Skip to main content

Advertisement

Log in

Association between non-alcoholic fatty liver disease and bone turnover markers in southwest China

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Introduction

Non-alcoholic fatty liver disease (NAFLD) is not considered only a liver disease but also associated with an increased risk of extra-hepatic diseases including bone metabolism disorders. In our study, we aim to explore the changes of several bone turnover markers (BTMs) under different fat deposition and stiffness levels of the liver.

Materials and methods

We analyzed the physical examination data of 3353 subjects from February 2018 to June 2021 in this study. The steatosis and stiffness of liver were quantitatively detected using the fat attenuation parameter (FAP) and liver stiffness measurements (LSM) of transient elastography (TE). Serum 25-hydroxyvitamin D3 (25(OH)D3), osteocalcin, carboxy-terminal collagen crosslinks (CTX), amino terminal elongation peptide of total type 1 procollagen (P1NP) were tested. Clinical and other biochemical data were also collected.

Results

With the increasing of FAP, the levels of 25(OH)D3 and osteocalcin decreased, the difference was statistically significant. No correlation was found between LSM and all the four BTMs. Logistic regression analysis revealed that FAP ≥ 244 dB/m was negatively correlated with 25(OH)D3 (in both males and females) and osteocalcin (only in males). No correlation was found between FAP ≥ 244 dB/m and P1NP or CTX.

Conclusion

The degree of liver adipose deposition was found to be negatively associated with the serum levels of 25(OH)D3 (in both males and females) and osteocalcin (only in males) in southwest China.

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

Access this article

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

References

  1. Baffy G, Brunt EM, Caldwell SH (2012) Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace. J Hepatol 56:1384–1391. https://doi.org/10.1016/j.jhep.2011.10.027

    Article  PubMed  Google Scholar 

  2. Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E (2018) Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15:11–20. https://doi.org/10.1038/nrgastro.2017.109

    Article  PubMed  Google Scholar 

  3. Adams LA, Anstee QM, Tilg H, Targher G (2017) Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases. Gut 66:1138–1153. https://doi.org/10.1136/gutjnl-2017-313884

    Article  PubMed  Google Scholar 

  4. Cui R, Sheng H, Rui X-F, Cheng X-Y, Sheng C-J, Wang J-Y, Qu S (2013) Low bone mineral density in Chinese adults with nonalcoholic fatty liver disease. Int J Endocrinol 2013:1–6. https://doi.org/10.1155/2013/396545

    Article  CAS  Google Scholar 

  5. Targher G, Lonardo A, Rossini M (2015) Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link? J Endocrinol Invest 38:817–825. https://doi.org/10.1007/s40618-015-0315-6

    Article  CAS  PubMed  Google Scholar 

  6. Umehara T (2018) Nonalcoholic fatty liver disease with elevated alanine aminotransferase levels is negatively associated with bone mineral density: cross-sectional study in U.S. adults. PLoS One 13:e0197900. https://doi.org/10.1371/journal.pone.0197900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sasso M, Beaugrand M, de Ledinghen V, Douvin C, Marcellin P, Poupon R, Sandrin L, Miette V (2010) Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound Med Biol 36:1825–1835. https://doi.org/10.1016/j.ultrasmedbio.2010.07.005

    Article  PubMed  Google Scholar 

  8. Mueller S, Sandrin L (2010) Liver stiffness: a novel parameter for the diagnosis of liver disease. Hepat Med 2:49–67. https://doi.org/10.2147/hmer.s7394

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ (2018) The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American association for the study of liver diseases. Hepatology 67:328–357. https://doi.org/10.1002/hep.29367

    Article  PubMed  Google Scholar 

  10. European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O (2016) EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 64:1388–1402. https://doi.org/10.1016/j.jhep.2015.11.004

    Article  Google Scholar 

  11. Ou X, Wang X, Wu X, Kong Y, Duan W, Zhou J, Sun D, Wang Y, You H, Jia J (2015) Comparison of FibroTouch and FibroScan for the assessment of fibrosis in chronic hepatitis B patients. Zhonghua Gan Zang Bing Za Zhi 23:103–106. https://doi.org/10.3760/cma.j.issn.1007-3418.2015.02.006

    Article  CAS  PubMed  Google Scholar 

  12. Qu Y, Song YY, Chen CW, Fu QC, Shi JP, Xu Y, Xie Q, Yang YF, Zhou YJ, Li LP, Xu MY, Cai XB, Zhang QD, Yu H, Fan JG, Lu LG (2021) Diagnostic performance of FibroTouch ultrasound attenuation parameter and liver stiffness measurement in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Clin Transl Gastroenterol 12:e00323. https://doi.org/10.14309/ctg.0000000000000323

    Article  PubMed  PubMed Central  Google Scholar 

  13. Jia J, Hou J, Ding H, Chen G, Xie Q, Wang Y, Zeng M, Zhao J, Wang T, Hu X, Schuppan D (2015) Transient elastography compared to serum markers to predict liver fibrosis in a cohort of Chinese patients with chronic hepatitis B. J Gastroenterol Hepatol 30:756–762. https://doi.org/10.1111/jgh.12840

    Article  CAS  PubMed  Google Scholar 

  14. Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Ledinghen V (2010) Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 51:454–462. https://doi.org/10.1002/hep.23312

    Article  CAS  PubMed  Google Scholar 

  15. Fabbrini E, Sullivan S, Klein S (2010) Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology 51:679–689. https://doi.org/10.1002/hep.23280

    Article  CAS  PubMed  Google Scholar 

  16. Jeon YK, Lee JG, Kim SS, Kim BH, Kim SJ, Kim YK, Kim IJ (2011) Association between bone mineral density and metabolic syndrome in pre- and postmenopausal women. Endocr J 58:87–93. https://doi.org/10.1507/endocrj.k10e-297

    Article  PubMed  Google Scholar 

  17. Collier J (2007) Bone disorders in chronic liver disease. Hepatology 46:1271–1278. https://doi.org/10.1002/hep.21852

    Article  CAS  PubMed  Google Scholar 

  18. Nelson JE, Roth CL, Wilson LA, Yates KP, Aouizerat B, Morgan-Stevenson V, Whalen E, Hoofnagle A, Mason M, Gersuk V, Yeh MM, Kowdley KV (2016) Vitamin D deficiency is associated with increased risk of non-alcoholic steatohepatitis in adults with non-alcoholic fatty liver disease: possible role for MAPK and NF-kappaB? Am J Gastroenterol 111:852–863. https://doi.org/10.1038/ajg.2016.51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang D, Lin H, Xia M, Aleteng Q, Li X, Ma H, Pan B, Gao J, Gao X (2016) Vitamin D levels are inversely associated with liver fat content and risk of non-alcoholic fatty liver disease in a Chinese middle-aged and elderly population: the Shanghai Changfeng study. PLoS One 11:e0157515. https://doi.org/10.1371/journal.pone.0157515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhai HL, Wang NJ, Han B, Li Q, Chen Y, Zhu CF, Chen YC, Xia FZ, Cang Z, Zhu CX, Lu M, Lu YL (2016) Low vitamin D levels and non-alcoholic fatty liver disease, evidence for their independent association in men in East China: a cross-sectional study (survey on prevalence in east China for metabolic diseases and risk factors (SPECT-China)). Br J Nutr 115:1352–1359. https://doi.org/10.1017/S0007114516000386

    Article  CAS  PubMed  Google Scholar 

  21. Dasarathy J, Periyalwar P, Allampati S, Bhinder V, Hawkins C, Brandt P, Khiyami A, McCullough AJ, Dasarathy S (2014) Hypovitaminosis D is associated with increased whole body fat mass and greater severity of non-alcoholic fatty liver disease. Liver Int 34:e118–e127. https://doi.org/10.1111/liv.12312

    Article  CAS  PubMed  Google Scholar 

  22. Bu FX, Armas L, Lappe J, Zhou Y, Gao G, Wang HW, Recker R, Zhao LJ (2010) Comprehensive association analysis of nine candidate genes with serum 25-hydroxy vitamin D levels among healthy Caucasian subjects. Hum Genet 128:549–556. https://doi.org/10.1007/s00439-010-0881-9

    Article  CAS  PubMed  Google Scholar 

  23. Nussler AK, Wildemann B, Freude T, Litzka C, Soldo P, Friess H, Hammad S, Hengstler JG, Braun KF, Trak-Smayra V, Godoy P, Ehnert S (2014) Chronic CCl4 intoxication causes liver and bone damage similar to the human pathology of hepatic osteodystrophy: a mouse model to analyse the liver-bone axis. Arch Toxicol 88:997–1006. https://doi.org/10.1007/s00204-013-1191-5

    Article  CAS  PubMed  Google Scholar 

  24. Patel YA, Henao R, Moylan CA, Guy CD, Piercy DL, Diehl AM, Abdelmalek MF (2016) Vitamin D is not associated with severity in NAFLD: results of a paired clinical and gene expression profile analysis. Am J Gastroenterol 111:1591–1598. https://doi.org/10.1038/ajg.2016.406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Saleem U, Mosley TH Jr, Kullo IJ (2010) Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 30:1474–1478. https://doi.org/10.1161/ATVBAHA.110.204859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tan A, Gao Y, Yang X, Zhang H, Qin X, Mo L, Peng T, Xia N, Mo Z (2011) Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey. Metabolism 60:1186–1192. https://doi.org/10.1016/j.metabol.2011.01.002

    Article  CAS  PubMed  Google Scholar 

  27. Liu JJ, Chen YY, Mo ZN, Tian GX, Tan AH, Gao Y, Yang XB, Zhang HY, Li ZX (2013) Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in adult males, South China. Int J Mol Sci 14:19782–19791. https://doi.org/10.3390/ijms141019782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Recker RR, Marin F, Ish-Shalom S, Moricke R, Hawkins F, Kapetanos G, de la Pena MP, Kekow J, Farrerons J, Sanz B, Oertel H, Stepan J (2009) Comparative effects of teriparatide and strontium ranelate on bone biopsies and biochemical markers of bone turnover in postmenopausal women with osteoporosis. J Bone Miner Res 24:1358–1368. https://doi.org/10.1359/jbmr.090315

    Article  CAS  PubMed  Google Scholar 

  29. Srivastava AK, MacFarlane G, Srivastava VP, Mohan S, Baylink DJ (2001) A new monoclonal antibody ELISA for detection and characterization of C-telopeptide fragments of type I collagen in urine. Calcif Tissue Int 69:327–336. https://doi.org/10.1007/s00223-001-1034-x

    Article  CAS  PubMed  Google Scholar 

  30. Deng H, Dai Y, Lu H, Li SS, Gao L, Zhu DL (2018) Analysis of the correlation between non-alcoholic fatty liver disease and bone metabolism indicators in healthy middle-aged men. Eur Rev Med Pharmacol Sci 22:1457–1462. https://doi.org/10.26355/eurrev_201803_14493

    Article  CAS  PubMed  Google Scholar 

  31. Iglesias P, Arrieta F, Piñera M, Botella-Carretero JI, Balsa JA, Zamarrón I, Menacho M, Díez JJ, Muñoz T, Vázquez C (2011) Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance. Clin Endocrinol 75:184–188. https://doi.org/10.1111/j.1365-2265.2011.04035.x

    Article  CAS  Google Scholar 

  32. Zhang M, Nie X, Yuan Y, Wang Y, Ma X, Yin J, Bao Y (2021) Osteocalcin alleviates nonalcoholic fatty liver disease in mice through GPRC6A. Int J Endocrinol 2021:9178616. https://doi.org/10.1155/2021/9178616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by Science and Technology Department of Sichuan Province, China. Approval NO. 2020YFS0557.

Author information

Authors and Affiliations

Authors

Contributions

YL and DL designed the study, YL and DL wrote the manuscript; YL and PS performed the data collection and analysis; YLassisted in data collection and document writing. All authors read and approved the manuscript.

Corresponding author

Correspondence to Dongyu Li.

Ethics declarations

Conflict of interest

All authors have no conflicts of interest.

Ethical approval

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the ethics committees of the Sichuan Provincial People’s Hospital (No. 407(2020)) and exempted from the informed consent of the retrospective analysis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Shuai, P., Liu, Y. et al. Association between non-alcoholic fatty liver disease and bone turnover markers in southwest China. J Bone Miner Metab 40, 712–719 (2022). https://doi.org/10.1007/s00774-022-01340-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-022-01340-8

Keywords

Navigation