Intensive cancer chemotherapy is known to cause bone defects, which currently lack treatments.
In this study, published in the journal Nutrients, researchers investigated the effects of polyphenol resveratrol (RES) in preventing bone defects in rats caused by methotrexate (MTX), a commonly used antimetabolite in childhood oncology.
Their tests on rats found that MTX treatment alone had a trend of causing reductions in growth plate thickness and metaphyseal primary spongiosa height when compared to controls.
Initially, treatment with RES did not appear promising, with a 10mg/kg dose actually causing further damage.
“This data suggests that combination usage of MTX with RES at 10 mg/kg dose further aggravate the MTX bone damage effect. Consequently, this study has focused analyses more on the supplementation treatment effect of RES at 1 mg/kg dose.”
At the lower dose, however, RES supplementation demonstrated protective effects against MTX-induced bone damage.
“RES supplementation at 1 mg/kg was found to be able to prevent the reduction in bone volume fraction in metaphyseal secondary spongiosa after acute MTX chemotherapy,” they wrote.
The researchers said rapid advances in oncology meant intensive chemotherapy was resulting in improved cure rates, especially for children with acute lymphoblastic leukaemia. However, one of the major health threats associated with these effective chemotherapy regimens is the irreversible detrimental effects on bone.
“Currently, therapeutic approaches to successfully prevent or control bone loss caused by MTX chemotherapy are still lacking. RES, a naturally-occurring molecule, has been identified to have moderate protective effects in optimising bone health including age-related bone loss despite the unclear mechanisms.
“However, the current study demonstrated a significantly reduced growth plate thickness, shorter primary spongiosa height, reduced trabecular bone volume, as well as increased marrow adiposity following acute MTX treatment. However, RES supplementation demonstrated protective effects against MTX-induced bone damage in this rat model study.
“Additionally, RES appeared to maintain the expression of osteogenic factors and was shown to reduce the extent of marrow adiposity induced by MTX chemotherapy. Furthermore, RES was shown to be able to suppress the expression of osteoclastogenic factors and inhibit osteoclast formation, suggesting its potential in preventing osteoclast formation and, thus, bone resorption following MTX chemotherapy.”
They said the results obtained from the study had increased their understanding of RES’ effect in protecting bone during MTX treatment.
“RES is suggested to be a potential candidate for the development of preventative strategies to prevent the bone-related complications during and/or after MTX chemotherapy. Further studies are required to investigate its optimal dosage and its action mechanisms in protecting bone during cancer chemotherapy, including using cancer-bearing models,” they added.
Nutrients 2017, 9(3), 255; doi:10.3390/nu9030255
“Effects of Resveratrol Supplementation on Methotrexate Chemotherapy-Induced Bone Loss”
Authors: Alice M. C. Lee, et al