Diabetic osteopathy and the IGF system in the Goto-Kakizaki rat

Objective: Diabetes mellitus is associated with an increased risk of osteopenia, fracture and Charcot arthropathy. Abnormalities of the IGF system commonly observed in diabetes may underlie this "diabetic osteopathy" as IGF-I and its binding proteins (IGFBPs) have been shown to affect osteoblast and osteoclast activity. Design: In type-2 diabetic and control rats we analyzed IGF-I and IGFBP-1 and -4 levels in serum, and notably, also the IGF-I levels in cortical bone, ankles and vertebrae by immunoassays. Osteopathy was assessed by radiography and dual energy X-ray absorptiometry. Results: In the diabetic rats IGF-I was significantly reduced in serum and diaphyseal bone while IGFBP-1 and IGFBP-4 were increased in serum. The periosteal and endosteal diameters were increased in the diaphysis of humerus and tibia (changes similar to those in elderly humans) while bone mineral density was reduced in long bone metaphyses and vertebrae. Conclusions: Our study demonstrates both systemic and local disturbances of the IGF-system in rats with type-2 diabetes, consistent with the observed enhanced endosteal erosion in long bone diaphyses, and osteopenia in metaphyses and vertebrae. Whether similar IGF-system changes contribute to osteopathy in patients with diabetes and if treatment of diabetes can reverse the osteopathy has yet to be explored. (C) 2008 Elsevier Ltd. All rights reserved.