Menon Viviane Barcellos, Moysés Rosa Maria Affonso, Gomes Samirah Abreu, de Carvalho Aluizio Barbosa, Jorgetti Vanda, Heilberg Ita Pfeferman
Nephrology Division, Federal University of São Paulo, São Paulo, Brazil; and.
Nephrology Division, University of São Paulo, São Paulo, Brazil.
Clin J Am Soc Nephrol. 2014 Jul;9(7):1263-70. doi: 10.2215/CJN.10030913. Epub 2014 Apr 24.
Increased bone resorption, low bone formation, and abnormal mineralization have been described in stone formers with idiopathic hypercalciuria. It has been previously shown that the receptor activator of NF-κB ligand mediates bone resorption in idiopathic hypercalciuria (IH). The present study aimed to determine the expression of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin in bone tissue from IH stone formers.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained for histomorphometry from 30 transiliac bone biopsies of idiopathic hypercalciuria stone-forming patients between 1992 and 2002 and 33 healthy individuals (controls). Serum parameters were obtained from their medical records.
Histomorphometry disclosed 21 IH patients with high and 9 IH patients with normal bone resorption. Importantly, eroded surfaces (ES/BS) from IH patients but not controls were significantly correlated with VDR immunostaining in osteoblasts (r=0.51; P=0.004), sclerostin immunostaining in osteocytes (r=0.41; P=0.02), and serum 1,25-dihydroxyvitamin D (r=0.55; P<0.01). Of note, both VDR and sclerostin immunostaining were significantly correlated with serum 1,25-dihydroxyvitamin D in IH patients (r=0.52; P=0.01 and r=0.53; P=0.02, respectively), although VDR and sclerostin expression did not differ between IH and controls. IH patients with high bone resorption exhibited a significantly stronger sclerostin immunostaining than IH patients with normal bone resorption. FGF-23 expression in osteocytes from IH patients did not differ from controls and was not correlated with any histomorphometric parameter.
These findings suggest the contribution of VDR and sclerostin, as well as 1,25-dihydroxyvitamin D, to increase bone resorption in idiopathic hypercalciuria but do not implicate FGF-23 in the bone alterations seen in these patients.
特发性高钙尿症结石形成者存在骨吸收增加、骨形成减少及矿化异常的情况。此前研究表明，核因子κB受体活化因子配体介导特发性高钙尿症（IH）中的骨吸收。本研究旨在确定IH结石形成者骨组织中成纤维细胞生长因子23（FGF - 23）、维生素D受体（VDR）和硬化蛋白的表达情况。
设计、研究地点、参与者及测量指标：对1992年至2002年间从30例特发性高钙尿症结石形成患者及33名健康个体（对照组）的髂骨活检中获取的未脱钙骨样本进行免疫组织化学分析，此前这些样本已用于组织形态计量学研究。血清参数从他们的病历中获取。
组织形态计量学显示，21例IH患者骨吸收高，9例IH患者骨吸收正常。重要的是，IH患者而非对照组的侵蚀表面（ES/BS）与成骨细胞中的VDR免疫染色显著相关（r = 0.51；P = 0.004），与骨细胞中的硬化蛋白免疫染色显著相关（r = 0.41；P = 0.02），与血清1,25 - 二羟维生素D显著相关（r = 0.55；P < 0.01）。值得注意的是，在IH患者中，VDR和硬化蛋白免疫染色均与血清1,25 - 二羟维生素D显著相关（分别为r = 0.52；P = 0.01和r = 0.53；P = 0.02），尽管IH患者与对照组之间VDR和硬化蛋白表达无差异。骨吸收高的IH患者硬化蛋白免疫染色显著强于骨吸收正常的IH患者。IH患者骨细胞中的FGF - 23表达与对照组无差异，且与任何组织形态计量学参数均无相关性。
这些发现提示VDR、硬化蛋白以及1,25 - 二羟维生素D在特发性高钙尿症骨吸收增加中起作用，但未表明FGF - 23与这些患者的骨改变有关。
