Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria.
This study was performed to assess whether treatment with prostaglandin synthesis inhibitors decreases calcium excretion in patients with idiopathic hypercalciuria. Nineteen hypercalciuric (12 with fasting hypercalciuria (FH), 7 with nonfasting hypercalciuria (NFH) and 8 control non-hypercalciuric stone formers were treated with sodium diclofenac, 50 mg t.i.d. for 2 weeks. After a washout phase, 7 FH patients received 200 mg/day of sulindac (a nonsteroidal antiinflammatory agent (NSAID) inactive on renal prostaglandin synthetase) for 14 more days. Diclofenac reduced urine calcium excretion in subjects with idiopathic hypercalciuria with either normal or elevated fasting urinary calcium (from 387 +/- 26 to 240 +/- 23 mg/day, P less than 0.001; and from 370 +/- 39 to 246 +/- 40 mg/day, P less than 0.05, respectively), whereas it was ineffective in normocalciuric stone formers. Similar antihypercalciuric effectiveness was exerted by sulindac in the seven FH patients. The antihypercalciuric action exerted by diclofenac in subjects with FH was associated with a significant increment in serum PTH (48 +/- 4 vs, 70 +/- 9 pmol/liter, P less than 0.05), whereas in NFH subjects, the antihypercalciuric effect of diclofenac on NFH was not associated with a change in parathyroid activity. Since the major effect of NSAIDs is to decrease prostaglandin synthesis, these data suggest that prostaglandins may play a pathogenetic role in idiopathic hypercalciuria. Furthermore, they suggest that PTH is suppressed in patients with FH, possibly due to stimulation of prostaglandin-mediated bone resorption process.
D000293:Adolescent; D000328:Adult; D001862:Bone Resorption; D002118:Calcium / Q000652:urine*; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D013467:Sulindac / Q000009:adverse effects / Q000627:therapeutic use
D010281:Parathyroid Hormone; D011453:Prostaglandins; D004008:Diclofenac; D013467:Sulindac; D002118:Calcium