Effects of nonsteroidal anti-inflammatory drugs and prostaglandins on osteoblastic functions

It has been reported that nonsteroidal anti-inflammatory drugs (NSAIDs) sup press bone repair and bone remodeling but only mildly inhibit bone minerali zation at the earlier stage of the repair process. We proposed that the pro liferation and/or the earlier stage of differentiation of osteoblasts may b e affected by NSAIDs. This study was designed to investigate whether NSAIDs affect the proliferation and/or differentiation of osteoblasts and whether these effects are prostaglandin (PG) mediated. The effects of PGE, and PGE ,, indomethacin, and ketorolac on thymidine incorporation, cell count, intr acellular alkaline phosphatase (ALP) activity, and Type I collagen content in osteoblast-enriched cultures derived from fetal calvaria were evaluated. The results showed that both PGs and NSAIDs inhibited DNA synthesis and ce ll mitosis in a time- and concentration-dependent manner. However, intracel lular ALP activity and Type I collagen content were stimulated at an earlie r stage of differentiation in osteoblasts. These results suggested that (i) the inhibitory effect of ketorolac on osteoblastic proliferation contribut es to its suppressive effects on bone repair and remodeling in vivo; (ii) P GEs and NSAIDs may be involved in matrix maturation and biologic bone miner alization in the earlier stage of osteoblast differentiation; and (iii) the effects of ketorolac and indomethacin on cell proliferation and differenti ation may not be through the inhibition of the synthesis of PGE, or PGE,. B IOCHEM PHARMACOL 58;6:983-990, 1999. (C) 1999 Elsevier Science Inc.