Histomorphometric evaluation of the influence of the diabetic metabolic state on bone defect healing depending on the defect size in spontaneously diabetic BB/OK rats

Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and impair bone repair in both humans and animals. The objective of this study was the detailed histomorphometric evaluation of the influence of the diabetic metabolic state on bone formation and remodeling during bone defect healing depending on the defect size in spontaneously diabetic BB/O(ttawa)K(arlsburg) rats, a rat strain that represents a close homology to IDDM in man. Based on blood-glucose values at the time of surgery, postoperative blood-glucose course, and postoperative insulin requirements, 80 spontaneously diabetic BB/OK rats were divided into groups with well-compensated or poorly compensated metabolic state. Forty LEW.1A rats served as normoglycemic controls. Using a Kirschner wire, bone defects of different sizes were created proximal to the knee joint space in both femora. Ten animals from each group were killed on postoperative days 7, 14, 24, and 42, and specimens were processed undecalcified for quantitative bone histomorphometry. In terms of bone histomorphometry, our study did not show any differences in bone defect healing between the groups where the defect size was 0.4 mm. Larger bone defects (0.8 mm) only showed significant differences in the structural calculations after the 24th postoperative day exclusively in poorly compensated diabetic rats compared to well-compensated diabetic and control rats (P< 0.05 or P< 0.01). In bone defect sizes more than 1.2 mm, severe mineralization disorders occurred within the first 14 days exclusively in rats with 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 in comparison to spontaneously diabetic rats with well-compensated diabetic metabolic state and control rats. These results demonstrate that the bone repair of minor bone defects (0.4 mm) is independent of the diabetic metabolic state in spontaneously diabetic BB/OK rats. In larger bone defects (more than 0.8 mm), the bone defect healing in spontaneously diabetic BB/OK rats is impaired exclusively in poorly compensated diabetic metabolic states. This study suggests that strictly controlled insulin treatment resulting in a well-compensated diabetic metabolic state will ameliorate the impaired histomorphometric parameters of IDDM bone defect healing.