Woitge H W, Pecherstorfer M, Li Y, Keck A V, Horn E, Ziegler R, Seibel M J
Department of Medicine I, University of Heidelberg, Heidelberg, Germany.
J Bone Miner Res. 1999 May;14(5):792-801. doi: 10.1359/jbmr.1999.14.5.792.
Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC-, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p < 0. 05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p < 0.01 vs. BC-), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p < 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.
尽管尿液中胶原蛋白降解产物的测定能有效评估骨吸收情况，但其临床应用因显著的分析和生物学变异性而受到阻碍。因此，已开发出用于测定血清中此类参数的免疫测定法。在本研究中，我们评估了三种新的骨转换血清标志物的性能，即I型胶原C端和N端末肽（S-CTX和S-NTX）以及骨唾液蛋白。将结果与尿总吡啶啉、总脱氧吡啶啉、I型胶原尿C端末肽（U-CTX）和I型胶原尿N端末肽（U-NTX）进行比较。研究人群包括健康男性（n = 27）、绝经前（n = 30）和绝经后（n = 31）女性、肝功能不全患者（HF，n = 24）、肾衰竭患者（RF，n = 30）、无骨转移（BC-，n = 24）和有骨转移（BC+，n = 30）的乳腺癌患者、原发性椎体骨质疏松症（OPO，n = 27）、原发性甲状旁腺功能亢进症（PHPT，n = 16）、活动性骨Paget病（n = 18）、多发性骨髓瘤（MM，n = 18）以及恶性肿瘤高钙血症患者在接受帕米膦酸治疗前后（HOM，n = 28）。在大多数代谢性骨病中，尿液和血清标志物的变化相似。然而，血清标志物改善了健康对照与OPO或PHPT之间的区分。在MM中，所有血清和尿液标志物均升高（与对照组相比，p < 0.05）。在BC+中，除U-CTX和S-CTX外，所有指标的显著升高均反映了骨骼受累情况（与BC-相比，p < 0.01）。在HOM中，帕米膦酸引起的生物标志物变化在U-CTX、S-CTX和S-NTX中最为明显。HF和RF与所有血清标志物水平升高相关（与对照组相比，p < 0.05）。总之，血清检测与尿液指标在反映骨吸收方面程度相同。由于血清标志物规避了尿液检测的一些局限性，其应用可能会改善对骨骼疾病的评估。
