Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease
Status:
Not yet recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
Nonalcoholic fatty liver disease (NAFLD) is a chronic, metabolic liver disease that is
closely related to obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) in
a bidirectional mode. NAFLD affects approximately 25% of the worldwide population. NAFLD
refers to a phenotypic spectrum, including steatosis, inflammation and fibrosis, which can
lead to cirrhosis and hepatocellular carcinoma in a minority of patients. However, despite
its high prevalence, morbidity and mortality, as well as the extensive research in the field,
there is not to-date a licensed medication specifically for NAFLD.
Emerging evidence supports a potential association between NAFLD and osteoporosis; the
prevalence of osteoporosis is probably higher in patients with NAFLD and, vise versa, the
prevalence of NAFLD may be higher in patients with osteoporosis. In this context, it has been
proposed that certain medications for osteoporosis may also prove to be beneficial to NAFLD.
Denosumab, a human monoclonal IgG2 antibody against the receptor activator of nuclear factor
kappa-B (NF-κB) ligand (RANKL), is currently an established treatment for osteoporosis and
other metabolic bone diseases. The axis RANKL-receptor activator of nuclear factor NF-κB
(RANK)-osteoprotegerin (OPG) has been demonstrated as a key regulator of bone metabolism and,
when dysregulated, it contributes to the pathogenesis of osteoporosis and other metabolic
bone diseases. Interestingly, experimental studies have shown that circulating and hepatic
RANKL may be upregulated in mice with diet-induced NAFLD, rendering RANKL a potential
contributor to the pathogenesis of NAFLD, and ideally, a promising pharmacological target.
On the other hand, bisphosphonates, another established, first-line treatment for
osteoporosis, are expected to have no significant effect on hepatic metabolism in patients
with NAFLD due to their pharmacokinetics and mechanism of action.
This is a prospective non-randomized study which aims to investigate the comparative effect
of denosumab versus bisphosphonates on hepatic steatosis and fibrosis in women with
postmenopausal osteoporosis and concomitant NAFLD.