Multivariate logistic regression analysis showed that serum IGF-I level was significantly lower in postmenopausal diabetic women with vertebral fractures than in those without fractures. Serum IGF-I level could be clinically useful for assessing the risk of vertebral fractures independent of BMD in postmenopausal women with type 2 diabetes. Introduction We investigated the relationships among serum IGF-I and C-peptide levels, BMD, and vertebral fractures in postmenopausal women with type 2 diabetes. Methods A total of 131 postmenopausal women with type 2 diabetes were consecutively recruited, and radiographic and biochemical characteristics were collected. Results Either IGF-I or C-peptide was not correlated with BMD at any site or bone metabolic markers, such as osteocalcin (OC) and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX). However, serum IGF-I level was significantly lower in subjects with vertebral fractures than in those without fractures (mean +/- SD: 106.9 +/- 50.0 vs. 142.8 +/- 50.8 ng/ml, p= 0.0006). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum IGF-I adjusted for the parameters described above as independent variables, IGF-I was selected as an index affecting the presence of vertebral fractures [ odds ratio=0.436, 95% confidential interval 0.234-0.814 per SD increase, p=0.0092]. This significance was almost the same after additional adjustment for lumbar BMD or C-peptide. Conclusions Serum IGF-I level could be clinically useful for assessing the risk of vertebral fractures independent of BMD in postmenopausal women with type 2 diabetes.