ROLE OF THE BONE IN THE PHYSIOPATHOLOGY OF IDIOPATHIC HYPERCALCIURIA - EFFECT OF AMINOBISPHOSPHONATE ALENDRONATE

Previous studies from our laboratory demonstrated that bone mineral co ntent is affected in patients with idiopathic hypercalciuria and that there is a correlation between bone mineral loss and in-vitro cytokine production. At the same time we found that short term treatment with alendronate decreased urinary calcium in these subjects. In the presen t study we have examined the long-term effects of alendronate treatmen t (10 mg/day for one year) on urinary calcium, urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric and 8 normoca lciuric stone formers. Clinical characteristics, as well as gender and age distribution were similar in both groups. Urinary calcium and hyd roxyproline, were measured monthly. Calcium excretion decreased signif icantly at the end of the first month, and remained lower thereafter ( 277 +/- 28, before vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p<0.01). Urinary hydroxyproline decreased significantly d uring the study (125.5 +/- 32.1 vs. 39.66 +/- 17.5 mg/g creatinine, p< 0.05). Serum calcium, glomerular filtration rate, and urinary sodium, did not change during the study. Lumbar spine bone density (trabecular bone) obtained with X ray absorptiometry revealed a significant incre ase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm(2) (p< 0.01). These c hanges were associated with a significant decrease in IL-1 alpha mRNA transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear cells, as tested by the reverse transcriptase polymerase c hain reaction. No changes were observed in bone cortical sites (femora l neck). Normocalciuric subjects showed no significant changes in urin ary calcium. In summary, the changes observed in urinary calcium excre tion and different bone metabolic parameters, suggest a role of bone i n the pathophysiology of idiopathic hypercalciuria.