Delayed remodeling in the early period of fracture healing in spontaneously diabetic BB/OK rats depending on the diabetic metabolic state

Abstract

Several clinical series, analyzing fracture healing in patients with insulin-dependent type 1 diabetes (IDDM) demonstrated significant incidence of delayed union, non-union, and pseudarthrosis. The purpose of this study was to examine the detailed histomorphometry and histology of bone formation and remodeling during fracture 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 man. A standardized fracture 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), 100 spontaneously diabetic BB/OK rats were divided into groups with well-compensated (n=50, 167±77 mg%; 244±68 mg%; 1.8±1.9 IU/kg) or poorly compensated (n=50, 380±89 mg%; 415±80 mg%; 6.0±1.0 IU/kg) metabolic state. Fifty LEW.1A rats served as the normoglycemic controls (97±15 mg%). Ten animals from each group were killed 1, 2, 3, 4 and 6 weeks after fracture and specimens were processed undecalcified for quantitative histomorphometry and for qualitative light microscopy. In terms of bone histomorphometry, within the first four weeks after fracture, severe mineralization disorders occurred exclusively in the rats with poorly compensated diabetic metabolic states with a significantly decrease of all fluorochrome-based parameters of mineralization, apposition, formation and timing of mineralization in comparison to the spontaneously diabetic rats with wellcompensated metabolic states and to the control rats. This was confirmed histologically. Early fracture healing in the spontaneously diabetic BB/OK rats is delayed exclusively in poorly compensated diabetic metabolic states, and 6 weeks after fracture, histomorphometrically significant deficits in the measured and dynamically calculated parameters remain. This study suggests that strictly controlled insulin treatment resulting in well-compensated diabetic metabolic states will ameliorate the impaired early mineralization and cell differentiation disorders of IDDM fracture healing.