Delmas P D
INSERM Research Unit 403 and Claude Bernard University of Lyon, Lyon, France.
J Bone Miner Res. 1999 Oct;14 Suppl 2:66-9. doi: 10.1002/jbmr.5650140213.
Although the measurement of total alkaline phosphatase activity in serum is a valid index to assess the activity of Paget's disease of bone and to monitor treatment efficacy, this marker may lack sensitivity in some cases. Among the various markers of bone formation and resorption that have been developed, serum bone specific alkaline phosphatase and procollagen I N-terminal peptide (PINP) for formation, urinary N-telopeptide (NTX) and alpha-C-telopeptide (CTX) for bone resorption have emerged as the most sensitive ones, and may be useful in the management of pagetic patients. We have recently shown that the beta-isomerization of type I collagen CTX is impaired in pagetic bone matrix characterized by the existence of woven bone, as compared to normal lamellar bone matrix. This abnormality results in a preferential urinary excretion of nonisomerized (alpha-CTX) over beta-isomerized (beta-CTX) that can be measured with specific immunoassays. Patients with active Paget's disease of bone are characterized by an abnormally high alpha/beta-CTX ratio which goes down to the normal range after bisphosphonate therapy, probably reflecting the lamellar structure of newly formed bone matrix in pagetic skeletal sites after treatment.
虽然血清中总碱性磷酸酶活性的测定是评估骨Paget病活性及监测治疗效果的有效指标，但该标志物在某些情况下可能缺乏敏感性。在已开发的各种骨形成和骨吸收标志物中，用于骨形成的血清骨特异性碱性磷酸酶和I型前胶原N端肽（PINP），以及用于骨吸收的尿N端肽（NTX）和α-C端肽（CTX）已成为最敏感的标志物，可能有助于Paget病患者的管理。我们最近发现，与正常板层骨基质相比，以编织骨存在为特征的Paget病骨基质中I型胶原CTX的β异构化受损。这种异常导致非异构化（α-CTX）比β异构化（β-CTX）更优先经尿液排泄，这可以通过特异性免疫测定法进行测量。活动性骨Paget病患者的特征是α/β-CTX比值异常高，双膦酸盐治疗后该比值降至正常范围，这可能反映了治疗后Paget病骨骼部位新形成骨基质的板层结构。
