Zoledronic acid improves muscle function in healthy mice treated with chemotherapy

Authors
BA Hain, B Jude, H Xu, DM Smuin, et al

Lab
Department of Cellular and Molecular Physiology, The Penn State College of Medicine, Hershey, PA, USA

Journal
Journal of Bone and Mineral Research

Abstract
Carboplatin is a chemotherapy drug used to treat solid tumors but also causes bone loss and muscle atrophy and weakness. Bone loss contributes to muscle weakness through bone_muscle crosstalk, which is prevented with the bisphosphonate zoledronic acid (ZA). We treated mice with carboplatin in the presence or absence of ZA to assess the impact of bone resorption on muscle. Carboplatin caused loss of body weight, muscle mass, and bone mass, and also led to muscle weakness as early as 7_days after treatment. Mice treated with carboplatin and ZA lost body weight and muscle mass but did not lose bone mass. In addition, muscle function in mice treated with ZA was similar to control animals. We also used the anti_TGF_ antibody (1D11) to prevent carboplatin_induced bone loss and showed similar results to ZA_treated mice. We found that atrogin_1 mRNA expression was increased in muscle from mice treated with carboplatin, which explained muscle atrophy. In mice treated with carboplatin for 1 or 3_days, we did not observe any bone or muscle loss, or muscle weakness. In addition, reduced caloric intake in the carboplatin treated mice did not cause loss of bone or muscle mass, or muscle weakness. Our results show that blocking carboplatin_induced bone resorption is sufficient to prevent skeletal muscle weakness and suggests another benefit to bone therapy beyond bone in patients receiving chemotherapy.

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)