title: Effect of methotrexate on fracture healing.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Satoh
authors.forename: Hans
authors.initials: H
authors.lastname: Mark
authors.forename: Peter
authors.initials: P
authors.lastname: Zachrisson
authors.forename: Björn
authors.initials: B
authors.lastname: Rydevik
authors.forename: Gunnar
authors.initials: G
authors.lastname: Byröd
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Konno
authors.forename: Miho
authors.initials: M
authors.lastname: Sekiguchi
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D005269:Femur / Q000187:drug effects; D017102:Fracture Healing / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D010012:Osteogenesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018501:Antirheumatic Agents; D050071:Bone Density Conservation Agents; D008727:Methotrexate