Wimalawansa S J
Department of Medicine (Endocrinology), Royal Postgraduate Medical School, London, United Kingdom.
Am J Med. 1995 Jul;99(1):36-42. doi: 10.1016/s0002-9343(99)80102-8.
Administration of estrogen or etidronate has been shown to increase bone mineral density in postmenopausal women. This 4-year, prospective, randomized study was carried out to monitor any added beneficial effect on bone mineral density when hormone-replacement therapy (HRT) was combined with etidronate.
Fifty-eight early postmenopausal women attending metabolic bone disease outpatient clinics were randomly allocated into four treatment groups and monitored for up to 4 years. All patients received 1.0 g/d of elemental calcium. In addition, group 1 received percutaneously administered HRT (n = 15); group 2, intermittent cyclical etidronate (ICE) (n = 14); group 3, HRT and ICE (n = 15); and group 4, calcium alone (n = 14). The bone mineral density (measured by dual-energy x-ray absorptiometry), biochemical variables of bone turnover, including bone-specific alkaline phosphatase, and urinary hydroxyproline:creatinine ratios were measured before treatment and at 2 and 4 years after treatment.
In patients who received the combined therapy, bone mineral density was increased in the vertebrae by 10.9% (P < 0.001) and in the femora by 7.25% (P < 0.001) at 4 years. For patients treated with ICE, the increase was 6.79% (P < 0.001) and 1.20% (P < 0.05), and with HRT, 6.78% (P < 0.001) and 4.01% (P < 0.01) in the vertebrae and femora, respectively. The group treated with calcium alone lost 3.81% (P < 0.01) and 4.96% (P < 0.01) of bone mineral density in vertebrae and femora. Patients who received no specific therapy lost 8.58% (P < 0.01) from vertebrae, and 7.83% (P < 0.01) from the femora over 4 years. Patients who received combined therapy had significantly higher bone mineral density in both vertebrae (P < 0.05) and femora (P < 0.01), in comparison to patients who were treated with HRT, or ICE, alone. Three of 9 patients (33%) in the ICE group developed osteomalacia, as shown by bone histomorphometry, whereas in women who received combined HRT and ICE therapies, none of the 11 patients tested had evidence of bone mineralization defects.
This 4-year, prospective, randomized study in early postmenopausal women showed an additive effect of ICE and HRT on the bone mineral density in both vertebrae and the hip. Furthermore, the combined therapy prevented the occurrence of osteomalacia associated with etidronate. This is the first study to demonstrate the effects of etidronate in early postmenopausal women, and the additive beneficial effects of HRT and ICE on bone mineral density.
已证实给予雌激素或依替膦酸可增加绝经后女性的骨矿物质密度。开展这项为期4年的前瞻性随机研究，以监测激素替代疗法（HRT）与依替膦酸联合使用时对骨矿物质密度的任何额外有益作用。
58名就诊于代谢性骨病门诊的绝经早期女性被随机分为4个治疗组，并进行长达4年的监测。所有患者均接受每日1.0 g元素钙治疗。此外，第1组接受经皮给予的HRT（n = 15）；第2组接受间歇性周期性依替膦酸（ICE）治疗（n = 14）；第3组接受HRT和ICE联合治疗（n = 15）；第4组仅接受钙剂治疗（n = 14）。在治疗前以及治疗后2年和4年测量骨矿物质密度（通过双能X线吸收法测量）、骨转换的生化指标，包括骨特异性碱性磷酸酶，以及尿羟脯氨酸：肌酐比值。
接受联合治疗的患者，4年后腰椎骨矿物质密度增加了10.9%（P < 0.001），股骨增加了7.25%（P < 0.001）。接受ICE治疗的患者，腰椎增加了6.79%（P < 0.001），股骨增加了1.20%（P < 0.05）；接受HRT治疗的患者，腰椎增加了6.78%（P < 0.001），股骨增加了4.01%（P < 0.01）。仅接受钙剂治疗的组，腰椎和股骨的骨矿物质密度分别降低了3.81%（P < 0.01）和4.96%（P < 0.01）。未接受特定治疗的患者在4年中腰椎骨矿物质密度降低了8.58%（P < 0.01），股骨降低了7.83%（P < 0.01）。与单独接受HRT或ICE治疗的患者相比，接受联合治疗的患者在腰椎（P < 0.05）和股骨（P < 0.01）的骨矿物质密度均显著更高。ICE组9名患者中有3名（33%）出现骨软化，骨组织形态计量学显示如此，而在接受HRT和ICE联合治疗的女性中，11名接受检测的患者均无骨矿化缺陷的证据。
这项针对绝经早期女性的为期4年的前瞻性随机研究表明，ICE和HRT对腰椎和髋部的骨矿物质密度有相加作用。此外，联合治疗预防了与依替膦酸相关的骨软化症的发生。这是第一项证明依替膦酸在绝经早期女性中的作用以及HRT和ICE对骨矿物质密度的相加有益作用的研究。
