@article{5abbfa3f519a4d69914bd9f8d4e91df6,
title = "Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy",
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-TGFβ 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.",
author = "Hain, {Brian A.} and Baptiste Jude and Haifang Xu and Smuin, {Dallas M.} and Fox, {Edward J.} and Elfar, {John C.} and Waning, {David L.}",
note = "Funding Information: DLW was supported by the NIH (CA205437), Phi Beta Psi Sorority, and the Pennsylvania Breast Cancer Coalition. BAH was supported by the Penn State Cancer Institute. Authors' roles: All contributing authors have agreed to submission of this manuscript for publication. BAH, BJ, and DLW conceived of the study. BAH, BJ, and DLW designed experiments, performed experiments, analyzed data, and interpreted results. DLW, EJF, and JCE designed experiments and interpreted results. BAH, BJ, HX, DMS, and DLW performed experiments. BAH and DLW wrote the manuscript. All authors approved the final version of the manuscript. DLW takes responsibility for the integrity of the data analysis. Funding Information: DLW was supported by the NIH (CA205437), Phi Beta Psi Sorority, and the Pennsylvania Breast Cancer Coalition. BAH was supported by the Penn State Cancer Institute. Authors' roles: All contributing authors have agreed to submission of this manuscript for publication. BAH, BJ, and DLW conceived of the study. BAH, BJ, and DLW designed experiments, performed experiments, analyzed data, and interpreted results. DLW, EJF, and JCE designed experiments and interpreted results. BAH, BJ, HX, DMS, and DLW performed experiments. BAH and DLW wrote the manuscript. All authors approved the final version of the manuscript. DLW takes responsibility for the integrity of the data analysis. Publisher Copyright: {\textcopyright} 2019 American Society for Bone and Mineral Research",
year = "2020",
month = feb,
day = "1",
doi = "10.1002/jbmr.3890",
language = "English (US)",
volume = "35",
pages = "368--381",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "2",
}