Fracture healing and biomarker expression in a diabetic Zucker rat model

Javier La Fontaine, Nathan A. Hunt, Stacey Curry, Tyler Kearney, Daniel Jupiter, Naohiro Shibuya, Lawrence A. Lavery

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)428-433
Number of pages6
JournalJournal of the American Podiatric Medical Association
Volume104
Issue number5
DOIs
StatePublished - Sep 1 2014
Externally publishedYes

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Macrophage Inflammatory Proteins
Zucker Rats
Fracture Healing
Biomarkers
Vascular Endothelial Growth Factor A
Cytokines
Femur
Logistic Models
Bone and Bones
Kaplan-Meier Estimate
Leptin
Ambulatory Surgical Procedures
Type 2 Diabetes Mellitus
Animal Models
Control Groups
Incidence
Serum

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Podiatry

Cite this

Fracture healing and biomarker expression in a diabetic Zucker rat model. / La Fontaine, Javier; Hunt, Nathan A.; Curry, Stacey; Kearney, Tyler; Jupiter, Daniel; Shibuya, Naohiro; Lavery, Lawrence A.

In: Journal of the American Podiatric Medical Association, Vol. 104, No. 5, 01.09.2014, p. 428-433.

Research output: Contribution to journalArticle

La Fontaine, Javier ; Hunt, Nathan A. ; Curry, Stacey ; Kearney, Tyler ; Jupiter, Daniel ; Shibuya, Naohiro ; Lavery, Lawrence A. / Fracture healing and biomarker expression in a diabetic Zucker rat model. In: Journal of the American Podiatric Medical Association. 2014 ; Vol. 104, No. 5. pp. 428-433.
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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.",
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N2 - 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.

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