Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Stenbäckinkatu 9, Helsinki, Finland.
Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Calcif Tissue Int. 2023 Jun;112(6):675-682. doi: 10.1007/s00223-023-01077-0. Epub 2023 Mar 22.
Autoimmune polyendocrine syndrome type-1 (APS1) is characterized by autoimmune manifestations affecting different organs from early childhood on. Immunological abnormalities, the resulting endocrinopathies, and their treatments may compromise bone health. For the first time in APS1, we analyzed transiliac bone biopsy samples by bone histomorphometry and quantitative backscattered electron imaging in three adult patients (female P1, 38 years; male P2, 47 years; male P3, 25 years). All had biallelic mutations in the autoimmune regulator gene and in addition to endocrinopathies, also significant bone fragility. Histomorphometry showed bone volume in the lower normal range for P1 (BV/TV, - 0.98 SD) and P3 (- 1.34 SD), mainly due to reduced trabecular thickness (TbTh, - 3.63 and - 2.87 SD). In P1, osteoid surface was low (OS/BS, - 0.96 SD); active osteoblasts and double labeling were seen only on cortical bone. P3 showed a largely increased bone turnover rate (BFR/BV, + 4.53 SD) and increased mineralization lag time (Mlt, + 3.40 SD). Increased osteoid surface (OS/BS, + 2.03 and + 4.71 SD for P2 and P3) together with a large proportion of lowly mineralized bone area (Trab CaLow, + 2.22 and + 9.81 SD for P2 and P3) and focal mineralization defects were consistent with abnormal mineralization. In all patients, the density and area of osteocyte lacunae in cortical and trabecular bone were similar to healthy adults. The bone tissue characteristics were variable and included decreased trabecular thickness, increased amount of osteoid, and abnormal mineralization which are likely to contribute to bone fragility in patients with APS1.
自身免疫性多内分泌腺综合征 1 型（APS1）的特征是从儿童早期开始，影响不同器官的自身免疫表现。免疫异常、由此产生的内分泌疾病及其治疗可能会损害骨骼健康。我们首次在 3 名成年 APS1 患者（女性 P1，38 岁；男性 P2，47 岁；男性 P3，25 岁）中通过骨组织形态计量学和定量背散射电子成像分析了髂骨骨活检样本。所有患者均存在自身免疫调节基因的双等位基因突变，除了内分泌疾病外，还存在明显的骨骼脆弱。组织形态计量学显示 P1（BV/TV，-0.98 SD）和 P3（-1.34 SD）的骨量处于较低的正常范围，主要是由于小梁厚度降低（TbTh，-3.63 和-2.87 SD）。在 P1 中，骨表面矿化率低（OS/BS，-0.96 SD）；仅在皮质骨上可见活跃的成骨细胞和双标记。P3 表现出较高的骨转换率（BFR/BV，+4.53 SD）和矿化延迟时间增加（Mlt，+3.40 SD）。增加的骨表面矿化率（OS/BS，P2 和 P3 分别为+2.03 和+4.71 SD），以及大量低矿化骨面积（Trab CaLow，P2 和 P3 分别为+2.22 和+9.81 SD）和局灶性矿化缺陷与异常矿化一致。在所有患者中，皮质骨和松质骨中骨细胞陷窝的密度和面积与健康成年人相似。骨组织特征具有变异性，包括小梁厚度降低、骨样组织增加和异常矿化，这可能导致 APS1 患者的骨骼脆弱。
