Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle

Table 1 Studies exploring the association between non-alcoholic fatty liver disease and bone mineral density

Ref.	Study population and sample size	Race/ethnicity	NAFLD assessment	Skeleton: segments	Main findings: BMD
Xia et al[11], 2016	Elderly men (n = 755) and postmenopausal women (n = 904) divided into quartiles of liver fat content (LFC)	Chinese	Liver quantitative US	Lumbar spine, hip, whole body	BMD in any skeletal segment was lower in the highest LFC quartile compared to the lowest quartile. LFC inversely correlated with BMD (all skeletal segments)
Cui et al[12], 2013	Men with NAFLD (n = 46) vs male controls (n = 53); postmenopausal women with NAFLD (n = 73) vs female controls (n = 52)	Chinese	Liver US	Lumbar spine, right hip, femoral neck	Lower BMD at the right hip in participants with NAFLD than controls (in both genders); lower BMD at the femoral neck in men with NAFLD vs controls. Negative association between NAFLD and BMD
Lee et al[13], 2016	Men with NAFLD (n = 1288) vs male controls (n = 2018); postmenopausal women with NAFLD (n = 1217) vs female controls (n = 2112)	Korean	Liver US	Lumbar spine and femoral neck	Negative association between femoral neck BMD and NAFLD in men; positive correlation between lumbar spine BMD and NAFLD in postmenopausal women
Moon et al[14], 2012	Premenopausal women with NAFLD (n = 162) vs controls (n = 54), and postmenopausal with NAFLD (n = 102) vs controls (n = 163)	Korean	Liver US	Lumbar spine	Higher BMD in the control group than postmenopausal women NAFLD; NAFLD negatively associated with BMD in postmenopausal women, but not premenopausal women
Purnak et al[15], 2012	Men (n = 52) and women (n = 50) with NAFLD vs healthy men (n = 28) and women (n = 26)	Caucasian	Liver US	Femur (neck, trochanter, intertrochanteric region and total femur) and lumbar spine	Lower lumbar spine and femoral neck BMD Z-scores in women with high ALT levels
Bhatt et al[16], 2013	Men (n = 129) and women (n = 33) with NAFLD vs controls (men, n = 109; women, n = 64)	Indian	Liver US	Trunk, pelvis, spine, whole body	Higher BMD values in NAFLD subjects than controls
Yang et al[17], 2016	Men with NAFLD (n = 249) vs male controls (n = 610)	Korean	Liver US	Right Hip	NAFLD negatively associated with right-hip BMD
Pacifico et al[18], 2013	Obese children with NAFLD (boys, n = 24, and girls, n = 20) vs obese controls (boys, n = 24, and girls, n = 20)	Caucasian	MRI + liver biopsy	Lumbar spine and whole body	Lower lumbar BMD Z-score in NAFLD children than controls. Negative association of lumbar BMD and whole-body BMD Z-scores with NASH
Pardee et al[19], 2012	Obese children( 10-17 yr) with (n = 38) or without (n = 38) NAFLD	Mixed (89.5% Hipanic, 10.5% non-Hispanic, White)	Liver biopsy	Whole body	Lower whole body BMD Z-score in children with NAFLD than children without NAFLD. Lower whole body BMD Z-score in children with NASH than children without NASH
Chang et al[20], 2015	Obese children and adolescents with NAFLD (n = 15) vs obese children and adolescents with NASH (n = 47) vs controls (n = 32)	Korean	Liver US (NAFLD); liver US + elevated serum aminotransferase levels (NASH)	Arm, leg, trunk, whole body	Age-matched BMD Z-scores were not different between groups
Pirgon et al[21], 2011	Obese children with NAFLD (boys, n = 19, and girls, n = 23) vs obese children (boys, n = 18, and girls, n = 22) and lean children (boys, n = 15, and girls, n = 15)	Caucasian (Turkish)	Liver US	Lumbar spine	Lower lumbar BMD-SDS in obese adolescents with NAFLD compared with obese and lean adolescents without NAFLD
Campos et al[22], 2012	Obese adolescents with NAFLD (n = 18) vs obese adolescents without NAFLD (n = 22)	Brazilian	Liver US	Whole body	Obese adolescents with NAFLD had a significantly lower values of BMC than their counterparts without NAFLD. No differences in BMD Z-scores

BMC: Bone mineral content; BMD-SDS: Bone mineral density-standard deviation score; BMD: Bone mineral density; LFC: Liver fat content; MRI: Magnetic resonance imaging; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; US: Ultrasound; ALT: Alanine aminotransferase.