Long term administration of prostaglandin inhibitors in vivo fail to influence cartilage and bone mineral metabolism in the rat.
Non-steroidal anti-inflammatory drugs are potent inhibitors of prostaglandin synthesis. Prostaglandins have been reported to stimulate bone resorption and to enhance 1,25(OH)2D3 production in vitro. In patients with osteoarthritis of the hip, non-steroidal anti-inflammatory drugs are associated with localized accelerated bone destruction. The mechanisms for some of the in vivo effects are unknown. The effects of prostaglandin inhibitors on normal bone and mineral homeostasis has not been established. Therefore 15 male Sprague-Dawley rats were given daily injections of indomethacin, 2 mg/kg s.c., for either 4 or 8 weeks (a dose known to inhibit fracture healing) and compared to 13 control rats given vehicle alone. Serum Ca, BGP and 1,25(OH)2D were measured serially until day 56 in nine of those administered indomethacin and in seven of the control animals. Bone histomorphometry with double tetracycline labelling and cartilage histology were performed after sacrifice on days 28 and 56. Compared to control animals serum ionized calcium, BGP and 1,25(OH)2D levels were not altered by indomethacin administration. Quantitative histomorphometric indices of bone formation and resorption as well as cartilage histology were not significantly different between the two groups. With time, however, serum bone Gla protein fell in the control and indomethacin-treated groups, while calcium and 1,25-dihydroxyvitamin D remained stable. The age related decline in this serum marker of bone turnover was accompanied by a parallel reduction in the level of bone remodelling activity. These reductions in bone formation and bone resorption were not retarded or enhanced by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
Boiskin
I
I
Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141.
Epstein
S
S
Ismail
F
F
Fallon
M D
MD
Levy
W
W
D000818:Animals; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood; D002356:Cartilage / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008903:Minerals / Q000378:metabolism*; D015675:Osteocalcin; D051381:Rats; D011919:Rats, Inbred Strains
D002135:Calcium-Binding Proteins; D008903:Minerals; D015675:Osteocalcin; D002117:Calcitriol; D002118:Calcium; D007213:Indomethacin