The effects of clindamycin on human osteoblasts in vitro

Clindamycin is an antibiotic frequently used in different local application forms for the treatment of prosthetic joint infections, chronic osteomyelitis or as infection prophylaxis in bone cement. No information is available regarding its direct effects on bone cells, although very high local effective antibiotic concentrations can be achieved.We cultured pooled osteoblasts, previously derived from human trabecular bone specimens of four healthy donors, with different concentrations of clindamycin (0-500 microg/ml) for 24, 48 and 72 h. Cell proliferation (MTT), cytotoxicity [lactate dehydrogenase (LDH)-activity], cell metabolism [alkaline phosphatase (ALP)-activity] and extracellular matrix calcification (Alizarin staining) were assessed after antibiotic treatment.Proliferation significantly decreased in a dose-dependent manner and reached 3.5% of control samples at 500 microg/ml at 72 h. LDH-activity was unaffected at lower concentrations but significantly increased at 500 microg/ml at 48 and 72 h. ALP-activity significantly increased at 10 microg/ml at 24 and 48 h and then decreased in a time- and dose-dependent manner. Calcification increased at 10 and 25 microg/ml, while it decreased or no calcification was found at concentrations of 50 microg/ml and above.We could demonstrate that clindamycin at lower concentrations stimulated the cell metabolism of human osteoblasts and that higher clindamycin levels of 500 microg/ml had cytotoxic effects. The observed effects of high clindamycin levels on human osteoblasts highlight a potential alteration of bone metabolism in vivo and have to be taken into account in local antibiotic administration, e.g., in clindamycin-impregnated bone cement, where such high antibiotic concentrations can be achieved.