Defects of early fracture-healing in experimental diabetes.

Macey, Laurel; Sugimura, Kana; Jingushi, Seiya; Terek, Richard M.; Borretos, J; Bolander, Mark E.

doi:10.2106/00004623-198971050-00014

Cited by 205 publications

(135 citation statements)

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“…1). The uncontrolled streptozotocin-induced diabetic disease process weakened the intact contralateral femurs during the 6-week study, similar to other diabetic models [10][11][12]24]. The mean torque to failure of the intact femurs in the nondiabetic group at 4 weeks was 1.6 to 2.1 times greater (p \ 0.009 for all comparisons) than the failure torques of the intact femurs in the three diabetic treatment groups ( Table 3).…”

Section: Resultssupporting

confidence: 70%

Osteogenic Protein-1 Overcomes Inhibition of Fracture Healing in the Diabetic Rat: A Pilot Study

Kidder

Chen

Schmidt

et al. 2008

Clin Orthop Relat Res

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Type I diabetes mellitus inhibits fracture healing and leads to an increase in complications. As a pilot study, we used a closed fracture model in the diabetic rat to address the question of whether osteogenic protein-1 (OP-1) in a collagen carrier can overcome this inhibition by increasing the area of the newly mineralized callus and femoral torque to failure compared with diabetic animals with fractures treated without OP-1. Diabetes was created in 54 rats by injection of streptozotocin. After 2 weeks, a closed femur fracture was created using a drop-weight impaction device. Each fracture site was immediately opened and treated with or without 25 lg OP-1 in a collagen carrier. Animals were euthanized after 2 or 4 weeks. Fracture healing was assessed by callus area from highresolution radiographs, callus strength from torsional failure testing, and undecalcified histologic analysis. The area of newly mineralized callus was greater in diabetic animals treated with 25 lg OP-1/carrier compared with diabetic animals with untreated fractures and with fractures treated with carrier alone. This increase in callus area did not translate into an equivalent increase in torque to failure. Osteogenic protein-1 showed some evidence of overcoming the inhibition of fracture healing in the diabetic rat.

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Section: Resultssupporting

confidence: 70%

Osteogenic Protein-1 Overcomes Inhibition of Fracture Healing in the Diabetic Rat: A Pilot Study

Kidder

Chen

Schmidt

et al. 2008

Clin Orthop Relat Res

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“…The impairment in bone strength and metabolism in diabetic animals [8] is alleviated with insulin treatment [7,16]. Fracture healing in a streptozotocin (STZ) induced DM model also appears to be improved, at least in part, by the application of exogenous insulin [14,21]. Our laboratory has investigated fracture healing in the DM BB Wistar rat, a laboratory animal that represents a close homology to human Type I DM [34].…”

Section: Introductionmentioning

confidence: 99%

The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus

Beam

Parsons

Lin

2002

Journal Orthopaedic Research

177

141

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Several clinical series, analyzing fracture healing in patients with diabetes mellitus (DM), demonstrated significant incidence of delayed union, non-union, and pseudarthrosis. In this study, analysis was performed to evaluate the effects of blood glucose (BG) control on fracture healing in the D M BB Wistar rat, a rat strain that represents a close homology to Type I DM in man. Our study showed decreased cell proliferation at the fracture site as well as decreased mechanical stiffness and bony content in the poorly controlled DM rats. To determine the effect of BG control, D M rats were treated with insulin sufficient to maintain physiologic BG levels throughout the course of the study. Values of cellular proliferation, biomechanical properties and callus bone content in tightly controlled DM animals were not significantly different from values of non-DM control values. This study suggests that insulin treatment with resultant improved BG control will ameliorate the impaired early and late parameters of D M fracture healing.

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“…Previous studies have shown a relationship between diabetes and delayed fracture healing and bone defects in human and animal models (5)(6)(7)(8)(9)(10)(11)(12)(13). Fracture healing is a complex process, involving a cascade of synthesis and activation of matrix-and cell-derived molecules that coordinate the restoration of mechanical stability at the fracture site.…”

Section: Introductionmentioning

confidence: 99%

“…These include reduction in blood supply and angiogenesis (1), a more severe inflammatory response (18,19), a decrease in collagen synthesis (6,20,21), a disturbance in the mineralization process (9,11,12), and an imbalance between bone resorption by osteoclasts and bone deposition by osteoblasts (22)(23)(24). Another contributing factor may be the advanced glycation end products, present in high levels in diabetic individuals, that amplify inflammatory events (25) and delay wound healing (26).…”

Section: Introductionmentioning

confidence: 99%

“…Fracture healing and bone defects have been extensively studied in a variety of diabetes models including spontaneously diabetic BB/O(ttawa)K(arlsburg) rats (9)(10)(11)(12), BB Wistar rats (8) and streptozotocin-induced diabetic rats (6,7). Alloxan exerts direct cytotoxic action on the pancreatic islets, thereby eliminating the production of insulin and causing severe hyperglycemia in the animal.…”

Section: Introductionmentioning

confidence: 99%

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Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture

Diniz

Amorim

Cavalcante-Neto

et al. 2008

Braz J Med Biol Res

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A closed fracture was performed on the left tibia of 3-month-old Wistar rats weighing 250 to 350 g that were either healthy (N = 24) or made diabetic with alloxan (N = 24) to investigate the effect of alloxan-induced diabetes on the course of bone fracture healing. Histomorphometric analysis of the fracture site was performed at 7, 14, 25, and 35 days. After 7 days, diabetic rats had significantly less cartilage (P = 0.045) and greater fibrous connective (P = 0.006) tissue formation at the fracture site compared to controls. In contrast, marked callus formation was seen in diabetic rats with significant osteogenesis (P = 0.011, P = 0.010, P = 0.010, respectively, for 14, 25, and 35 days) and chondrogenesis (P = 0.028, P = 0.033, P = 0.019) compared to controls. Radiographic analysis revealed a displaced fracture with poor bone fragment alignment and delayed consolidation at these times in the diabetic group. The levels of alkaline phosphatase were significantly higher in diabetic rats at 25 days (P = 0.009). These results suggest that the initial excessive formation of fibrous connective tissue associated with delay in chondrogenesis and osteogenesis may not provide suitable stability of the fractured site, contributing to the inappropriate alignment of fragments and an increase in the volume of callus in later stages of repair. The resulting displaced fracture in diabetic rats requires long periods for remodeling and complete bone consolidation.

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Defects of early fracture-healing in experimental diabetes.

Cited by 205 publications

References 0 publications

Osteogenic Protein-1 Overcomes Inhibition of Fracture Healing in the Diabetic Rat: A Pilot Study

Osteogenic Protein-1 Overcomes Inhibition of Fracture Healing in the Diabetic Rat: A Pilot Study

The effects of blood glucose control upon fracture healing in the BB Wistar rat with diabetes mellitus

Alloxan-induced diabetes delays repair in a rat model of closed tibial fracture

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