Skip to main content

Advertisement

SpringerLink
Log in

Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Whether chronic HCV, a disease characterized by systemic inflammation, impacts bone mineral density (BMD) independent of cirrhosis is unknown.

Aim

We aimed to evaluate the association between BMD, systemic inflammation, and markers of bone turnover in chronic HCV without cirrhosis.

Methods

Non-cirrhotics, 40–60 years old, with chronic HCV underwent measurement of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of systemic inflammation and bone turnover. By Chi-squared or t test, we compared those with normal versus low BMD.

Results

Of the 60 non-cirrhotics, 53 % were female and 53 % Caucasian. Mean (SD) age was 53.3 years (5.7), total bilirubin 0.7 mg/dL (0.3), creatinine 0.8 mg/dL (0.2), and body mass index 28.4 kg/m2 (6.5). Low BMD was observed in 42 %: 30 % had osteopenia, 12 % had osteoporosis. Elevated tumor necrosis factor α, interleukin-6, and C-reactive protein levels were found in 26, 32, and 5 %, respectively, but did not differ by BMD group (p > 0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5 mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5 ng/mL) [p < 0.05], but similar bone-specific alkaline phosphatase, serum C-telopeptide, and parathyroid hormone levels.

Conclusions

Low BMD is prevalent in 40- to 60-year-old non-cirrhotics with chronic HCV, but not associated with systemic inflammatory markers. Elevated P1NP levels may help to identify those at increased risk of bone complications in this population. Chronic HCV should be considered a risk factor for bone loss, prompting earlier BMD assessments in both men and women.

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

References

  1. Armstrong GL, Wasley A, Simard EP, et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144:705–714.

    Article  PubMed  Google Scholar 

  2. Freeman A. Estimating progression to cirrhosis in chronic hepatitis C virus infection. Hepatology. 2001;34:809–816. doi:10.1053/jhep.2001.27831.

    Article  CAS  PubMed  Google Scholar 

  3. Gallego-Rojo FJ, Gonzalez-Calvin JL, Muñoz-Torres M, et al. Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis. Hepatology. 1998;28:695–699. doi:10.1002/hep.510280315.

    Article  CAS  PubMed  Google Scholar 

  4. Monegal A, Navasa M, Guañabens N, et al. Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation. Calcif Tissue Int. 1997;60:148–154.

    Article  CAS  PubMed  Google Scholar 

  5. Diamond T, Stiel D, Lunzer M, et al. Osteoporosis and skeletal fractures in chronic liver disease. Gut. 1990;31:82–87.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Chen CC, Wang SS, Jeng FS, Lee SD. Metabolic bone disease of liver cirrhosis: is it parallel to the clinical severity of cirrhosis? J Gastroenterol Hepatol. 1996;11:417–421.

    Article  CAS  PubMed  Google Scholar 

  7. Kim WR, Terrault NA, Pedersen RA, et al. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology. 2009;137:1680–1686. doi:10.1053/j.gastro.2009.07.047.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Carey EJ, Balan V, Kremers WK, Eileen HJ. Osteopenia and osteoporosis in patients with end-stage liver disease caused by hepatitis C and alcoholic liver disease: not just a cholestatic problem. Liver Transpl. 2003;9:1166–1173. doi:10.1053/jlts.2003.50242.

    Article  PubMed  Google Scholar 

  9. Leidig-Bruckner G, Hosch S, Dodidou P, et al. Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet. 2001;357:342–347. doi:10.1016/S0140-6736(00)03641-2.

    Article  CAS  PubMed  Google Scholar 

  10. Arteh J, Narra S, Nair S. Prevalence of vitamin D deficiency in chronic liver disease. Dig Dis Sci. 2009;55:2624–2628. doi:10.1007/s10620-009-1069-9.

    Article  PubMed  Google Scholar 

  11. George J. Bone mineral density and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol. 2009;15:3516. doi:10.3748/wjg.15.3516.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Goral V. Hepatic osteodystrophy and liver cirrhosis. World J Gastroenterol. 2010;16:1639. doi:10.3748/wjg.v16.i13.1639.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Schiefke I, Fach A, Wiedmann M, et al. Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol. 2005;11:1843–1847.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Itoh Y, Okanoue T, Ohnishi N, et al. Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1999;94:1332–1340. doi:10.1111/j.1572-0241.1999.01083.x.

    Article  CAS  PubMed  Google Scholar 

  15. Zylberberg H, Rimaniol AC, Pol S, et al. Soluble tumor necrosis factor receptors in chronic hepatitis C: a correlation with histological fibrosis and activity. J Hepatol. 1999;30:185–191.

    Article  CAS  PubMed  Google Scholar 

  16. Gough AK, Lilley J, Eyre S, et al. Generalised bone loss in patients with early rheumatoid arthritis. Lancet. 1994;344:23–27.

    Article  CAS  PubMed  Google Scholar 

  17. Bjarnason I, Macpherson A, Mackintosh C, et al. Reduced bone density in patients with inflammatory bowel disease. Gut. 1997;40:228–233.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Mauro M, Radovic V, Armstrong D. Improvement of lumbar bone mass after infliximab therapy in Crohn’s disease patients. Can J Gastroenterol. 2007;21:637–642.

    PubMed Central  PubMed  Google Scholar 

  19. Schett G, Kiechl S, Weger S, et al. High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med. 2006;166:2495–2501. doi:10.1001/archinte.166.22.2495.

    Article  CAS  PubMed  Google Scholar 

  20. Cauley JA, Danielson ME, Boudreau RM, et al. Inflammatory markers and incident fracture risk in older men and women: the health aging and body composition study. J Bone Miner Res. 2007;22:1088–1095. doi:10.1359/jbmr.070409.

    Article  CAS  PubMed  Google Scholar 

  21. Li P, Schwarz EM, O’Keefe RJ, et al. RANK signaling is not required for TNFα-mediated increase in CD11bhi osteoclast precursors but is essential for mature osteoclast formation in TNFα-mediated inflammatory arthritis. J Bone Miner Res. 2003;19:207–213. doi:10.1359/JBMR.0301233.

    Article  Google Scholar 

  22. Gillespie MT. Impact of cytokines and T lymphocytes upon osteoclast differentiation and function. Arthritis Res Ther. 2007;9:103. doi:10.1186/ar2141.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13:156–163. doi:10.1038/nm1538.

    Article  CAS  PubMed  Google Scholar 

  24. Vincent C, Findlay DM, Welldon KJ, et al. Pro-inflammatory cytokines TNF-related weak inducer of apoptosis (TWEAK) and TNFα induce the mitogen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts*. J Bone Miner Res. 2009;24:1434–1449. doi:10.1359/jbmr.090305.

    Article  CAS  PubMed  Google Scholar 

  25. U.S. Preventive Services Task Force. Screening for osteoporosis: U.S. preventive services task force recommendation statement. Ann Intern Med. 2011;154:356–364. doi:10.7326/0003-4819-154-5-201103010-00307.

    Article  Google Scholar 

  26. Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995;19:1409–1417.

    Article  CAS  PubMed  Google Scholar 

  27. Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–612.

    Article  PubMed Central  PubMed  Google Scholar 

  28. WHO (1994) Assessment of Fracture Risk and Its Application to Screening for Postmenopausal Osteoporosis. World Health Organization technical report series 1–136.

  29. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the institute of medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96:53–58. doi:10.1210/jc.2010-2704.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (2012) Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep 61:1–32.

  31. Moyer VA, U.S. Preventive Services Task Force. Screening for hepatitis C virus infection in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013;159:349–357. doi:10.7326/0003-4819-159-5-201309030-00672.

    Article  PubMed  Google Scholar 

  32. Davis GL, Alter MJ, El Serag H, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2012;138:513.e6–521.e6. doi:10.1053/j.gastro.2009.09.067.

    Google Scholar 

  33. National Center for Health Statistics (2012) Osteoporosis or low bone mass at the femur neck or lumbar spine in older adults: United States, 2005–2008. NCHS data brief 1–8.

  34. Centers for Disease Control and Prevention (2002) Osteoporosis: National Health and Nutrition Examination Survey. 1–2.

  35. Khan N, Abbas AM, Almukhtar RM, Khan A. Prevalence and predictors of low bone mineral density in males with ulcerative colitis. J Clin Endocrinol Metab. 2013;98:2368–2375. doi:10.1210/jc.2013-1332.

    Article  CAS  PubMed  Google Scholar 

  36. Weijden MAC, Claushuis TAM, Nazari T, et al. High prevalence of low bone mineral density in patients within 10 years of onset of ankylosing spondylitis: a systematic review. Clin Rheumatol. 2012;31:1529–1535. doi:10.1007/s10067-012-2018-0.

    Article  PubMed Central  PubMed  Google Scholar 

  37. Lodder MC. Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density. Ann Rheum Dis. 2004;63:1576–1580. doi:10.1136/ard.2003.016253.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Haugeberg G, Uhlig T, Falch JA, et al. Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register. Arthritis Rheum. 2000;43:522–530. doi:10.1002/1529-0131(200003)43:3<522:AID-ANR7>3.0.CO;2-Y.

    Article  CAS  PubMed  Google Scholar 

  39. Srivastava AK, Bhattacharyya S, Li X, et al. Circadian and longitudinal variation of serum C-telopeptide, osteocalcin, and skeletal alkaline phosphatase in C3H/HeJ mice. Bone. 2001;29:361–367.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to thank Cindy J. Lai, MD, and Miranda Surjadi, NP, for their assistance with subject recruitment. This study was funded by a Clinical Research Award from the American College of Gastroenterology Institute and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 TR000004.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA, 94143, USA

    Jennifer C. Lai, Jacob Zipperstein, Blanca Lizaola, Samuel Tseng & Norah A. Terrault

  2. Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Dolores M. Shoback

Authors
  1. Jennifer C. Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dolores M. Shoback
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacob Zipperstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Blanca Lizaola
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Samuel Tseng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Norah A. Terrault
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jennifer C. Lai.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lai, J.C., Shoback, D.M., Zipperstein, J. et al. Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C. Dig Dis Sci 60, 1813–1819 (2015). https://doi.org/10.1007/s10620-014-3507-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-014-3507-6

Keywords

Search

Navigation