title: Immunoexpression of IGF1, IGF2, and osteopontin in craniofacial bone repair associated with autogenous grafting in rat models treated with alendronate sodium.
abstract: OBJECTIVE
  The aim of this study was to verify the likely influence of presurgical administration of low doses of alendronate sodium in craniofacial bone repair and correlate the histological frame found on reparative tissue to the immunohistochemical presence of IGF1, IGF2, and osteopontin (OP).
  
  
  METHODS
  In total, 120 rats were randomly allocated into four groups: group C (control), group OA (autogenous bone), group B (bisphosphonates), and group OA-B (autogenous bone + bisphosphonates). Groups B and OA-B received alendronate sodium (ALN) 0.01 mg/kg subcutaneously on alternate days for 4 weeks. Groups C and OA received saline solution. Critical 5-mm defects were created in rat calvaria, which were filled with blood clot in groups C and B and with autogenous bone in groups OA and OA-B. The animals were euthanized at 15 or 30 days postoperatively. Histological analysis and immunohistochemistry of IGF1, IGF2, and OP proteins was performed. Immunohistochemistry evaluated the expression in cells and extracellular matrix.
  
  
  RESULTS
  Groups C and B revealed healing predominantly characterized by connective tissue. In groups OA and OA-B, healing of connective tissue and neoformation of compact bone was observed. Expression of IGF1 an OP was present in all specimens. IGF1 expression in cells was more pronounced in groups OA and OA-B 15 days postoperatively. The expression of IGF2 was only observed in groups OA and OA-B, with greater intensity in group OA-B 30 days postoperatively. OP expression was only observed in cells and not in the extracellular matrix and was more pronounced in group OA 15 days postoperatively.
  
  
  CONCLUSIONS
  The application of systemic ALN at a dose of 0.01 mg/kg did not improve cranial bone matrix deposition. Nevertheless, the expression of IGF1 and OP and a slight marking of IGF2 were observed especially in groups OA and OA-B in the wound healing process. Future studies should assess higher doses of ALN to verify its influence on bone repair.
  
  
  CONCLUSIONS
  The systemic use of ALN 0.01 mg/kg on alternate days 4 weeks prior to surgery did not interfere with bone repair.
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Paulo Roberto
authors: PR
authors: Camati
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Allan Fernando
authors: AF
authors: Giovanini
authors: ILAPEO, Rua Jacarezinho, 656 - Mercês. CEP, Curitiba, PR, 80710-150, Brazil.
authors: Hugo Eduardo
authors: HE
authors: de Miranda Peixoto
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Cassiana Majewski
authors: CM
authors: Schuanka
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Maria Cecília
authors: MC
authors: Giacomel
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Melissa Rodrigues
authors: MR
authors: de Araújo
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: João César
authors: JC
authors: Zielak
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil.
authors: Rafaela
authors: R
authors: Scariot
authors: Universidade Positivo, Rua Prof. Pedro Viriato Parigot de Sousa, 5300 Campo Comprido. ZIP, Curitiba, PR, 81280-330, Brazil. tdeliberador@gmail.com.
authors: Tatiana Miranda
authors: TM
authors: Deliberador
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D053495:Osteopontin / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000601:surgery*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D050071:Bone Density Conservation Agents; D053495:Osteopontin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D019386:Alendronate
keywords: Bisphosphonates; Bone healing; IGF1; IGF2; Osteopontin; Rats