Bone H G, Greenspan S L, McKeever C, Bell N, Davidson M, Downs R W, Emkey R, Meunier P J, Miller S S, Mulloy A L, Recker R R, Weiss S R, Heyden N, Musliner T, Suryawanshi S, Yates A J, Lombardi A
Michigan Bone and Mineral Clinic, Detroit, Michigan 48236, USA.
J Clin Endocrinol Metab. 2000 Feb;85(2):720-6. doi: 10.1210/jcem.85.2.6393.
The bisphosphonate alendronate and conjugated equine estrogens are both widely used for the treatment of postmenopausal osteoporosis. Acting by different mechanisms, these two agents decrease bone resorption and thereby increase or preserve bone mineral density (BMD). The comparative and combined effects of these medications have not been rigorously studied. This prospective, double blind, placebo-controlled, randomized clinical trial examined the effects of oral alendronate and conjugated estrogen, in combination and separately, on BMD, biochemical markers of bone turnover, safety, and tolerability in 425 hysterectomized postmenopausal women with low bone mass. In addition, bone biopsy with histomorphometry was performed in a subset of subjects. Treatment included placebo, alendronate (10 mg daily), conjugated equine estrogen (CEE; 0.625 mg daily), or alendronate (10 mg daily) plus CEE (0.625 mg daily) for 2 yr. All of the women received a supplement of 500 mg calcium daily. At 2 yr, placebo-treated patients showed a mean 0.6% loss in lumbar spine BMD, compared with mean increases in women receiving alendronate, CEE, and alendronate plus CEE of 6.0% (P < 0.001 vs. placebo), 6.0% (P < 0.001 vs. placebo), and 8.3% (P < 0.001 vs. placebo and CEE; P = 0.022 vs. alendronate), respectively. The corresponding changes in total proximal femur bone mineral density were +4.0%, +3.4%, +4.7%, and +0.3% for the alendronate, estrogen, alendronate plus estrogen, and placebo groups, respectively. Both alendronate and CEE significantly decreased biochemical markers of bone turnover, specifically urinary N-telopeptide of type I collagen and serum bone-specific alkaline phosphatase. The alendronate plus CEE combination produced slightly greater decreases in these markers than either treatment alone, but the mean absolute values remained within the normal premenopausal range. Alendronate, alone or in combination with CEE, was well tolerated. In the subset of patients who underwent bone biopsies, histomorphometry showed normal bone histology with the expected decrease in bone turnover, which was somewhat more pronounced in the combination group. Thus, alendronate and estrogen produced favorable effects on BMD. Combined use of alendronate and estrogen produced somewhat larger increases in BMD than either agent alone and was well tolerated.
双膦酸盐阿仑膦酸钠和结合马雌激素均广泛用于治疗绝经后骨质疏松症。这两种药物作用机制不同，均可减少骨吸收，从而增加或维持骨矿物质密度（BMD）。但尚未对这两种药物的比较及联合效果进行严格研究。这项前瞻性、双盲、安慰剂对照、随机临床试验，研究了口服阿仑膦酸钠和结合雌激素单独及联合使用，对425名低骨量的绝经后子宫切除女性的BMD、骨转换生化标志物、安全性和耐受性的影响。此外，还对部分受试者进行了骨活检及组织形态计量学分析。治疗方案包括安慰剂、阿仑膦酸钠（每日10毫克）、结合马雌激素（CEE；每日0.625毫克），或阿仑膦酸钠（每日10毫克）加CEE（每日0.625毫克），为期2年。所有女性均每日补充500毫克钙。2年后，安慰剂治疗组患者腰椎BMD平均降低0.6%，而接受阿仑膦酸钠、CEE、阿仑膦酸钠加CEE治疗的女性BMD平均增加，分别为6.0%（与安慰剂相比，P<0.001）、6.0%（与安慰剂相比，P<0.001）和8.3%（与安慰剂和CEE相比，P<0.001；与阿仑膦酸钠相比，P=0.022）。阿仑膦酸钠组、雌激素组、阿仑膦酸钠加雌激素组和安慰剂组股骨近端总骨矿物质密度的相应变化分别为+4.0%、+3.4%、+4.7%和+0.3%。阿仑膦酸钠和CEE均显著降低了骨转换生化标志物，特别是尿I型胶原N-端肽和血清骨特异性碱性磷酸酶。阿仑膦酸钠加CEE联合治疗比单独使用任何一种药物在这些标志物上的降低幅度略大，但平均绝对值仍在绝经前正常范围内。阿仑膦酸钠单独使用或与CEE联合使用耐受性良好。在接受骨活检的患者亚组中，组织形态计量学显示骨组织学正常，骨转换预期降低，联合治疗组更为明显。因此，阿仑膦酸钠和雌激素对BMD产生了有益影响。阿仑膦酸钠和雌激素联合使用比单独使用任何一种药物在BMD上的增加幅度更大，且耐受性良好。
