Delmas P D, Hardy P, Garnero P, Dain M
INSERM Research Unit 403, Hôpital E. Herriot, Lyon, France.
Bone. 2000 Jun;26(6):553-60. doi: 10.1016/s8756-3282(00)00271-4.
Hormone replacement therapy (HRT) induces a rapid decrease in biochemical markers of bone turnover that correlate with a subsequent increase in bone mineral density (BMD). To determine the utility of bone markers in the management of postmenopausal women receiving HRT, we analyzed the relationship between changes in four markers (serum osteocalcin and bone alkaline phosphatase [BAP], serum and urinary C-telopeptide of type I collagen [CTX]) and changes in spine BMD in 569 women treated for 2 years with different doses of a matrix transdermal 17beta-estradiol patch in two placebo-controlled trials. Using a logistic regression model, we found that both the percent change from baseline and the actual value of resorption markers at 3 and 6 months of treatment were predictive of BMD response at 2 years. Comparable results were obtained with formation markers at 6 months only. We determined the sensitivity, probably of positive BMD response, and corresponding cutoff value of markers at 3 and 6 months with a specificity set at a level of 0.90, so that <10% of women classified with markers as responders, i.e., as having a subsequent increase in BMD at 2 years >/=2.26%, would be false positive. All markers provided a high probability of positive BMD response ranging from 0.82 to 0.91, with a sensitivity higher for resorption than for formation markers, and sometimes improved in a model combining the percent change and the actual value of marker under HRT. For example, a decrease in serum CTX >/= 33% at 3 months of HRT provided a 68% sensitivity and 87% probability of positive BMD response at 2 years for a 90% specificity. At 6 months, a decrease in urinary CTX >/= 53% provided a 68% sensitivity and 91% probability of a positive BMD response for a 90% specificity. Half of false-negative cases at 3 months will be correctly identified by a subsequent urinary CTX measurement at 6 months. We conclude that the short-term change in bone markers reflects long-term changes of BMD in postmenopausal women treated with HRT. Our data suggest that bone turnover markers can be used to monitor the BMD response to HRT at the individual level. Whether such monitoring could improve long-term compliance to HRT should be tested prospectively.
激素替代疗法（HRT）可使骨转换的生化标志物迅速下降，这与随后骨矿物质密度（BMD）的增加相关。为了确定骨标志物在接受HRT的绝经后女性管理中的效用，我们在两项安慰剂对照试验中分析了569名接受不同剂量基质透皮17β-雌二醇贴片治疗2年的女性中四种标志物（血清骨钙素和骨碱性磷酸酶 [BAP]、血清和尿I型胶原C-末端肽 [CTX]）的变化与脊柱BMD变化之间的关系。使用逻辑回归模型，我们发现治疗3个月和6个月时，与基线相比的变化百分比以及吸收标志物的实际值均可预测2年时的BMD反应。仅在6个月时使用形成标志物可获得类似结果。我们确定了3个月和6个月时标志物对BMD阳性反应的敏感性及相应的临界值，设定特异性水平为0.90，以使被标志物分类为反应者（即2年时BMD随后增加≥2.26%）的女性中<10%为假阳性。所有标志物对BMD阳性反应的概率均较高，范围为0.82至0.91，吸收标志物的敏感性高于形成标志物，在HRT下结合标志物变化百分比和实际值的模型中有时会有所改善。例如，HRT 3个月时血清CTX下降≥33%，对于90%的特异性，2年时BMD阳性反应的敏感性为68%，概率为87%。在6个月时，尿CTX下降≥53%，对于90%的特异性，BMD阳性反应的敏感性为68%，概率为91%。3个月时一半的假阴性病例将在6个月时通过随后的尿CTX测量被正确识别。我们得出结论，绝经后接受HRT治疗的女性中，骨标志物的短期变化反映了BMD的长期变化。我们的数据表明，骨转换标志物可用于在个体水平监测对HRT的BMD反应。这种监测是否能提高对HRT的长期依从性应进行前瞻性测试。
