Shankar Subramanian, Hosking David J
Command Hospital (Air Force), Bangalore, India.
J Bone Miner Res. 2006 Dec;21 Suppl 2:P22-7. doi: 10.1359/jbmr.06s204.
Biochemical measurements of bone turnover provide an objective assessment of disease activity and the response to treatment. Alkaline phosphatase is the best characterized of the bone turnover markers and reflects the extent and activity of Paget's disease. However, in addition to bone-specific alkaline phosphatase (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP) as formation markers. A variety of telopeptides (C-terminal telopeptide of type I collagen, [CTX], N-telopeptide of type I collagen [NTX]) or cross-link breakdown products of type 1 collagen can be used to assess bone resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all perform similarly in diagnosis and in evaluating the response to treatment, but the general availability, low interassay variation, and inexpensiveness of Total ALP makes it the best test for routine use. Measurement of the biological variability of the different markers in stable, untreated Paget's disease indicates how great a change (critical difference) is needed to define a true alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy induced change/critical difference ratio during antiresorptive treatment. Some of the resorption markers show more complex changes in response to treatment. Pyridinoline (PYD) or deoxypyridinoline (DPD) cross-links of type 1 collagen are excreted in urine either as free or as peptide bound moieties, but it is the latter which decrease by the greatest amount in response to bisphosphonate therapy. Newly formed type 1 collagen contains an aspartyl-glycine motif (alphaCTX), which undergoes spontaneous isoaspartyl formation to betaCTX as the bone ages. In untreated Paget's disease, the alphaCTX is raised proportionately more (16-fold) than betaCTX (3-fold) and decreases in response to bisphosphonate therapy to a greater extent than betaCTX (measured in the sCTX assay). As bisphosphonates have become more potent, the aim of treatment has shifted toward the achievement of a rate of bone turnover in the lower part of the reference range. This is important because the duration of remission of disease activity is strongly determined by the post treatment nadir bone turnover.
骨转换的生化检测可对疾病活动度及治疗反应进行客观评估。碱性磷酸酶是特征最明确的骨转换标志物，反映了佩吉特病的程度和活动度。然而，除了骨特异性碱性磷酸酶（骨ALP）外，还有骨钙素（OC）和I型前胶原N端前肽（P1NP）作为形成标志物。多种端肽（I型胶原C端端肽[CTX]、I型胶原N端端肽[NTX]）或I型胶原的交联降解产物可用于评估骨吸收。总碱性磷酸酶（总ALP）、骨ALP和P1NP在诊断及评估治疗反应方面表现相似，但总ALP的广泛可用性、低检测间变异及低成本使其成为常规使用的最佳检测项目。对稳定的、未经治疗的佩吉特病中不同标志物的生物学变异性进行测量，可表明需要多大的变化（临界差异）才能定义疾病活动度的真正改变。在抗吸收治疗期间，骨ALP、P1NP和NTX显示出最高的治疗诱导变化/临界差异比。一些吸收标志物在治疗反应中显示出更复杂的变化。I型胶原的吡啶啉（PYD）或脱氧吡啶啉（DPD）交联物以游离或肽结合部分的形式排泄到尿液中，但后者在双膦酸盐治疗反应中减少的量最大。新形成的I型胶原含有天冬氨酰 - 甘氨酸基序（αCTX），随着骨龄增长，其会自发形成异天冬氨酰转化为βCTX。在未经治疗的佩吉特病中，αCTX升高的比例（16倍）比βCTX（3倍）更高，并且在双膦酸盐治疗反应中比βCTX下降的程度更大（在sCTX检测中测量）。随着双膦酸盐效力增强，治疗目标已转向实现参考范围下限的骨转换率。这很重要，因为疾病活动度缓解的持续时间很大程度上取决于治疗后骨转换的最低点。
