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Front. Endocrinol. | doi: 10.3389/fendo.2019.00587

Therapeutic Irradiation: Consequences for Bone and Bone Marrow Adipose

  • 1Maine Medical Center Research Institute, United States
  • 2University of Maine, United States
  • 3Sackler School of Graduate Biomedical Sciences, Tufts University, United States

Radiotherapy continues to be one of the most accepted medical treatments for cancer. Localized irradiation is the most common treatment for prostate, pancreatic, rectal, cervical and endometrial malignancies. Conventional localized fractions are total doses of 30-62Gy at 1.8-2Gy per fraction, with administration of ~60Gy often used for tumor ablation. However, even the lowest dose of localized irradiation exposure can result in adverse complications to adjacent organs, tissues, and vessels, which absorb a portion of the treatment. Skeletal complications are common amongst cancer patients undergoing these localized treatments. Irradiation exposure causes deterioration to the overall quantity and quality of bone by interfering with the trabecular architecture through increased osteoclast activity and decreased osteoblast activity. Irradiation-induced bone damage parallels adipocyte infiltration of the bone marrow (BM) resulting in compositional alterations of the microenvironment that may further affect bone quality and disease state. There may also be direct effects of irradiation on the BM adipocyte/pre-adipocyte, although in vitro findings do not always agree and cellular response is dependent on irradiation dosage. Hematopoietic cells also become apoptotic upon irradiation, which causes a range of skeletal effects. Bone loss leaves patients at a greater risk for osteopenia, osteoporosis, osteonecrosis, and skeletal fractures that drastically reduce quality of life. Osteoanabolic agents stimulate bone formation and reduce fracture risk in patients with low bone density; thus, osteoanabolic or anti-resorptive agents may be useful co-treatments with irradiation. This review discusses these topics and proposes further research directions using novel or combination therapies to enhance bone health during irradiation.

Keywords: irradiation, bone marrow adipose tissue, Bone marrow microenviroment, osteoblast, Adipocyte

Received: 13 May 2019; Accepted: 09 Aug 2019.

Edited by:

Nathalie Bravenboer, VU University Medical Center, Netherlands

Reviewed by:

ELENI DOUNI, Agricultural University of Athens, Greece
Monica De Mattei, University of Ferrara, Italy  

Copyright: © 2019 Costa and Reagan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Michaela R. Reagan, Maine Medical Center Research Institute, Scarborough, Maine, United States, michaela.r.reagan@gmail.com