Johnell Olof, Scheele Wim H, Lu Yili, Reginster Jean-Yves, Need Allan G, Seeman Ego
Department of Orthopaedics, Universiteitssjukhuset MAS, Malmø, Sweden.
J Clin Endocrinol Metab. 2002 Mar;87(3):985-92. doi: 10.1210/jcem.87.3.8325.
Both raloxifene (RLX) and alendronate (ALN) can treat and prevent new vertebral fractures, increase bone mineral density (BMD), and decrease biochemical markers of bone turnover in postmenopausal women with osteoporosis. This phase 3, randomized, double-blind 1-yr study assessed the effects of combined RLX and ALN in 331 postmenopausal women with osteoporosis (femoral neck BMD T-score, less than -2). Women (aged < or = 75 yr; > or = 2 yr since their last menstrual period) received placebo, RLX 60 mg/d, ALN 10 mg/d, or RLX 60 mg/d and ALN 10 mg/d combined. At baseline, 6 and 12 months, BMD was measured by dual x-ray absorptiometry. The bone turnover markers serum osteocalcin, bone-specific alkaline phosphatase, and urinary N- and C-telopeptide corrected for creatinine were measured. The effects of RLX and ALN were considered to be independent and additive if the interaction effect was not statistically significant (P > 0.10) in a two-way ANOVA model. All changes in BMD and bone markers at 12 months were different between placebo and each of the active treatment groups, and between the RLX and RLX+ALN groups (P < 0.05). On average, lumbar spine BMD increased by 2.1, 4.3, and 5.3% from baseline with RLX, ALN, and RLX+ALN, respectively. The increase in femoral neck BMD in the RLX+ALN group (3.7%) was greater than the 2.7 and 1.7% increases in the ALN (P = 0.02) and RLX (P < 0.001) groups, respectively. The changes from baseline to 12 months in bone markers ranged from 7.1 to -16.0% with placebo, -23.8 to -46.5% with RLX, -42.3 to -74.2% with ALN, and -54.1 to -81.0% in the RLX+ALN group. RLX and ALN increased lumbar spine and femoral neck BMD, and decreased osteocalcin and C-telopeptide corrected for creatinine in an additive and independent manner, because the interaction effects were not significant. Although the ALN group had changes in BMD and bone markers that were approximately twice the magnitude as in the RLX group, it is not known how well these changes correlate to the clinical outcome of fracture. RLX+ALN reduced bone turnover more than either drug alone, resulting in greater BMD increment, but whether this difference reflects better fracture risk reduction was not assessed in this study.
雷洛昔芬（RLX）和阿仑膦酸盐（ALN）均可治疗和预防绝经后骨质疏松症女性的新发椎体骨折，增加骨矿物质密度（BMD），并降低骨转换的生化标志物水平。这项为期1年的3期随机双盲研究评估了联合使用RLX和ALN对331名绝经后骨质疏松症女性（股骨颈BMD T值小于-2）的影响。女性（年龄≤75岁；自末次月经以来≥2年）接受安慰剂、60 mg/d的RLX、10 mg/d的ALN或联合使用60 mg/d的RLX和10 mg/d的ALN。在基线、6个月和12个月时，通过双能X线吸收法测量BMD。测量骨转换标志物血清骨钙素、骨特异性碱性磷酸酶以及校正肌酐后的尿N-端和C-端肽。如果在双向方差分析模型中交互作用效应无统计学意义（P>0.10），则认为RLX和ALN的作用是独立且相加的。12个月时，安慰剂组与各活性治疗组之间以及RLX组与RLX+ALN组之间，BMD和骨标志物的所有变化均存在差异（P<0.05）。平均而言，RLX、ALN和RLX+ALN组的腰椎BMD相对于基线分别增加了2.1%、4.3%和5.3%。RLX+ALN组股骨颈BMD的增加（3.7%）分别大于ALN组（2.7%）和RLX组（1.7%）（P=0.02和P<0.001）。从基线到12个月，安慰剂组骨标志物的变化范围为7.1%至-16.0%，RLX组为-23.8%至-46.5%，ALN组为-42.3%至-74.2%，RLX+ALN组为-54.1%至-81.0%。由于交互作用不显著，RLX和ALN以相加且独立的方式增加了腰椎和股骨颈的BMD，并降低了骨钙素和校正肌酐后的C-端肽水平。虽然ALN组BMD和骨标志物的变化幅度约为RLX组的两倍，但尚不清楚这些变化与骨折临床结局的关联程度。RLX+ALN比单独使用任何一种药物都更能降低骨转换，导致BMD增加幅度更大，但本研究未评估这种差异是否反映了更好的骨折风险降低效果。
