Treatment of nonalcoholic fatty liver disease with an anti-osteoporotic medication: A hypothesis on drug repurposing

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a disease of high prevalence without any approved treatment. Nonalcoholic steatohepatitis (NASH) is an advanced phenotype of the disease and the main focus of ongoing clinical trials. Denosumab, a human monoclonal antibody, which binds and inhibits the receptor activator of nuclear factor kappa-B ligand (RANKL), is a licensed medication for postmenopausal, male and glucocorticoid-induced osteoporosis, as well as for metastatic bone disease associated with specific cancers. Hepatic RANKL upregulation has been shown in a transgenic mice model.

Hypothesis: We hypothesized that hepatic RANKL upregulation may be associated with hepatic steatosis and inflammation, thus playing a role in the pathogenesis of NAFLD.

Conclusion: If this hypothesis is verified, denosumab, an established anti-osteoporotic medication, may be considered as a candidate for NASH in drug-repurposing studies.

Keywords: Denosumab; Fibrosis; Metabolic (dysfunction)-associated fatty liver disease; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Osteoprotegerin; Receptor activator of nuclear factor kappa-Β ligand.