Journal of Endocrinological Investigation

Title: Association between Bone Mineral Density and Nonalcoholic Fatty Liver Disease in Korean Adults

Authors: Soon Hang Lee, MD1, Jae Moon Yun, MD, MPH1, Sang Hyuck Kim, MD1, Young Gyun Seo, MD1, Hyeyeon Min, MD1, Euiheon Chung, MD1, In Sun Ryou,

MD1 and Belong Cho, MD, MPH, PhD1

1Department of Family Medicine, Seoul National University Hospital, Seoul, Korea

Corresponding author: Be Long Cho, MD, MPH, PhD

Department of Family Medicine, Seoul National University

College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea

Tel: +82.2-2072-0847, Fax: +82.2-766-3276

E-mail: [email protected]

1 Table S1 General characteristics of the study population Male Female (n=3306) (n=3328) mean ± SD mean ± SD Age (years) 56.492 ± 8.794 62.826 ± 6.345 Weight (kg) 68.799 ± 9.632 56.763 ± 7.809 168.85 Height (cm) ± 6.023 154.531 ± 5.558 3 BMI (kg/m2) 24.095 ± 2.860 23.777 ± 3.097 WC (cm) 87.614 ± 8.260 84.250 ± 8.747 127.52 SBP (mmHg) ± 15.348 126.567 ± 16.299 8 DBP (mmHg) 77.405 ± 10.774 75.059 ± 16.044 FPG (mg/dL) 98.935 ± 24.238 96.773 ± 21.028 197.29 TC (mg/dL) ± 37.162 206.263 ± 38.289 9 128.28 TG (mg/dL) ± 85.236 110.773 ± 62.523 1 HDL (mg/dL) 51.487 ± 13.367 58.849 ± 10.020 120.24 LDL (mg/dL) ± 34.877 125.312 ± 35.989 3 AST (IU/L) 27.314 ± 14.202 25.429 ± 11.205 ALT (IU/L) 30.547 ± 20.351 23.575 ± 15.551 γ-GTP (IU/L) 46.919 ± 58.310 27.401 ± 0.154 eGFR (mL/min/1.73 m2) 83.226 ± 15.306 84.703 ± 16.988 Mean lumbar BMD (L1-L4) (g/cm2) 1.203 ± 0.132 1.007 ± 0.175 Femoral neck BMD (g/cm2) 0.945 ± 0.133 0.767 ± 0.110 Hepatosteatosis grade Normal (Grade 0) 2018 (61.04) 2111 (63.43) Mild (Grade 1) 644 (19.48) 708 (21.27)

2 Moderate (Grade 2) 572 (17.30) 474 (14.24) Severe (Grade 3) 72 (2.18) 35 (1.05) HSCRP (mg/L) <1 mg/L 1,994 (60.31) 2105 (63.25) 1-3 mg/L 900 (27.22) 852 (25.60) ≥3 412 (12.46) 371 (11.15) Current smoking status No 2,314 (34.18) 3248 (83.44) Yes 992 (65.82) 80 (2.40) Current alcohol consumption status No 1,130 (34.79) 2777 (83.44) Yes 2,176 (65.21) 551 (16.56) Physical activity No 2,450 (74.11) 2,698 (79.97) Yes 856 (25.89) 630 (18.93) BMI: body mass index; WC: waist circumference; DBP: diastolic blood pressure; SBP: systolic blood pressure; FPG: fasting plasma glucose; TC: total cholesterol; TG: triglycerides; HDL: high-density lipoprotein; LDL: low- density lipoprotein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; γ-GTP: γ- glutamyltranspeptidase; eGFR: estimated glomerular filtration rate; BMD: bone mineral density; HSCRP: high- sensitivity C-reactive protein.

3 Table S2 Univariate regression analysis: the effect of the study variables on BMD

Mean lumbar Femoral neck BMD spine (L1- L4) β (95% CI) p t Age (years) -0.0068 -0.0073 < 0.001* -0.0079 -0.0082 -0.0075 < 0.001* o t Weight (kg) 0.0094 0.0090 < 0.001* 0.0069 0.0067 0.0072 < 0.001* o t Height (cm) 0.0107 0.0103 < 0.001* 0.0084 0.0081 0.0087 < 0.001* o BMI t 0.0149 0.0133 < 0.001* 0.0095 0.0084 0.0106 < 0.001* (kg/m2) o t WC (cm) 0.0057 0.0051 < 0.001* 0.0036 0.0032 0.0039 < 0.001* o SBP t 0.0003 0.0000 0.024* 0.0001 -0.0001 0.0003 0.234 (mmHg) o DBP t 0.0006 0.0003 < 0.001* 0.0006 0.0003 0.0008 < 0.001* (mmHg) o FPG t 0.0006 0.0004 < 0.001* 0.0003 0.0002 0.0005 < 0.001* (mg/dL) o t TC (mg/dL) -0.0004 -0.0005 < 0.001* -0.0002 -0.0002 -0.0001 0.001* o TG t 0.0262 0.0169 < 0.001* 0.0186 0.0119 0.0254 < 0.001* (mg/dL) o HDL t -0.0024 -0.0027 < 0.001* -0.0018 -0.0020 -0.0016 < 0.001* (mg/dL) o

4 LDL t -0.0002 -0.0003 0.001* 0.0000 -0.0001 0.0001 0.979 (mg/dL) o t AST (IU/L) 0.0010 0.0006 < 0.001* 0.0006 0.0003 0.0009 < 0.001* o t ALT (IU/L) 0.0016 0.0014 < 0.001* 0.0012 0.0010 0.0014 < 0.001* o γ-GTP t 0.0002 0.0001 < 0.001* 0.0001 0.0000 0.0001 < 0.001* (IU/L) o t NAFLD 0.0491 0.0395 < 0.001* 0.0247 0.0177 0.0317 < 0.001* o eGFR (mL/min/1. 73 m2) ≥90 t 60–89 0.0251 0.0150 < 0.001* 0.0154 0.0080 0.0227 < 0.001* o t 30–59 0.0526 0.0290 < 0.001* -0.0024 -0.0194 0.0147 0.785 o t 15–29 0.0912 -0.0238 0.120 0.0008 -0.0827 0.0843 0.985 o t ≤15 -0.1744 -0.3944 0.120 -0.1911 -0.3507 -0.0315 0.019 o HSCRP <1 mg/L t 1–3 mg/L 0.0175 0.0066 0.002* 0.0049 -0.0030 0.0128 0.228 o t ≥3 mg/L 0.0158 0.0009 0.037* -0.0047 -0.0155 0.0061 0.392 o Current smoking status No t Yes 0.0806 0.0680 < 0.001* 0.0741 0.0650 0.0832 < 0.001* o Current alcohol consumptio

5 n status No t Yes 0.1161 0.1070 < 0.001* 0.0882 0.0816 0.0948 < 0.001* o Physically active No t Yes 0.0236 0.0123 < 0.001* 0.0313 0.0231 0.0394 < 0.001* o * p < 0.05 BMD: bone mineral density; NAFLD: nonalcoholic fatty liver disease; BMI: body mass index; WC: waist circumference; DBP: diastolic blood pressure; SBP: systolic blood pressure; FPG: fasting plasma glucose; TC: total cholesterol; TG: triglycerides; HDL: high-density lipoprotein; LDL: low-density lipoprotein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; γ-GTP: γ-glutamyltranspeptidase; HSCRP: high-sensitivity C-reactive protein; eGFR: estimated glomerular filtration rate.

Table S3 Summary of the regression analysis of the correlation between BMD and NAFLD in Group 1 (normal and mild steatosis) Model 2 Model 3 p β p β p Men Lumbar spine BMD 0.176 0.013 0.134 0.015 0.072 Femoral neck BMD 0.337 -0.003 0.590 -0.002 0.711 Postmenopausal women Lumbar spine BMD 0.375 0.007 0.323 0.010 0.163 Femoral neck BMD 0.633 -0.002 0.672 -0.001 0.837 Model 1 included age, body mass index (BMI), alanine aminotransferase (ALT) level, smoking status, alcohol consumption status Model 2 included age, BMI, waist circumference, ALT, high-sensitivity C-reactive protein, smoking status, alcohol consumption status, physical activity Model 3 included the same as model 2 plus diastolic blood pressure, fasting plasma glucose, triglyceride level, high-density lipoprotein level, estimated glomerular filtration rate

6 BMD: bone mineral density; NAFLD: non-alcoholic fatty liver disease

Table S4 Summary of the regression analysis for postmenopausal woman (responded as being menopausal) Model 1 Model 3 β β p β p Postmenopausal women Lumbar spine BMD 0.046 0.042 0.006 0.041 0.008 Femoral neck BMD 0.012 0.010 0.302 0.009 0.356 Model 1 included age, body mass index (BMI), alanine aminotransferase (ALT) level, smoking status, alcohol consumption status Model 2 included age, BMI, waist circumference, ALT, high-sensitivity C-reactive protein leel, smoking status, alcohol consumption status, physical activity Model 3 included the same as model 2 plus diastolic blood pressure, fasting plasma glucose, triglyceride level, high-density lipoprotein level, estimated glomerular filtration rate BMD: bone mineral density