LABORATORY AND ANIMAL STUDIES

Effects of Steroid, Nonsteroidal Anti-inflammatory Drugs and COX-2 Selective Inhibitors on Proliferation and Cytotoxicity in Human Osteoblasts
ML Ho, JK Chang, CJ Li, GJ Wang
Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress bone repair and remodeling in vivo. Our previous studies showed that NSAIDs inhibited osteoblast proliferation and induced cell death in fetal rat osteoblast cultures. However, the NSAIDs effects on the functions of human osteoblasts remain unclear. Newly developed selective cyclo-oxygenase 2 (COX-2) inhibitors, celecoxib and refecoxib, were reported to have lower risk of gastrointestinal complications than traditional nonsteroidal anti-inflammatory drugs. Recent reports showed that refecoxib decreased bone ingrowth in an animal study. However, the effects of COX-2 selective inhibitors on human osteoblast are rarely investigated. In this study, the effects of steroid, non-selective and selective COX-2 inhibitors on proliferation, cell cycle kinetics and cytotoxicity in cultured human osteoblast were examined. Indomethacin, ketorolac, piroxicam and diclofenac (10-5 and 10-4M); dexamethasone (10-7 and 10-6M); Celecoxib and DFU, an analogue of rofecoxib, (10-7-10-4M) were tested for 24 or 48 hr in human osteoblast cultures. In this study, we found that COX-2 selective inhibitor, celecoxib and DFU, significantly inhibited proliferation, arrest cell cycle and had cytotoxicity after 24 hr treatments in cultured human osteoblasts. However, the inhibitory effect on proliferation could be reversed if withdrew the agents for 24 hr. Indomethacin, ketorolac, diclofenac and piroxicam also significantly inhibited proliferation and arrested cell cycle at G0/G1 phase, but no cytotoxic effects in human osteoblasts. These results suggest that the COX-2 selective and non-selective NSAIDs may affect osteoblastic functions through different mechanisms.