Effects of cefuroxime on human osteoblasts in vitro

Abstract

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 microg/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 microg/mL had little or no effect on cellular proliferation. Proliferation was significantly stimulated at 250 and 1000 microg/mL at each time. LDH-activity significantly increased at the highest concentration of 1000 microg/mL at 72 h. ALP-activity first increased at lower concentrations and then significantly decreased at 1000 microg/mL at 48 and 72 h. Similar to ALP-activity, calcification increased at lower concentrations and was not detectable at 1000 microg/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.

Effect of dual delivery of antibiotics (vancomycin and cefazolin) and BMP-7 from chitosan microparticles on Staphylococcus epidermidis and pre-osteoblasts in vitro

“…This indicates that cefazolin itself improves osteoblast viability and proliferation. This observation is also in support with another study, which observed an increase in the alkaline phosphate activity in the presence of cephalosporins [45,46]. On the other hand, vancomycin concentration of 1000 μg/ml was found to be toxic to OB-6 cell line, even in presence of BMP-7, which indicates its toxicity [45].…”

Effect of various concentrations of antibiotics on osteogenic cell viability and activity

“…Despite the difference in treatment duration between the current and previous studies, our data are consistent with several other studies in which shorter time periods were used and/or difference cell types were studied. 12,14,15,[17][18][19][20][21][22][23] This similarity both adds validity to our data and suggests that the negative effects imparted by high levels of antibiotics in this study may be a result of changes that occur at early time points.…”

“…18 Previous studies showed a potential benefit of antibiotics on osteogenic potential, especially the cephalosporins. For example, the cephalosporin cefurotoxime has the potential to increase ALP activity and proliferation, 23 and a cefazolin-loaded biodegradable polypeptide multilayer nanofilm improved osteoblast viability and proliferation. 12 Although we did not use the same doses as others for the cephalosporins, and although not significant, we observed a trend for increases in ALP activity for the cephalosporins as well (Fig.…”

The effect of teicoplanin on fracture healing: an experimental study

“…Salzman et al [23] used high doses of cefuroxime locally in the osteoblast environment and demonstrated increased new bone formation by elevation of alkaline phosphatase level. It has been suggested that, due to this feature, cefuroxime combined with cement could be used clinically to increase the periprosthetic new bone formation.…”