The Association between the Serum C-Peptide Level and Bone Mineral Density

OBJECTIVE Although serum C-peptide was previously considered biologically inactive, a growing number of recent studies have shown that it is an active peptide with important physiologic functions. The present study aimed to investigate the association of serum C-peptide level with bone mineral density (BMD) in residents of the United States. METHODS The study included 6,625 participants aged 12-85 years. Total and regional BMD were measured using dual-energy X-ray absorptiometry. Stratified multiple linear regression analysis was performed to determine the association of the serum C-peptide level with BMD. Three regression models were produced for each stratum. All models were adjusted for ethnicity, height, weight, education level, physical activity, smoking status, alcohol use, triglycerides and creatinine level, and models 2 and 3 were further adjusted for the fasting plasma glucose (FPG) and alkaline phosphatase (ALP) levels, respectively. RESULTS Sex-specific results showed a significant association between the serum C-peptide level and total BMD in both sexes. Stratified analyses based on age and body mass index showed that serum C-peptide levels were significantly negatively associated with most regional BMD, and most of these associations remained significant after stratification based on the serum insulin level. CONCLUSION The serum C-peptide level was significantly negatively associated with the total and most regional BMD. These findings suggest that serum C-peptide may have biological activity associated with bone metabolism and therefore serum C-peptide control is advisable in order to reduce the risk of low bone mineral density.