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Effect of methotrexate on fracture healing.

Journal article
Authors Koichiro Satoh
Hans Mark
Peter Zachrisson
Björn Rydevik
Gunnar Byröd
Shin-Ichi Kikuchi
Shin-Ichi Konno
Miho Sekiguchi
Published in Fukushima journal of medical science
Volume 57
Issue 1
Pages 11-8
ISSN 0016-2590
Publication year 2011
Published at Institute of Clinical Sciences, Department of Orthopaedics
Pages 11-8
Language en
Keywords Fracture healing, Methotrexate, bone formation
Subject categories Orthopaedics


Low doses of methotrexate (MTX) are safe and effective for treating adult and juvenile rheumatoid arthritis. However, because this powerful anti-inflammatory drug might negatively influence the healing of wounds and fractures, MTX administration is often stopped during surgical procedures. The present study assesses the effects of low- and high-dose MTX on early inflammatory processes and bone healing in an experimental model of fracture. Thirty male Sprague-Dawley rats were assigned to low- and high-dose MTX and control groups. A femur was cut using a reciprocating saw and a 2-mm fracture gap was made using a fixator. One or four weeks thereafter, macrophages were immunostained and new bone formation was histomorphometrically measured. Significantly less new bone was formed in the high-dose MTX, than in the control group (p< 0.01), whereas bone formation did not significantly differ between the low-dose MTX and control groups. These results suggested that a low dose of MTX does not affect the early process of endochondral bone formation during fracture healing, whereas a high dose might delay the progress of new periosteal bone formation. Although more macrophages were found in the groups treated with MTX, their impact on surrounding inflammatory processes remains unclear.

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