Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes

Summary: In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass.Introduction: It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density.Methods: Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay.Results: rteen percent of the population had osteoporosis and 38 % had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group (p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = −0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013).Conclusions: These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes.