The influence on human osteoblasts in vitro of non-steroidal anti-inflammatory drugs which act on different cyclooxygenase enzymes.
There is increasing evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can adversely affect bone repair. We have, therefore, studied the in vitro effects of NSAIDs, which differentially inhibit cyclooxygenases (COX), the prostaglandin/thromboxane synthesising enzymes, on human osteoblasts. Indomethacin and the new nitric oxide (NO)-donating NSAIDs block the activity of both COX-1 and COX-2. Indomethacin and 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulphonal) phenyl-2 (5H)-furanone (DFU) reduced osteoblast numbers in a dose-dependant manner and increased collagen synthesis and alkaline phosphatase activity. The reduction in osteoblast numbers was not caused by loss of adhesion and was reversible. Neither NSAID influenced DNA synthesis. There was no difference between the effects of indomethacin and DFU. NO-NSAIDs did not affect cell numbers. These results suggest that care should be taken when administering NSAIDs to patients with existing skeletal problems and that NO-NSAIDs may be safer.
Evans
C E
CE
Medical School, University of Manchester, Manchester, England.
Butcher
C
C
D000082:Acetaminophen / Q000009:adverse effects / Q000031:analogs & derivatives; D000469:Alkaline Phosphatase / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects / Q000031:analogs & derivatives; D002452:Cell Count; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004247:DNA / Q000096:biosynthesis; D005480:Flurbiprofen / Q000009:adverse effects / Q000031:analogs & derivatives*; D005663:Furans / Q000009:adverse effects; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D009566:Nitrates / Q000009:adverse effects; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D010006:Osteoblasts / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D009566:Nitrates; D020030:Nitric Oxide Donors; C095631:nitroflurbiprofen; D009569:Nitric Oxide; D000082:Acetaminophen; D005480:Flurbiprofen; D003094:Collagen; D004247:DNA; D011451:Prostaglandin-Endoperoxide Synthases; D000469:Alkaline Phosphatase; C102148:nitroaspirin; C478738:4-(nitroxy)butanoic acid 4-acetylaminophenyl ester; D001241:Aspirin; D007213:Indomethacin