Bone toxicity of locally applied aminoglycosides

The effect of tobramycin on osteoblasts was studied. Osteoblastlike cells from the MG-63 human osteosarcoma cell line were grown in antibiotic-free media and exposed to concentrations of tobramycin: First at order of magnitude intervals between 0 and 10,000 µg/ml, and then at closer intervals between 100 and 1,000 µg/ml to more accurately define toxic levels. Cell number and³H-thymidine incorporation at 0, 24 and 72 h were determined. Similarly, primary cultures of rat osteoblasts were exposed to the same concentrations of tobramycin to confirm the validity of the MG-63 cell line as a model for nontransformed cells. The results of this study demonstrate that local levels of tobramycin of ≤ 200 μg/ml have little or no effect on osteoblast replication. Concentrations of 400 μg/ml significantly decreased cell replication, and concentrations of 10,000 (µg/ml caused cell death. Results obtained with primary rat osteoblast cultures were similar to those obtained from the MG-63 cultures at the tested tobramycin concentrations.