title: No deleterious effect of low dose methotrexate on titanium implant osseointegration in a rabbit model.
abstract: OBJECTIVE
  To evaluate the effect of low dose methotrexate alone or in combination with glucocorticoid treatment on titanium implant osseointegration.
  
  
  METHODS
  Groups of 6-8 adult New Zealand White rabbits were treated for 18 weeks with saline (control), methotrexate, glucocorticoid, or methotrexate plus glucocorticoid. The animals received a titanium implant in the tibia at week 6. Lumbar spine and tibia bone mineral densities were analyzed before and after treatment. Histomorphometric analysis of bone cortical thickness, total bone area around the implant, and % of bone to implant contact was performed.
  
  
  RESULTS
  After 18 weeks, the change in the bone mineral density in the lumbar spines and tibias in the methotrexate group was comparable to the control group (0.035 vs. 0.055 g/cm² and 0.021 vs. 0.041 g/cm², respectively). In contrast, both the glucocorticoid group and glucocorticoid plus methotrexate group had significant reductions at both sites. Histomorphometric analysis of the tibia in the control and methotrexate groups revealed no significant changes in cortical thickness (133 vs. 126 μm), total bone area around the implant (33 vs. 30%), or bone to implant contact (40 vs. 38%). In contrast, glucocorticoid group had significant reductions compared to controls in tibia cortical thickness (99 vs. 133 μm), total bone area around the implant (24 vs. 33%), and bone to implant contact (27 vs. 40%). Similar reductions were observed in the glucocorticoid plus methotrexate group.
  
  
  CONCLUSIONS
  Our results demonstrate that low dose methotrexate treatment does not affect titanium implant osseointegration, suggesting that this therapy is safe for surgical procedures requiring a titanium implant.
authors.affiliation: Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, Brazil. bcarvas@hotmail.com
authors.forename: Janaina Badin
authors.initials: JB
authors.lastname: Carvas
authors.forename: Rosa Maria Rodrigues
authors.initials: RM
authors.lastname: Pereira
authors.forename: Eloisa
authors.initials: E
authors.lastname: Bonfá
authors.forename: Celey Aparecida
authors.initials: CA
authors.lastname: Silveira
authors.forename: Luiz Lapa
authors.initials: LL
authors.lastname: Lima
authors.forename: Valéria de Falco
authors.initials: Vde F
authors.lastname: Caparbo
authors.forename: Suzana Beatriz Veríssimo de
authors.initials: SB
authors.lastname: Mello
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D015519:Bone Density; D005938:Glucocorticoids / Q000008:administration & dosage; D008297:Male; D008422:Materials Testing; D008727:Methotrexate / Q000008:administration & dosage*; D023421:Models, Animal; D016348:Osseointegration / Q000187:drug effects*; D011817:Rabbits; D013977:Tibia; D013997:Time Factors; D014025:Titanium; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D014025:Titanium; D008727:Methotrexate