Expression of fibroblast growth factor 23, vitamin D receptor, and sclerostin in bone tissue from hypercalciuric stone formers

Abstract

Background and objectives: 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.

Results: 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.

Conclusions: 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.

Keywords: FGF-23; VDR; hypercalciuria; immunohistochemistry; sclerostin.

Figure 1.

Bone immunostaining quantification (%) of fibroblast growth factor 23 (FGF-23), vitamin D receptor (VDR), and sclerostin (Scl). Idiopathic hypercalciuria patients with high (black bars; n=21) or normal (white bars; n=9) bone resorption defined by eroded surface (*P=0.03 versus white bars). The quantification of immunostaining was determined by the ratio of positive to total number of stained cells in bone tissue.

Figure 2.

Immunohistochemistry for FGF-23, VDR, and Scl in bone tissue (positive immunostaining is shown in red). No differences between the patterns of FGF-23 immunostaining in osteocytes (arrows) in (A) a patient with high bone resorption, (D) a patient with normal bone resorption, and (G) a control patient are observed. Examples of higher expression of VDR in osteoblasts (arrows) and Scl immunostaining in osteocytes (arrows) from an idiopathic hypercalciuria patient with high bone resorption are given in B and C, respectively, contrasting with the fewer stained cells in an idiopathic hypercalciuria patient with normal bone resorption (E and F for VDR and Scl, respectively) and a control individual (H and I, respectively). Original magnification, ×200.