P =.０００７）的下降百分比显著大于单纯HRT治疗的受试者。两组在上消化道或药物相关副作用方面无差异。总之,我们的数据表明，阿仑膦酸钠联合HRT使用3年耐受性良好，且能显著增加绝经后骨质疏松中国女性腰椎和髋部的BMD。该方案安全，可用于对单一药物无满意反应或骨密度极低且存在多种风险的受试者。然而，本研究并未表明HRT加阿仑膦酸钠对BMD的影响是否大于单独使用阿仑膦酸钠。
