Effect of Long-Term Use of Tenofovir (TDF) on Bone Density in Patients With Chronic Hepatitis B
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: TDF (Tenofovir).
- Who it may be relevant to
- Registry conditions: Tenofovir Disoproxil Fumarate, Bone Density, Chronic HBV Infection. Basic parameters: 18 years — 60 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Egypt
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
This study aims to evaluate the effect of long-term use of Tenofovir Disoproxil Fumarate (TDF) on bone density in patients with chronic hepatitis B virus (HBV) infection. Tenofovir is a widely used antiviral medication for the treatment of HBV. While it is generally well tolerated, some studies have reported potential adverse effects on bone mineral density, particularly with long-term use. The objective of this research is to assess whether extended TDF therapy is associated with reduced bone density or increased risk of osteopenia or osteoporosis in adult patients with chronic HBV infection. The study will involve clinical evaluation and radiological assessment of bone health using dual-energy X-ray absorptiometry (DEXA) scans, as well as relevant biochemical markers. This investigation will provide important data on the long-term safety profile of Tenofovir in relation to bone health and help guide future clinical decisions for the management of chronic hepatitis B.
Detailed description
Hepatitis B is a viral infection that affects approximately 257 million people worldwide, with an estimated 820,000 deaths annually due to HBV-related complications. It is a leading cause of liver cirrhosis and hepato-cellular carcinoma (HCC), making it a major global public health concern .
The diagnosis of Chronic Hepatitis B (CHB) is established by the persistence of Hepatitis B surface antigen (HBsAg) for more than six months . Some patients with chronic HBV infection may experience acute exacerbation, potentially progressing to acute-on-chronic liver failure (ACLF), a condition with a high mortality rate despite intensive supportive care and resource utilization. While liver transplantation is considered a potential life-saving treatment for ACLF, its widespread clinical application is limited due to donor shortages and high financial costs. Therefore, early intervention and treatment are crucial in managing patients with ACLF .
The primary goals of antiviral therapy in CHB are to suppress viral replication and promote the loss of HBV-related antigens . Currently, there are two major classes of antiviral agents approved for treating CHB: Interferon-Alpha and Nucleos(t)ide Analogues (NUCs). Among the NUCs, Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF), and Tenofovir Alafenamide (TAF) are the most widely used first-line treatments. These agents are effective, orally administered, and generally well-tolerated. However, long-term treatment is often required, as premature discontinuation may lead to virological relapse and liver failure.
TDF is considered one of the most potent antiviral agents against both HBV and HIV. However, it has been associated with bone toxicity, primarily through the development of osteoporosis via multiple mechanisms. Intracellular accumulation of TDF can lead to proximal tubular dysfunction and Fanconi syndrome, resulting in hypophosphatemic osteomalacia . Additionally, TDF has been shown to reduce osteoblast gene expression, impairing osteoblast function and decreasing bone formation .
Moreover, TDF-induced reduction in phosphate reabsorption in the proximal renal tubules can lead to bone disease, including hypouricemia and hypophosphatemia, ultimately contributing to osteomalacia and an increased risk of fractures. In contrast, TAF exhibits greater plasma stability, and therefore, its impact on renal and bone toxicity may be significantly lower
Interventions
- Drug TDF (Tenofovir)
ANTIVIRAL TREATMENT FOR CHRONIC HEPATITIS B VIRUS INFECTION
Primary outcome measures
- Percent Change in Bone Mineral Density (BMD) [Time frame: Baseline to 5 years post-TDF initiation]
Eligibility criteria
Inclusion criteria
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Inclusion criteria
Adult male or female patients aged 18 to 60 years.
Diagnosed as HBV-positive.
Long-term use of Tenofovir Disoproxil Fumarate (TDF) for more than five years.
Exclusion criteria
Presence of other chronic liver diseases.
Diagnosed with Chronic Kidney Disease (CKD), regardless of etiology.
Patients who refuse to participate in the study.
Patients on combination therapy, including:
Interferon and Nucleoside analogue combination therapy.
Multiple nucleoside analogue combination therapy.
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Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Egypt · 1 center
- Faculty of Medicine, Assuit — Asyut
Publications
- Han Y, Zeng A, Liao H, Liu Y, Chen Y, Ding H. The efficacy and safety comparison between tenofovir and entecavir in treatment of chronic hepatitis B and HBV related cirrhosis: A systematic review and Meta-analysis. Int Immunopharmacol. 2017 Jan;42:168-175. doi: 10.1016/j.intimp.2016.11.022. Epub 2016 Dec 1. PMID 27915131
- Kara AV, Yildirim Y, Ozcicek F, Aldemir MN, Arslan Y, Bayan K, Celen MK. Effects of entecavir, tenofovir and telbivudine treatment on renal functions in chronic hepatitis B patients. Acta Gastroenterol Belg. 2019 Apr-Jun;82(2):273-277. PMID 31314188
- Perazella MA. Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney Int. 2010 Dec;78(11):1060-3. doi: 10.1038/ki.2010.344. PMID 21076445
- Jeong S, Shin HP, Kim HI. Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B. Intervirology. 2022;65(2):94-103. doi: 10.1159/000519440. Epub 2021 Nov 3. PMID 34731856
- Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014 Dec 6;384(9959):2053-63. doi: 10.1016/S0140-6736(14)60220-8. Epub 2014 Jun 18. PMID 24954675
- Nguyen MH, Wong G, Gane E, Kao JH, Dusheiko G. Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy. Clin Microbiol Rev. 2020 Feb 26;33(2):e00046-19. doi: 10.1128/CMR.00046-19. Print 2020 Mar 18. PMID 32102898
- Chien RN, Liaw YF. Current Trend in Antiviral Therapy for Chronic Hepatitis B. Viruses. 2022 Feb 21;14(2):434. doi: 10.3390/v14020434. PMID 35216027
- Castillo AB, Tarantal AF, Watnik MR, Martin RB. Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). J Orthop Res. 2002 Nov;20(6):1185-9. doi: 10.1016/S0736-0266(02)00074-8. PMID 12472227
Identifiers
NCT: NCT06990438 · TDF ON BONE HEALTH