Buschke-Ollendorff syndrome is a rare autosomal dominant condition caused by pathogenic variants in LEMD3 and characterized by connective tissue nevi and sclerotic bone abnormalities known as osteopoikilosis. The bone phenotype in Buschke-Ollendorff syndrome including osteopoikilosis remains unclear. We investigated bone turnover markers, pelvis and crura X-rays; lumbar spine and femoral neck DXA; bone activity by NaF-PET/CT, bone structure by μCT and dynamic histomorphometry in adults with Buschke-Ollendorff syndrome. Two women aged 25 and 47 years with a BMI of 30 and 32 kg/m2, respectively, were included in the investigation. Bone turnover markers were within normal range. aBMD Z-scores were comparable to that of controls in the lumbar spine and increased at the hip. Radiographies exposed spotted areas in crura and pelvis, and NaF-PET/CT exposed abnormal pattern of irregular shaped NaF uptake in the entire skeleton. In both biopsies, μCT showed trabecular structure comparable to that of controls with stellate shaped sclerotic noduli within the cavity and on the endocortex. Histomorphometric analyses of the sclerotic lesions revealed compact lamellar bone with a normal bone remodeling rate, but partly replaced by modeling-based bone formation. Woven bone was not observed in the nodules. Therefore, while bone turnover and BMD were largely within normal reference range in patients with the Buschke-Ollendorff syndrome, osteosclerotic lesions appear to emerge due to modeling-based bone formation with secondary bone remodeling. These observations indicate that LEMD3 may be important for the activation of bone lining cells leading to modeling-based bone formation.

中文翻译：

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基于建模的骨形成将小梁转化为 Buschke-Ollendorff 综合征硬化区域中的皮质骨。两名携带 LEMD3 变异的女性的案例研究

Buschke-Ollendorff 综合征是一种罕见的常染色体显性遗传病，由 LEMD3 中的致病性变异引起，其特征是结缔组织痣和称为骨质疏松症的硬化骨异常。Buschke-Ollendorff 综合征（包括骨质疏松症）的骨表型尚不清楚。我们研究了骨转换标志物、骨盆和下肢 X 光片；腰椎和股骨颈 DXA；成人 Buschke-Ollendorff 综合征的 NaF-PET/CT 骨活性、μCT 骨结构和动态组织形态测量学。调查中包括两名年龄分别为 25 岁和 47 岁、BMI 分别为 30 和 32 kg/m2 的女性。骨转换指标在正常范围内。aBMD Z 值在腰椎与对照组相当，在髋部增加。射线照相暴露了脚和骨盆的斑点区域，NaF-PET/CT 揭示了整个骨骼中不规则形状的 NaF 摄取的异常模式。在两次活检中，μCT 显示的小梁结构与对照组相当，腔内和内皮层上有星状硬化结节。硬化病变的组织形态学分析显示致密的板层骨具有正常的骨重塑率，但部分被基于建模的骨形成所取代。在结节中未观察到编织骨。因此，虽然 Buschke-Ollendorff 综合征患者的骨转换和 BMD 在很大程度上处于正常参考范围内，但由于基于模型的骨形成和继发性骨重塑，骨硬化病变似乎出现。这些观察结果表明 LEMD3 可能对激活骨内衬细胞导致基于建模的骨形成很重要。