DECREASED OSTEOBLAST ACTIVITY IN SPONTANEOUSLY DIABETIC RATS - IN-VIVO STUDIES ON THE PATHOGENESIS

Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused by serum-borne factors. To explore its pat hogenesis, we carried out experiments in diabetic and nondiabetic BB r ats, using plasma osteocalcin concentrations (OC) as a marker for oste oblast activity. In nondiabetic rats, the iv infusion of glucose (30%, 4 d) did not change OC; sc insulin infusion (4 U/d, 14 d) reduced OC by 27% (p < 0.01). In diabetic rats, OC were decreased from the first day of glycosuria (71 +/- 5% of paired controls), declining exponentia lly to 24 +/- 3% after 5 wk. Insulin infusion (1,2, and 3 U/d, 14 d) p roduced gradual restoration of OC. OC were better correlated with insu lin-like growth factor-I (IGF-I) than with insulin levels in these exp eriments. OC were dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73 +/- 8 vs 22 +/- 4 mu g/L before ADX; p < 0.0 01), but not if corticosterone was administered. Ligand blotting of IG F binding proteins showed a marked decrease in two bands (44-49 and 32 -35 kDa) 10-14 d after diabetes onset; the density of these bands was increased, but not normalized after ADX. Thus, decreased osteoblast ac tivity is present from the onset of diabetes, is dependent on endogeno us corticosterone, and cannot be reproduced by hyperglycemia in nondia betic rats.