Hepatic osteodystrophy: An underrecognized metabolic bone disease

Table 1 Prevalence of hepatic osteodystrophy according to the aetiologies of liver disease

Disease	Ref.	n	Age (Year)	Post-menopausal (% of women)	Cirrhosis (%)	Osteoporosis prevalence
Alcoholic liver disease	Kim et al[14], 2003	18	50	0	0	22
Wilson disease	Weiss et al[7], 2015	14	36	NR	38	9
HBV disease	Schiefke et al[15], 2005	13	49	NR	18	15
HCV disease	Schiefke et al[15], 2005	30	49	NR	18	20
MAFLD	Lee et al[9], 2016	6634	Men > 40 and postmenopausal women	50	NR	3.3% (male), 10.4 % (female)
Primary biliary cirrhosis	Seki et al[16], 2017	128	61	100	0	26

HCV: Hepatitis C virus; HBV: Hepatitis B virus; MAFLD: Metabolic dysfunction-associated fatty liver disease; NR: Not record.

Table 2 Pathophysiological factors behind the development of hepatic osteodystrophy according to the aetiologies of liver disease

Disease	Pathophysiological factors	Ref.
Alcoholic liver disease	Direct toxic effect of ethanol on osteoblast	[55-58]
	Reduced IGF1/prostaglandins
	Reduced VDBP and hydroxylation of vitamin D Increased proinflammatory cytokines (IL-1, IL-6, and TNF-α)
	Alcoholic neuropathy and myopathy
Cholestatic liver disease	Enhanced IL-17 mediated bone loss	[59-61]
	Reduced Vit D and VDBP
	Increased oncofetal fibronectin inhibiting bone formation
MASLD	Increased proinflammatory cytokines (IL-1, IL-6, and TNF-α)	[48,62-64]
	Increased RANKL and IL-17A mediated bone loss
	Decreased Fetuin-A level leading to reduced bone mass
	Reduced IGF-1, FGF21, and IGFBP1
	Increased osteopontin level mediated bone loss
	Reduced LCAT and defect in reverse cholesterol transport
Viral hepatitis	Increased serum level of serum levels of soluble TNF receptor p55	[65-68]
	Increased RANKL mediated bone loss
	Iron overload
	Anti-viral drug mediated bone loss

MASLD: Metabolic dysfunction associated steatotic liver disease; IGF: Insulin like growth factor 1; IL: Interleukin; RANKL: Receptor activator ratio of nuclear factor kappa ligand; VDBP: Vitamin D binding protein; TNF-α: Tumor necrosis factor-alpha; LCAT: Lecithin-cholesterol acyltransferase; FGF21: Fibroblast growth factor 21; IGFBP1: Insulin-like growth factor binding protein 1.