title: Fracture healing and biomarker expression in a diabetic Zucker rat model.
abstract: BACKGROUND
  Persons with diabetes have a higher incidence of fractures compared with persons without diabetes. However, there is little published information concerning the deleterious effect of late-stage diabetes on fracture healing. There are no studies using animal models that evaluate the effect of advanced diabetes on fracture healing. The purpose of our study was to evaluate cytokine expression, specifically macrophage inflammatory protein 1 (MIP-1) and vascular endothelial growth factor, in fracture healing in a type 2 diabetes rat model.
  
  
  METHODS
  We evaluated biomarker expression after femur fracture using a rat model. The two groups consisted of 24 Zucker diabetic rats (study group) and 12 Zucker lean rats (control group). An independent reviewer was used to assess delayed union. We evaluated serum samples 2, 4, 7, and 14 days after surgery for MIP-1, vascular endothelial growth factor, leptin, and other cytokine levels.
  
  
  RESULTS
  At 3 weeks, Kaplan-Meier estimates showed that 45.8% of femur fractures in Zucker diabetic rats had healed, whereas 81.8% of those in Zucker lean rats had healed (P = .02). A logistic regression model to predict fast healing that included the three cytokines and diabetes status showed that the only factor achieving significance was MIP-1α. Vascular endothelial growth factor was the only biomarker to show significance compared with delayed healing.
  
  
  CONCLUSIONS
  These results confirm significant differences in biomarker expression between diabetic and nondiabetic rats during bone healing. The key factors for bone healing may appear early in the healing process, whereas differences in diabetes versus nondiabetes are seen later in the healing process. Increased levels of MIP-1α were associated with the likelihood of delayed healing.
authors.forename: Javier La
authors.initials: JL
authors.lastname: Fontaine
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Hunt
authors.forename: Stacey
authors.initials: S
authors.lastname: Curry
authors.forename: Tyler
authors.initials: T
authors.lastname: Kearney
authors.forename: Daniel
authors.initials: D
authors.lastname: Jupiter
authors.forename: Naohiro
authors.initials: N
authors.lastname: Shibuya
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Lavery
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood*; D003921:Diabetes Mellitus, Experimental; D005269:Femur / Q000293:injuries / Q000601:surgery*; D017102:Fracture Healing / Q000502:physiology*; D050723:Fractures, Bone / Q000601:surgery*; D016015:Logistic Models; D023421:Models, Animal; D011924:Rats, Zucker; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D015415:Biomarkers; D054405:Chemokine CCL3; D042461:Vascular Endothelial Growth Factor A