DOI QR코드

DOI QR Code

Relationship Between Non-alcoholic Fatty Liver Disease and Decreased Bone Mineral Density: A Retrospective Cohort Study in Korea

  • Sung, Jisun (Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine) ;
  • Ryu, Seungho (Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Song, Yun-Mi (Department of Family Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cheong, Hae-Kwan (Department of Social and Preventive Medicine, Sungkyunkwan University School of Medicine)
  • Received : 2020.04.16
  • Accepted : 2020.06.23
  • Published : 2020.09.30

Abstract

Objectives: The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods: This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient's age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results: Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions: NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.

Keywords

References

  1. WHO Scientific Group on the Prevention and Management of Osteoporosis. Prevention and management of osteoporosis: report of a WHO scientific group; 2003 [cited 2020 Mar 1]. Available from: https://apps.who.int/iris/handle/10665/42841.
  2. Kim YA. Osteoporosis or low bone mass in adults aged 50 years old and above in Republic of Korea, 2008-2011. Public Health Wkly Rep 2013;7(42):939-942 (Korean).
  3. Ha YC, Kim HY, Jang S, Lee YK, Kim TY. Economic burden of osteoporosis in South Korea: claim data of the National Health Insurance Service from 2008 to 2011. Calcif Tissue Int 2017; 101(6):623-630. https://doi.org/10.1007/s00223-017-0320-1
  4. Chung YS. Current and upcoming treatments for osteoporosis. J Rheum Dis 2012;19(1):4-10 (Korean). https://doi.org/10.4078/jrd.2012.19.1.4
  5. Choi JM, Kim CB. Obesity management and scientific evidence. J Korean Med Assoc 2011;54(3):250-265 (Korean). https://doi.org/10.5124/jkma.2011.54.3.250
  6. Korea Centers for Disease Control and Prevention. Korea health statistics 2015: Korea National Health and Nutrition Examination Survey (KNHANES VI-3) [cited 2020 Mar 1]. Available from: https://knhanes.cdc.go.kr/knhanes/sub04/sub04_03.do?classType=7 (Korean).
  7. World Health Organization. Global status report on noncommunicable diseases 2010 [cited 2020 Mar 1]. Available from: https://apps.who.int/iris/handle/10665/44579.
  8. Cao JJ. Effects of obesity on bone metabolism. J Orthop Surg Res 2011;6:30. https://doi.org/10.1186/1749-799X-6-30
  9. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 2007;92(5):1640-1646. https://doi.org/10.1210/jc.2006-0572
  10. Zhao LJ, Jiang H, Papasian CJ, Maulik D, Drees B, Hamilton J, et al. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 2008; 23(1):17-29. https://doi.org/10.1359/jbmr.070813
  11. Kim JH, Choi HJ, Kim MJ, Shin CS, Cho NH. Fat mass is negatively associated with bone mineral content in Koreans. Osteoporos Int 2012;23(7):2009-2016. https://doi.org/10.1007/s00198-011-1808-6
  12. Shapses SA, Pop LC, Wang Y. Obesity is a concern for bone health with aging. Nutr Res 2017;39:1-13. https://doi.org/10.1016/j.nutres.2016.12.010
  13. Walsh JS, Vilaca T. Obesity, type 2 diabetes and bone in adults. Calcif Tissue Int 2017;100(5):528-535. https://doi.org/10.1007/s00223-016-0229-0
  14. Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of nonalcoholic fatty liver disease. Clin Mol Hepatol 2013;19(4):325-348. https://doi.org/10.3350/cmh.2013.19.4.325
  15. Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 2014;371(12):1131-1141. https://doi.org/10.1056/NEJMra1011035
  16. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010;363(14):1341-1350. https://doi.org/10.1056/NEJMra0912063
  17. Targher G, Lonardo A, Rossini M. Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link? J Endocrinol Invest 2015;38(8):817-825. https://doi.org/10.1007/s40618-015-0315-6
  18. Lee SH, Yun JM, Kim SH, Seo YG, Min H, Chung E, et al. Association between bone mineral density and nonalcoholic fatty liver disease in Korean adults. J Endocrinol Invest 2016;39(11): 1329-1336. https://doi.org/10.1007/s40618-016-0528-3
  19. Moon SS, Lee YS, Kim SW. Association of nonalcoholic fatty liver disease with low bone mass in postmenopausal women. Endocrine 2012;42(2):423-429. https://doi.org/10.1007/s12020-012-9639-6
  20. Xia MF, Lin HD, Yan HM, Bian H, Chang XX, Zhang LS, et al. The association of liver fat content and serum alanine aminotransferase with bone mineral density in middle-aged and elderly Chinese men and postmenopausal women. J Transl Med 2016; 14:11. https://doi.org/10.1186/s12967-016-0766-3
  21. Yang HJ, Shim SG, Ma BO, Kwak JY. Association of nonalcoholic fatty liver disease with bone mineral density and serum osteocalcin levels in Korean men. Eur J Gastroenterol Hepatol 2016;28(3):338-344. https://doi.org/10.1097/MEG.0000000000000535
  22. Chen HJ, Yang HY, Hsueh KC, Shen CC, Chen RY, Yu HC, et al. Increased risk of osteoporosis in patients with nonalcoholic fatty liver disease: a population-based retrospective cohort study. Medicine (Baltimore) 2018;97(42):e12835. https://doi.org/10.1097/md.0000000000012835
  23. Shen Z, Cen L, Chen X, Pan J, Li Y, Chen W, et al. Increased risk of low bone mineral density in patients with non-alcoholic fatty liver disease: a cohort study. Eur J Endocrinol 2020;182(2): 157-164. https://doi.org/10.1530/eje-19-0699
  24. World Health Organization. The Asia-Pacific perspective: redefining obesity and its treatment; 2000 [cited 2020 Mar 1]. Available from: https://apps.who.int/iris/handle/10665/206936.
  25. Kim CW, Yun KE, Jung HS, Chang Y, Choi ES, Kwon MJ, et al. Sleep duration and quality in relation to non-alcoholic fatty liver disease in middle-aged workers and their spouses. J Hepatol 2013;59(2):351-357. https://doi.org/10.1016/j.jhep.2013.03.035
  26. Cui R, Sheng H, Rui XF, Cheng XY, Sheng CJ, Wang JY, et al. Low bone mineral density in Chinese adults with nonalcoholic fatty liver disease. Int J Endocrinol 2013;2013:396545. https://doi.org/10.1155/2013/396545
  27. Kim G, Kim KJ, Rhee Y, Lim SK. Significant liver fibrosis assessed using liver transient elastography is independently associated with low bone mineral density in patients with non-alcoholic fatty liver disease. PLoS One 2017;12(7):e0182202. https://doi.org/10.1371/journal.pone.0182202
  28. Pardee PE, Dunn W, Schwimmer JB. Non-alcoholic fatty liver disease is associated with low bone mineral density in obese children. Aliment Pharmacol Ther 2012;35(2):248-254. https://doi.org/10.1111/j.1365-2036.2011.04924.x
  29. Poggiogalle E, Donini LM, Lenzi A, Chiesa C, Pacifico L. Non-alcoholic fatty liver disease connections with fat-free tissues: a focus on bone and skeletal muscle. World J Gastroenterol 2017;23(10):1747-1757. https://doi.org/10.3748/wjg.v23.i10.1747
  30. Yun EY, Kim CR. Estimation of survival function and median survival time in interval-censored data. Korean J Appl Stat 2010;23(3):521-531 (Korean). https://doi.org/10.5351/KJAS.2010.23.3.521
  31. Park SH, Kim J, Nam CM. Comparison of estimation methods of Cox proportional hazards model with interval-censored data. J Health Info Stat 2015;40(3):53-59 (Korean).
  32. Lee TC, Zeng L, Thompson DJ, Dean CB. Comparison of imputation methods for interval censored time-to-event data in joint modelling of tree growth and mortality. Can J Stat 2011; 39(3):438-457.

Cited by

  1. Hepatic fibrosis is associated with an increased rate of decline in bone mineral density in men with nonalcoholic fatty liver disease vol.15, pp.6, 2020, https://doi.org/10.1007/s12072-021-10254-y
  2. NAFLD Associated Comorbidity vol.10, 2020, https://doi.org/10.31146/1682-8658-ecg-194-10-5-13