COMBINED FLURBIPROFEN AND CYCLOSPORINE-A DOES NOT ATTENUATE BONE LOSSAND EXAGGERATES RENAL IMPAIRMENT

Cyclosporine (CsA) is a potent immunosuppressant that has revolutioniz ed the success of organ transplantation. Flurbiprofen (FB), a propioni c acid derivative NSAID, has been demonstrated in vivo to reduce osteo clast numbers in normal rats, The aim of this experiment was to determ ine whether addition of FB to CsA-treated rats could prevent the bone changes associated with CsA therapy, Forty-eight 10-12-week-old male S prague-Dawley rats were randomized to receive, daily for 28 days: (1) CsA vehicle p.o. plus FB vehicle sc; (2) CsA (15 mg/kg) p.o. plus FB v ehicle sc, (3) CsA vehicle p.o. plus FB (1.5 mg/kg) sc; and (4) CsA (1 5 mg/kg) p.o. plus FB (1.5 mg/kg) sc. Rats were weighed and venous blo od sampled at baseline, 14 days, and 28 days for determination of gluc ose, Ca++, BUN, creatinine, PTH, osteocalcin, and 1,25(OH)(2) vitamin D. Tibiae were removed following killing, after double labeling for hi stomorphometry, Body mass was significantly lower than control in all rats receiving CsA on days 14 and 28 while blood glucose was only elev ated in the CsA alone group, Day 28 BUN and creatinine were significan tly elevated in the CsA group and the combination of CsA and FB reveal ed an exacerbation of this trend, Vitamin D and osteocalcin were consi stently increased in the CsA and CsA/EB groups, Bone histomorphometry showed evidence of trabecular osteopenia in CsA and CsA/EB groups, CsA alone resulted in elevated bone turnover, FB was unable to prevent th e trabecular bone loss induced by CsA therapy, This experiment indicat es no role for FB as a therapeutic option in CsA-induced bone disease at the given doses and duration of treatment by virtue of its lack of bone sparing ability and adverse renal effects when the two drugs are administered concurrently.