Uday Suma, Högler Wolfgang
Department of Endocrinology and Diabetes, Birmingham Women's and Children's Hospital, Steelhouse Lane, Birmingham, B4 6NH, UK.
Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Calcif Tissue Int. 2025 Jun 30;116(1):91. doi: 10.1007/s00223-025-01398-2.
Defective mineralization of bone matrix results in osteomalacia, which universally affects the skeletal system and dentition and manifests alongside the clinically and radiologically more obvious growth plate disorder rickets in young children. Given that radiological signs of osteomalacia are limited, most hypomineralization disorders are diagnosed based on their clinical features and/or typical biochemical signatures, especially after the closure of growth plates. Evaluation of histomorphometry (HM) parameters and bone mineral density distribution (BMDD) via quantitative backscattered electron imaging (qBEI) from transiliac bone biopsy samples enables the exploration of the true skeletal disease burden of osteomalacia and the assessment of the impact of treatment. The diagnosis of various acquired and heritable disorders of osteomalacia based on clinical, biochemical, radiological and biomaterial HM features is discussed here. The most common acquired cause of osteomalacia remains dietary calcium and solar/dietary vitamin D deficiencies. Rare heritable causes result from mutations in genes involved in calcitriol synthesis and action (resulting in calcipaenia), fibroblast growth factor 23 production or degradation or tubulopathies (resulting in phosphopaenia) or reduced hydrolysis of the mineralization blocker inorganic pyrophosphate (resulting from hypophosphatasia). On bone biopsy, osteomalacia manifests as increased osteoid indices on static HM, with mineralization lag on tetracycline-labelled dynamic HM. Calcipaenic disorders typically display additional HM features of secondary hyperparathyroidism which include increased osteocyte surface from increased bone turnover, peritrabecular marrow fibrosis and cortical thinning. BMDD in osteomalacic conditions shows an increased amount of lowly mineralized bone tissue and increased heterogeneity in mineralization when compared to normal individuals. Medical assessment should focus on identification of biochemical disease signatures which differ between these osteomalacic entities but are essential for early diagnosis and treatment monitoring, with the aim of achieving full matrix mineralization and prevention of this hidden disease.
骨基质矿化缺陷会导致骨软化症，该病普遍影响骨骼系统和牙列，并与幼儿临床上和放射学上更为明显的生长板紊乱佝偻病同时出现。鉴于骨软化症的放射学征象有限，大多数矿化不足疾病是根据其临床特征和/或典型生化指标来诊断的，尤其是在生长板闭合之后。通过对经髂骨活检样本进行定量背散射电子成像（qBEI）来评估组织形态计量学（HM）参数和骨矿物质密度分布（BMDD），有助于探究骨软化症的真正骨骼疾病负担，并评估治疗效果。本文讨论了基于临床、生化、放射学和生物材料HM特征对各种获得性和遗传性骨软化症疾病的诊断。骨软化症最常见的获得性病因仍然是饮食中钙和阳光/饮食中维生素D缺乏。罕见的遗传性病因是由于参与骨化三醇合成和作用的基因发生突变（导致钙减少）、成纤维细胞生长因子23产生或降解异常或肾小管疾病（导致磷减少），或矿化阻滞剂无机焦磷酸水解减少（由低磷酸酯酶症引起）。在骨活检中，骨软化症在静态HM上表现为类骨质指数增加，在四环素标记的动态HM上表现为矿化延迟。钙减少性疾病通常还表现出继发性甲状旁腺功能亢进的其他HM特征，包括骨转换增加导致骨细胞表面增加、骨小梁周围骨髓纤维化和皮质变薄。与正常个体相比，骨软化症患者的BMDD显示矿化程度低的骨组织数量增加，矿化异质性增加。医学评估应侧重于识别这些骨软化症实体之间不同的生化疾病特征，这些特征对于早期诊断和治疗监测至关重要，目的是实现完全的基质矿化并预防这种隐匿性疾病。
