Childhood cancer chemotherapy-induced bone damage: pathobiology and protective effects of resveratrol and other nutraceuticals.
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.
['Su|Yu-Wen|YW|', 'Chen|Ke-Ming|KM|', 'Hassanshahi|Mohammadhossein|M|', 'Tang|Qian|Q|', 'Howe|Peter R|PR|', 'Xian|Cory J|CJ|']
D000964:Antimetabolites, Antineoplastic D001862:Bone Resorption D002454:Cell Differentiation D002648:Child D019587:Dietary Supplements D006801:Humans D008727:Methotrexate D009369:Neoplasms D020011:Protective Agents D000077185:Resveratrol D013267:Stilbenes
cancer chemotherapy bone loss bone cell fish oil flavonoids