Diminished bone formation in experimental diabetes. Relationship to osteoid maturation and mineralization.
The pathogenesis of osteopenia in clinical diabetes remains uncertain. Thus, bone formation, mineralization, and resorption were measured over a 10-day period using double-tetracycline labeling of bone in control (C, N = 18), untreated diabetic (I-, N = 14), and insulin-treated diabetic (I+, N = 16) rats. Diabetes was induced by the intravenous (i.v.) injection of streptozotocin (STZ), 90 mg/kg, in citrate buffer. Bone and matrix (osteoid) formation and apposition were decreased by 50% from C values in I- rats (P less than 0.05), but were unchanged in I+ rats. Osteoid seam width and osteoid area were also less in I- (P less than 0.05), but similar in I+, when compared with C. In untreated diabetic rats that continued to actively form new bone, osteoid maturation and mineralization were not diminished when adjusted for the rate of bone formation. However, 5 of 14 untreated and 2 of 16 insulin-treated diabetic animals showed no uptake of tetracycline into bone (Chi-square, 8.54; P less than 0.05), suggesting a defect in mineralization in a subset of diabetic rats. Measurements of serum glucose, calcium, and phosphorus concentrations, of urinary excretion rates for glucose, calcium, and phosphorus, and of creatinine clearance failed to correlate with the changes in bone growth and histology observed. The results indicate heterogeneity in the response of bone in diabetes, and suggest that bone formation and osteoid volume are reduced early in the course of this disorder. These data in short-term diabetes support previous observations in both man and rat that indicate a state of low bone turnover in diabetes.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001846:Bone Development; D001862:Bone Resorption; D001842:Bone and Bones / Q000032:analysis*; D002118:Calcium / Q000097:blood / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008903:Minerals / Q000032:analysis*; D051381:Rats
D001786:Blood Glucose; D007328:Insulin; D008903:Minerals; D002118:Calcium