title: The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.
abstract: BACKGROUND
  Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats.
  
  
  METHODS
  Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed.
  
  
  RESULTS
  When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment.
  
  
  CONCLUSIONS
  It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes.
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors: Samantha Cristine Santos X B
authors: SC
authors: Cavalcanti
authors: Department of General Pathology, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil.
authors: Luciana
authors: L
authors: Corrêa
authors: Department of Internal Medicine, Rheumatology Division, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
authors: Suzana Beatriz Veríssimo
authors: SB
authors: Mello
authors: Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: jgcluz@usp.br.
authors: João Gualberto C
authors: JG
authors: Luz
mesh_terms: D000469:Alkaline Phosphatase / Q000032:analysis / Q000187:drug effects; D000818:Animals; D001284:Atrophy; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000473:pathology; D002146:Bony Callus / Q000187:drug effects / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D003238:Connective Tissue / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D051445:Fibrocartilage / Q000187:drug effects / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D008335:Mandibular Condyle / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D008337:Mandibular Fractures / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D010012:Osteogenesis / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013704:Temporomandibular Joint / Q000187:drug effects / Q000293:injuries; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D000469:Alkaline Phosphatase; D008727:Methotrexate
keywords: Animal model; Mandibular condyle; Maxillary fractures; Methotrexate; Temporomandibular joint