Altered bone metabolism of idiopathic hypercalciuria - A possible role for nitric oxide

The pathogenesis of idiopathic hypercalciuria has not yet elucidated, but a correlation between hypercalciuria and altered bone metabolism has been proposed. Since nitric oxide (NO) modifies osteoclasts' activity, a possible role for NO in the control of bone metabolism and in the pathophysiology of idiopathic hypercalciuria (Hi) can be suggested. To test this hypothesis, 49 patients affected by IH, on normal calcium diet (NCD) were assayed for plasma levels of creatinine (Cr), Ca++, ALP, b-ALP, PTH, calcitriol, BGP, along with 24 hrs urinary excretion of Cr, hydroxyproline (uHP), nitrite and nitrate (NO2-/NO3-). uHP was also evaluated in a spot urine sample either during NCD or after low calcium diet (LCD). Following LCD, Hi patients were grouped in fasting IH (FH) and absorptive IH CAH). Vertebral BMD in IH was lower vs controls (C), (Zscore=-0.92+/-0.17 us 0.27+/-0.25, p<0.002). PTH, calcitriol and BGP were not different in FH or AH and C. FH showed an increase in b-ALP us C (34.4+/-2.3 us 25.9+/-2.3 Un, p<0.03), and higher uHP in spot urines, either on NCD (14.1+/-0.7 vs 9.2+/-0.8 mg/g uCr, p<0.01) or after LCD (22.0+/-1.2 us 16.9+/-1.7, p<0.05). Interestingly, NO2-/NO3- urinary excretion in FH was lower vs AH and C (0.238+/-0.021 vs 0.273+/-0.022 mmol/mmol uCr, p<0.001, and vs 0.281+/-0.019, p<0.001), with no difference between AH and C. This study confirm the presence of an altered bone metabolism and lower BMD in FH and the decreased NO production in FH could participate to their higher bone turnover