Delmas P D
University Claude Bernard, Lyon, France.
Endocrinol Metab Clin North Am. 1990 Mar;19(1):1-18.
There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties, significant advances have been made in the last few years in the bone marker field. In the future, the development of a battery of several bone-specific markers that indicate various aspects of the complex mechanisms of bone formation, resorption, and mineralization is likely to provide new tools for the diagnosis and management of bone diseases.
目前尚无理想的骨形成标志物，但循环骨钙素是目前最令人满意的。新进展包括使用绵羊骨钙素64和人骨钙素85作为免疫原以及单克隆抗体，这些可能识别骨吸收过程中释放的骨钙素片段。骨碱性磷酸酶的特异性检测、前胶原片段及其他与骨相关的非胶原蛋白的检测，将有助于更精确地评估正常和病理状态下复杂的成骨细胞功能。寻找一种敏感且特异的骨吸收标志物颇具挑战，因为在破骨细胞性骨吸收过程中，骨基质的所有成分都可能降解为微小肽段。通过骨特异性单克隆抗体检测吡啶交联物以及可能的抗酒石酸酸性磷酸酶，是该领域最切实的进展。这些标志物需要与通过髂嵴活检直接测量骨转换获得的数据进行比较以验证其有效性。然而，应记住，循环标志物反映的是整个骨骼的总体活性，包括皮质骨、皮质下骨和小梁骨包膜，它们在正常和异常状态下具有不同的重塑速率。如果骨骼的总转换率不变，循环标志物将无法检测到骨某一区域细胞活性的特定缺陷。相反，骨组织形态计量学仅限于小梁骨包膜的小区域，但能在细胞水平检测到特定缺陷。应牢记这些差异，因为越来越多的证据表明，例如，骨质疏松患者治疗前后不同附属/中轴及皮质/小梁区域的骨量和骨转换有所不同。最后，单一标志物在某些疾病中可能有价值，而在其他疾病中则不然（如骨Paget病中的血清骨钙素）。尽管存在这些困难，但在过去几年中骨标志物领域已取得显著进展。未来，开发一系列能够指示骨形成、吸收和矿化复杂机制各个方面的多种骨特异性标志物，可能为骨疾病的诊断和管理提供新工具。
