TY - JOUR
T1 - Diabetic osteopathy and the IGF system in the Goto-Kakizaki rat
AU - Ahmad, Tashfeen
AU - Ugarph-Morawski, Anna
AU - Lewitt, Moira S.
AU - Li, Jian
AU - Sääf, Maria
AU - Brismar, Kerstin
N1 - Funding Information:
This study was supported by Grants from the Swedish Medical Research Council (00034, 13107, 04224), Swedish Diabetes Association, Swedish Foundation for Strategic Research, the Lundberg Foundation, family Persson Foundation and the Aga Khan University, Karachi, Pakistan. We thank Prof. Claes-Göran Östenson from the Department of Molecular Medicine, Endocrine and Diabetes Unit at Karolinska Hospital, Stockholm for supplying the GK rats, and Dr. E. Martin Spencer from the Laboratory of Growth and Development, California Pacific Medical Center Research Institute, San Francisco, CA, USA for the IGFBP-4 assays.
PY - 2008/10
Y1 - 2008/10
N2 - 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.
AB - 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.
KW - Bone mineral density
KW - Diabetes mellitus type-2
KW - Goto-Kakizaki rat
KW - Insulin-like growth factor 1
KW - Insulin-like growth factor binding protein 1
KW - Insulin-like growth factor binding protein 4
UR - http://www.scopus.com/inward/record.url?scp=46749124702&partnerID=8YFLogxK
U2 - 10.1016/j.ghir.2008.02.003
DO - 10.1016/j.ghir.2008.02.003
M3 - Article
C2 - 18381245
AN - SCOPUS:46749124702
SN - 1096-6374
VL - 18
SP - 404
EP - 411
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 5
ER -
