title: Bone formation around titanium implants in the rat tibia: role of insulin.
abstract: OBJECTIVE
  Clinical and experimental studies show, with few exceptions, that type 1 diabetes mellitus is associated with a delay in bone repair around endosseous implants. The effect of insulin in bone repair/remodeling is not completely understood. The aim of this study was to investigate the course of histological and ultrastructural changes of the osseointegration process under the influence of insulin.
  
  
  METHODS
  Titanium implants were inserted into the tibiae of male Wistar rats. Animals were divided into three groups: 1) rats with alloxan-induced diabetes; 2) diabetic rats treated with isophane insulin (2 IU/day); and 3) matching controls. Histological and histomorphometric analysis of bone-implant sections were performed 10 and 21 days after implant placement.
  
  
  RESULTS
  Relative to control values, rats with alloxan-induced diabetes exhibited a 50% reduction in the area of formed bone (P < 0.001) and in the surface of contact between bone and implant (P < 0.01) 21 days after implant placement. There were no significant differences between groups 10 days after surgery. Values returned to normal levels in diabetic rats after insulin treatment. Presence of chondrocyte-like cells surrounded by a cartilaginouslike matrix in diabetic rats suggests a delay in the process of bone repair. Ultrastructural characteristics of bone-implant interface in diabetic rats treated with insulin resembled those observed in controls.
  
  
  CONCLUSIONS
  The data presented suggest that bone repair around endosseous implants is regulated, at least in part, by insulin. The results imply that the control of the metabolic status of the diabetic patient is essential for a successful osseointegration.
authors.affiliation: Division of Dentistry, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: José T
authors.initials: JT
authors.lastname: Siqueira
authors.forename: Simone C
authors.initials: SC
authors.lastname: Cavalher-Machado
authors.forename: Victor E
authors.initials: VE
authors.lastname: Arana-Chavez
authors.forename: Paulina
authors.initials: P
authors.lastname: Sannomiya
mesh_terms: D000496:Alloxan; D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002356:Cartilage / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D015921:Dental Implants; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007336:Insulin, Isophane / Q000627:therapeutic use; D008297:Male; D008854:Microscopy, Electron; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D013977:Tibia / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D014025:Titanium
chemical_list: D015921:Dental Implants; D007004:Hypoglycemic Agents; D007328:Insulin; D007336:Insulin, Isophane; D000496:Alloxan; D014025:Titanium