Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment

Fan, Chiaming; Cool, Johanna C.; Scherer, Michaela; Foster, Bruce K.; Shandala, Tetyana; Tapp, Heather; Chen, Xian

doi:10.1016/j.bone.2008.09.014

Cited by 69 publications

(102 citation statements)

References 34 publications

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“…To ensure consistency across treatment groups, the same number and type of long bone (2 femurs, 1 tibia, and 2 humeri) were flushed and combined consistently between all animals. The bone marrow samples were then resuspended in basal minimum essential medium (␣-MEM; Sigma) containing 10% FBS (Invitrogen, Carlsbad, CA), 50 g/ml penicillin-streptomycin (Pen-Strep; Invitrogen, Carlsbad, CA), 15 mM HEPES (Sigma), and 130 M L-ascorbate (Sigma), as described (12).…”

Section: Methodsmentioning

confidence: 99%

“…Stained sections were used for morphometric measurements of growth plate total heights, heights of primary spongiosa, and bone volume of primary and secondary spongiosa metaphyseal bone using image analysis software AnalySIS (Olympus). Briefly, the entire height of the growth plate along an axis oriented 90°to the transverse of the growth plate and parallel to the longitudinal axis of the tibial bone was measured (12,48,49,51,52). Similarly, the average primary spongiosa zonal height at the metaphysis was also obtained using the same software (12,48,49,51,52).…”

Section: Methodsmentioning

confidence: 99%

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Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss

Nadhanan

Abimosleh

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Raghu Nadhanan R, Abimosleh SM, Su YW, Scherer MA, Howarth GS, Xian CJ. Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss. Am J Physiol Endocrinol Metab 302: E1440 -E1449, 2012. First published March 20, 2012; doi:10.1152/ajpendo.00587.2011Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day Ϫ1 ·rat Ϫ1 ) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H2O ϩ Sal, H2O ϩ 5-FU, EO ϩ 5-FU, and EO ϩ Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H2O ϩ 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNF␣, osteoclast marker receptor activator of nuclear factor-B, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss.receptor activator of nuclear factor-B ligand; tumor necrosis factor-␣; anti-inflammatory ANTI-CANCER CHEMOTHERAPY can cause significant adverse effects on tissues, including the bone, in both pediatric and adult cancer patients (25). Short stature, low bone mass or osteoporosis, and/or fractures are some skeletal side effects that are due to chemotherapy among pediatric patients and adult survivors (32, 38, 46). Experimental studies in rats have also shown that drugs such as methotrexate (MTX), cisplatin, doxorubicin, etoposide, cyclophosphamide, and 5-fluorouracil (5-FU) can cause a reduction in bone growth and bone mass (50 -52). 5-FU is an antimetabolite drug commonly used to treat adult patients suffering from colorectal and breast cancer, whereas in children 5-FU is used to treat childhood solid tumours (27, 36). 5-FU inhibits thymidylate synthase, an enzyme required to synthesize thymine nucleotide, which is important for synthesis of DNA and RNA (27). In an acute 5-FU chemotherapy model in rats, reduced primary spongiosa heigh...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss

Nadhanan

Abimosleh

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…38 High-dose MTX can damage the growth plate and primary bone, and the long-term use of MTX can reduce primary bone formation, likely due to decreased osteoblast function as well as increased osteoclast formation and function. 54,55 Methylenetetrahydrofolate reductase (MTHFR) polymorphisms can lead to mild to moderate increases in plasma homocysteine levels with homocysteinemia, leading to an increased risk of venous thrombosis. 56,57 Alkylating agents may harm gonadal function and lead to primary hypogonadism, which compromises bone mineralization if not adequately treated.…”

Section: Nonglucocorticoid Drugsmentioning

confidence: 99%

Osteonecrosis in children with acute lymphoblastic leukemia

et al. 2016

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“…The measurements on four separate sections for each sample were then averaged and expressed as percentages of the total injury site area (Chung et al 2006). In addition, to examine treatment effects on the uninjured areas of growth plate, images of the growth plate areas adjacent to the injury site were taken, and zonal height measurements were done on the resting zone, proliferative zone and hypertrophic zone by image analysis as described previously (Fan et al 2009). …”

Section: Elisa For Bevacizumabmentioning

confidence: 99%

The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage

Chung¹,

Foster²,

Chen³

2014

Journal of Endocrinology

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Damaging effects of chronic low-dose methotrexate usage on primary bone formation in young rats and potential protective effects of folinic acid supplementary treatment

Cited by 69 publications

References 34 publications

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss

Osteonecrosis in children with acute lymphoblastic leukemia

The potential role of VEGF-induced vascularisation in the bony repair of injured growth plate cartilage

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