Prestwood K M, Gunness M, Muchmore D B, Lu Y, Wong M, Raisz L G
Center on Aging and Division of Endocrinology and Metabolism, University of Connecticut Health Center, Farmington 06030-5215, USA.
J Clin Endocrinol Metab. 2000 Jun;85(6):2197-202. doi: 10.1210/jcem.85.6.6654.
Raloxifene HCl, a selective estrogen receptor modulator, has been shown to increase bone mineral density (BMD) and decrease biochemical markers of bone turnover in postmenopausal women without stimulatory effects on the breast and uterus. However, it is not known whether the changes in BMD and bone turnover are associated with changes at the tissue level, nor how changes with raloxifene compare with estrogen. In this randomized, double blind study, we evaluated the effects of raloxifene (Evista, 60 mg/day) or conjugated equine estrogens (CEE; Premarin, 0.625 mg/day) on bone architecture, bone turnover, and BMD. Iliac crest bone biopsies were obtained at baseline and at the end of the study after double tetracycline labeling and were analyzed for standard histomorphometric indexes. Serum and urinary biochemical markers of bone turnover were measured at baseline and at 4, 10, 18, and 24 weeks of treatment. Total body, lumbar spine, and hip BMD were measured at baseline and at the end of the study by dual energy x-ray absorptiometry. Activation frequency and bone formation rate/bone volume were significantly decreased from baseline in the CEE, but not in the raloxifene, group. Bone mineralization did not change in either group. Most markers of bone resorption and formation decreased in both groups, but to a greater degree in the CEE group (P < .05). Total body and lumbar spine BMD increased from baseline in both groups, with a greater increase in the CEE group (P < 0.05). Hip BMD significantly increased from baseline in the raloxifene group, but the change was not different from that in the CEE group. These results suggest that raloxifene reduces bone turnover and increases bone density, although to a lesser extent than CEE. Thus, raloxifene is an alternative to CEE for the prevention and treatment of osteoporosis in postmenopausal women.
盐酸雷洛昔芬是一种选择性雌激素受体调节剂，已被证明可增加绝经后妇女的骨矿物质密度（BMD）并降低骨转换的生化指标，且对乳腺和子宫无刺激作用。然而，尚不清楚BMD和骨转换的变化是否与组织水平的变化相关，也不清楚雷洛昔芬的变化与雌激素相比如何。在这项随机双盲研究中，我们评估了雷洛昔芬（易维特，60毫克/天）或结合马雌激素（CEE；倍美力，0.625毫克/天）对骨结构、骨转换和BMD的影响。在基线时以及在双四环素标记后的研究结束时获取髂嵴骨活检样本，并分析标准组织形态计量学指标。在基线时以及治疗的第4、10、18和24周测量骨转换的血清和尿液生化指标。在基线时以及研究结束时通过双能X线吸收法测量全身、腰椎和髋部的BMD。CEE组的激活频率和骨形成率/骨体积较基线时显著降低，但雷洛昔芬组未降低。两组的骨矿化均未改变。两组中大多数骨吸收和形成指标均下降，但CEE组下降程度更大（P<0.05）。两组的全身和腰椎BMD均较基线时增加，CEE组增加幅度更大（P<0.05）。雷洛昔芬组的髋部BMD较基线时显著增加，但变化与CEE组无差异。这些结果表明，雷洛昔芬可降低骨转换并增加骨密度，尽管程度低于CEE。因此，雷洛昔芬是绝经后妇女预防和治疗骨质疏松症的CEE替代药物。
