Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease

Phase

Condition

Liver Disease

Osteoporosis

Primary Biliary Cholangitis

Treatment

Denosumab

Alendronate Sodium

Clinical Study ID

NCT05493761

88235

Ages > 40
Female

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

postmenopausal women aged > 40 years
diagnosis of osteoporosis, or osteopenia and Fracture Assessment Risk (FRAX) scoreindicative for initiation of anti-osteoporotic treatment, or osteopenia and historyof low-energy fracture. Evaluation of osteopenia and osteoporosis will be based onbone mineral density (BMD) of the lumbar spine and/or the femoral neck of thenon-dominant hip measured with dual energy X-ray absorptiometry (DXA)
diagnosis of NAFLD based on non-invasive indices of hepatic steatosis
written informed consent

Exclusion

Exclusion Criteria:

mean ethanol consumption >10 g/day
a history of other chronic liver disease (e.g., viral hepatitis, autoimmunehepatitis, primary sclerosing cholangitis, primary biliary cholangitis and overlapsyndromes, drug-induced liver injury, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
liver cirrhosis
any malignancy
chronic kidney disease
uncontrolled hypothyroidism or hyperthyroidism
use of the following medications within a 12-month period before baseline associatedwith drug-induced fatty liver: interferon, tamoxifen, amiodarone, aloperidin,glucocorticosteroids, anabolic steroids, any medication against tuberculosis,epilepsy or viruses, methotrexate, parenteral nutrition
use of the following medications within a 12-month period before baseline associatedprobably with improvement in fatty liver: vitamin E, pioglitazone, insulin,glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucoseco-transporter-2 inhibitors (SGLT-2), orlistat, ursodeoxycholic acid
use of any anti-osteoporotic medication within a 12-month period before baseline,except for calcium and vitamin D

Study Design

Denosumab

December 23, 2022

September 30, 2026

Connect with a study center

1st Department of Obstetrics and Gynecology, School, of Medicine, Aristotle University of Thessaloniki
Thessaloniki, 56403
Greece
Site Not Available
424 General Military Hospital
Thessaloníki, 56429
Greece
Site Not Available
Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki
Thessaloníki, 54642
Greece
Site Not Available

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