Russell R G, Beard D J, Cameron E C, Douglas D L, Forrest A R, Guilland-Cumming D, Paterson A D, Poser J, Preston C J, Milford-Ward A, Woodhead S, Kanis J A
Metab Bone Dis Relat Res. 1981;3(4-5):255-62. doi: 10.1016/0221-8747(81)90041-2.
The two most commonly used biochemical markers of bone turnover are the serum alkaline phosphatase and the urinary excretion of peptide-bound hydroxyproline, both of which are increased in Paget's disease. Serum alkaline phosphatase is assumed to be derived from osteoblasts during the process of bone formation, whereas small peptides containing hydroxyproline are excreted in the urine following the degradation of bone collagen. The alkaline phosphatase is probably the more useful measurement for diagnosis and for following response to treatment, whereas hydroxyproline, although very sensitive, presents technical difficulties in collection and measurement. Several other biochemical changes in Paget's disease indicate abnormal bone metabolism. These include increased urinary excretion of hydroxylysine and its glycosides derived from collagen, as well as the release into the circulation and subsequent urinary excretion of fragments of pro-collagen indicative of increased collagen formation. Proteins specific to bone, such as osteocalcin, are increased in serum, bone, such as osteocalcin, are increased in serum, as are various enzymes possibly derived from bone cells, including acid phosphatase and proline imino-peptidase. Treatment of Paget's disease results in a fall in urinary hydroxyproline before alkaline phosphatase. This indicates that drug treatment, whether with diphosphonates, calcitonin or mithramycin, has a primary action to inhibit bone resorption, with a subsequent adaptive reduction in bone formation rate.
骨转换最常用的两种生化标志物是血清碱性磷酸酶和肽结合羟脯氨酸的尿排泄量，这两者在佩吉特病中均升高。血清碱性磷酸酶被认为是在骨形成过程中由成骨细胞产生的，而含羟脯氨酸的小肽在骨胶原降解后经尿液排泄。碱性磷酸酶可能是用于诊断和监测治疗反应更有用的指标，而羟脯氨酸虽然非常敏感，但在收集和测量方面存在技术困难。佩吉特病的其他一些生化变化表明骨代谢异常。这些变化包括源自胶原的羟赖氨酸及其糖苷的尿排泄增加，以及前胶原片段释放入循环并随后经尿液排泄，这表明胶原形成增加。骨特异性蛋白，如骨钙素，在血清中增加，各种可能源自骨细胞的酶，包括酸性磷酸酶和脯氨酸亚氨基肽酶，在血清中也增加。佩吉特病的治疗会使尿羟脯氨酸在碱性磷酸酶之前下降。这表明无论是用双膦酸盐、降钙素还是光辉霉素进行药物治疗，其主要作用都是抑制骨吸收，随后骨形成率会适应性降低。
