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. 1990 Jan;31(1):82–87. doi: 10.1136/gut.31.1.82

Osteoporosis and skeletal fractures in chronic liver disease.

T Diamond 1, D Stiel 1, M Lunzer 1, M Wilkinson 1, J Roche 1, S Posen 1
PMCID: PMC1378345  PMID: 2318434

Abstract

In order to determine the prevalence and severity of hepatic osteodystrophy by non-invasive means we compared 115 consecutive ambulant patients with histologically proven chronic liver disease to 113 age and sex matched control subjects. Methods used included the assessment of fracture prevalence rates, spinal radiography, and measurements of bone mineral density in the spine and the forearm. Spinal and peripheral fractures were more prevalent in the patients than in the control subjects (p less than 0.03 and p less than 0.01 respectively). The type of the underlying liver disease did not significantly affect the fracture prevalence rates, but alcoholic patients sustained more peripheral fractures than patients with other hepatic disorders (p less than 0.05). The bone mineral densities of the spines and the forearms were significantly reduced in male patients of all age groups and in female patients aged 60 years or more (p less than 0.001 for men and p less than 0.01 for women for both measurements). The prevalence rates of spinal and forearm osteoporosis were twice as high among patients with liver disease than in control subjects regardless of the definitions used. The presence of cirrhosis and hypogonadism were major risk factors for development of both spinal (Beta coef = 0.190 and 0.176; SE = 0.079 and 0.086 respectively) and forearm osteoporosis (Beta coef = 0.20 and 0.29; SE = 0.073 and 0.80 respectively). Spinal bone density was the predominant determinant of spinal fractures (Beta coef = -0.007; SE = 0.001), while hypogonadism (Beta coef = 0.363; SE = 0.075) and cirrhosis (Beta coef = 0.185; SE = 0.068) were the major predictors of peripheral fractures. The concentrations of serum calcium and serum vitamin D metabolites and the use of corticosteroids were apparently without effect on the prevalence of skeletal fractures or bone density.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ATKINSON M., NORDIN B. E., SHERLOCK S. Malabsorption and bone disease in prolonged obstructive jaundice. Q J Med. 1956 Jul;25(99):299–312. [PubMed] [Google Scholar]
  2. Acute and chronic hepatitis revisited. Review by an international group. Lancet. 1977 Oct 29;2(8044):914–919. [PubMed] [Google Scholar]
  3. Barbatis C., Grases P., Shepherd H. A., Chapman R. W., Trowell J., Jewell D. P., McGee J. O. Histological features of sclerosing cholangitis in patients with chronic ulcerative colitis. J Clin Pathol. 1985 Jul;38(7):778–783. doi: 10.1136/jcp.38.7.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bikle D. D., Genant H. K., Cann C., Recker R. R., Halloran B. P., Strewler G. J. Bone disease in alcohol abuse. Ann Intern Med. 1985 Jul;103(1):42–48. doi: 10.7326/0003-4819-103-1-42. [DOI] [PubMed] [Google Scholar]
  5. Cann C. E., Genant H. K., Kolb F. O., Ettinger B. Quantitative computed tomography for prediction of vertebral fracture risk. Bone. 1985;6(1):1–7. doi: 10.1016/8756-3282(85)90399-0. [DOI] [PubMed] [Google Scholar]
  6. Compston J. E. Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease. Gut. 1986 Sep;27(9):1073–1090. doi: 10.1136/gut.27.9.1073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cummings S. R., Kelsey J. L., Nevitt M. C., O'Dowd K. J. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev. 1985;7:178–208. doi: 10.1093/oxfordjournals.epirev.a036281. [DOI] [PubMed] [Google Scholar]
  8. Cuthbert J. A., Pak C. Y., Zerwekh J. E., Glass K. D., Combes B. Bone disease in primary biliary cirrhosis: increased bone resorption and turnover in the absence of osteoporosis or osteomalacia. Hepatology. 1984 Jan-Feb;4(1):1–8. doi: 10.1002/hep.1840040101. [DOI] [PubMed] [Google Scholar]
  9. DELBARRE F. [Osteoporosis in hemochromatosis]. Sem Hop. 1960 Dec 20;36:3279–3294. [PubMed] [Google Scholar]
  10. Dalén N., Lamke B. Bone mineral losses in alcoholics. Acta Orthop Scand. 1976 Aug;47(4):469–471. doi: 10.3109/17453677608988722. [DOI] [PubMed] [Google Scholar]
  11. Devogelaer J. P., Crabbé J., Nagant de Deuxchaisnes C. Bone mineral density in Addison's disease: evidence for an effect of adrenal androgens on bone mass. Br Med J (Clin Res Ed) 1987 Mar 28;294(6575):798–800. doi: 10.1136/bmj.294.6575.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Diamond T. H., Stiel D., Lunzer M., McDowall D., Eckstein R. P., Posen S. Hepatic osteodystrophy. Static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease. Gastroenterology. 1989 Jan;96(1):213–221. [PubMed] [Google Scholar]
  13. Dibble J. B., Sheridan P., Hampshire R., Hardy G. J., Losowsky M. S. Osteomalacia, vitamin D deficiency and cholestasis in chronic liver disease. Q J Med. 1982;51(201):89–103. [PubMed] [Google Scholar]
  14. Fareed J., Messmore H. L., Bermes E. W. New perspectives in coagulation testing. Clin Chem. 1980 Sep;26(10):1380–1391. [PubMed] [Google Scholar]
  15. Farrell G. C., Zaluzny L. Accuracy and clinical utility of simplified tests of antipyrine metabolism. Br J Clin Pharmacol. 1984 Oct;18(4):559–565. doi: 10.1111/j.1365-2125.1984.tb02504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feitelberg S., Epstein S., Ismail F., D'Amanda C. Deranged bone mineral metabolism in chronic alcoholism. Metabolism. 1987 Apr;36(4):322–326. doi: 10.1016/0026-0495(87)90201-0. [DOI] [PubMed] [Google Scholar]
  17. Finkelstein J. S., Klibanski A., Neer R. M., Greenspan S. L., Rosenthal D. I., Crowley W. F., Jr Osteoporosis in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med. 1987 Mar;106(3):354–361. doi: 10.7326/0003-4819-106-3-. [DOI] [PubMed] [Google Scholar]
  18. Fonseca V., Epstein O., Gill D. S., Menon R. K., Thomas M., McIntyre N., Dandona P. Hyperparathyroidism and low serum osteocalcin despite vitamin D replacement in primary biliary cirrhosis. J Clin Endocrinol Metab. 1987 May;64(5):873–877. doi: 10.1210/jcem-64-5-873. [DOI] [PubMed] [Google Scholar]
  19. Genant H. K., Steiger P., Block J. E., Glueer C. C., Ettinger B., Harris S. T. Quantitative computed tomography: update 1987. Calcif Tissue Int. 1987 Oct;41(4):179–186. doi: 10.1007/BF02555236. [DOI] [PubMed] [Google Scholar]
  20. Gollan J. L. Diagnosis of hemochromatosis. Gastroenterology. 1983 Feb;84(2):418–421. [PubMed] [Google Scholar]
  21. Hahn T. J. Corticosteroid-induced osteopenia. Arch Intern Med. 1978 May 15;138(Spec No):882–885. [PubMed] [Google Scholar]
  22. Herlong H. F., Recker R. R., Maddrey W. C. Bone disease in primary biliary cirrhosis: histologic features and response to 25-hydroxyvitamin D. Gastroenterology. 1982 Jul;83(1 Pt 1):103–108. [PubMed] [Google Scholar]
  23. Hodgson S. F., Dickson E. R., Wahner H. W., Johnson K. A., Mann K. G., Riggs B. L. Bone loss and reduced osteoblast function in primary biliary cirrhosis. Ann Intern Med. 1985 Dec;103(6 ):855–860. doi: 10.7326/0003-4819-103-6-855. [DOI] [PubMed] [Google Scholar]
  24. Kato Y., Epstein O., Dick R., Sherlock S. Radiological patterns of cortical bone modelling in women with chronic liver disease. Clin Radiol. 1982 May 3;33(3):313–317. doi: 10.1016/s0009-9260(82)80276-6. [DOI] [PubMed] [Google Scholar]
  25. Kehayoglou A. K., Holdsworth C. D., Agnew J. E., Whelton M. J., Sherlock S. Bone disease and calcium absorption in primary biliary cirrhosis with special reference to vitamin-D therapy. Lancet. 1968 Apr 6;1(7545):715–718. doi: 10.1016/s0140-6736(68)92164-8. [DOI] [PubMed] [Google Scholar]
  26. Kleerekoper M., Ingham J. P., McCarthy S. W., Posen S. Parathyroid hormone assay in primary hyperparathyroidism: experiences with a radioimmunoassay based on commercially available reagents. Clin Chem. 1974 Mar;20(3):369–375. [PubMed] [Google Scholar]
  27. Lalor B. C., France M. W., Powell D., Adams P. H., Counihan T. B. Bone and mineral metabolism and chronic alcohol abuse. Q J Med. 1986 May;59(229):497–511. [PubMed] [Google Scholar]
  28. Laval-Jeantet A. M., Cann C. E., Roger B., Dallant P. A postprocessing dual energy technique for vertebral CT densitometry. J Comput Assist Tomogr. 1984 Dec;8(6):1164–1167. doi: 10.1097/00004728-198412000-00024. [DOI] [PubMed] [Google Scholar]
  29. Long R. G., Meinhard E., Skinner R. K., Varghese Z., Wills M. R., Sherlock S. Clinical, biochemical, and histological studies of osteomalacia, osteoporosis, and parathyroid function in chronic liver disease. Gut. 1978 Feb;19(2):85–90. doi: 10.1136/gut.19.2.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matloff D. S., Kaplan M. M., Neer R. M., Goldberg M. J., Bitman W., Wolfe H. J. Osteoporosis in primary biliary cirrhosis: effects of 25-hydroxyvitamin D3 treatment. Gastroenterology. 1982 Jul;83(1 Pt 1):97–102. [PubMed] [Google Scholar]
  31. McElduff A., Wilkinson M., Ward P., Posen S. Forearm mineral content in normal men: relationship to weight, height and plasma testosterone concentrations. Bone. 1988;9(5):281–283. doi: 10.1016/8756-3282(88)90010-5. [DOI] [PubMed] [Google Scholar]
  32. Mitchison H. C., Malcolm A. J., Bassendine M. F., James O. F. Metabolic bone disease in primary biliary cirrhosis at presentation. Gastroenterology. 1988 Feb;94(2):463–470. doi: 10.1016/0016-5085(88)90438-6. [DOI] [PubMed] [Google Scholar]
  33. Mobarhan S. A., Russell R. M., Recker R. R., Posner D. B., Iber F. L., Miller P. Metabolic bone disease in alcoholic cirrhosis: a comparison of the effect of vitamin D2, 25-hydroxyvitamin D, or supportive treatment. Hepatology. 1984 Mar-Apr;4(2):266–273. doi: 10.1002/hep.1840040216. [DOI] [PubMed] [Google Scholar]
  34. Monnier L. H., Colette C., Ribot C., Mion C., Mirouze J. Evidence for 25-hydroxyvitamin D deficiency as a factor contributing to osteopenia in diabetic patients with idiopathic haemochromatosis. Eur J Clin Invest. 1980 Jun;10(3):183–187. doi: 10.1111/j.1365-2362.1980.tb00018.x. [DOI] [PubMed] [Google Scholar]
  35. Nordin B. E. The definition and diagnosis of osteoporosis. Calcif Tissue Int. 1987 Feb;40(2):57–58. doi: 10.1007/BF02555705. [DOI] [PubMed] [Google Scholar]
  36. Odvina C. V., Wergedal J. E., Libanati C. R., Schulz E. E., Baylink D. J. Relationship between trabecular vertebral body density and fractures: a quantitative definition of spinal osteoporosis. Metabolism. 1988 Mar;37(3):221–228. doi: 10.1016/0026-0495(88)90099-6. [DOI] [PubMed] [Google Scholar]
  37. Parfitt A. M. Trabecular bone architecture in the pathogenesis and prevention of fracture. Am J Med. 1987 Jan 26;82(1B):68–72. doi: 10.1016/0002-9343(87)90274-9. [DOI] [PubMed] [Google Scholar]
  38. Paterson C. R., Losowsky M. S. The bones in chronic liver disease. Scand J Gastroenterol. 1967;2(4):293–300. doi: 10.3109/00365526709180085. [DOI] [PubMed] [Google Scholar]
  39. Reinbold W. D., Genant H. K., Reiser U. J., Harris S. T., Ettinger B. Bone mineral content in early-postmenopausal and postmenopausal osteoporotic women: comparison of measurement methods. Radiology. 1986 Aug;160(2):469–478. doi: 10.1148/radiology.160.2.3726129. [DOI] [PubMed] [Google Scholar]
  40. Robinson B., Wagstaffe C., Roche J., Clifton-Bligh P., Posen S. Is there a place for forearm osteodensitometry in clinical screening studies? Med J Aust. 1987 Mar 16;146(6):297–300. doi: 10.5694/j.1326-5377.1987.tb120265.x. [DOI] [PubMed] [Google Scholar]
  41. SAVILLE P. D. CHANGES IN BONE MASS WITH AGE AND ALCOHOLISM. J Bone Joint Surg Am. 1965 Apr;47:492–499. [PubMed] [Google Scholar]
  42. Sambrook P. N., Eisman J. A., Yeates M. G., Pocock N. A., Eberl S., Champion G. D. Osteoporosis in rheumatoid arthritis: safety of low dose corticosteroids. Ann Rheum Dis. 1986 Nov;45(11):950–953. doi: 10.1136/ard.45.11.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Schnitzler C. M., Solomon L. Bone changes after alcohol abuse. S Afr Med J. 1984 Nov 10;66(19):730–734. [PubMed] [Google Scholar]
  44. Seeman E., Melton L. J., 3rd, O'Fallon W. M., Riggs B. L. Risk factors for spinal osteoporosis in men. Am J Med. 1983 Dec;75(6):977–983. doi: 10.1016/0002-9343(83)90878-1. [DOI] [PubMed] [Google Scholar]
  45. Seshadri M. S., Frankel T. L., Lissner D., Mason R. S., Posen S. Bioactive parathyroid hormone in the rat: effects of calcium and calcitriol. Endocrinology. 1985 Dec;117(6):2417–2423. doi: 10.1210/endo-117-6-2417. [DOI] [PubMed] [Google Scholar]
  46. Stellon A. J., Davies A., Compston J., Williams R. Bone loss in autoimmune chronic active hepatitis on maintenance corticosteroid therapy. Gastroenterology. 1985 Nov;89(5):1078–1083. doi: 10.1016/0016-5085(85)90212-4. [DOI] [PubMed] [Google Scholar]
  47. Stellon A. J., Webb A., Compston J. E. Bone histomorphometry and structure in corticosteroid treated chronic active hepatitis. Gut. 1988 Mar;29(3):378–384. doi: 10.1136/gut.29.3.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Stellon A. J., Webb A., Compston J., Williams R. Low bone turnover state in primary biliary cirrhosis. Hepatology. 1987 Jan-Feb;7(1):137–142. doi: 10.1002/hep.1840070127. [DOI] [PubMed] [Google Scholar]
  49. Verbanck M., Verbanck J., Brauman J., Mullier J. P. Bone histology and 25-OH vitamin D plasma levels in alcoholics without cirrhosis. Calcif Tissue Res. 1977 May;22 (Suppl):538–541. doi: 10.1007/BF02064155. [DOI] [PubMed] [Google Scholar]
  50. Williams J. W., Vera S. R., Peters T. G., Luther R. W., Bhattacharya S., Spears H., Graham A., Pitcock J. A., Crawford A. J., Palmieri G. M. Biliary excretion of aluminum in aluminum osteodystrophy with liver disease. Ann Intern Med. 1986 Jun;104(6):782–785. doi: 10.7326/0003-4819-104-6-782. [DOI] [PubMed] [Google Scholar]
  51. Williamson J. M., Chalmers D. M., Clayden A. D., Dixon M. F., Ruddell W. S., Losowsky M. S. Primary biliary cirrhosis and chronic active hepatitis: an examination of clinical, biochemical, and histopathological features in differential diagnosis. J Clin Pathol. 1985 Sep;38(9):1007–1012. doi: 10.1136/jcp.38.9.1007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Xing S., Cekan S. Z., Diczfalusy U., Falk O., Gustafsson S. A., Akerlöf E., Björkhem I. Validation of radioimmunoassay for estradiol-17 beta by isotope dilution-mass spectrometry and by a test of radiochemical purity. Clin Chim Acta. 1983 Dec 15;135(2):189–201. doi: 10.1016/0009-8981(83)90135-3. [DOI] [PubMed] [Google Scholar]
  53. de Vernejoul M. C., Bielakoff J., Herve M., Gueris J., Hott M., Modrowski D., Kuntz D., Miravet L., Ryckewaert A. Evidence for defective osteoblastic function. A role for alcohol and tobacco consumption in osteoporosis in middle-aged men. Clin Orthop Relat Res. 1983 Oct;(179):107–115. [PubMed] [Google Scholar]

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