Increased Risk of Non-alcoholic Fatty Liver Disease Fibrosis is Closely Associated with Osteoporosis in Women but Not in Men with Type 2 Diabetes

Overview

Journal Endocr Connect

Specialty Endocrinology

Date 2022 Sep 21

PMID 36129166

Authors

Zhiyan Yu

Yueyue Wu

Rui Zhang

Yue Li

Shufei Zang

Jun Liu

Affiliations

Soon will be listed here.

Abstract

Background: This study aimed to investigate the association of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis with osteoporosis in postmenopausal women and men over 50 years of age with type 2 diabetes (T2DM).

Methods: In this study, 1243 patients with T2DM (T2DM with coexistent NAFLD, n = 760; T2DM with no NAFLD, n = 483) were analysed. Non-invasive markers, NAFLD fibrosis score (NFS) and fibrosis index based on four factors (FIB-4), were applied to evaluate NAFLD fibrosis risk.

Results: There was no significant difference in bone mineral density (BMD) between the NAFLD group and the non-NAFLD group or between males and females after adjusting for age, BMI and gender. In postmenopausal women, there was an increased risk of osteoporosis (odds ratio (OR): 4.41, 95% CI: 1.04-18.70, P = 0.039) in the FIB-4 high risk group compared to the low risk group. Similarly, in women with high risk NFS, there was an increased risk of osteoporosis (OR: 5.98, 95% CI: 1.40-25.60, P = 0.043) compared to the low risk group. Among men over 50 years old, there was no significant difference in bone mineral density between the NAFLD group and the non-NAFLD group and no significant difference between bone mineral density and incidence of osteopenia or osteoporosis among those with different NAFLD fibrosis risk.

Conclusion: There was a significant association of high risk for NAFLD liver fibrosis with osteoporosis in postmenopausal diabetic women but not men. In clinical practice, gender-specific evaluation of osteoporosis is needed in patients with T2DM and coexistent NAFLD.

Citing Articles

Association between liver fibrosis and osteoporosis in adults aged 50 and older: insights from the Bushehr Elderly Health Program.

Soltani A, Aghakhani A, Dehghanbanadaki H, Majidi Z, Rezaei-Tavirani M, Shafiee G J Diabetes Metab Disord. 2025; 24(1):65.

PMID: 39927178 PMC: 11803014. DOI: 10.1007/s40200-025-01574-z.

Effects of Metabolic Dysfunction-Associated Steatotic Liver Disease on Bone Density and Fragility Fractures: Associations and Mechanisms.

Khanmohammadi S, Kuchay M J Obes Metab Syndr. 2024; 33(2):108-120.

PMID: 38740429 PMC: 11224928. DOI: 10.7570/jomes24004.

Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.

Chondrogianni M, Kyrou I, Androutsakos T, Flessa C, Menenakos E, Chatha K Front Endocrinol (Lausanne). 2024; 15:1344376.

PMID: 38524631 PMC: 10957571. DOI: 10.3389/fendo.2024.1344376.

The relationship between advanced liver fibrosis and osteoporosis in type 2 diabetes patients with MAFLD.

Pan B, Zhao Y, Chen C, Cai J, Li K, Wang Y Endocrine. 2024; 85(1):206-221.

PMID: 38367145 DOI: 10.1007/s12020-024-03724-4.

Predicting fibrosis progression in non-alcoholic fatty liver disease patients using the FAST Score: A paired biopsy study.

Sariyar N, Kani H, Ataizi Celikel C, Yilmaz Y Hepatol Forum. 2024; 5(1):33-36.

PMID: 38283271 PMC: 10809337. DOI: 10.14744/hf.2023.2023.0021.

References

Williams C, Stengel J, Asike M, Torres D, Shaw J, Contreras M . Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Gastroenterology. 2010; 140(1):124-31. DOI: 10.1053/j.gastro.2010.09.038. View

Seeman E . Periosteal bone formation--a neglected determinant of bone strength. N Engl J Med. 2003; 349(4):320-3. DOI: 10.1056/NEJMp038101. View

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):817-25. DOI: 10.1007/s40618-015-0315-6. View

Napoli N, Chandran M, Pierroz D, Abrahamsen B, Schwartz A, Ferrari S . Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2016; 13(4):208-219. DOI: 10.1038/nrendo.2016.153. View

Ballestri S, Nascimbeni F, Baldelli E, Marrazzo A, Romagnoli D, Targher G . Ultrasonographic fatty liver indicator detects mild steatosis and correlates with metabolic/histological parameters in various liver diseases. Metabolism. 2017; 72:57-65. DOI: 10.1016/j.metabol.2017.04.003. View

Mantovani A, Gatti D, Zoppini G, Lippi G, Bonora E, Byrne C . Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children: A Meta-Analysis. Hepatology. 2019; 70(3):812-823. DOI: 10.1002/hep.30538. View

Walshe J . Copper: not too little, not too much, but just right. Based on the triennial Pewterers Lecture delivered at the National Hospital for Neurology, London, on 23 March 1995. J R Coll Physicians Lond. 1995; 29(4):280-8. PMC: 5401339. View

Cui R, Sheng H, Rui X, Cheng X, Sheng C, Wang J . Low bone mineral density in chinese adults with nonalcoholic Fatty liver disease. Int J Endocrinol. 2013; 2013:396545. PMC: 3747470. DOI: 10.1155/2013/396545. View

Qaseem A, Forciea M, Denberg T, Barry M, Cooke M, Fitterman N . Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. Ann Intern Med. 2017; 166(11):818-839. DOI: 10.7326/M15-1361. View

10.

Nakchbandi I . Osteoporosis and fractures in liver disease: relevance, pathogenesis and therapeutic implications. World J Gastroenterol. 2014; 20(28):9427-38. PMC: 4110574. DOI: 10.3748/wjg.v20.i28.9427. View

11.

Yang H, Shim S, Ma B, Kwak J . Association of nonalcoholic fatty liver disease with bone mineral density and serum osteocalcin levels in Korean men. Eur J Gastroenterol Hepatol. 2015; 28(3):338-44. PMC: 4739310. DOI: 10.1097/MEG.0000000000000535. View

12.

. Standards of medical care in diabetes--2014. Diabetes Care. 2013; 37 Suppl 1:S14-80. DOI: 10.2337/dc14-S014. View

13.

Loosen S, Roderburg C, Demir M, Qvartskhava N, Keitel V, Kostev K . Non-alcoholic fatty liver disease (NAFLD) is associated with an increased incidence of osteoporosis and bone fractures. Z Gastroenterol. 2021; 60(8):1221-1227. DOI: 10.1055/a-1482-9236. View

14.

Culafic D, Djonic D, Culafic-Vojinovic V, Ignjatovic S, Soldatovic I, Vasic J . Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis. Osteoporos Int. 2014; 26(1):253-9. DOI: 10.1007/s00198-014-2849-4. View

15.

Upala S, Jaruvongvanich V, Wijarnpreecha K, Sanguankeo A . Nonalcoholic fatty liver disease and osteoporosis: a systematic review and meta-analysis. J Bone Miner Metab. 2016; 35(6):685-693. DOI: 10.1007/s00774-016-0807-2. View

16.

Mantovani A, Dauriz M, Gatti D, Viapiana O, Zoppini G, Lippi G . Systematic review with meta-analysis: non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density. Aliment Pharmacol Ther. 2019; 49(4):375-388. DOI: 10.1111/apt.15087. View

17.

Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S . Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2014; 61(5):1547-54. DOI: 10.1002/hep.27368. View

18.

Younossi Z . Non-alcoholic fatty liver disease - A global public health perspective. J Hepatol. 2018; 70(3):531-544. DOI: 10.1016/j.jhep.2018.10.033. View

19.

Gaudio A, Lasco A, Morabito N, Atteritano M, Vergara C, Catalano A . Hepatic osteodystrophy: does the osteoprotegerin/receptor activator of nuclear factor-kB ligand system play a role?. J Endocrinol Invest. 2005; 28(8):677-82. DOI: 10.1007/BF03347549. View

20.

Kozuka H . [Interactive exhibition of heavy metal toxicity in bone metabolism. From the viewpoint of deductive toxicology]. Yakugaku Zasshi. 1995; 115(3):157-69. DOI: 10.1248/yakushi1947.115.3_157. View