Zervou Zografia, Bevers Melissa S A M, Wyers Caroline E, Bruggenwirth Hennie T, Demirdas Serwet, van den Bergh Joop P, Zillikens M Carola
Department of Internal Medicine, Erasmus MC Bone Center, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.
Department of Internal Medicine, VieCuri Medical Center, Tegelseweg 210, 5912 BL, Venlo, The Netherlands.
J Bone Miner Res. 2025 Feb 2;40(2):241-250. doi: 10.1093/jbmr/zjae186.
X-linked osteoporosis, caused by PLS3 genetic variants, is a rare bone disease, clinically affecting mainly men. Limited data are available on bone microarchitecture and genotype-phenotype correlations in this disease. Our aims were to assess bone microarchitecture and strength in adults with PLS3 variants using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to explore differences in the phenotype from HR-pQCT between PLS3 variants. HR-pQCT scans were obtained from the distal radius and tibia of 13 men and 3 women with PLS3 variants. Results were compared with age- and sex-matched controls from a normative dataset from literature and expressed as Z-scores. Median age was 46 yr for men and 48 yr for women. In men, total bone area was large (median Z-score: 1.33 radius; 1.46 tibia) due to a large trabecular area (+1.73 radius; +1.87 tibia), while the cortical area was small (-2.61 radius; -2.84 tibia). Total volumetric bone mineral density (BMD) was low due to low trabecular (-3.46 radius; -3.37 tibia) and cortical BMD (-2.87 radius; -2.26 tibia). Regarding bone microarchitecture, the largest deviations were found in trabecular number (-2.18 radius; -1.64 tibia), trabecular separation (+2.32 radius; +1.65 tibia), and cortical thickness (-2.99 radius; -2.46 tibia), whereas trabecular thickness and cortical porosity were normal (-0.36 and -0.58 radius; 0.09 and -0.79 tibia). Additionally, failure load was low (-2.39 radius; -2.2 tibia). Results in the women deviated less from normative data. Men with frameshift/nonsense variants seemed to have more deviant trabecular and cortical microarchitecture and strength, at both scan locations, than those with missense/in-frame insertion variants. In conclusion, HR-pQCT provides valuable insights into bone area, BMD, microarchitecture, and strength in adults with PLS3 variants and can be used to explore genotype-phenotype relationships. Longitudinal analyses in larger groups are needed to study the natural course of the disease and treatment effects.
由PLS3基因变异引起的X连锁骨质疏松症是一种罕见的骨骼疾病，临床上主要影响男性。关于这种疾病的骨微结构和基因型-表型相关性的数据有限。我们的目的是使用高分辨率外周定量计算机断层扫描（HR-pQCT）评估患有PLS3变异的成年人的骨微结构和强度，并探讨PLS3变异之间HR-pQCT表型的差异。对13名男性和3名患有PLS3变异的女性的桡骨远端和胫骨进行了HR-pQCT扫描。将结果与来自文献的标准数据集的年龄和性别匹配的对照组进行比较，并表示为Z值。男性的中位年龄为46岁，女性为48岁。在男性中，由于小梁面积较大（桡骨中位Z值：1.33；胫骨1.46），总骨面积较大，而皮质面积较小（桡骨-2.61；胫骨-2.84）。由于小梁骨密度（桡骨-3.46；胫骨-3.37）和皮质骨密度（桡骨-2.87；胫骨-2.26）较低，总体积骨矿物质密度（BMD）较低。关于骨微结构，在小梁数量（桡骨-2.18；胫骨-1.64）、小梁间距（桡骨+2.32；胫骨+1.65）和皮质厚度（桡骨-2.99；胫骨-2.46）方面发现了最大偏差，而小梁厚度和皮质孔隙率正常（桡骨-0.36和-0.58；胫骨0.09和-0.79）。此外，破坏载荷较低（桡骨-2.39；胫骨-2.2）。女性的结果与标准数据的偏差较小。与错义/框内插入变异的男性相比，具有移码/无义变异的男性在两个扫描部位的小梁和皮质微结构及强度似乎更异常。总之，HR-pQCT为患有PLS3变异的成年人的骨面积、骨密度、微结构和强度提供了有价值的见解，可用于探索基因型-表型关系。需要在更大的群体中进行纵向分析，以研究疾病的自然病程和治疗效果。
