Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease

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.

Conditions

• Nonalcoholic Fatty Liver
• Osteoporosis, Postmenopausal

Interventions

DRUG

Denosumab

60 mg (1ml) administered subcutaneously once every 6 months for 12 months (totally 2 injections). Patients will also be supplemented with calcium carbonate (1000 mg/d) and cholecalciferol (800 IU/day), according to the recent guidelines.

DRUG

Alendronate Sodium

70 mg (1 tablet) administered per os once weekly for 12 months. Patients will also be supplemented with calcium carbonate (1000 mg/d) and cholecalciferol (800 IU/day), according to the recent guidelines.

Sponsors & Collaborators

• 424 General Military Hospital

  collaborator OTHER

• Aristotle University Of Thessaloniki

  lead OTHER

Principal Investigators

• Ilias D Vachliotis, MD, PhDc · School of Medicine, Aristotle University of Thessaloniki

• Athanasios D Anastasilakis, MD, PhD · 424 General Military Hospital, Thessaloniki, Greece

• Antonis Goulas, MD, PhD · School of Medicine, Aristotle University of Thessaloniki

• Dimitrios G Goulis, MD, PhD · School of Medicine, Aristotle University of Thessaloniki

• Stergios A Polyzos, MD, PhD · School of Medicine, Aristotle University of Thessaloniki

• Zoe A Efstathiadou, MD, PhD · Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki

• Vasileios Rafailidis, MD, PhD · School of Medicine, Aristotle University of Thessaloniki

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

40 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-12-23

Primary Completion

2026-07-31

Completion

2026-09-30

FDA Drug

Yes

Countries

• Greece

Study Locations