Harris S T, Eriksen E F, Davidson M, Ettinger M P, Moffett A H, Baylink D J, Crusan C E, Chines A A
University of California, San Francisco 94117, USA.
J Clin Endocrinol Metab. 2001 May;86(5):1890-7. doi: 10.1210/jcem.86.5.7505.
Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined therapy with bisphosphonate and HRT is likely to be used in clinical practice, and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postmenopausal women received daily treatment with conjugated equine estrogens (0.625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion of the investigator. The primary efficacy end point was the percent change from baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were also assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spine BMD were observed in both treatment groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between the two groups was not statistically significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant (P < 0.05) at the femoral neck and midshaft radius. Both combined risedronate-HRT and HRT-only produced significant decreases in the biochemical markers of bone turnover, with somewhat greater decreases in the combined treatment group. Bone biopsy data showed normal bone structure and normal mineralization with either treatment. Expected decreases in bone turnover were observed and were greater in the combined treatment group (68-79% reduction relative to baseline values, P < 0.005). Overall, combined treatment had a safety profile similar to that of HRT-only, including bone and gastrointestinal safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favorable effect on BMD similar to that of HRT alone at the lumbar spine and slightly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.
激素替代疗法（HRT）和双膦酸盐在绝经后骨质疏松症的预防和治疗中均有效。双膦酸盐与HRT的联合疗法可能会在临床实践中使用，但其疗效和安全性方面的数据有限。这是一项为期1年的双盲、安慰剂对照研究，524名绝经后女性接受每日共轭马雌激素（0.625毫克）单独治疗或与利塞膦酸钠（5毫克）联合治疗。未行子宫切除术的女性由研究者酌情给予醋酸甲羟孕酮（每日或周期性，最高5毫克）。主要疗效终点是1年时腰椎平均骨密度（BMD）相对于基线的变化百分比。还评估了股骨近端和前臂的BMD变化、骨转换标志物以及组织学和组织形态计量学。12个月时，两个治疗组的腰椎BMD均较基线有显著（P < 0.05）增加（仅HRT组为4.6%；利塞膦酸钠 - HRT联合组为5.2%）；两组之间的差异无统计学意义。两种疗法均使12个月时股骨颈（分别为1.8%和2.7%）、股骨粗隆（3.2%和3.7%）、桡骨远端（1.7%和1.6%）以及桡骨干中部（0.4%和0.7%）的BMD显著增加。两组在股骨颈和桡骨干中部的差异具有统计学意义（P < 0.05）。利塞膦酸钠 - HRT联合组和仅HRT组均使骨转换的生化标志物显著降低，联合治疗组的降低幅度略大。骨活检数据显示两种治疗的骨结构和矿化均正常。观察到骨转换如预期降低，联合治疗组降低幅度更大（相对于基线值降低68 - 79%，P < 0.005）。总体而言，联合治疗的安全性与仅HRT组相似，包括骨骼和胃肠道安全性。总之，利塞膦酸钠与HRT联合治疗对BMD的影响在腰椎与仅HRT相似，在股骨颈和桡骨干中部略高于仅HRT且具有显著差异。联合治疗耐受性良好，对骨骼无不良影响。
