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Bone mineral density and trabecular bone score in treatment-naïve patients with non-cirrhotic hepatitis C virus infection

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Abstract

Summary

We studied 112 treatment-naïve chronic HCV patients without cirrhosis, and we found that, especially HCV+ postmenopausal women, they had lower TBS and BMD values than healthy controls. This suggests that HCV infection is an independent risk factor for osteoporosis, and therefore, screening for osteoporosis in postmenopausal HCV+ women should be considered.

Purpose

To know whether patients in earlier stages of chronic HCV infection are at increased risk of developing low bone mass and bone microarchitectural changes and whether there is an association between bone metabolism and the severity of the liver disease.

Methods

We studied 112 treatment-naïve chronic HCV outpatients and 233 healthy age- and sex-matched controls. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. Serum 25(OH)D, PTH, P1NP, and CTX were determined by electrochemiluminescence.

Results

TBS values were significantly lower in HCV patients than in controls, both considering the population as a whole (1.337 ± 0.119 vs. 1.377 ± 0.122; p < 0.005) and after stratifying by sex (1.347 ± 0.12 vs. 1.381 ± 0.13 in men and 1.314 ± 0.10 vs. 1.369 ± 0.11 in women). The difference remained significant (p < 0.0001 in all cases) after adjusting for confounders. BMD was also lower in HCV patients (lumbar spine, 0.935 ± 0.151 vs. 0.991 ± 0.143 g/cm2, p 0.001; femoral neck, 0.764 ± 0.123 vs. 0.818 ± 0.123 g/cm2, p 0.0001; total hip, 0.926 ± 0.148 vs. 0.963 ± 0.132 g/cm2, p 0.02), although, after adjustment, differences kept a clear trend towards statistical significance in women at the lumbar spine and femoral neck. However, in men and at the total hip in women, differences were no longer significant. We find no relationship between these parameters and the severity of the disease. No significant difference was observed in PTH and 25OHD status after adjustment. Finally, serum P1NP, but not CTX, was higher in HCV patients.

Conclusions

Our findings suggest that HCV infection is an independent risk factor for osteoporosis, especially among postmenopausal women. Therefore, the appropriateness of screening for osteoporosis in postmenopausal HCV-positive women should be considered.

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References

  1. Pawlotsky JM, Negro F, Aghemo A, Berenguer M, Dalgard O, Dusheiko G, Marra F, Puoti M, Wedemeyer H (2018) EASL recommendations on treatment of hepatitis C. J Hepatol 69:461–511

    Article  Google Scholar 

  2. Blach S, Zeuzem S, Manns M, Altraif I, Duberg AS, Muljono DH, Waked I, Alavian SM, Lee MH, Negro F, Abaalkhail F, Abdou A, Abdulla M, Rached AA, Aho I, Akarca U, al Ghazzawi I, al Kaabi S, al Lawati F, al Namaani K, al Serkal Y, al-Busafi SA, al-Dabal L, Aleman S, Alghamdi AS, Aljumah AA, al-Romaihi HE, Andersson MI, Arendt V, Arkkila P, Assiri AM, Baatarkhuu O, Bane A, Ben-Ari Z, Bergin C, Bessone F, Bihl F, Bizri AR, Blachier M, Blasco AJ, Mello CEB, Bruggmann P, Brunton CR, Calinas F, Chan HLY, Chaudhry A, Cheinquer H, Chen CJ, Chien RN, Choi MS, Christensen PB, Chuang WL, Chulanov V, Cisneros L, Clausen MR, Cramp ME, Craxi A, Croes EA, Dalgard O, Daruich JR, de Ledinghen V, Dore GJ, el-Sayed MH, Ergör G, Esmat G, Estes C, Falconer K, Farag E, Ferraz MLG, Ferreira PR, Flisiak R, Frankova S, Gamkrelidze I, Gane E, García-Samaniego J, Khan AG, Gountas I, Goldis A, Gottfredsson M, Grebely J, Gschwantler M, Pessôa MG, Gunter J, Hajarizadeh B, Hajelssedig O, Hamid S, Hamoudi W, Hatzakis A, Himatt SM, Hofer H, Hrstic I, Hui YT, Hunyady B, Idilman R, Jafri W, Jahis R, Janjua NZ, Jarčuška P, Jeruma A, Jonasson JG, Kamel Y, Kao JH, Kaymakoglu S, Kershenobich D, Khamis J, Kim YS, Kondili L, Koutoubi Z, Krajden M, Krarup H, Lai MS, Laleman W, Lao WC, Lavanchy D, Lázaro P, Leleu H, Lesi O, Lesmana LA, Li M, Liakina V, Lim YS, Luksic B, Mahomed A, Maimets M, Makara M, Malu AO, Marinho RT, Marotta P, Mauss S, Memon MS, Correa MCM, Mendez-Sanchez N, Merat S, Metwally AM, Mohamed R, Moreno C, Mourad FH, Müllhaupt B, Murphy K, Nde H, Njouom R, Nonkovic D, Norris S, Obekpa S, Oguche S, Olafsson S, Oltman M, Omede O, Omuemu C, Opare-Sem O, Øvrehus ALH, Owusu-Ofori S, Oyunsuren TS, Papatheodoridis G, Pasini K, Peltekian KM, Phillips RO, Pimenov N, Poustchi H, Prabdial-Sing N, Qureshi H, Ramji A, Razavi-Shearer D, Razavi-Shearer K, Redae B, Reesink HW, Ridruejo E, Robbins S, Roberts LR, Roberts SK, Rosenberg WM, Roudot-Thoraval F, Ryder SD, Safadi R, Sagalova O, Salupere R, Sanai FM, Avila JFS, Saraswat V, Sarmento-Castro R, Sarrazin C, Schmelzer JD, Schréter I, Seguin-Devaux C, Shah SR, Sharara AI, Sharma M, Shevaldin A, Shiha GE, Sievert W, Sonderup M, Souliotis K, Speiciene D, Sperl J, Stärkel P, Stauber RE, Stedman C, Struck D, Su TH, Sypsa V, Tan SS, Tanaka J, Thompson AJ, Tolmane I, Tomasiewicz K, Valantinas J, van Damme P, van der Meer AJ, van Thiel I, van Vlierberghe H, Vince A, Vogel W, Wedemeyer H, Weis N, Wong VWS, Yaghi C, Yosry A, Yuen MF, Yunihastuti E, Yusuf A, Zuckerman E, Razavi H (2017) Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet Gastroenterol Hepatol 2:161–176

    Article  Google Scholar 

  3. Razavi H, Robbins S, Zeuzem S, Negro F, Buti M, Duberg AS, Roudot-Thoraval F, Craxi A, Manns M, Marinho RT, Hunyady B, Colombo M, Aleman S, Antonov K, Arkkila P, Athanasakis K, Blach S, Blachier M, Blasco AJ, Calinas F, Calleja JL, Christensen PB, Cramp ME, Croes E, de Knegt RJ, de Ledinghen V, Delile JM, Estes C, Falconer K, Färkkilä M, Flisiak R, Frankova S, Gamkrelidze I, García-Samaniego J, Genov J, Gerstoft J, Gheorghe L, Goldis A, Gountas I, Gregorčič S, Gschwantler M, Gunter J, Halota W, Harcouet L, Hézode C, Hoffmann P, Horvath G, Hrstic I, Jarčuška P, Jelev D, Jeruma A, Kåberg M, Kieran J, Kondili LA, Kotzev I, Krarup H, Kristian P, Lagging M, Laleman W, Lázaro P, Liakina V, Lukšić B, Maimets M, Makara M, Mateva L, Maticic M, Mennini FS, Mitova R, Moreno C, Mossong J, Murphy K, Nde H, Nemecek V, Nonkovic D, Norris S, Oltman M, Øvrehus ALH, Papatheodoridis G, Pasini K, Razavi-Shearer D, Razavi-Shearer K, Reesink HW, Reic T, Rozentale B, Ryder SD, Salupere R, Sarmento-Castro R, Sarrazin C, Schmelzer JD, Schréter I, Seguin-Devaux C, Simojoki K, Simonova M, Smit PJ, Souliotis K, Speiciene D, Sperl J, Stärkel P, Struck D, Sypsa V, Thornton L, Tolmane I, Tomasiewicz K, Valantinas J, van Damme P, van de Vijver D, van der Meer AJ, van Santen D, van Vlierberghe H, Vandijck D, Vella S, Videčnik-Zorman J, Vogel W, Weis N, Hatzakis A (2017) Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study. Lancet Gastroenterol Hepatol 2:325–336

    Article  Google Scholar 

  4. Lee MH, Yang HI, Yuan Y, L’Italien G, Chen CJ (2014) Epidemiology and natural history of hepatitis C virus infection. World J Gastroenterol 20:9270–9280

    PubMed  PubMed Central  Google Scholar 

  5. Wedemeyer H, Duberg AS, Buti M, Rosenberg WM, Frankova S, Esmat G, Örmeci N, van Vlierberghe H, Gschwantler M, Akarca U, Aleman S, Balık İ, Berg T, Bihl F, Bilodeau M, Blasco AJ, Brandão Mello CE, Bruggmann P, Calinas F, Calleja JL, Cheinquer H, Christensen PB, Clausen M, Coelho HSM, Cornberg M, Cramp ME, Dore GJ, Doss W, el-Sayed MH, Ergör G, Estes C, Falconer K, Félix J, Ferraz MLG, Ferreira PR, García-Samaniego J, Gerstoft J, Giria JA, Gonçales FL Jr, Guimarães Pessôa M, Hézode C, Hindman SJ, Hofer H, Husa P, Idilman R, Kåberg M, Kaita KDE, Kautz A, Kaymakoglu S, Krajden M, Krarup H, Laleman W, Lavanchy D, Lázaro P, Marinho RT, Marotta P, Mauss S, Mendes Correa MC, Moreno C, Müllhaupt B, Myers RP, Nemecek V, Øvrehus ALH, Parkes J, Peltekian KM, Ramji A, Razavi H, Reis N, Roberts SK, Roudot-Thoraval F, Ryder SD, Sarmento-Castro R, Sarrazin C, Semela D, Sherman M, Shiha GE, Sperl J, Stärkel P, Stauber RE, Thompson AJ, Urbanek P, van Damme P, van Thiel I, Vandijck D, Vogel W, Waked I, Weis N, Wiegand J, Yosry A, Zekry A, Negro F, Sievert W, Gower E (2014) Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat 21:60–89

    Article  Google Scholar 

  6. Chhatwal J, Wang X, Ayer T, Kabiri M, Chung RT, Hur C, Donohue JM, Roberts MS, Kanwal F (2016) Hepatitis C disease burden in the United States in the era of oral direct-acting antivirals. Hepatology 64:1442–1450

    Article  CAS  Google Scholar 

  7. Kamar N, Marion O, Abravanel F, Izopet J, Dalton HR (2016) Extrahepatic manifestations of hepatitis E virus. Liver Int 36:467–472

    Article  Google Scholar 

  8. Guarino M, Loperto I, Camera S, Cossiga V, Di Somma C, Colao A et al (2016) Osteoporosis across chronic liver disease. Osteoporos Int 27:1967–1977

    Article  CAS  Google Scholar 

  9. Guanyabens N, Parés A (2012) Osteoporosis en la cirrosis hepática. Gastroenterol Hepatol 35:411–420

    Article  Google Scholar 

  10. George J, Ganesh HK, Acharya S, Bandgar TR, Shivane V, Karvat A, Bhatia SJ, Shah S, Menon PS, Shah N (2009) Bone mineral density and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol 15:3516–3522

    Article  CAS  Google Scholar 

  11. Schiefke I, Fach A, Wiedmann M, Aretin AV, Schenker E, Borte G, Wiese M, Moessner J (2005) Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection. World J Gastroenterol 11:1843–1847

    Article  CAS  Google Scholar 

  12. Dong HV, Cortés YI, Shiau S, Yin MT (2014) Osteoporosis and fractures in HIV/hepatitis C virus coinfection: a systematic review and meta-analysis. AIDS 28:2119–2131

    Article  Google Scholar 

  13. Biver E, Calmy A, Rizzoli R (2017) Bone health in HIV and hepatitis B or C infections. Ther Adv Musculoskelet Dis 9:22–34

    Article  CAS  Google Scholar 

  14. Di Carlo P, Siracusa L, Mazzola G, Colletti P, Soresi M, Giannitrapani L et al (2015) Vitamin D and osteoporosis in HIV/HCV coinfected patients: a literature review. Int J Endocrinol 2015:969040

    Article  Google Scholar 

  15. Lai JC, Shoback DM, Zipperstein J, Lizaola B, Tseng S, Terrault NA (2015) Bone mineral density, bone turnover, and systemic inflammation in non-cirrhotics with chronic hepatitis C. Dig Dis Sci 60:1813–1819

    Article  CAS  Google Scholar 

  16. Lin JC, Hsieh TY, Wu CC, Chen PJ, Chueh TH, Chang WK, Chu HC (2012) Association between chronic hepatitis C virus infection and bone mineral density. Calcif Tissue Int 91:423–429

    Article  CAS  Google Scholar 

  17. Pelazas-González R, González-Reimers E, Alemán-Valls MR, Santolaria-Fernández F, López-Prieto J, González-Díaz A, Gómez-Sirvent JL, de la Vega-Prieto MJ (2013) Bone alterations in hepatitis C virus infected patients. Eur J Intern Med 24:92–96

    Article  Google Scholar 

  18. Orsini LGS, Pinheiro MM, Castro CHM, Silva AEB, Szejnfeld VL (2013) Bone mineral density measurements, bone markers and serum vitamin D concentrations in men with chronic non-cirrhotic untreated hepatitis C. PLoS One 8:8–12

    Google Scholar 

  19. Chen CH, Lin CL, Kao CH (2015) Relation between hepatitis C virus exposure and risk of osteoporosis: a nationwide population-based study. Med (United States) 94:e2086

    CAS  Google Scholar 

  20. McCloskey EV, Odén A, Harvey NC, Leslie WD, Hans D, Johansson H et al (2016) A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX. J Bone Miner Res 31:940–948

    Article  Google Scholar 

  21. Martineau P, Leslie WD (2017) Trabecular bone score (TBS): method and applications. Bone 104:66–72

    Article  CAS  Google Scholar 

  22. Olmos JM, Hernández JL, García-Velasco P, Martínez J, Llorca J, González-Macías J (2016) Serum 25-hydroxyvitamin D, parathyroid hormone, calcium intake, and bone mineral density in Spanish adults. Osteoporos Int 27:105–113

    Article  CAS  Google Scholar 

  23. Martínez J, Olmos JM, Hernández JL, Pinedo G, Llorca J, Obregón E, Valero C, González-Macías J (2009) Bone turnover markers in Spanish postmenopausal women. The Camargo cohort study. Clin Chim Acta 409:70–74

    Article  Google Scholar 

  24. Kanis JA (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 4:368–381

    Article  CAS  Google Scholar 

  25. Del Rio LM, Winzenrieth R, Cormier C, Di Gregorio S (2013) Is bone microarchitecture status of the lumbar spine assessed by TBS related to femoral neck fracture? A Spanish case-control study. Osteoporos Int 24:991–998

    Article  Google Scholar 

  26. Nakchbandi IA (2014) Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications. World J Gastroenterol 20:9427–9438

    PubMed  PubMed Central  Google Scholar 

  27. Chinnaratha MA, Chaudhary S, Doogue M, Mccormick RJ, Woodman RJ, Wigg AJ (2015) Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis. Intern Med J 45:1230–1235

    Article  CAS  Google Scholar 

  28. Kawelke N, Bentmann A, Hackl N, Hager HD, Feick P, Geursen A, Singer MV, Nakchbandi IA (2008) Isoform of fibronectin mediates bone loss in patients with primary biliary cirrhosis by suppressing bone formation. J Bone Miner Res 23:1278–1286

    Article  CAS  Google Scholar 

  29. Janes CH, Rolland Dickson E, Okazaki R, Bonde S, McDonagh AF, Riggs BL (1995) Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice. J Clin Invest 95:2581–2586

    Article  CAS  Google Scholar 

  30. Moschen AR, Kaser A, Stadlmann S, Millonig G, Kaser S, Mühllechner P, Habior A, Graziadei I, Vogel W, Tilg H (2005) The RANKL/OPG system and bone mineral density in patients with chronic liver disease. J Hepatol 43:973–983

    Article  Google Scholar 

  31. Wijarnpreecha K, Thongprayoon C, Panjawatanan P, Phatharacharukul P, Ungprasert P (2018) Hepatitis C virus infection and risk of osteoporosis: a meta-analysis. Saudi J Gastroenterol 23:216–221

    Google Scholar 

  32. Martineau P, Leslie WD, Johansson H, Oden A, McCloskey EV, Hans D, Kanis JA (2017) Clinical utility of using lumbar spine trabecular bone score to adjust fracture probability: the Manitoba BMD Cohort. J Bone Miner Res 32:1568–1574

    Article  Google Scholar 

  33. Maalouf NM, Zhang S, Drechsler H, Brown GR, Tebas P, Bedimo R (2013) Hepatitis C Co-infection and severity of liver disease as risk factors for osteoporotic fractures among HIV-infected patients. J Bone Miner Res 28:2577–2583

    Article  Google Scholar 

  34. Bedimo RJ, Adams-Huet B, Poindexter J, Brown G, Farukhi I, Castanon R, Turner D, Moore T, Tebas P, Maalouf NM (2018) The differential effects of human immunodeficiency virus and hepatitis C virus on bone microarchitecture and fracture risk. Clin Infect Dis 66:1442–1447

    Article  CAS  Google Scholar 

  35. Corazza GR, Trevisani F, Di Stefano M, De Notariis S, Veneto G, Cecchetti L et al (2000) Early increase of bone resorption in patients with liver cirrhosis secondary to viral hepatitis. Dig Dis Sci 45:1392–1399

    Article  CAS  Google Scholar 

  36. Li P, Schwarz EM, O’Keefe RJ, Ma L, Boyce BF, Xing L (2004) RANK Signaling is not required for TNF-mediated increase in CD11(hi) osteoclast precursors but is essential for mature osteoclast formation in TNF-mediated inflammatory arthritis. J Bone Miner Res 19:207–213

    Article  CAS  Google Scholar 

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Funding

This study received funding by grants from the Instituto de Salud Carlos III (PI18/00762 and PIE15/00079), Ministerio de Economía y Competitividad, Spain, that included FEDER funds from the EU.

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Correspondence to José L. Hernández.

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The study was approved by the local Ethics Committee (Comité Ético de Investigación Clínica de Cantabria-IDIVAL, internal code: 2016.003), and all the subjects gave written informed consent.

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Olmos-Martínez, J.M., Hernández, J.L., Fábrega, E. et al. Bone mineral density and trabecular bone score in treatment-naïve patients with non-cirrhotic hepatitis C virus infection. Arch Osteoporos 15, 72 (2020). https://doi.org/10.1007/s11657-020-00752-1

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