Relationships between dimethylarginine and the presence of vertebral fractures in type 2 diabetes mellitus

Summary Objective  Although previous studies suggested that nitric oxide (NO) could affect bone metabolism, little is known about whether asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is associated with the risk of osteoporotic fractures. Methods  A cross-sectional study was carried out to examine the associations of serum dimethylarginines with bone mineral density (BMD), bone turnover markers, and the presence of vertebral fractures in 226 men and 152 postmenopausal women with type 2 diabetes. Results  In subjects with vertebral fractures, there was significantly higher serum ADMA in men (0·61 ± 0·20 [mean ± SD] vs 0·55 ± 0·19 μm, P = 0·030) and symmetric dimethylarginine (SDMA) in postmenopausal women (0·72 ± 0·37 vs 0·56 ± 0·16 μm, P < 0·001) than in those without fractures. In men with vertebral fractures, serum ADMA was negatively correlated with Z-score at one-third radius (multiple regression β = −0·28, p = 0·016), and SDMA was positively correlated with serum osteocalcin (β = 0·38, P = 0·044) and urinary N-terminal cross-linked telopeptide of type-I collagen (β = 0·40, P = 0·027). In addition, serum ADMA in men and SDMA in postmenopausal women were positively associated with the presence of vertebral fractures after adjusting for age, duration of diabetes, and lumbar BMD (multiple logistic regression odds ratio [OR] = 1·36, P = 0·044 and OR = 1·78, P = 0 .006, respectively). Conclusions  We report, for the first time, that serum dimethylarginines may be independent risk factors for prevalent vertebral fractures in patients with type 2 diabetes.