Idiopathic hypercalciuria: O2-NO relationship and altered bone metabolism

The pathogenesis of idiopathic hypercatciuria (IH) has not been elucidated yet, but a correlation between IH and altered bone metabolism has been prop osed. Since nitric oxide (NO) regulates osteoclasts' bone resorption, a pos sible role for NO can be suggested. in this study we evaluated iNOS gene ex pression by reverse transcription of mRNA from monocytes, followed by polym erase chain reaction in patients with IH subdivided into fasting (FH) and a bsorptive (AH) hypercalciuria. Since superoxide (O-2(-)), which metabolizes NO, is overproducted by osteoclasts during bone resorption, peroxynitrite plasma level was evaluated as index of O-2(-). Vertebral BMD in IH as a who le group was lower vs controls (C) (Z score=-1.78+/-0.2 vs 0.51+/-0.25, p<0 .001), but only FH patients showed a reduced bone density (2.13+/-0.18 vs 0 .51+/-0.25, p<0.0001). PTH and calcitriol were not different. FH showed an increase in b-ALP vs AH and C (41.1+/-2.6 vs 30.4+/-3.9 vs 26.6+/-3.6 U/l p <0.02), and higher uHP, either on NCD (17.7+/-1.6 vs 11.4+/-1.3 mg/g uCr, p <0.04) or after LCD (26.7+/-2.5 vs 16.7+/-1.9, p<0.01). Cells from FH patie nts, but not from both AH patients and C, expressed iNOS. Peroxynitrite pla sma level was elevated in FH (0.30+/-0.07) mu mol/l while not detectable in AH and C. This study confirms an altered bone metabolism only in FH which shows an abnormal NO system. The increased iNOS gene expression in FH, in f act, points toward an altered NO system's activity downstream the generatio n of NO. A possible interaction of NO with O-2(-) which breaks down NO, and the role of this interaction in the pathophysiology of IH is discussed. (J . Endocrinol. Invest. 23: 78-83, 2000) (C)2000, Editrice Kurtis.