Improving Metabolic Control Reverses the Histomorphometric and Biomechanical Abnormalities of an Experimentally Induced Bone Defect in Spontaneously Diabetic Rats

Abstract

Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and to impair fracture-healing in both humans and animals. The objective of this study was to examine changes in the histomorphometric and mechanical parameters of bone and remodeling during bone-defect healing, depending on the diabetic metabolic state in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in humans. A standardized bone-defect model was chosen and based on blood-glucose values at the time of surgery (mg%), postoperative blood-glucose course (mg%), and postoperative insulin requirements (IU/kg). A total of 120 spontaneously diabetic BB/OK rats were divided into groups with a well-compensated (n = 60; 169 +/- 102 mg%; 230 +/- 126 mg%; and 2.2 +/- 1.1 IU/ kg) or poorly compensated (n = 60; 380 +/- 159 mg%; 359 +/- 89 mg%; and 5.4 +/- 1.1 IU/kg) metabolic state. Sixty LEW.1A rats served as the normoglycemic controls (93 +/- 19 mg%). Fifteen animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were processed undecalcified for quantitative bone histomorphometry and for biomechanical testing. Our study showed in terms of bone histomorphometry, within the first 14 days, that severe mineralization disorders occurred exclusively in the rats with a poorly compensated diabetic metabolic state with a highly significant (P < 0.001) or significant (P < 0.01) decrease of all fluorochrome-based parameters of mineralization, apposition, formation and timing of mineralization, as well as significantly decreased values of biomechanical properties (P < 0.05) in comparison to the spontaneously diabetic rats with a well-compensated metabolic state and to the control rats. Bone-defect healing in spontaneously diabetic BB/ OK rats is retarded exclusively in a poorly compensated diabetic metabolic state. This study suggests that strictly controlled insulin treatment resulting in a well-compensated diabetic metabolic state will ameliorate the impaired early and late parameters of IDDM bone-defect healing.

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

“…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).…”

Why metabolism matters in elective orthopedic surgery: A review

“…It has also been reported that systemic insulin treatment reverses this impaired bone healing (Macey et al 1989, Follak et al 2004. However, these studies do not discriminate between a direct effect of insulin on the bone and indirect systemic effects on skeletal metabolism.…”

MANAGEMENT OF ENDOCRINE DISEASE: Diabetes and osteoporosis: cause for concern?

“…Diabetes has been characterized as a disease of low bone turnover both by histomorphometry in rodent studies (11,12,13,14,15) and in two studies in human subjects (one involving six patients with T2D, two patients with T1D, and the other involving five patients with T2D and four controls) (16,17). However, another study in 18 T1D human patients did not show any differences in their markers of mineral apposition or bone structure (18).…”