Effect of Anti-osteoporotic Medications on Hepatic Steatosis and Fibrosis of Women With Postmenopausal Osteoporosis and Nonalcoholic Fatty Liver Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 6
- 主要终点
- Hepatic steatosis: Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No masking
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
"Denosumab"
35 postmenopausal women with low bone mineral density (BMD) and NAFLD will receive denosumab.
干预措施: Denosumab (Drug)
"Alendronate"
35 postmenopausal women with low bone mineral density (BMD) and NAFLD will receive alendronate.
干预措施: Alendronate Sodium (Drug)
结局指标
主要结局
Hepatic steatosis: Ultrasound-Guided Attenuation Parameter (UGAP) measured on an ultrasound machine GE Logiq E10s.
时间窗: 12 months
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.
次要结局
- Hepatic fibrosis: liver stiffness (LS) measured with 2D Shear Wave Elastography (2D SWE) on an ultrasound machine GE Logiq E10s.(12 months)
- Hepatic steatosis non-invasive index: Fatty Liver Index (FLI).(12 months)
- Hepatic steatosis non-invasive index: Hepatic Steatosis Index (HSI).(12 months)
- Hepatic fibrosis non-invasive index: NAFLD fibrosis score (NFS).(12 months)
- Hepatic fibrosis non-invasive index: Fibrosis-4 index (FIB-4).(12 months)
- Hepatic fibrosis non-invasive index: AST-to-Platelet Ratio Index (APRI).(12 months)
- Serum adipokines: leptin(12 months)
- Serum adipokines: adiponectin(12 months)
- Liver function tests: alanine aminotransferase (ALT).(12 months)
- Liver function tests: aspartate aminotransferase (AST)(12 months)
- Insulin resistance index: Homeostasis Model Assessment - Insulin Resistance (HOMA-IR)(12 months)
- Lipid profile: total cholesterol(12 months)
- Lipid profile: triglycerides(12 months)
- Lipid profile: high-density lipoprotein cholesterol (HDL-C)(12 months)
- Lipid profile: low-density lipoprotein cholesterol (LDL-C)(12 months)
研究者
Stergios A Polyzos
Associate Professor of Pharmacology
Aristotle University Of Thessaloniki