Effects of cefuroxime on human osteoblasts in vitro

The local application of antibiotics in bone cement achieves high local effective antibiotic concentrations. Cefuroxime is widely used for antibiotic prophylaxis in orthopedic surgery, and several reports highlighted a beneficial outcome if cefuroxime-impregnated bone cement was used, but there is a lack of information of direct cefuroxime effects on human bone cells. We, therefore, cultured osteoblasts, previously derived from human trabecular bone specimens and used as a cell-pool further on, with different concentrations of cefuroxime (0-1000 μg/mL) for 24, 48, or 72 h. For reversibility testing, osteoblasts were cultivated for 24 h with cefuroxime followed by 48 h without antibiotics. 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. Cefuroxime concentrations of 25-100 μg/mL had little or no effect on cellular proliferation. Proliferation was significantly stimulated at 250 and 1000 μg/mL at each time. LDH-activity significantly increased at the highest concentration of 1000 μg/mL at 72 h. ALP-activity first increased at lower concentrations and then significantly decreased at 1000 μg/mL at 48 and 72 h. Similar to ALP-activity, calcification increased at lower concentrations and was not detectable at 1000 μg/mL. All revealed effects at 24 h were at least partially reversible. In the present study, we demonstrated that cefuroxime at lower concentrations had no inhibiting effects on human osteoblasts. In contrast, higher concentrations significantly altered osteoblastic function. When administered locally in total joint arthroplasty, for example, in antibiotic-impregnated bone cement, cefuroxime might critically impair osteoblastic function and periprosthetic bone metabolism.