Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro

We studied the inhibitory effects of the fluoroquinolones levofloxacin. cip rofloxacin, and trovafloxacin on growth and extracellular matrix mineraliza tion in MC3T3-E1 osteoblast-like cell cultures. Levofloxacin had the least inhibitory effect on cell growth, with a 50% inhibitory concentration of ap proximately 80 mug/ml at 48 and 72 hours. Ciprofloxacin had an intermediate degree of inhibition, with a 50% inhibitory concentration of 40 mug/ml at 48 and 72 hours. Trovafloxacin exerted a profound inhibitory effect on cell growth, with a 50% inhibitory concentration of 0.5 mug/ml, lower than clin ically achievable serum levels. The decreased cell counts with up to 2.5 mu g/ml of trovafloxacin and with up to 40 mug/ml of ciprofloxacin were not as sociated with decreased rates of 5-bromo-2'-deoxyuridine incorporation per cell. Alatrovafloxacin, the L-alanyl-1-alanine prodrug of trovafloxacin, ex erted effects on proliferation and 5-bromo-2'-deoxyuridine incorporation si milar to thr,se of the parent compound. The quinolones evaluated also inhib ited extracellular matrix mineralization by MC3T3-E1 cells. Treatment of co nfluent cultures with trovafloxacin, ciprofloxacin, or levofloxacin resulte d in strong inhibition of calcium deposition, as determined on day 14 by al izarin red staining, and biochemical analysis. The effect was apparent with 2.5-5 mug/ml of each of the three antibiotics tested and progressively inc reased to more than a 90% decline in the calcium/protein ratio with 20-30 m ug/ml antibiotic concentration. Further in vivo studies are advocated to ev aluate the relevance of the in vitro cytotoxicity reported here to bone hea ling in orthopaedic patients.