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Nonalcoholic Fatty LiverPhase 4OsteoNAFLDNCT05493761

Effect of Anti-osteoporotic Medications on Nonalcoholic Fatty Liver Disease

A Phase 4 study testing Denosumab and Alendronate Sodium in people with Nonalcoholic Fatty Liver and Osteoporosis, Postmenopausal, run by Aristotle University Of Thessaloniki at 3 sites in Greece.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 40 years and older, women only
What is being tested?
Denosumab and Alendronate Sodium
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
3 sitesGreece
Study dates
23 Dec 2022to 16 Jul 2026
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • mean ethanol consumption >10 g/day
  • a history of other chronic liver disease (e.g., viral hepatitis, autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cholangitis and overlap syndromes, drug-induced liver injury, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency)
  • liver cirrhosis
  • any malignancy
  • chronic kidney disease
  • uncontrolled hypothyroidism or hyperthyroidism
Show all 9Show fewer
  • use of the following medications within a 12-month period before baseline associated with 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 associated probably with improvement in fatty liver: vitamin E, pioglitazone, insulin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose co-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

Trial locations and contacts

3 sites in 1 country.

Greece3 sites

  • Department of Endocrinology, "Hippokration" General Hospital of Thessaloniki

    Thessaloniki, 54642

  • 1st Department of Obstetrics and Gynecology, School, of Medicine, Aristotle University of Thessaloniki

    Thessaloniki, 56403

  • 424 General Military Hospital

    Thessaloniki, 56429

Other trials in Greece

About this study

Official title: Effect of Anti-osteoporotic Medications on Hepatic Steatosis and Fibrosis of Women With Postmenopausal Osteoporosis and Nonalcoholic Fatty Liver Disease

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.

Read more

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.

Being tested
Denosumab, Alendronate Sodium
Keywords
nonalcoholic fatty liver disease, hepatic steatosis, hepatic fibrosis, bisphosphonates, denosumab, postmenopausal osteoporosis, treatment, alendronate, nonalcoholic steatohepatitis, NAFLD, NASH, elastography, metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis
Medical subject headings
Non-alcoholic Fatty Liver Disease, Osteoporosis, Postmenopausal, Fatty Liver, Liver Cirrhosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DenosumabDrug

    Also called Prolia

    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.

  • Alendronate SodiumDrug

    Also called Fosamax

    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.

Study groups in NCT05493761
Study groupRoleWhat they receive
"Denosumab"Experimental35 postmenopausal women with low bone mineral density (BMD) and NAFLD will receive denosumab.
Receives: Drug: Denosumab
"Alendronate"Active comparator35 postmenopausal women with low bone mineral density (BMD) and NAFLD will receive alendronate.
Receives: Drug: Alendronate Sodium

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Hepatic steatosis: Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s.

    1. Between-within group interactions in UGAP (baseline to endpoint)
    2. Between groups difference in change in UGAP (baseline to endpoint)

    UGAP is a non-invasive index based on the attenuation quantification of the ultrasound beam through the hepatic parenchyma, thus used for hepatic steatosis quantification. Cut-off values of > 0.53 dB/cm/MHz, >0.60 dB/cm/MHz, and >0.65 dB/cm/MHz have been proposed for the diagnosis of steatosis grade S1, S2, and S3, respectively.

    Measured: 12 months

Secondary outcomes (15)

  1. Hepatic fibrosis: liver stiffness (LS) measured with 2D Shear Wave Elastography (2D SWE) on an ultrasound machine GE Logiq E10s.

    1. Between-within group interactions in LS (baseline to endpoint)
    2. Between groups difference in change in LS (baseline to endpoint)

    2D SWE is a non-invasive tool measuring the hepatic parenchyma stiffness, thus indirectly suggesting fibrosis stage (F). Cut-offs values of <8.27 kPa, 8.27-9.39 kPa, 9.40-11.88 kPa and >11.88 kPa have been proposed for F0-F1, F2, F3, and F4, respectively.

    Measured: 12 months

  2. Hepatic steatosis non-invasive index: Fatty Liver Index (FLI).

    1. Between-within group interactions in FLI (baseline to endpoint)
    2. Between groups difference in changes in FLI (baseline to endpoint)

    FLI is a non-invasive hepatic steatosis index, which is based on BMI, waist circumference, GGT and triglycerides. FLI ≥60 is associated with the presence of steatosis, while FLI <30 rules out the presence of steatosis.

    Measured: 12 months

  3. Hepatic steatosis non-invasive index: Hepatic Steatosis Index (HSI).

    1. Between-within group interactions in HSI (baseline to endpoint)
    2. Between groups difference in changes and HSI (baseline to endpoint)

    HSI is a non-invasive hepatic steatosis index, which is based on AST, ALT, BMI, gender and the presence or not of T2DM. HSI ≥36 is associated with the presence of steatosis, while HSI <30 rules out the presence of steatosis.

    Measured: 12 months

  4. Hepatic fibrosis non-invasive index: NAFLD fibrosis score (NFS).

    1. Between-within group interactions in NFS (baseline to endpoint)
    2. Between groups difference in changes in NFS (baseline to endpoint)

    NFS is a non-invasive hepatic fibrosis index, which is based on age, BMI, AST, ALT, platelets, albumin and the presence or not of T2DM. NFS >0.675 is associated with high probability of advanced hepatic fibrosis (F3-F4), while NFS <-1.455 is associated with low probability of advanced hepatic fibrosis (F3-F4).

    Measured: 12 months

  5. Hepatic fibrosis non-invasive index: Fibrosis-4 index (FIB-4).

    1. Between-within group interactions in FIB-4 (baseline to endpoint)
    2. Between groups difference in changes in FIB-4 (baseline to endpoint)

    FIB-4 is a non-invasive hepatic fibrosis index, which is based on age, AST, ALT and platelets. FIB-4 ≥2.67 is associated with high probability of advanced hepatic fibrosis (F3-F4), while FIB-4 <1.3 (when age <65 years) or <2.0 (when age ≥65 years) is associated with low probability of advanced hepatic fibrosis (F3-F4).

    Measured: 12 months

  6. Hepatic fibrosis non-invasive index: AST-to-Platelet Ratio Index (APRI).

    1. Between-within group interactions in APRI (baseline to endpoint)
    2. Between groups difference in changes in APRI (baseline to endpoint)

    APRI is a non-invasive hepatic fibrosis index, which is based on AST, ALT and platelets. APRI ≥1 is associated with high probability of advanced hepatic fibrosis (F3-F4), while APRI <0.5 is associated with low probability of advanced hepatic fibrosis (F3-F4).

    Measured: 12 months

  7. Liver function tests: alanine aminotransferase (ALT).

    Between-within group interactions in ALT (baseline to endpoint)

    The normal range for ALT is 4-36 U/L, but it may be different in different laboratories. Higher values may indicate hepatocellular injury.

    Measured: 12 months

  8. Liver function tests: aspartate aminotransferase (AST)

    Between-within group interactions in AST (baseline to endpoint)

    The normal range for AST is 8-33 U/L, but it may be different in different laboratories. Higher values may indicate hepatocellular injury.

    Measured: 12 months

  9. Insulin resistance index: Homeostasis Model Assessment - Insulin Resistance (HOMA-IR)

    Between-within group interactions in HOMA-IR (baseline to endpoint)

    HOMA-IR is calculated by the formula: fasting glucose (mg/dl) × insulin (mU/L)/405, and indicates the degree of insulin resistance; higher scores indicate greater insulin resistance. A HOMA-IR value ≥2.5 is indicative of insulin resistance.

    Measured: 12 months

  10. Lipid profile: total cholesterol

    Between-within group interactions in total cholesterol (baseline to endpoint)

    Total cholesterol levels <200mg/dl are considered acceptable, 200-239 mg/dl are borderline high, and ≥240 mg/dl are considered high; however, these cut-offs differentiate according to other cardiovascular risk factors.

    Measured: 12 months

  11. Lipid profile: triglycerides

    Between-within group interactions in triglycerides (baseline to endpoint)

    Triglycerides levels <150mg/dl are considered acceptable, 150-199 mg/dl are borderline high, and ≥200 mg/dl are considered high.

    Measured: 12 months

  12. Lipid profile: low-density lipoprotein cholesterol (LDL-C)

    Between-within group interactions in LDL-C (baseline to endpoint)

    LDL-C levels <100mg/dl are considered optimal, 100-129 mg/dl are borderline high, and >130 mg/dl are considered high; however, these cut-offs differentiate according to other cardiovascular risk factors.

    Measured: 12 months

  13. Lipid profile: high-density lipoprotein cholesterol (HDL-C)

    Between-within group interactions in HDL-C (baseline to endpoint)

    For women, the normal range for HDL-C is 50-90 mg/dl. Higher HDL-C are regarded as better.

    Measured: 12 months

  14. Serum adipokines: leptin

    Between-within group interactions in leptin (baseline to endpoint)

    For women, the normal range for leptin is 5-15 ng/ml, but it may be different for different ELISA kits.

    Measured: 12 months

  15. Serum adipokines: adiponectin

    Between-within group interactions in adiponectin (baseline to endpoint)

    The normal range for adiponectin is 5-30 μg/ml, but it may be different for different ELISA kits.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2022
  2. Study start23 Dec 2022
  3. Primary completion16 Jul 2026
  4. Study completion16 Jul 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Multicenter, non-randomized, non-blinded, parallel group, one-year clinical trial
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05493761
Sponsor's protocol ID
88235
Acronym
OsteoNAFLD
Status last verified
Jul 2026
First submitted
24 Jul 2022
Last updated
23 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: There is a plan to make IPD and related data dictionaries available

Publications

  • Makri E, Goulas A, Polyzos SA. Epidemiology, Pathogenesis, Diagnosis and Emerging Treatment of Nonalcoholic Fatty Liver Disease. Arch Med Res. 2021 Jan;52(1):25-37. doi: 10.1016/j.arcmed.2020.11.010. Epub 2020 Dec 14.

    PubMed 33334622

  • Polyzos SA, Goulas A. Treatment of nonalcoholic fatty liver disease with an anti-osteoporotic medication: A hypothesis on drug repurposing. Med Hypotheses. 2021 Jan;146:110379. doi: 10.1016/j.mehy.2020.110379. Epub 2020 Nov 7.

    PubMed 33208241

  • Filip R, Radzki RP, Bienko M. Novel insights into the relationship between nonalcoholic fatty liver disease and osteoporosis. Clin Interv Aging. 2018 Oct 4;13:1879-1891. doi: 10.2147/CIA.S170533. eCollection 2018.

    PubMed 30323574

  • Anastasilakis AD, Polyzos SA, Makras P. THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis. Eur J Endocrinol. 2018 Jul;179(1):R31-R45. doi: 10.1530/EJE-18-0056. Epub 2018 Apr 24.

    PubMed 29691303

  • Zhong L, Yuan J, Huang L, Li S, Deng L. RANKL Is Involved in Runx2-Triggered Hepatic Infiltration of Macrophages in Mice with NAFLD Induced by a High-Fat Diet. Biomed Res Int. 2020 May 25;2020:6953421. doi: 10.1155/2020/6953421. eCollection 2020.

    PubMed 32596356

  • Rinotas V, Niti A, Dacquin R, Bonnet N, Stolina M, Han CY, Kostenuik P, Jurdic P, Ferrari S, Douni E. Novel genetic models of osteoporosis by overexpression of human RANKL in transgenic mice. J Bone Miner Res. 2014;29(5):1158-69. doi: 10.1002/jbmr.2112.

    PubMed 24127173

  • Vachliotis ID, Anastasilakis AD, Goulas A, Goulis DG, Polyzos SA. Nonalcoholic fatty liver disease and osteoporosis: A potential association with therapeutic implications. Diabetes Obes Metab. 2022 Sep;24(9):1702-1720. doi: 10.1111/dom.14774. Epub 2022 Jun 14.

    PubMed 35589613

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Denosumab and Alendronate Sodium in people with Nonalcoholic Fatty Liver and Osteoporosis, Postmenopausal, run by Aristotle University Of Thessaloniki at 3 sites in Greece.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Hepatic steatosis: Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s. (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05493761, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.

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