Association between low C-peptide and fragility fractures in postmenopausal women without diabetes

Y. Ferro, C. Russo, D. Russo, C. Gazzaruso, A. Coppola, P. Gallotti, V. Zambianchi, M. Fodaro, S. Romeo, E. Galliera, M. G. Marazzi, M. M.C. Romanelli, S. Giannini, A. Pujia, T. Montalcini

Research output: Contribution to journalArticlepeer-review


Purpose: C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. Methods: A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients’ fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. Results: Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = −0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = −1.097, ES = 0.401, p = 0.006, 95% CI 0.15–0.73; B = −15.6, SE = 4.17, p < 0.001, CI 0.001–0.002; B = −24.8, SE = 5.23, p < 0.001, CI 0001–0.002; respectively). Conclusions: This study confirms an inverse association between serum C-peptide levels and a history of fractures in postmenopausal women without diabetes. These results suggest that C-peptidemay exert an effect on bone mineral density. However, further large-scale studies are needed to corroborate this finding and investigate the potential underlying mechanisms involved.

Original languageEnglish
Pages (from-to)1091-1098
Number of pages8
JournalJournal of Endocrinological Investigation
Issue number10
Publication statusPublished - Oct 1 2017


  • C-Peptide
  • Diabetes
  • Fractures
  • Osteoporosis
  • Postmenopausal women

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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