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Fish oil in comparison to folinic acid for protection against adverse effects of methotrexate chemotherapy on bone
Author(s) -
Raghu Nadhanan Rethi,
Fan ChiaMing,
Su YuWen,
Howe Peter R.C.,
Xian Cory J.
Publication year - 2014
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22565
Subject(s) - folinic acid , osteoclast , bone marrow , bone resorption , adipogenesis , endocrinology , medicine , chemistry , osteoblast , bone density , rosiglitazone , proinflammatory cytokine , bone mineral , osteoporosis , pharmacology , cancer research , chemotherapy , biochemistry , inflammation , adipose tissue , insulin , in vitro , fluorouracil , receptor
Methotrexate (MTX) chemotherapy is known to cause bone loss which lacks specific preventative treatments, although clinically folinic acid is often used to reduce MTX toxicity in soft tissues. This study investigated damaging effects of MTX injections (0.75 mg/kg/day for 5 days) in rats and potential protective benefits of fish oil (0.25, 0.5, or 0.75 ml/100 g/day) in comparison to folinic acid (0.75 mg/kg) in the tibial metaphysis. MTX treatment significantly reduced height of primary spongiosa and volume of trabecular bone while reducing density of osteoblasts. Consistently, MTX reduced osteogenic differentiation but increased adipogenesis of bone marrow stromal cells, accompanied by lower mRNA expression of osteogenic transcription factors Runx2 and Osx, but an up‐regulation of adipogenesis‐related genes FABP4 and PPAR‐γ. MTX also increased osteoclast density, bone marrow osteoclast formation, and mRNA expression of proinflammatory cytokines IL‐1, IL‐6, TNF‐α, and RANKL/OPG ratio in bone. Fish oil (0.5 or 0.75 ml/100 g) or folinic acid supplementation preserved bone volume, osteoblast density, and osteogenic differentiation, and suppressed MTX‐induced cytokine expression, osteoclastogenesis, and adipogenesis. Thus, fish oil at 0.5 ml/100 g or above is as effective as folinic acid in counteracting MTX‐induced bone damage, conserving bone formation, suppressing resorption and marrow adiposity, suggesting its therapeutic potential in preventing bone loss during MTX chemotherapy. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:587–596, 2014.