Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BMI:

Body mass index

WC:

Waist circumference

HC:

Hip circumference

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

DXA:

Dual X-ray absorptiometry

BMD:

Bone mineral density

CTx:

C-Terminal telopeptide of type I collagen

NTx:

N-Terminal telopeptide of type I collagen

25OH-vitamin D:

25-Hydroxy-vitamin D

References

  1. Reginster JY, Burlet N (2006) Osteoporosis: a still increasing prevalence. Bone 38:S4–S9

    Article  PubMed  Google Scholar 

  2. Melton LJ III, Chrischilles EA, Cooper C, Lane AW, Riggs BL (1992) Perspective: how many women have osteoporosis? J Bone Miner Res 7:1005–1010

    Article  PubMed  Google Scholar 

  3. Nguyen TV, Center JR, Eisman JA (2000) Osteoporosis in elderly men and women: effects of dietary calcium, physical activity, and body mass index. J Bone Miner Res 15:322–331

    Article  CAS  PubMed  Google Scholar 

  4. Montalcini T, Romeo S, Ferro Y, MigliaccioV Gazzaruso C, Pujia A (2013) Osteoporosis in chronic inflammatory disease: the role of malnutrition. Endocrine 43:59–64

    Article  CAS  PubMed  Google Scholar 

  5. Greenfield DM, Eastell R (2001) Risk factors for ankle fracture. Osteoporos Int 12:97–103

    Article  CAS  PubMed  Google Scholar 

  6. Montalcini T, Gallotti P, Coppola A, Zambianchi V, Fodaro M, Galliera E, Marazzi MG, Romeo S, Giannini S, Corsi Romanelli MM, Pujia A, Gazzaruso C (2015) Association between low C-peptide and low lumbar bone mineral density in postmenopausal women without diabetes. Osteoporos Int 26:1639–1646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhukouskaya VV, Eller-Vainicher C, Shepelkevich AP, Dydyshko Y, Cairoli E, Chiodini I (2015) Bone health in type 1 diabetes: focus on evaluation and treatment in clinical practice. J Endocrinol Invest 38:941–950

    Article  CAS  PubMed  Google Scholar 

  8. Hills CE, Brunskill NJ (2008) Intracellular signalling by C-peptide. Exp Diabetes Res 2008:635158

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wahren J, Kallas A, Sima AA (2012) The clinical potential of C-peptide replacement in type 1 diabetes. Diabetes 61:761–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bhatt MP, Lim YC, Hwang J, Na S, Kim YM, Ha KS (2013) C-peptide prevents hyperglycemia induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes 62:243–253

    Article  CAS  PubMed  Google Scholar 

  11. Steffes MW, Sibley S, Jackson M, Thomas W (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26:832–836

    Article  PubMed  Google Scholar 

  12. Lachin JM, McGee P, Palmer JP (2014) Impact of C-peptide preservation on metabolic and clinical outcomes in the Diabetes Control and Complications Trial. Diabetes 63:739–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gubitosi-Klug RA (2014) The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: summary and future directions. Diabetes Care 37:44–49

    Article  PubMed  Google Scholar 

  14. Hills CE, Brunskill NJ, Squires PE (2010) C-peptide as a therapeutic tool in diabetic nephropathy. Am J Nephrol 31:389–397

    Article  CAS  PubMed  Google Scholar 

  15. Calcutt NA, Cooper ME, Kern TS, Schmidt AM (2009) Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov 8:417–429

    Article  CAS  PubMed  Google Scholar 

  16. López-Ibarra PJ, Pastor MM, Escobar-Jiménez F, Pardo MD, González AG, Luna JD, Requena ME, Diosdado MA (2001) Bone mineral density at time of clinical diagnosis of adult-onset type 1diabetes mellitus. Endocr Pract 7:346–351

    Article  PubMed  Google Scholar 

  17. Abrahamsen B, van Staa T, Ariely R, Olson M, Cooper C (2009) Excess mortality following hip fracture: a systematic epidemiological review. Osteoporos Int 20:1633–1650

    Article  CAS  PubMed  Google Scholar 

  18. Felson DT, Kiel DP, Anderson JJ, Kannel WB (1988) Alcohol consumption and hip fractures: the Framingham Study. Am J Epidemiol 128:1102–1110

    Article  CAS  PubMed  Google Scholar 

  19. Centers for Disease Control and Prevention Tobacco use among adults—United States (2006) MMWR 55:1145–1148

  20. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Mineral Res 8:1137–1148

    Article  CAS  Google Scholar 

  21. Montalcini T, Gorgone G, Federico D, Ceravolo R, Emanuele V, Sesti G, Perticone F, Pujia A (2005) Association of LDL cholesterol with carotid atherosclerosis in menopausal women affected bythe metabolic syndrome. Nutr Metab Cardiovasc Dis 15:368–372

    Article  PubMed  Google Scholar 

  22. Montalcini T, Terracciano R, Romeo S, Foti D, Gulletta E, Costanzo FS, Pujia A (2012) Postmenopausal women with carotid atherosclerosis: potential role of the serum calcium levels. Nutr Metab Cardiovasc Dis 23:1141–1146

    Article  Google Scholar 

  23. Glynn NW, Meilahn EN, Charron M, Anderson SJ, Kuller LH, Cauley JA (1995) Determinants of bone mineral density in older men. J Bone Miner Res 10:1769–1777

    Article  CAS  PubMed  Google Scholar 

  24. Report of a WHO Study Group (1994) World Health Organization: assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organ Tech Rep Ser 843:1–129

    Google Scholar 

  25. Lamprinoudi T, Mazza E, Ferro Y, Brogneri S, Foti D, Gulletta E, Iocco M, Gazzaruso C, Romeo S, Pujia A, Montalcini T (2014) The link between nutritional parameters and bone mineral density in women: results of a screening programme for osteoporosis. J Transl Med 12:46

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ying L, Hua L, Yasuto S (2013) The association between the serum C-peptide level and bone mineral density. PLoS One 8:e83107

    Article  Google Scholar 

  27. Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes & a meta-analysis. Osteoporos Int 18:427–444

    Article  CAS  PubMed  Google Scholar 

  28. Hothersall EJ, Livingstone SJ, Looker HC, Ahmed SF, Cleland S, Leese GP, Lindsay RS, McKnight J, Pearson D, Philip S, Wild SH, Colhoun HM (2014) Contemporary risk of hip fracture in type 1 and type 2 diabetes: a national registry study from Scotland. J Bone Miner Res 29:1054–1060

    Article  PubMed  Google Scholar 

  29. Saha MT, Sievänen H, Salo MK, Tulokas S, Saha HH (2009) Bone mass and structure in adolescents with type 1 diabetes compared to healthy peers. Osteoporos Int 20:1401–1406

    Article  CAS  PubMed  Google Scholar 

  30. MaurelDB Boisseau N, Benhamou CL, Jaffre C (2012) Alcohol and bone: review of dose effects and mechanisms. Osteoporos Int 23:1–16

    Article  Google Scholar 

  31. WheaterG Elshahaly M, Tuck SP, Datta HK, van Laar JM (2013) The clinical utility of bone marker measurements in osteoporosis. J Transl Med 11:201

    Article  Google Scholar 

  32. Francis MJ, Lees RL, Trujillo E, Martín-Vasallo P, Heersche JN, Mobasheri A (2002) ATPase pumps in osteoclasts and osteoblasts. Int J Biochem Cell Biol 34:459–476

    Article  CAS  PubMed  Google Scholar 

  33. Russo C, Lazzaro V, Gazzaruso C, Maurotti S, Ferro Y, Pingitore P, Fumo F, Coppola A, Gallotti P, Zambianchi V, Fodaro M, Galliera E, Marazzi MG, CorsiRomanelli MM, Giannini S, Romeo S, Pujia A, Montalcini T (2017) Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human Osteoblast-like cells (Saos-2). Mol Cell Endocrinol 442:134–141

    Article  CAS  PubMed  Google Scholar 

  34. Kazafeos K (2011) Incretin effect: GLP-1, GIP, DPP4. Diabetes Res Clin Pract 93(S1):S32–S36

    CAS  PubMed  Google Scholar 

  35. Lu N, Sun H, Yu J, Wang X, Liu D, Zhao L, Sun L, Zhao H, Tao B, Liu J (2015) Glucagon-like peptide-1 receptor agonist Liraglutide has anabolic bone effects in ovariectomized rats without diabetes. PLoS One 10:e0132744

    Article  PubMed  PubMed Central  Google Scholar 

  36. Yamada C, Yamada Y, Tsukiyama K, Yamada K, Udagawa N, Takahashi N, Tanaka K, Drucker DJ, Seino Y, Inagaki N (2008) Themurine glucagon-like peptide-1 receptor is essential for control of bone resorption. Endocrinology 149:574–579

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Nutrition Unit, Department of Medical and Surgical Science, University Magna Graecia, Catanzaro, 88100, Italy

    Y. Ferro, C. Russo, S. Romeo & A. Pujia

  2. Department of Health Science, University Magna Graecia, Catanzaro, 88100, Italy

    D. Russo

  3. Internal and Emergency Medicine and Centre for Applied Clinical Research (Ce.R.C.A.) Clinical Institute “Beato Matteo”, Vigevano, 27029, Italy

    C. Gazzaruso, A. Coppola, P. Gallotti, V. Zambianchi & M. Fodaro

  4. Department of Molecular and Clinical Medicine, Sahlgrenska Center for Cardiovascolar and Metabolic Research, University of Gothenburg, Göteborg, 42246, Sweden

    S. Romeo

  5. Department of Biomedical, Surgical and Dental Science, University of Milan and Orthopaedic Institute IRCCS Galeazzi, 20161, Milan, Italy

    E. Galliera

  6. Department of Health Biomedical Science, University of Milan and Unit of SMEL-1 Clinical Pathology Unit, San Donato Hospital IRCCS, San Donato Milanese, 20097, Milan, Italy

    M. G. Marazzi & M. M. C. Romanelli

  7. Department of Medical and Surgical Sciences, University of Padova, 35128, Padua, Italy

    S. Giannini

  8. National Research Council, Center for Aging Studies of Padova, 35128, Padua, Italy

    S. Giannini

  9. Menopause Clinic, Department of Clinical and Experimental Medicine, University Magna Graecia, Campus Universitario Germaneto, Viale S. Venuta, floor III, Catanzaro, 88100, Italy

    T. Montalcini

Authors
  1. Y. Ferro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Gazzaruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Coppola
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. Gallotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. Zambianchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Fodaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. Romeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E. Galliera
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M. G. Marazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M. M. C. Romanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. S. Giannini
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A. Pujia
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. T. Montalcini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Montalcini.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The investigation was conducted according to the principles expressed in the Declaration of Helsinki.

Informed consent

The participants signed informed consent.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ferro, Y., Russo, C., Russo, D. et al. Association between low C-peptide and fragility fractures in postmenopausal women without diabetes. J Endocrinol Invest 40, 1091–1098 (2017). https://doi.org/10.1007/s40618-017-0672-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40618-017-0672-4

Keywords

Search

Navigation