Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2016, Article ID 1423462, 12 pages
http://dx.doi.org/10.1155/2016/1423462
Review Article

Diagnosis and Management of Cirrhosis-Related Osteoporosis

Department of Internal Medicine, Botucatu Medical School, Universidade Estadual Paulista (UNESP), Av. Prof. Mário Rubens Guimarães Montenegro, s/n, Distrito de Rubião Jr., 18 608 917 Botucatu, SP, Brazil

Received 9 July 2016; Accepted 3 October 2016

Academic Editor: Fumio Imazeki

Copyright © 2016 Lívia Alves Amaral Santos and Fernando Gomes Romeiro. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. A. Luxon, “Bone disorders in chronic liver diseases,” Current Gastroenterology Reports, vol. 13, no. 1, pp. 40–48, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. N. Guañabens and A. Parés, “Management of osteoporosis in liver disease,” Clinics and Research in Hepatology and Gastroenterology, vol. 35, no. 6-7, pp. 438–445, 2011. View at Publisher · View at Google Scholar
  3. S. Giannini, M. Nobile, M. Ciuffreda et al., “Long-term persistence of low bone density in orthotopic liver transplantation,” Osteoporosis International, vol. 11, no. 5, pp. 417–424, 2000. View at Publisher · View at Google Scholar · View at Scopus
  4. J. E. Hay, “Osteoporosis in liver diseases and after liver transplantation,” Journal of Hepatology, vol. 38, no. 6, pp. 856–865, 2003. View at Publisher · View at Google Scholar · View at Scopus
  5. H. Bownik and S. Saab, “Health-related quality of life after liver transplantation for adult recipients,” Liver Transplantation, vol. 15, no. 2, pp. S42–S49, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. D. Kaemmerer, B. Schmidt, G. Lehmann, G. Wolf, U. Settmacher, and M. Hommann, “Treatment of bone loss in patients with chronic liver disease awaiting liver transplantation,” Transplantation Research, vol. 1, no. 1, article 7, 2012. View at Publisher · View at Google Scholar · View at Scopus
  7. A. Alcalde Vargas, J. M. Pascasio Acevedo, I. Gutiérrez Domingo et al., “Prevalence and characteristics of bone disease in cirrhotic patients under evaluation for liver transplantation,” Transplantation Proceedings, vol. 44, no. 6, pp. 1496–1498, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. A. Gatta, A. Verardo, M. Di Pascoli, S. Giannini, and M. Bolognesi, “Hepatic osteodystrophy,” Clinical Cases in Mineral and Bone Metabolism, vol. 11, no. 3, pp. 185–191, 2014. View at Google Scholar · View at Scopus
  9. L. A. A. Santos, T. B. Lima, L. Augusti et al., “Handgrip strength as a predictor of bone mineral density in outpatients with cirrhosis,” Journal of Gastroenterology and Hepatology, vol. 31, no. 1, pp. 229–234, 2016. View at Publisher · View at Google Scholar · View at Scopus
  10. R. G. Long, E. Meinhard, R. K. Skinner, Z. Varghese, M. R. Wills, and S. Sherlock, “Clinical, biochemical, and histological studies of osteomalacia, osteoporosis, and parathyroid function in chronic liver disease,” Gut, vol. 19, no. 2, pp. 85–90, 1978. View at Publisher · View at Google Scholar · View at Scopus
  11. P. R. Mills, R. Vallance, G. Birnie et al., “A prospective survey of radiological bone and joint changes in primary biliary cirrhosis,” Clinical Radiology, vol. 32, no. 3, pp. 297–302, 1981. View at Publisher · View at Google Scholar · View at Scopus
  12. J. A. Cuthbert, C. Y. C. Pak, and J. E. Zerwekh, “Bone disease in primary biliary cirrhosis: increased bone resorption and turnover in the absence of osteoporosis or osteomalacia,” Hepatology, vol. 4, no. 1, pp. 1–8, 1984. View at Publisher · View at Google Scholar · View at Scopus
  13. J. A. Jorge-Hernandez, C. E. Gonzalez-Reimers, A. Torres-Ramirez et al., “Bone changes in alcoholic liver cirrhosis. A histomorphometrical analysis of 52 cases,” Digestive Diseases and Sciences, vol. 33, no. 9, pp. 1089–1095, 1988. View at Publisher · View at Google Scholar · View at Scopus
  14. T. H. Diamond, “Metabolic bone disease in primary biliary cirrhosis,” Journal of Gastroenterology and Hepatology, vol. 5, no. 1, pp. 66–81, 1990. View at Publisher · View at Google Scholar · View at Scopus
  15. N. Guanabens, A. Pares, L. Marinoso et al., “Factors influencing the development of metabolic bone disease in primary biliary cirrhosis,” American Journal of Gastroenterology, vol. 85, no. 10, pp. 1356–1362, 1990. View at Google Scholar · View at Scopus
  16. E. Meys, E. Fontanges, N. Fourcade, A. Thomasson, M. Pouyet, and P. D. Delmas, “Bone loss after orthotopic liver transplantation,” The American Journal of Medicine, vol. 97, no. 5, pp. 445–450, 1994. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Monegal, M. Navasa, N. Guañabens et al., “Osteoporosis and bone mineral metabolism disorders in cirrhotic patients referred for orthotopic liver transplantation,” Calcified Tissue International, vol. 60, no. 2, pp. 148–154, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. J. George, H. K. Ganesh, S. Acharya et al., “Bone mineral density and disorders of mineral metabolism in chronic liver disease,” World Journal of Gastroenterology, vol. 15, no. 28, pp. 3516–3522, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. R. K. Bansal, M. Kumar, P. R. Sachdeva, and A. Kumar, “Prospective study of profile of hepatic osteodystrophy in patients with non-choleastatic liver cirrhosis and impact of bisphosphonate supplementation,” United European Gastroenterology Journal, vol. 4, no. 1, pp. 77–83, 2016. View at Publisher · View at Google Scholar
  20. J.-Y. Reginster and N. Burlet, “Osteoporosis: a still increasing prevalence,” Bone, vol. 38, no. 2, supplement 1, pp. S4–S9, 2006. View at Publisher · View at Google Scholar · View at Scopus
  21. J. D. Collier, M. Ninkovic, and J. E. Compston, “Guidelines on the management of osteoporosis associated with chronic liver disease,” Gut, vol. 50, supplement 1, pp. i1–i9, 2002. View at Google Scholar · View at Scopus
  22. G. López-Larramona, A. J. Lucendo, S. González-Castillo, and J. M. Tenias, “Hepatic osteodystrophy: an important matter for consideration in chronic liver disease,” World Journal of Hepatology, vol. 3, no. 12, pp. 300–307, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. R. Lupoli, A. Di Minno, G. Spadarella et al., “The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies,” Clinical Endocrinology, vol. 84, no. 1, pp. 30–38, 2016. View at Publisher · View at Google Scholar · View at Scopus
  24. Z. Savic, D. Damjanov, N. Curic et al., “Vitamin D status, bone metabolism and bone mass in patients with alcoholic liver cirrhosis,” Bratislava Medical Journal, vol. 115, no. 9, pp. 573–578, 2014. View at Publisher · View at Google Scholar · View at Scopus
  25. N. Guañabens, D. Cerdá, A. Monegal et al., “Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirrhosis,” Gastroenterology, vol. 138, no. 7, pp. 2348–2356, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. E. Seeman, “The structural and biomechanical basis of the gain and loss of bone strength in women and men,” Endocrinology and Metabolism Clinics of North America, vol. 32, no. 1, pp. 25–38, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. N. Guanabens and A. Pares, “Liver and bone,” Archives of Biochemistry and Biophysics, vol. 503, no. 1, pp. 84–94, 2010. View at Google Scholar
  28. M. Solaymani-Dodaran, T. R. Card, G. P. Aithal, and J. West, “Fracture risk in people with primary biliary cirrhosis: a population-based cohort study,” Gastroenterology, vol. 131, no. 6, pp. 1752–1757, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. M. A. Chinnaratha, S. Chaudhary, M. Doogue, R. J. Mccormick, R. J. Woodman, and A. J. Wigg, “Prevalence of hepatic osteodystrophy and vitamin D deficiency in cirrhosis,” Internal Medicine Journal, vol. 45, no. 12, pp. 1230–1235, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. T. Diamond, D. Stiel, M. Lunzer, M. Wilkinson, and S. Posen, “Ethanol reduces bone formation and may cause osteoporosis,” The American Journal of Medicine, vol. 86, no. 3, pp. 282–288, 1989. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Diamond, D. Stiel, and S. Posen, “Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or others factors?” Annals of Internal Medicine, vol. 110, no. 6, pp. 430–436, 1989. View at Publisher · View at Google Scholar · View at Scopus
  32. T. H. Diamond, D. Stiel, M. Lunzer, D. McDowall, R. P. Eckstein, and S. Posen, “Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease,” Gastroenterology, vol. 96, no. 1, pp. 213–221, 1989. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Newman, C. Minns Lowe, and K. Barker, “Spinal orthoses for vertebral osteoporosis and osteoporotic vertebral fracture: a systematic review,” Archives of Physical Medicine and Rehabilitation, vol. 97, no. 6, pp. 1013–1025, 2016. View at Publisher · View at Google Scholar · View at Scopus
  34. D. L. Kendler, D. C. Bauer, K. S. Davison et al., “Vertebral fractures: clinical importance and management,” American Journal of Medicine, vol. 129, no. 2, pp. e221–e221, 2016. View at Google Scholar
  35. O. R. Pavel, M. Popescu, L. Novac et al., “Postmenopausal osteoporosis—clinical, biological and histopathological aspects,” Romanian Journal of Morphology and Embryology, vol. 57, no. 1, pp. 121–130, 2016. View at Google Scholar
  36. D. Marshall, O. Johnell, and H. Wedel, “Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures,” British Medical Journal, vol. 312, no. 7041, pp. 1254–1259, 1996. View at Publisher · View at Google Scholar · View at Scopus
  37. R. W. Gasser, “Cholestasis and metabolic bone disease—a clinical review,” Wiener Medizinische Wochenschrift, vol. 158, no. 19-20, pp. 553–557, 2008. View at Publisher · View at Google Scholar · View at Scopus
  38. J. P. Nolan, “The role of intestinal endotoxin in liver injury: a long and evolving history,” Hepatology, vol. 52, no. 5, pp. 1829–1835, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. F. G. Romeiro, F. da Silva Yamashiro, M. F. Américo et al., “Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: a randomized double-blind study,” BMC Gastroenterology, vol. 13, article 13, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Dai, D. Lin, J. Zhang et al., “Chronic alcohol ingestion induces osteoclastogenesis and bone loss through IL-6 in mice,” The Journal of Clinical Investigation, vol. 106, no. 7, pp. 887–895, 2000. View at Publisher · View at Google Scholar · View at Scopus
  41. J. L. Gonzalez-Calvin, F. Gallego-Rojo, R. Fernandez-Perez, F. Casado-Caballero, E. Ruiz-Escolano, and E. G. Olivares, “Osteoporosis, mineral metabolism, and serum soluble tumor necrosis factor receptor p55 in viral cirrhosis,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 9, pp. 4325–4330, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. G. Schett, S. Kiechl, K. Redlich et al., “Soluble RANKL and risk of nontraumatic fracture,” The Journal of the American Medical Association, vol. 291, no. 9, pp. 1108–1113, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. D. Hegedus, V. Ferencz, P. L. Lakatos et al., “Decreased bone density, elevated serum osteoprotegerin, and β-cross-laps in Wilson disease,” Journal of Bone and Mineral Research, vol. 17, no. 11, pp. 1961–1967, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. F. Szalay, D. Hegedus, P. Laszlo Lakatos et al., “High serum osteoprotegerin and low RANKL in primary biliary cirrhosis,” Journal of Hepatology, vol. 38, no. 4, pp. 395–400, 2003. View at Publisher · View at Google Scholar · View at Scopus
  45. A. R. Moschen, A. Kaser, S. Stadlmann et al., “The RANKL/OPG system and bone mineral density in patients with chronic liver disease,” Journal of Hepatology, vol. 43, no. 6, pp. 973–983, 2005. View at Publisher · View at Google Scholar · View at Scopus
  46. P. Peris, L. Alvarez, J. Oriola et al., “Collagen type Iα1 gene polymorphism in idiopathic osteoporosis in men,” Rheumatology, vol. 39, no. 11, pp. 1222–1225, 2000. View at Publisher · View at Google Scholar · View at Scopus
  47. P. L. Lakatos, E. Bajnok, I. Tornai et al., “Insulin-like growth factor I gene microsatellite repeat, collagen type Iα1 gene Sp1 polymorphism, and bone disease in primary biliary cirrhosis,” European Journal of Gastroenterology and Hepatology, vol. 16, no. 8, pp. 753–759, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Parés and N. Guañabens, “Treatment of bone disorders in liver disease,” Journal of Hepatology, vol. 45, no. 3, pp. 445–453, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Grossmann, R. Hoermann, L. Gani et al., “Low testosterone levels as an independent predictor of mortality in men with chronic liver disease,” Clinical Endocrinology, vol. 77, no. 2, pp. 323–328, 2012. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Sinclair, M. Grossmann, P. J. Gow, and P. W. Angus, “Testosterone in men with advanced liver disease: abnormalities and implications,” Journal of Gastroenterology and Hepatology, vol. 30, no. 2, pp. 244–251, 2015. View at Publisher · View at Google Scholar · View at Scopus
  51. T. M. Kelly, C. Q. Edwards, A. W. Meikle, and J. P. Kushner, “Hypogonadism in hemochromatosis: reversal with iron depletion,” Annals of Internal Medicine, vol. 101, no. 5, pp. 629–632, 1984. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Guggenbuhl, Y. Deugnier, J. F. Boisdet et al., “Bone mineral density in men with genetic hemochromatosis and HFE gene mutation,” Osteoporosis International, vol. 16, no. 12, pp. 1809–1814, 2005. View at Publisher · View at Google Scholar · View at Scopus
  53. H. Bell, N. Raknerud, J. A. Falch, and E. Haug, “Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis,” European Journal of Endocrinology, vol. 132, no. 4, pp. 444–449, 1995. View at Publisher · View at Google Scholar · View at Scopus
  54. G. López-Larramona, A. J. Lucendo, and L. González-Delgado, “Alcoholic liver disease and changes in bone mineral density,” Revista Espanola de Enfermedades Digestivas, vol. 105, no. 10, pp. 609–621, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. G. López-Larramona, A. J. Lucendo, and J. M. Tenías, “Association between nutritional screening via the Controlling Nutritional Status index and bone mineral density in chronic liver disease of various etiologies,” Hepatology Research, vol. 45, no. 6, pp. 618–628, 2015. View at Publisher · View at Google Scholar · View at Scopus
  56. B. Y. Reed, J. E. Zerwekh, K. Sakhaee, N. A. Breslau, F. Gottschalk, and C. Y. Pak, “Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis,” Journal of Bone and Mineral Research, vol. 10, no. 8, pp. 1218–1224, 1995. View at Google Scholar
  57. F. J. Gallego-Rojo, J. L. Gonzalez-Calvin, M. Muñoz-Torres, J. L. Mundi, R. Fernandez-Perez, and D. Rodrigo-Moreno, “Bone mineral density, serum insulin-like growth factor I, and bone turnover markers in viral cirrhosis,” Hepatology, vol. 28, no. 3, pp. 695–699, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. P. Peris, A. Pares, N. Guanabens et al., “Reduced spinal and femoral bone mass and deranged bone mineral metabolism in chronic alcoholics,” Alcohol and Alcoholism, vol. 27, no. 6, pp. 619–625, 1992. View at Google Scholar · View at Scopus
  59. P. Peris, A. Parés, N. Guañabens et al., “Bone mass improves in alcoholics after 2 years of abstinence,” Journal of Bone and Mineral Research, vol. 9, no. 10, pp. 1607–1612, 1994. View at Google Scholar · View at Scopus
  60. K. Yamasaki and H. Hagiwara, “Excess iron inhibits osteoblast metabolism,” Toxicology Letters, vol. 191, no. 2-3, pp. 211–215, 2009. View at Publisher · View at Google Scholar · View at Scopus
  61. C. H. Janes, E. R. Dickson, R. Okazaki, S. Bonde, A. F. McDonagh, and B. L. Riggs, “Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice,” Journal of Clinical Investigation, vol. 95, no. 6, pp. 2581–2586, 1995. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Weinreb, R. D. Pollak, and Z. Ackerman, “Experimental cholestatic liver disease through bile-duct ligation in rats results in skeletal fragility and impaired osteoblastogenesis,” Journal of Hepatology, vol. 40, no. 3, pp. 385–390, 2004. View at Publisher · View at Google Scholar · View at Scopus
  63. S. Ruiz-Gaspà, N. Guañabens, A. Enjuanes et al., “Lithocholic acid downregulates vitamin D effects in human osteoblasts,” European Journal of Clinical Investigation, vol. 40, no. 1, pp. 25–34, 2010. View at Publisher · View at Google Scholar
  64. K. V. N. Menon, P. Angulo, S. Weston, E. R. Dickson, and K. D. Lindor, “Bone disease in primary biliary cirrhosis: independent indicators and rate of progression,” Journal of Hepatology, vol. 35, no. 3, pp. 316–323, 2001. View at Publisher · View at Google Scholar · View at Scopus
  65. M. M. J. Guichelaar, M. Malinchoc, J. Sibonga, B. L. Clarke, and J. E. Hay, “Bone metabolism in advanced cholestatic liver disease: analysis by bone histomorphometry,” Hepatology, vol. 36, no. 4, part 1, pp. 895–903, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. D. L. H. Smith, N. J. Shire, N. B. Watts, T. Schmitter, G. Szabo, and S. D. Zucker, “Hyperbilirubinemia is not a major contributing factor to altered bone mineral density in patients with chronic liver disease,” Journal of Clinical Densitometry, vol. 9, no. 1, pp. 105–113, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Prince, E. Christensen, and C. Gluud, “Glucocorticosteroids for primary biliary cirrhosis,” Cochrane Database of Systematic Reviews, no. 2, Article ID CD003778, 2005. View at Google Scholar · View at Scopus
  68. F. N. R. Van Berkum, R. Beukers, J. C. Birkenhäger, P. P. M. Kooij, S. W. Schalm, and H. A. P. Pols, “Bone mass in women with primary biliary cirrhosis: the relation with histological stage and use of glucocorticoids,” Gastroenterology, vol. 99, no. 4, pp. 1134–1139, 1990. View at Publisher · View at Google Scholar · View at Scopus
  69. K. G. Saag, “Glucocorticoid-induced osteoporosis,” Endocrinology and Metabolism Clinics of North America, vol. 32, no. 1, pp. 135–157, 2003. View at Publisher · View at Google Scholar · View at Scopus
  70. D. Jia, C. A. O'Brien, S. A. Stewart, S. C. Manolagas, and R. S. Weinstein, “Glucocorticoids act directly on osteoclasts to increase their life span and reduce bone density,” Endocrinology, vol. 147, no. 12, pp. 5592–5599, 2006. View at Publisher · View at Google Scholar · View at Scopus
  71. X. Whittier and K. G. Saag, “Glucocorticoid-induced Osteoporosis,” Rheumatic Disease Clinics of North America, vol. 42, no. 1, pp. 177–189, 2016. View at Publisher · View at Google Scholar
  72. R. S. Weinstein, R. L. Jilka, A. Michael Parfitt, and S. C. Manolagas, “Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts end osteocytes by glucocorticoids potential mechanisms of their deleterious effects on bone,” The Journal of Clinical Investigation, vol. 102, no. 2, pp. 274–282, 1998. View at Publisher · View at Google Scholar · View at Scopus
  73. J. Arteh, S. Narra, and S. Nair, “Prevalence of vitamin D deficiency in chronic liver disease,” Digestive Diseases and Sciences, vol. 55, no. 9, pp. 2624–2628, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. E. Cholongitas, E. Theocharidou, J. Goulis, E. Tsochatzis, E. Akriviadis, and K. Burroughs, “Review article: the extra-skeletal effects of vitamin D in chronic hepatitis C infection,” Alimentary Pharmacology and Therapeutics, vol. 35, no. 6, pp. 634–646, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Lips, “Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications,” Endocrine Reviews, vol. 22, no. 4, pp. 477–501, 2001. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Mounach, Z. Ouzzif, G. Wariaghli et al., “Primary biliary cirrhosis and osteoporosis: a case-control study,” Journal of Bone and Mineral Metabolism, vol. 26, no. 4, pp. 379–384, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. P. Malik, R. W. Gasser, G. Kemmler et al., “Low bone mineral density and impaired bone metabolism in young alcoholic patients without liver cirrhosis: a cross-sectional study,” Alcoholism: Clinical and Experimental Research, vol. 33, no. 2, pp. 375–381, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. G. W. McCaughan and R. B. Feller, “Osteoporosis in chronic liver disease: pathogenesis, risk factors, and management,” Digestive Diseases, vol. 12, no. 4, pp. 223–231, 1994. View at Google Scholar · View at Scopus
  79. K. V. Kowdley, M. J. Emond, J. A. Sadowski, and M. M. Kaplan, “Plasma vitamin K1 level is decreased in primary biliary cirrhosis,” American Journal of Gastroenterology, vol. 92, no. 11, pp. 2059–2061, 1997. View at Google Scholar · View at Scopus
  80. S. Nishiguchi, S. Shimoi, H. Kurooka et al., “Randomized pilot trial of vitamin k2 for bone loss in patients with primary biliary cirrhosis,” Journal of Hepatology, vol. 35, no. 4, pp. 543–545, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. Y. Koshihara, K. Hoshi, R. Okawara, H. Ishibashi, and S. Yamamoto, “Vitamin K stimulates osteoblastogenesis and inhibits osteoclastogenesis in human bone marrow cell culture,” Journal of Endocrinology, vol. 176, no. 3, pp. 339–348, 2003. View at Publisher · View at Google Scholar · View at Scopus
  82. Y. Hiruma, K.-I. Nakahama, H. Fujita, and I. Morita, “Vitamin K2 and geranylgeraniol, its side chain component, inhibited osteoclast formation in a different manner,” Biochemical and Biophysical Research Communications, vol. 314, no. 1, pp. 24–30, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. S. Cockayne, J. Adamson, S. Lanham-New et al., “Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials,” Archives of Internal Medicine, vol. 166, no. 12, pp. 1256–1261, 2006. View at Publisher · View at Google Scholar
  84. I. A. Nakchbandi and S. W. van der Merwe, “Current understanding of osteoporosis associated with liver disease,” Nature Reviews Gastroenterology & Hepatology, vol. 6, no. 11, pp. 660–670, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. J. L. Gonzalez-calvin, A. Garcia-sanchez, V. Bellot, M. Munoz-torres, E. Raya-alvarez, and D. Salvatierra-rios, “Mineral metabolism, osteoblastic function and bone mass in chronic alcoholism,” Alcohol and Alcoholism, vol. 28, no. 5, pp. 571–579, 1993. View at Google Scholar · View at Scopus
  86. F. Santolaria, E. González-Reimers, J. L. Pérez-Manzano et al., “Osteopenia assessed by body composition analysis is related to malnutrition in alcoholic patients,” Alcohol, vol. 22, no. 3, pp. 147–157, 2000. View at Publisher · View at Google Scholar · View at Scopus
  87. E. González-Reimers, J. Alvisa-Negrín, F. Santolaria-Fernández et al., “Prognosis of osteopenia in chronic alcoholics,” Alcohol, vol. 45, no. 3, pp. 227–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. K. M. Kim, H. S. Choi, M. Choi, and H. Y. Chung, “Calcium and Vitamin D supplementations: 2015 position statement of the korean society for bone and mineral research,” Journal of Bone Metabolism, vol. 22, no. 4, pp. 143–149, 2015. View at Publisher · View at Google Scholar
  89. I. Loria, C. Albanese, M. Giusto et al., “Bone disorders in patients with chronic liver disease awaiting liver transplantation,” Transplantation Proceedings, vol. 42, no. 4, pp. 1191–1193, 2010. View at Publisher · View at Google Scholar · View at Scopus
  90. W. Leslie, “AGA technical review on osteoporosis in hepatic disorders,” Gastroenterology, vol. 125, no. 3, pp. 941–966, 2003. View at Publisher · View at Google Scholar
  91. N. Guañabens, A. Monegal, A. Muxi et al., “Patients with cirrhosis and ascites have false values of bone density: implications for the diagnosis of osteoporosis,” Osteoporosis International, vol. 23, no. 4, pp. 1481–1487, 2012. View at Publisher · View at Google Scholar · View at Scopus
  92. E. D. Labio, D. B. Del Rosario, S. I. Strasser, G. W. McCaughan, and B. A. Crawford, “Effect of ascites on bone density measurement in cirrhosis,” Journal of Clinical Densitometry, vol. 10, no. 4, pp. 391–394, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. M. A. Valero, C. Loinaz, L. Larrodera, M. Leon, E. Moreno, and F. Hawkins, “Calcitonin and bisphosphonates treatment in bone loss after liver transplantation,” Calcified Tissue International, vol. 57, no. 1, pp. 15–19, 1995. View at Publisher · View at Google Scholar · View at Scopus
  94. D. Chappard, B. Plantard, M. Petitjean, C. Alexandre, and G. Riffat, “Alcoholic cirrhosis and osteoporosis in men: a light and scanning electron microscopy study,” Journal of Studies on Alcohol, vol. 52, no. 3, pp. 269–274, 1991. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Kim, H. Lee, K. S. Kang, K. Chun, and G. S. Hwang, “Protective effect of Korean Red Ginseng against glucocorticoid-induced osteoporosis in vitro and in vivo,” Journal of Ginseng Research, vol. 39, no. 1, pp. 46–53, 2015. View at Publisher · View at Google Scholar
  96. T. Waldman, R. Sarbaziha, C. N. B. Merz, and C. Shufelt, “Calcium supplements and cardiovascular disease: a review,” American Journal of Lifestyle Medicine, vol. 9, no. 4, pp. 298–307, 2015. View at Publisher · View at Google Scholar · View at Scopus
  97. C. S. Shin and K. M. Kim, “The risks and benefits of calcium supplementation,” Endocrinology and Metabolism, vol. 30, no. 1, pp. 27–34, 2015. View at Publisher · View at Google Scholar · View at Scopus
  98. S. Shiomi, K. Masaki, D. Habu et al., “Calcitriol for bone disease in patients with cirrhosis of the liver,” Journal of Gastroenterology and Hepatology, vol. 14, no. 6, pp. 547–552, 1999. View at Publisher · View at Google Scholar · View at Scopus
  99. M. J. Bolland, W. Leung, V. Tai et al., “Calcium intake and risk of fracture: systematic review,” British Medical Journal, vol. 351, Article ID h4580, 2015. View at Publisher · View at Google Scholar · View at Scopus
  100. C. Mateo Pascual, R. Julián Viñals, M. V. Castell Alcalá, R. Queipo, and A. Otero Piume, “Evaluation of adherence to treatment with calcium and Vitamin D in the elderly in a basic health area,” Revista de Calidad Asistencial, vol. 31, no. 1, pp. 10–17, 2016. View at Publisher · View at Google Scholar · View at Scopus
  101. J. S. Crippin, R. A. Jorgensen, E. R. Dickson, and K. D. Lindor, “Hepatic osteodystrophy in primary biliary cirrhosis: effects of medical treatment,” The American Journal of Gastroenterology, vol. 89, no. 1, pp. 47–50, 1994. View at Google Scholar · View at Scopus
  102. S. P. Pereira, J. O'Donohue, C. Moniz et al., “Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1-year controlled trial,” Alimentary Pharmacology and Therapeutics, vol. 19, no. 5, pp. 563–570, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. T. Diamond, D. Stiel, and S. Posen, “Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis,” Journal of Bone and Mineral Research, vol. 6, no. 1, pp. 39–43, 1991. View at Google Scholar · View at Scopus
  104. “Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI,” JAMA, vol. 276, no. 17, pp. 1389–1396, 1996.
  105. J. E. Rossouw, G. L. Anderson, R. L. Prentice et al., “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial,” The Journal of the American Medical Association, vol. 288, no. 3, pp. 321–333, 2002. View at Publisher · View at Google Scholar
  106. R. H. Boone, A. M. Cheung, L. M. Girlan, and E. J. Heathcote, “Osteoporosis in primary biliary cirrhosis: a randomized trial of the efficacy and feasibility of estrogen/progestin,” Digestive Diseases and Sciences, vol. 51, no. 6, pp. 1103–1112, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. European Association for the Study of the Liver, “EASL Clinical Practice Guidelines: management of cholestatic liver diseases,” Journal of Hepatology, vol. 51, no. 2, pp. 237–267, 2009. View at Publisher · View at Google Scholar
  108. H. Isoniemi, J. Appelberg, C.-G. Nilsson, P. Mäkelä, J. Risteli, and K. Höckerstedt, “Transdermal estrogen therapy improves lipid profile and osteoporosis in postmenopausal liver transplant patients,” Transplantation Proceedings, vol. 33, no. 1-2, pp. 1472–1473, 2001. View at Publisher · View at Google Scholar · View at Scopus
  109. R. Olsson, L.-Å. Mattsson, K. Obrant, and D. Mellström, “Estrogen-progestogen therapy for low bone mineral density in primary biliary cirrhosis,” Liver, vol. 19, no. 3, pp. 188–192, 1999. View at Publisher · View at Google Scholar · View at Scopus
  110. S. Ormarsdóttir, H. Mallmin, T. Naessén et al., “An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis,” Journal of Internal Medicine, vol. 256, no. 1, pp. 63–69, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. A. Floreani, M. Chiaramonte, S. Giannini et al., “Longitudinal study on osteodystrophy in primary biliary cirrhosis (PBC) and a pilot study on calcitonin treatment,” Journal of Hepatology, vol. 12, no. 2, pp. 217–223, 1991. View at Publisher · View at Google Scholar · View at Scopus
  112. A. Floreani, F. Zappala, W. Fries et al., “A 3-year pilot study with 1,25-dihydroxyvitamin D, calcium, and calcitonin for severe osteodystrophy in primary biliary cirrhosis,” Journal of Clinical Gastroenterology, vol. 24, no. 4, pp. 239–244, 1997. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Camisasca, A. Crosignani, P. M. Battezzati et al., “Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis,” Hepatology, vol. 20, no. 3, pp. 633–637, 1994. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Kleerekoper and D. B. Mendlovic, “Sodium fluoride therapy of postmenopausal osteoporosis,” Endocrine Reviews, vol. 14, no. 3, pp. 312–323, 1993. View at Publisher · View at Google Scholar · View at Scopus
  115. N. Guañabens, A. Parés, L. del Rio et al., “Sodium fluoride prevents bone loss in primary biliary cirrhosis,” Journal of Hepatology, vol. 15, no. 3, pp. 345–349, 1992. View at Publisher · View at Google Scholar · View at Scopus
  116. N. Guanabens, A. Pares, A. Monegal et al., “Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis: preliminary results after 2 years,” Gastroenterology, vol. 113, no. 1, pp. 219–224, 1997. View at Publisher · View at Google Scholar · View at Scopus
  117. C. Levy, D. M. Harnois, P. Angulo, R. Jorgensen, and K. D. Lindor, “Raloxifene improves bone mass in osteopenic women with primary biliary cirrhosis: results of a pilot study,” Liver International, vol. 25, no. 1, pp. 117–121, 2005. View at Publisher · View at Google Scholar · View at Scopus
  118. A. Yurci, A. O. Kalkan, O. Ozbakir et al., “Efficacy of different therapeutic regimens on hepatic osteodystrophy in chronic viral liver disease,” European Journal of Gastroenterology and Hepatology, vol. 23, no. 12, pp. 1206–1212, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. H. L. Reeves, R. M. Francis, D. M. Manas, M. Hudson, and C. P. Day, “Intravenous bisphosphonate prevents symptomatic osteoporotic vertebral collapse in patients after liver transplantation,” Liver Transplantation and Surgery, vol. 4, no. 5, pp. 404–409, 1998. View at Publisher · View at Google Scholar · View at Scopus
  120. N. Guañabens, A. Parés, I. Ros et al., “Alendronate is more effective than etidronate for increasing bone mass in osteopenic patients with primary biliary cirrhosis,” The American Journal of Gastroenterology, vol. 98, no. 10, pp. 2268–2274, 2003. View at Publisher · View at Google Scholar · View at Scopus
  121. C. O. Zein, R. A. Jorgensen, B. Clarke et al., “Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial,” Hepatology, vol. 42, no. 4, pp. 762–771, 2005. View at Publisher · View at Google Scholar · View at Scopus
  122. N. Guañabens, A. Monegal, D. Cerdá et al., “Randomized trial comparing monthly ibandronate and weekly alendronate for osteoporosis in patients with primary biliary cirrhosis,” Hepatology, vol. 58, no. 6, pp. 2070–2078, 2013. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Ninkovic, S. Love, B. D. M. Tom, P. W. P. Bearcroft, G. J. M. Alexander, and J. E. Compston, “Lack of effect of intravenous pamidronate on fracture incidence and bone mineral density after orthotopic liver transplantation,” Journal of Hepatology, vol. 37, no. 1, pp. 93–100, 2002. View at Publisher · View at Google Scholar · View at Scopus
  124. S. Vedi, M. Ninkovic, N. J. Garrahan, G. J. M. Alexander, and J. E. Compston, “Effects of a single infusion of pamidronate prior to liver transplantation: a bone histomorphometric study,” Transplant International, vol. 15, no. 6, pp. 290–295, 2002. View at Publisher · View at Google Scholar · View at Scopus
  125. P. Dodidou, T. Bruckner, S. Hosch et al., “Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation,” Osteoporosis International, vol. 14, no. 1, pp. 82–89, 2003. View at Publisher · View at Google Scholar · View at Scopus
  126. P. Pennisi, A. Trombetti, E. Giostra, G. Mentha, R. Rizzoli, and C. E. Fiore, “Pamidronate and osteoporosis prevention in liver transplant recipients,” Rheumatology International, vol. 27, no. 3, pp. 251–256, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. G. Millonig, I. W. Graziadei, D. Eichler et al., “Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study,” Liver Transplantation, vol. 11, no. 8, pp. 960–966, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. B. A. Crawford, E. D. Labio, S. I. Strasser, and G. W. McCaughan, “Vitamin D replacement for cirrhosis-related bone disease,” Nature Clinical Practice Gastroenterology and Hepatology, vol. 3, no. 12, pp. 689–699, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. F. Atamaz, S. Hepguler, M. Akyildiz, Z. Karasu, and M. Kilic, “Effects of alendronate on bone mineral density and bone metabolic markers in patients with liver transplantation,” Osteoporosis International, vol. 17, no. 6, pp. 942–949, 2006. View at Publisher · View at Google Scholar · View at Scopus
  130. M. Bodingbauer, T. Wekerle, B. Pakrah et al., “Prophylactic bisphosphonate treatment prevents bone fractures after liver transplantation,” American Journal of Transplantation, vol. 7, no. 7, pp. 1763–1769, 2007. View at Publisher · View at Google Scholar · View at Scopus
  131. B. M. Misof, M. Bodingbauer, P. Roschger et al., “Short-term effects of high-dose zoledronic acid treatment on bone mineralization density distribution after orthotopic liver transplantation,” Calcified Tissue International, vol. 83, no. 3, pp. 167–175, 2008. View at Publisher · View at Google Scholar · View at Scopus
  132. A. Monegal, N. Guañabens, M. J. Suárez et al., “Pamidronate in the prevention of bone loss after liver transplantation: a randomized controlled trial,” Transplant International, vol. 22, no. 2, pp. 198–206, 2009. View at Publisher · View at Google Scholar
  133. M. Ablikim, M. N. Achasov, X. C. Ai et al., “Observation of e+e-π0π0hc and a neutral charmoniumlike structure Zc(4020)0,” Physical Review Letters, vol. 113, no. 21, Article ID 212002, 2014. View at Publisher · View at Google Scholar