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Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link?

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Abstract

Purpose

Liver diseases are associated with decreased bone mineral density (BMD) and evidence suggests that nonalcoholic fatty liver disease (NAFLD) affects several extra-hepatic organs, interacting with the regulation of multiple endocrine and metabolic pathways. This review focuses on the rapidly expanding body of evidence that supports a strong association between NAFLD and the risk of decreased BMD, expression of low bone mass (osteoporosis), or reduced mineralization (osteomalacia).

Methods

We identified studies by searching PubMed for original articles published in English through March 2015 using the keywords “nonalcoholic fatty liver disease” or “fatty liver” combined with “bone mineral density”, “osteoporosis”, or “osteomalacia”.

Results

Recent cross-sectional and case–control studies involving both adults and children have consistently shown that patients with NAFLD exhibit a greater prevalence of decreased BMD compared with age-, sex-, and body mass index-matched healthy controls. Accumulating clinical and experimental evidence suggests that NAFLD may contribute to the pathophysiology of low BMD, possibly through the direct contribution of NAFLD to whole-body and hepatic insulin resistance and/or the systemic release of multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators.

Conclusions

Although more research is needed before firm conclusions can be drawn, it appears that there is a non-chance, statistical association between NAFLD and low BMD. This finding argues for more careful monitoring and evaluation of BMD among patients with NAFLD. The potential contribution of NAFLD itself to the development and progression of decreased BMD warrants further study.

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References

  1. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ, American Association for the Study of Liver Diseases; American College of Gastroenterology; American Gastroenterological Association (2012) The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Am J Gastroenterol 107:811–826

    Article  PubMed  Google Scholar 

  2. Anstee QM, Targher G, Day CP (2012) Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat Rev Gastroenterol Hepatol 10:330–344

    Article  Google Scholar 

  3. Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P (2015) NAFLD a precursor of the metabolic syndrome. Dig Liv Dis 47:181–190

    Article  Google Scholar 

  4. Armstrong MJ, Adams LA, Canbay A, Syn WK (2014) Extrahepatic complications of nonalcoholic fatty liver disease. Hepatology 59:1174–1197

    Article  CAS  PubMed  Google Scholar 

  5. Targher G, Day CP, Bonora E (2010) Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363:1341–1350

    Article  CAS  PubMed  Google Scholar 

  6. Targher G, Chonchol M, Pichiri I, Zoppini G (2011) Risk of cardiovascular disease and chronic kidney disease in diabetic patients with non-alcoholic fatty liver disease: just a coincidence? J Endocrinol Invest 34:544–551

    CAS  PubMed  Google Scholar 

  7. Ballestri S, Lonardo A, Bonapace S, Byrne CD, Loria P, Targher G (2014) Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol 20:1724–1745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Targher G, Chonchol MB, Byrne CD (2014) CKD and nonalcoholic fatty liver disease. Am J Kidney Dis 64:638–652

    Article  PubMed  Google Scholar 

  9. Pirgon O, Bilgin H, Tolu I, Odabas D (2011) Correlation of insulin sensitivity with bone mineral status in obese adolescents with nonalcoholic fatty liver disease. Clin Endocrinol (Oxf) 75:189–195

    Article  CAS  Google Scholar 

  10. Campos RM, de Piano A, da Silva PL, Carnier J, Sanches PL, Corgosinho FC, Masquio DC, Lazaretti-Castro M, Oyama LM, Nascimento CM, Tock L, de Mello MT, Tufik S, Dâmaso AR (2012) The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy. Endocrine 42:146–156

    Article  CAS  PubMed  Google Scholar 

  11. Pardee PE, Dunn W, Schwimmer JB (2012) Non-alcoholic fatty liver disease is associated with low bone mineral density in obese children. Aliment Pharmacol Ther 35:248–254

    Article  CAS  PubMed  Google Scholar 

  12. Purnak T, Beyazit Y, Ozaslan E, Efe C, Hayretci M (2012) The evaluation of bone mineral density in patients with nonalcoholic fatty liver disease. Wien Klin Wochenschr 124:526–531

    Article  CAS  PubMed  Google Scholar 

  13. Moon SS, Lee YS, Kim SW (2012) Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women. Endocrine 42:423–429

    Article  CAS  PubMed  Google Scholar 

  14. Li M, Xu Y, Xu M, Ma L, Wang T, Liu Y, Dai M, Chen Y, Lu J, Liu J, Bi Y, Ning G (2012) Association between nonalcoholic fatty liver disease (NAFLD) and osteoporotic fracture in middle-aged and elderly Chinese. J Clin Endocrinol Metab 97:2033–2038

    Article  CAS  PubMed  Google Scholar 

  15. Pacifico L, Bezzi M, Lombardo CV, Romaggioli S, Ferraro F, Bascetta S, Chiesa C (2013) Adipokines and C-reactive protein in relation to bone mineralization in pediatric nonalcoholic fatty liver disease. World J Gastroenterol 19:4007–4014

    Article  PubMed Central  PubMed  Google Scholar 

  16. Bhatt SP, Nigam P, Misra A, Guleria R, Qadar Pasha MA (2013) Independent associations of low 25-hydroxyvitamin D and high parathyroid hormonal levels with nonalcoholic fatty liver disease in Asian Indians residing in north India. Atherosclerosis 230:157–163

    Article  CAS  PubMed  Google Scholar 

  17. Cui R, Sheng H, Rui XF, Cheng XY, Sheng CJ, Wang JY, Qu S (2013) Low bone mineral density in Chinese adults with nonalcoholic fatty liver disease. Int J Endocrinol 2013:396545

    Article  PubMed Central  PubMed  Google Scholar 

  18. de Paula FJ, Horowitz MC, Rosen CJ (2010) Novel insights into the relationship between diabetes and osteoporosis. Diabetes Metab Res Rev 26:622–630

    Article  PubMed Central  PubMed  Google Scholar 

  19. Arikan S, Tuzcu A, Bahceci M, Ozmen S, Gokalp D (2012) Insulin resistance in type 2 diabetes mellitus may be related to bone mineral density. J Clin Densitom 15:186–190

    Article  PubMed  Google Scholar 

  20. Faulhaber GA, Premaor MO, Moser Filho HL, Silla LM, Furlanetto TW (2009) Low bone mineral density is associated with insulin resistance in bone marrow transplant subjects. Bone Marrow Transpl 43:953–957

    Article  CAS  Google Scholar 

  21. Greco EA, Francomano D, Fornari R, Marocco C, Lubrano C, Papa V, Wannenes F, Di Luigi L, Donini LM, Lenzi A, Aversa A, Migliaccio S (2013) Negative association between trunk fat, insulin resistance and skeleton in obese women. World J Diabetes 4:31–39

    Article  PubMed Central  PubMed  Google Scholar 

  22. Redlich K, Smolen JS (2012) Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov 11:234–250

    Article  CAS  PubMed  Google Scholar 

  23. Zou W, Hakim I, Tschoep K, Endres S, Bar-Shavit Z (2001) Tumor necrosis factor-alpha mediates RANK ligand stimulation of osteoclast differentiation by an autocrine mechanism. J Cell Biochem 83:70–83

    Article  CAS  PubMed  Google Scholar 

  24. Nanes MS (2003) Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene 321:1–15

    Article  CAS  PubMed  Google Scholar 

  25. Lee HL, Yi T, Woo KM, Ryoo HM, Kim GS, Baek JH (2010) Msx2 mediates the inhibitory action of TNF alpha on osteoblast differentiation. Exp Mol Med 42:437–445

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Ochi H, Hara Y, Tagawa M, Shinomiya K, Asou Y (2010) The roles of TNFR1 in lipopolysaccharide induced bone loss: dual effects of TNFR1 on bone metabolism via osteoclastogenesis and osteoblast survival. J Orthop Res 28:657–663

    CAS  PubMed  Google Scholar 

  27. Peterson CA, Heffernan ME (2008) Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (Lond) 5:10

    Article  Google Scholar 

  28. Syn WK, Choi SS, Liaskou E, Karaca GF, Agboola KM, Oo YH, Mi Z, Pereira TA, Zdanowicz M, Malladi P, Chen Y, Moylan C, Jung Y, Bhattacharya SD, Teaberry V, Omenetti A, Abdelmalek MF, Guy CD, Adams DH, Kuo PC, Michelotti GA, Whitington PF, Diehl AM (2011) Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis. Hepatology 53:106–115

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Fujisawa R, Tamura M (2012) Acidic bone matrix proteins and their roles in calcification. Front Biosci 17:1891–1903

    Article  CAS  Google Scholar 

  30. Ishijima M, Rittling SR, Yamashita T, Tsuji K, Kurosawa H, Nifuji A, Denhardt DT, Noda M (2001) Enhancement of osteoclastic bone resorption and suppression of osteoblastic bone formation in response to reduced mechanical stress do not occur in the absence of osteopontin. J Exp Med 193:399–404

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Confavreux CB (2011) Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int 79(suppl 121):S14–S19

    Article  Google Scholar 

  32. Chapman J, Miles PD, Ofrecio JM, Neels JG, Yu JG, Resnik JL, Wilkes J, Talukdar S, Thapar D, Johnson K, Sears DD (2010) Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice. PLoS One 5:e13959

    Article  PubMed Central  PubMed  Google Scholar 

  33. Chang IC, Chiang TI, Yeh KT, Lee H, Cheng YW (2010) Increased serum osteopontin is a risk factor for osteoporosis in menopausal women. Osteoporos Int 21:1401–1409

    Article  CAS  PubMed  Google Scholar 

  34. Kennedy OD, Brennan O, Rackard SM, Staines A, O’Brien FJ, Taylor D, Lee TC (2009) Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery. J Orthop Res 27:303–309

    Article  PubMed  Google Scholar 

  35. Reid P, Holen I (2009) Pathophysiological roles of osteoprotegerin (OPG). Eur J Cell Biol 88:1–17

    Article  CAS  PubMed  Google Scholar 

  36. Blázquez-Medela AM, López-Novoa JM, Martínez-Salgado C (2011) Osteoprotegerin and diabetes associated pathologies. Curr Mol Med 11:401–416

    Article  PubMed  Google Scholar 

  37. Yilmaz Y, Yonal O, Kurt R, Oral AY, Eren F, Ozdogan O, Ari F, Celikel CA, Korkmaz S, Ulukaya E, Imeryuz N, Kalayci C, Avsar E (2010) Serum levels of osteoprotegerin in the spectrum of nonalcoholic fatty liver disease. Scand J Clin Lab Invest 70:541–546

    Article  CAS  PubMed  Google Scholar 

  38. Patterson-Buckendahl P (2011) Osteocalcin is a stress-responsive neuropeptide. Endocr Regul 45:99–110

    Article  CAS  PubMed  Google Scholar 

  39. Pietschmann P, Resch H, Krexner E, Woloszczuk W, Willvonseder R (1991) Decreased serum osteocalcin levels in patients with postmenopausal osteoporosis. Acta Med Austriaca 18:114–116

    CAS  PubMed  Google Scholar 

  40. Fernandez-Real JM, Ortega F, Gómez-Ambrosi J, Salvador J, Frühbeck G, Ricart W (2010) Circulating osteocalcin concentrations are associated with parameters of liver fat infiltration and increase in parallel to decreased liver enzymes after weight loss. Osteoporos Int 21:2101–2107

    Article  CAS  PubMed  Google Scholar 

  41. Yilmaz Y, Kurt R, Eren F, Imeryuz N (2011) Serum osteocalcin levels in patients with nonalcoholic fatty liver disease: association with ballooning degeneration. Scand J Clin Lab Invest 71:631–636

    Article  CAS  PubMed  Google Scholar 

  42. Dou J, Ma X, Fang Q, Hao Y, Yang R, Wang F, Zhu J, Bao Y, Jia W (2013) Relationship between serum osteocalcin levels and non-alcoholic fatty liver disease in Chinese men. Clin Exp Pharmacol Physiol 40:282–288

    Article  CAS  PubMed  Google Scholar 

  43. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Müller C, Carling D, Kahn BB (2002) Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415:339–343

    Article  CAS  PubMed  Google Scholar 

  44. Ebihara K, Kusakabe T, Hirata M, Masuzaki H, Miyanaga F, Kobayashi N, Tanaka T, Chusho H, Miyazawa T, Hayashi T, Hosoda K, Ogawa Y, DePaoli AM, Fukushima M, Nakao K (2007) Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab 92:532–541

    Article  CAS  PubMed  Google Scholar 

  45. Polyzos SA, Kountouras J, Mantzoros CS (2015) Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism 64:60–78

    Article  CAS  PubMed  Google Scholar 

  46. Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976–989

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Zeadin MG, Butcher MK, Shaughnessy SG, Werstuck GH (2012) Leptin promotes osteoblast differentiation and mineralization of primary cultures of vascular smooth muscle cells by inhibiting glycogen synthase kinase (GSK)-3b. Biochem Biophys Res Commun 425:924–930

    Article  CAS  PubMed  Google Scholar 

  48. DeMambro VE, Maile L, Wai C, Kawai M, Cascella T, Rosen CJ, Clemmons D (2012) Insulin-like growth factor-binding protein-2 is required for osteoclast differentiation. J Bone Miner Res 27:390–400

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Tsuji K, Maeda T, Kawane T, Matsunuma A, Horiuchi N (2010) Leptin stimulates fibroblast growth factor-23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient ob/ob mice. J Bone Miner Res 25:1711–1723

    Article  CAS  PubMed  Google Scholar 

  50. Dimitri P, Jacques RM, Paggiosi M, King D, Walsh J, Taylor ZA, Frangi AF, Bishop N, Eastell R (2014) Leptin may play a role in bone microstructural alterations in obese children. J Clin Endocrinol Metab 100:594–602

    Article  PubMed  Google Scholar 

  51. Musso G, Gambino R, Cassader M (2010) Emerging molecular targets for the treatment of non-alcoholic fatty liver disease. Annu Rev Med 61:375–392

    Article  CAS  PubMed  Google Scholar 

  52. Ramezani-Moghadam M, Wang J, Ho V, Iseli TJ, Alzahrani B, Xu A, van der Poorten D, Qiao L, George J, Hebbard L (2015) Adiponectin reduces hepatic stellate cell migration by promoting tissue inhibitor of metalloproteinase-1 (TIMP-1) secretion. J Biol Chem 290:5533–5542

    Article  CAS  PubMed  Google Scholar 

  53. Luo XH, Guo LJ, Xie H, Yuan LQ, Wu XP, Zhou HD, Liao EY (2006) Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway. J Bone Miner Res 21:1648–1656

    Article  CAS  PubMed  Google Scholar 

  54. Williams GA, Wang Y, Callon KE, Watson M, Lin JM, Lam JB, Costa JL, Orpe A, Broom N, Naot D, Reid IR, Cornish J (2009) In vitro and in vivo effects of adiponectin on bone. Endocrinology 150:3603–3610

    Article  CAS  PubMed  Google Scholar 

  55. Wang QP, Yang L, Li XP, Xie H, Liao EY, Wang M, Luo XH (2012) Effects of 17-beta-estradiol on adiponectin regulation of the expression of osteoprotegerin and receptor activator of nuclear factor-kB ligand. Bone 51:515–523

    Article  CAS  PubMed  Google Scholar 

  56. Tu Q, Zhang J, Dong LQ, Saunders E, Luo E, Tang J, Chen J (2011) Adiponectin inhibits osteoclastogenesis and bone resorption via APPL1-mediated suppression of Akt1. J Biol Chem 286:12542–12553

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Targher G, Pichiri I, Lippi G (2012) Vitamin D, thrombosis, and hemostasis: more than skin deep. Semin Thromb Hemost 38:114–124

    Article  CAS  PubMed  Google Scholar 

  58. Targher G, Bertolini L, Scala L, Cigolini M, Zenari L, Falezza G, Arcaro G (2007) Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 17:517–524

    Article  CAS  PubMed  Google Scholar 

  59. Barchetta I, Angelico F, Del Ben M, Baroni MG, Pozzilli P, Morini S (2011) Cavallo MG (2011) Strong association between non-alcoholic fatty liver disease (NAFLD) and low 25(OH)-vitamin D levels in an adult population with normal serum liver enzymes. BMC Med 9:85

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Targher G, Scorletti E, Mantovani A, Byrne CD (2013) Nonalcoholic fatty liver disease and reduced serum vitamin D3 levels. Metab Syndr Relat Disord 11:217–228

    Article  CAS  PubMed  Google Scholar 

  61. Nobili V, Giorgio V, Liccardo D, Bedogni G, Morino G, Alisi A, Cianfarani S (2014) Vitamin D levels and liver histological alterations in children with nonalcoholic fatty liver disease. Eur J Endocrinol 170:547–553

    Article  CAS  PubMed  Google Scholar 

  62. Barchetta I, Carotti S, Labbadia G, Gentilucci UV, Muda AO, Angelico F, Silecchia G, Leonetti F, Fraioli A, Picardi A, Morini S, Cavallo MG (2012) Liver vitamin D receptor, CYP2R1, and CYP27A1 expression: relationship with liver histology and vitamin D3 levels in patients with nonalcoholic steatohepatitis or hepatitis C virus. Hepatology 56:2180–2187

    Article  CAS  PubMed  Google Scholar 

  63. Laird E, McNulty H, Ward M, Hoey L, Mc Sorley E, Wallace JM, Carson E, Molloy AM, Healy M, Casey MC, Cunningham C, Strain JJ (2014) Vitamin D deficiency is associated with inflammation in older Irish adults. J Clin Endocrinol Metab 99:1807–1815

    Article  CAS  PubMed  Google Scholar 

  64. Villaggio B, Soldano S, Cutolo M (2012) 1,25-dihydroxyvitamin D3 down-regulates aromatase expression and inflammatory cytokines in human macrophages. Clin Exp Rheumatol 30:934–938

    PubMed  Google Scholar 

  65. Hallsworth K, Thoma C, Moore S, Ploetz T, Anstee QM, Taylor R, Day CP, Trenell MI (2015) Nonalcoholic fatty liver disease is associated with higher levels of objectively measured sedentary behaviour and lower levels of physical activity than matched healthy controls. Frontline Gastroenterol 6:44–51

    Article  PubMed Central  PubMed  Google Scholar 

  66. Chastin SF, Mandrichenko O, Helbostadt JL, Skelton DA (2014) Associations between objectively measured sedentary behaviour and physical activity with bone mineral density in adults and older adults, the NHANES study. Bone 64:254–262

    Article  CAS  PubMed  Google Scholar 

  67. Choudhary NS, Tomar M, Chawla YK, Bhadada SK, Khandelwal N, Dhiman RK, Duseja A, Bhansali A (2011) Hepatic osteodystrophy is common in patients with noncholestatic liver disease. Dig Dis Sci 56:3323–3327

    Article  CAS  PubMed  Google Scholar 

  68. Santori C, Ceccanti M, Diacinti D, Attilia ML, Toppo L, D’Erasmo E, Romagnoli E, Mascia ML, Cipriani C, Prastaro A, Carnevale V, Minisola S (2008) Skeletal turnover, bone mineral density, and fractures in male chronic abusers of alcohol. J Endocrinol Invest 31:321–326

    Article  CAS  PubMed  Google Scholar 

  69. Yurci A, Yucesoy M, Unluhizarci K, Torun E, Gursoy S, Baskol M, Guven K, Ozbakir O (2011) Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis. Clin Res Hepatol Gastroenterol 35:845–854

    Article  CAS  PubMed  Google Scholar 

  70. Bang UC, Benfield T, Bendtsen F, Hyldstrup L, Beck Jensen JE (2014) The risk of fractures among patients with cirrhosis or chronic pancreatitis. Clin Gastroenterol Hepatol 12:320–326

    Article  PubMed  Google Scholar 

  71. Sinclair M, Grossmann M, Gow PJ, Angus PW (2015) Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol 30:244–251

    Article  PubMed  Google Scholar 

  72. Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP (2004) Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extra-hepatic disease. Gastroenterology 126:586–597

    Article  CAS  PubMed  Google Scholar 

  73. Lonardo A, Adinolfi LE, Restivo L, Ballestri S, Romagnoli D, Baldelli E, Nascimbeni F, Loria P (2014) Pathogenesis and significance of hepatitis C virus steatosis: an update on survival strategy of a successful pathogen. World J Gastroenterol 20:7089–7103

    Article  PubMed Central  PubMed  Google Scholar 

  74. Orsini LG, Pinheiro MM, Castro CH, Silva AE, 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:e81652

    Article  PubMed Central  PubMed  Google Scholar 

  75. Ohlsson C, Sjögren K (2015) Effects of the gut microbiota on bone mass. Trends Endocrinol Metab 26:69–74

    Article  CAS  PubMed  Google Scholar 

  76. Mehal WZ (2013) The Gordian Knot of dysbiosis, obesity and NAFLD. Nat Rev Gastroenterol Hepatol 10:637–644

    Article  PubMed  Google Scholar 

  77. Matsubara T, Li F, Gonzalez FJ (2013) FXR signaling in the enterohepatic system. Mol Cell Endocrinol 368:17–29

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Li T, Chiang JY (2015) Bile acids as metabolic regulators. Curr Opin Gastroenterol 31:159–165

    Article  PubMed  Google Scholar 

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The authors declare that there are no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants (that were performed by any of the authors of this article) were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article article does not contain any studies with animals performed by any of the authors.

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Authors and Affiliations

  1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126, Verona, Italy

    G. Targher

  2. Outpatient Liver Clinic and Division of Internal Medicine – Department of Biomedical, Metabolic and Neural Sciences, NOCSAE, Baggiovara, Azienda USL, Modena, Italy

    A. Lonardo

  3. Section of Rheumatology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy

    M. Rossini

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  1. G. Targher
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Correspondence to G. Targher.

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

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