TY - JOUR
T1 - Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria
AU - Filipponi, Paolo
AU - Mannarelli, Carla
AU - Pacifici, Roberto
AU - Grossi, Enzo
AU - Moretti, Ivano
AU - Tini, Sauro
AU - Carloni, Carlo
AU - Blass, Andrea
AU - Morucci, Piero
AU - Hruska, Keith A.
AU - Avioli, Louis V.
PY - 1988/8/1
Y1 - 1988/8/1
N2 - 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 nonhypercalciuric 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<0.001; and from 370±39 to 246±40 mg/day, P<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<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.
AB - 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 nonhypercalciuric 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<0.001; and from 370±39 to 246±40 mg/day, P<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<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.
KW - Diclofenac
KW - Hypercalciuria
KW - Sulindac prostaglandin synthesis
UR - http://www.scopus.com/inward/record.url?scp=0023694396&partnerID=8YFLogxK
U2 - 10.1007/BF02555148
DO - 10.1007/BF02555148
M3 - Article
C2 - 3142668
AN - SCOPUS:0023694396
SN - 0171-967X
VL - 43
SP - 61
EP - 66
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 2
ER -