Childhood cancer chemotherapy–induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals

• Published in: Annals of the New York Academy of Sciences Vol. 1403; no. 1; pp. 109 - 117
• Main Authors: Su, Yu‐Wen, Chen, Ke‐Ming, Hassanshahi, Mohammadhossein, Tang, Qian, Howe, Peter R., Xian, Cory J.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2017
• Subjects: Activation; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Biocompatibility; Biomedical materials; Bone cancer; bone cell; Bone growth; Bone loss; Bone marrow; Bone resorption; Bone Resorption - chemically induced; Bone Resorption - prevention & control; Cancer; cancer chemotherapy; Cell Differentiation - drug effects; Chemotherapy; Child; Children; Cytokines; Defects; Dietary Supplements; Fatty acids; fish oil; flavonoids; Functional foods & nutraceuticals; Genistein; Humans; Inflammation; Methotrexate; Methotrexate - adverse effects; Methotrexate - therapeutic use; Neoplasms - drug therapy; NF-κB protein; Population growth; Protective Agents - therapeutic use; Resveratrol; Stilbenes - therapeutic use; Wnt protein; bone cell; flavonoids; bone loss; cancer chemotherapy; fish oil
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13380

Intensive cancer chemotherapy causes significant bone loss, for which the mechanisms remain unclear and effective treatments are lacking. This is a significant issue particularly for childhood cancers, as the most common ones have a >75% cure rate following chemotherapy; there is an increasing population of survivors who live with chronic bone defects. Studies suggest that these defects are the result of reduced bone from increased marrow fat formation and increased bone resorption following chemotherapy. These changes probably result from altered expression/activation of regulatory molecules or pathways regulating skeletal cell formation and activity. Treatment with methotrexate, an antimetabolite commonly used in childhood oncology, has been shown to increase levels of proinflammatory/pro‐osteoclastogenic cytokines (e.g., enhanced NF‐κB activation), leading to increased osteoclast formation and bone resorption, as well as to attenuate Wnt signaling, leading to both decreased bone and increased marrow fat formation. In recent years, understanding the mechanisms of action and potential health benefits of selected nutraceuticals, including resveratrol, genistein, icariin, and inflammatory fatty acids, has led to preclinical studies that, in some cases, indicate efficacy in reducing chemotherapy‐induced bone defects. We summarize the supporting evidence.