Bone mineral metabolism in experimental diabetes mellitus: osteocalcin as a measure of bone remodeling.
The etiology of diabetic osteopenia has not been established. The value of serum osteocalcin (BGP) as a marker of the bone abnormalities and the possible role of the polyol pathway in diabetic osteopenia were investigated. Three groups of rats were studied over 7 weeks: group D (n = 12), rats with streptozotocin (55 mg/kg)-induced diabetes given saline by gavage; group DS (n = 12), rats with streptozotocin-induced diabetes given the aldose reductase inhibitor sorbinil (25 mg/kg) daily by gavage; and group C (n = 6), saline-injected controls. Circulating levels of ionized calcium, BGP, amino-terminal PTH, and glucose were measured on days 0, 7, 14, 28, and 49. Tibial bone specimens were examined for the presence of aldose reductase by immunocytochemistry and by histomorphometry after tetracycline labeling. Diabetic rats with or without sorbinil treatment failed to gain weight [group D, 234 +/- 26 g; group DS, 217.0 +/- 40 g; group C, 310 +/- 33 g (mean +/- SD)]. Serum BGP levels decreased significantly in the diabetic rats within 7 days and remained lower throughout the study. BGP values on day 7 were: group D, 47.7 +/- 4.9 ng/ml; group DS, 65.9 +/- 5.5 ng/ml; and group C, 90.4 +/- 4 ng/ml (mean +/- SEM). Serum PTH levels were similar in all groups, except for day 49, when an increase in the D group was observed. Bone histomorphometry showed decreased bone remodeling in the D group, which confirmed the serum BGP findings. Aldose reductase was detectable in the small blood vessels and in bone itself. Sorbinil failed to influence the biochemical or bone histomorphometric abnormalities associated with diabetes. Serum BGP may be a valuable marker for the decreased bone remodeling in insulinopenic diabetes.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007700:Kinetics; D008297:Male; D008903:Minerals / Q000378:metabolism; D015675:Osteocalcin; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013977:Tibia
D002135:Calcium-Binding Proteins; D007093:Imidazoles; D048289:Imidazolidines; D008903:Minerals; D010281:Parathyroid Hormone; D015675:Osteocalcin; D003404:Creatinine; D000449:Aldehyde Reductase; C026411:sorbinil; D002118:Calcium