Bell N H, Hollis B W, Shary J R, Eyre D R, Eastell R, Colwell A, Russell R G
Department of Medicine, Medical University of South Carolina.
Am J Med. 1994 Apr;96(4):349-53. doi: 10.1016/0002-9343(94)90065-5.
The results of experimental studies with animals indicated that prostaglandins stimulate bone resorption, that skeletal production of prostaglandin E2 is enhanced by ovariectomy and is diminished by 17 beta-estradiol, and that the nonsteroidal anti-inflammatory drug (NSAID) naproxyn prevents bone loss after ovariectomy. Studies were carried out to investigate the effects of the NSAID diclofenac sodium on bone and mineral metabolism in premenopausal women and to compare the effects of diclofenac sodium and conjugated estrogens on bone and mineral metabolism in postmenopausal women.
Ten healthy premenopausal women and 17 healthy postmenopausal women were studied while not being treated and again after 4 weeks of treatment with diclofenac sodium, 150 mg per day in divided doses (both groups), and conjugated estrogens, 0.625 mg per day (postmenopausal women). Cross-linked N-telopeptides of type I collagen were measured in the urine as an index of bone resorption. The postmenopausal women were separated into two groups, responders and nonresponders, based on their response to conjugated estrogens as assessed by linear discriminant analysis for groups. Conjugated estrogens lowered urinary N-telopeptides of type I collagen in responders, but not in nonresponders.
Urinary cross-linked N-telopeptides were higher in the eight postmenopausal women responders than in the nine postmenopausal nonresponders or in the premenopausal women, and were not altered by diclofenac sodium in premenopausal women. In the eight postmenopausal women with higher rates of bone resorption, diclofenac sodium and conjugated estrogens significantly lowered both urinary calcium concentration and urinary cross-linked N-telopeptides. The effects of the two drugs were comparable.
The preliminary results demonstrate that, at the dose used, diclofenac sodium is almost as effective as conjugated estrogens for decreasing bone loss in postmenopausal women. Further studies will be needed to determine whether diclofenac sodium can prevent postmenopausal bone loss.
动物实验研究结果表明，前列腺素可刺激骨吸收，卵巢切除可增强骨骼中前列腺素E2的生成，而17β-雌二醇可使其减少，非甾体抗炎药萘普生可预防卵巢切除后的骨质流失。开展本研究旨在调查非甾体抗炎药双氯芬酸钠对绝经前女性骨与矿物质代谢的影响，并比较双氯芬酸钠与结合雌激素对绝经后女性骨与矿物质代谢的影响。
对10名健康绝经前女性和17名健康绝经后女性在未接受治疗时进行研究，并在接受双氯芬酸钠（两组均为每日150 mg，分剂量服用）和结合雌激素（绝经后女性每日0.625 mg）治疗4周后再次进行研究。检测尿中I型胶原交联N-端肽，作为骨吸收指标。根据线性判别分析评估的绝经后女性对结合雌激素的反应，将其分为反应者和无反应者两组。结合雌激素可降低反应者尿中I型胶原N-端肽水平，但对无反应者无效。
8名绝经后女性反应者的尿交联N-端肽水平高于9名绝经后无反应者或绝经前女性，绝经前女性使用双氯芬酸钠后该指标未发生改变。在8名骨吸收速率较高的绝经后女性中，双氯芬酸钠和结合雌激素均显著降低了尿钙浓度和尿交联N-端肽水平。两种药物的效果相当。
初步结果表明，在所使用的剂量下，双氯芬酸钠在降低绝经后女性骨质流失方面几乎与结合雌激素同样有效。需要进一步研究以确定双氯芬酸钠是否能够预防绝经后骨质流失。
