Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, USA.
Bone. 2021 May;146:115900. doi: 10.1016/j.bone.2021.115900. Epub 2021 Feb 20.
Patients with osteoporosis-associated WNT1 or PLS3 mutations have unique bone histomorphometric features and osteocyte-specific hormone expression patterns.
To investigate the effects of WNT1 and PLS3 mutations on bone material properties.
Transiliac bone biopsies were evaluated by quantitative backscattered electron imaging, immunohistochemistry, and bone histomorphometry.
Ambulatory patients.
Three pediatric and eight adult patients with WNT1 or PLS3 mutations.
Bone mineralization density distribution and osteocyte protein expression was evaluated in 11 patients and repeated in six patients who underwent repeat biopsy after 24 months of teriparatide treatment.
Bone mineralization density distribution and protein expression.
Children with WNT1 or PLS3 mutations had heterogeneous bone matrix mineralization, consistent with bone modeling during growth. Bone matrix mineralization was homogenous in adults and increased throughout the age spectrum. Teriparatide had very little effect on matrix mineralization or bone formation in patients with WNT1 or PLS3 mutations. However, teriparatide decreased trabecular osteocyte lacunae size and increased trabecular bone FGF23 expression.
The contrast between preserved bone formation with heterogeneous mineralization in children and low bone turnover with homogenous bone mineral content in adults suggests that WNT1 and PLS3 have differential effects on bone modeling and remodeling. The lack of change in matrix mineralization in response to teriparatide, despite clear changes in osteocyte lacunae size and protein expression, suggests that altered WNT1 and PLS3 expression may interfere with coupling of osteocyte, osteoblast, and osteoclast function. Further studies are warranted to determine the mechanism of these changes.
患有与 WNT1 或 PLS3 突变相关的骨质疏松症的患者具有独特的骨组织形态计量学特征和破骨细胞特异性激素表达模式。
研究 WNT1 和 PLS3 突变对骨材料特性的影响。
通过定量背散射电子成像、免疫组织化学和骨组织形态计量学评估髂嵴骨活检。
门诊患者。
3 名儿科和 8 名患有 WNT1 或 PLS3 突变的成年患者。
在 11 名患者中评估骨矿化密度分布和破骨细胞蛋白表达，并在接受特立帕肽治疗 24 个月后进行重复活检的 6 名患者中重复评估。
骨矿化密度分布和蛋白表达。
患有 WNT1 或 PLS3 突变的儿童的骨基质矿化具有异质性，与生长期间的骨建模一致。成年人的骨基质矿化是同质的，并贯穿整个年龄谱增加。特立帕肽对 WNT1 或 PLS3 突变患者的基质矿化或骨形成几乎没有影响。然而，特立帕肽减少了小梁骨破骨细胞陷窝的大小，并增加了小梁骨 FGF23 的表达。
儿童保留的骨形成与异质矿化之间的对比，以及成年人低骨转换与同质骨矿物质含量之间的对比表明，WNT1 和 PLS3 对骨建模和重塑有不同的影响。尽管破骨细胞陷窝大小和蛋白表达发生了明显变化，但特立帕肽对基质矿化无变化表明，改变的 WNT1 和 PLS3 表达可能干扰破骨细胞、成骨细胞和破骨细胞功能的偶联。需要进一步研究以确定这些变化的机制。
