RANKL Is a Mediator of Bone Resorption in Idiopathic Hypercalciuria

Abstract

This study aimed to determine the expression of osteoprotegerin, receptor activator of nuclear factor kappaB ligand, interleukin-1alpha, transforming growth factor-beta, and basic fibroblast growth factor in stone-forming patients with idiopathic hypercalciuria. Immunohistochemical analysis was performed in undecalcified bone samples previously obtained from 36 transiliac bone biopsies of patients who had idiopathic hypercalciuria and whose histomorphometry had shown lower bone volume, increased bone resorption, and prolonged mineralization lag time. Bone expression of receptor activator of nuclear factor kappaB ligand and osteoprotegerin was significantly higher in patients with idiopathic hypercalciuria versus control subjects. Transforming growth factor-beta immunostaining was lower in patients with idiopathic hypercalciuria than in control subjects and correlated directly with mineralization surface. Interleukin-1alpha and basic fibroblast growth factor staining did not differ between groups. Receptor activator of nuclear factor kappaB ligand bone expression was significantly higher in patients who had idiopathic hypercalciuria and exhibited higher versus normal bone resorption. A higher expression of receptor activator of nuclear factor kappaB ligand in bone tissue suggests that increased bone resorption in patients with idiopathic hypercalciuria is mediated by receptor activator of nuclear factor kappaB ligand. Osteoprotegerin bone expression might have been secondarily increased in an attempt to counteract the actions of receptor activator of nuclear factor kappaB ligand. The low bone expression of transforming growth factor-beta could contribute to the delayed mineralization found in such patients.