Protective effect of teriparatide against vancomycin-induced cytotoxicity in osteoblasts.

Kentaro Tsuji, Soichiro Kimura, Kazuhiro Tateda, Hiroshi Takahashi

Journal: Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2023;28(6):1384-1391

PMID: 36371341

Abstract

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 cytotoxicity. The treatment practices involving osteogenesis-promoting drugs vary widely. Teriparatide, an anabolic agent, highly promotes bone formation by inducing osteoblast activation, increasing bone formation 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 °C in a humidified incubator containing 5% CO. The experimental concentrations of vancomycin (2500, 5000, and 7500 μg/mL) were determined based on previous reports and our preliminary 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 phosphatase activity, and alizarin red S staining.

RESULTS

Teriparatide showed a recovery effect when vancomycin (7500 μg/mL) was administered only for 24 h. Microscopic examination revealed that teriparatide had a protective effect on osteoblasts exposed to 7500 μg/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 teriparatide concomitantly with vancomycin.

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Address: Department of Orthopaedic Surgery, Toho University School of Medicine, 6-11-1 Omori-nishi, Ota-ku 143-8541, Tokyo, Japan.; Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, 5-21-16 Omori-nishi, Ota-ku 143-8540, Tokyo, Japan; Division of Infection Prevention and Control, Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, 16-10 Kamishinano, Totsuka-ku, Yohokaha 244-0806, Kanagawa, Japan. Electronic address: [email protected].; Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, 5-21-16 Omori-nishi, Ota-ku 143-8540, Tokyo, Japan.

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