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

P>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 center dot 61 +/- 0 center dot 20 [mean +/- SD] vs 0 center dot 55 +/- 0 center dot 19 mu m, P = 0 center dot 030) and symmetric dimethylarginine (SDMA) in postmenopausal women (0 center dot 72 +/- 0 center dot 37 vs 0 center dot 56 +/- 0 center dot 16 mu m, P < 0 center dot 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 beta = -0 center dot 28, p = 0 center dot 016), and SDMA was positively correlated with serum osteocalcin (beta = 0 center dot 38, P = 0 center dot 044) and urinary N-terminal cross-linked telopeptide of type-I collagen (beta = 0 center dot 40, P = 0 center dot 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 center dot 36, P = 0 center dot 044 and OR = 1 center dot 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.