Protective effect of teriparatide against vancomycin-induced cytotoxicity in osteoblasts

Background: Intrawound vancomycin powder is effective in preventing surgical site infection after spine surgery. In a previous study, vancomycin-induced cytotoxicity in osteoblasts was investigated in vitro, and vitamin D3 was verified to be a candidate drug aiding recovery from vancomycin-induced cyto-toxicity. The treatment practices involving osteogenesis-promoting drugs vary widely. Teriparatide, an anabolic agent, highly promotes bone formation by inducing osteoblast activation, increasing bone for-mation and mineral density, and preventing vertebral fractures. Hence, teriparatide may be administered in combination with vancomycin. Methods: MC3T3-E1 cells were cultured in minimum essential medium supplemented with 10% fetal bovine serum at 37 degrees C in a humidified incubator containing 5% CO2. The experimental concentrations of vancomycin (2500, 5000, and 7500 mg/mL) were determined based on previous reports and our pre-liminary experiments. Teriparatide (100 ng/mL) was administered concomitantly to prevent cytotoxicity in osteoblasts, using pulsed vancomycin for 24 h (measured at 1, 3, and 7 days). Cell numbers and morphological changes in cells treated with vancomycin or vancomycin plus 100 ng/mL teriparatide were measured. Osteoblast differentiation was assessed using alkaline phosphatase staining, alkaline phos-phatase activity, and alizarin red S staining. Results: Teriparatide showed a recovery effect when vancomycin (7500 mg/mL) was administered only for 24 h. Microscopic examination revealed that teriparatide had a protective effect on osteoblasts exposed to 7500 mg/mL vancomycin. Addition of teriparatide led to the recovery of alkaline phosphatase staining and alizarin red staining. Conclusion: Vancomycin-induced cytotoxicity in osteoblasts could be inhibited by administering ter-iparatide concomitantly with vancomycin. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).