IDIOPATHIC HYPERCALCIURIA: O2-NO RELATIONSHIP AND ALTERED BONE METABOLISM

The pathogenesis of idiopathic hypercalciuria (IH) has not been elucidated yet,
but a correlation between IH and altered bone metabolism has been proposed. Since
nitric oxide (NO) regulates osteoclasts' bone resorption, a possible role for NO
can be suggested. In this study we evaluated iNOS gene expression by reverse
transcription of mRNA from monocytes, followed by polymerase chain reaction in
patients with IH subdivided into fasting (FH) and absorptive (AH) hypercalciuria.
Since superoxide (O2-), which metabolizes NO, is overproduced by osteoclasts
during bone resorption, peroxynitrite plasma level was evaluated as index of O2-.
Vertebral BMD in IH as a whole 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 30.1+/-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 patients, but not from both AH patients and C, expressed iNOS.
Peroxynitrite plasma level was elevated in FH (0.30+/-0.07) pmol/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
fact, points toward an altered NO system's activity downstream the generation of
NO. A possible interaction of NO with O2-, which breaks down NO, and the role of
this interaction in the pathophysiology of IH is discussed.