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.