Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Immunology and Infectiology, Medical University of Vienna, Vienna, Austria.
J Bone Miner Res. 2011 Jul;26(7):1584-92. doi: 10.1002/jbmr.344.
Male idiopathic osteoporosis (MIO) is a metabolic bone disease that is characterized by low bone mass, microstructural alterations, and increased fracture risk in otherwise healthy men. Although the detailed pathophysiology of MIO has yet to be clarified, evidence increasingly suggests an osteoblastic defect as the underlying cause. In this study we tested the hypothesis that the expression profile of certain osteoblastic or osteoblast-related genes (ie, WNT10B, RUNX2, Osterix, Osteocalcin, SOST, RANKL, and OPG) is different in iliac crest biopsies of MIO patients when compared with healthy controls. Furthermore, we investigated the relation of local gene expression characteristics with histomorphometric, microstructural, and clinical features. Following written informed consent and diligent clinical patient characterization, iliac crest biopsies were performed in nine men. While RNA extraction, reverse-transcription, and real-time polymerase chain reactions (PCRs) were performed on one biopsy, a second biopsy of each patient was submitted for histomorphometry and micro-computed tomography (µCT). Age-matched bone samples from forensic autopsies served as controls. MIO patients displayed significantly reduced WNT10B, RUNX2, RANKL, and SOST expression. Performing µCT for the first time in MIO biopsies, we found significant decreases in trabecular number and connectivity density. Trabecular separation was increased significantly, but trabecular thickness was similar in both groups. Histomorphometry revealed decreased BV/TV and osteoid volume and fewer osteoclasts in MIO. By providing evidence for reduced local WNT10B, RUNX2, and RANKL gene expression and histomorphometric low turnover, our data support the osteoblast dysfunction model discussed for MIO. Further, MIO seems to lead to a different microstructural pathology than age-related bone loss.
男性特发性骨质疏松症（MIO）是一种代谢性骨病，其特征是骨量低、微观结构改变和健康男性骨折风险增加。尽管 MIO 的详细病理生理学尚未阐明，但越来越多的证据表明成骨细胞缺陷是其潜在原因。在这项研究中，我们检验了这样一个假设，即在 MIO 患者的髂嵴活检中，某些成骨细胞或与成骨细胞相关的基因（即 WNT10B、RUNX2、Osterix、骨钙素、SOST、RANKL 和 OPG）的表达谱与健康对照组不同。此外，我们还研究了局部基因表达特征与组织形态计量学、微观结构和临床特征的关系。在获得书面知情同意书并对患者进行详细临床特征描述后，对 9 名男性进行了髂嵴活检。在对其中一个活检样本进行 RNA 提取、逆转录和实时聚合酶链反应（PCR）的同时，还对每位患者的另一个活检样本进行了组织形态计量学和微计算机断层扫描（µCT）检测。从法医尸检中获得年龄匹配的骨样本作为对照组。MIO 患者的 WNT10B、RUNX2、RANKL 和 SOST 表达明显减少。首次在 MIO 活检中进行 µCT 检查，我们发现骨小梁数量和连通密度显著降低。骨小梁分离显著增加，但两组之间的骨小梁厚度相似。组织形态计量学显示 MIO 中 BV/TV 和类骨质体积减少，破骨细胞减少。通过提供局部 WNT10B、RUNX2 和 RANKL 基因表达减少和组织形态计量学低转换的证据，我们的数据支持了讨论中的 MIO 成骨细胞功能障碍模型。此外，MIO 似乎导致与年龄相关的骨丢失不同的微观结构病理学。
