POSSIBLE ROLE OF CYTOKINES ON THE BONE-MINERAL LOSS IN IDIOPATHIC HYPERCALCIURIA

Decreased bone mass has been reported in patients with idiopathic hype rcalciuria. Previous studies, using bioassays, have suggested a role o f interleukin-1 (IL-1), in the decreased bone mineral density (BMD) of fasting hypercalciuria. The present study was designed to determine w hich IL-1 fraction (alpha or beta) correlates with bone resorption and whether other known bone resorting cytokines like interleukin-6 (IL-6 ) and tumor necrosis factor alpha (TNF-alpha) may play a role in this process. Cytokines production was determined by quantitative and speci fic analysis, enzyme-linked immunosorbent assay (ELISA) and reverse tr anscriptase polymerase chain reaction (RT-PCR). Dual-energy X-ray abso rptiometry and cytokine production by unstimulated and lipopolysacchar ide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) were d etermined in a group of 29 patients with recurrent nephrolithiasis (17 hypercalciurics and 12 normocalciurics), and 12 healthy controls. The hypercalciuric subjects showed lower vertebral BMD than the normocalc iuric or normal controls. There was no difference in spinal or femoral BMD between absorptive or fasting hypercalciurics. A significant nega tive correlation existed between urinary calcium excretion and vertebr al BMD (r = -0.55, P < 0.01). Basal IL-1 alpha production correlated w ith vertebral BMD (r = -0.45, P < 0.02). This correlation was not seen with IL-1 beta, IL-6 or TNF-alpha production. LPS-induced IL-6 and TN F-alpha production were enhanced in the hypercalciuric patients, when compared to normocalciurics or controls. Control and normocalciuric su bjects showed minimal amounts of IL-1 alpha mRNA. In contrast, hyperca lciuric patients showed a significant increase of spontaneous IL-1 alp ha mRNA transcription. These results suggest that different cytokines could be involved in the bone resorption process observed in hypercalc iuria.