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Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy.

Authors
  • Hain, Brian A1
  • Jude, Baptiste1
  • Xu, Haifang1
  • Smuin, Dallas M2
  • Fox, Edward J2, 3
  • Elfar, John C2, 3
  • Waning, David L1, 3, 4
  • 1 Department of Cellular and Molecular Physiology, The Penn State College of Medicine, Hershey, PA, USA.
  • 2 Department of Orthopaedics and Rehabilitation, The Penn State College of Medicine, Hershey, PA, USA.
  • 3 Center for Orthopaedic Research and Translational Science, Hershey, PA, USA.
  • 4 Penn State Cancer Institute, Hershey, PA, USA.
Type
Published Article
Journal
Journal of Bone and Mineral Research
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 15, 2019
Identifiers
DOI: 10.1002/jbmr.3890
PMID: 31614017
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

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