Tenofovir Disoproxil FumarateNCT06990438
Effect of Long-Term Use of Tenofovir (TDF) on Bone Density in Patients With Chronic Hepatitis B
An observational study of Tenofovir Disoproxil Fumarate and Bone Density, run by Assiut University at 1 site in Egypt.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Tenofovir Disoproxil Fumarate, Bone Density, Chronic HBV Infection
- What is being tested?
- TDF (Tenofovir)
- How many people
- 172 participants
- Where
- 1 siteEgypt
- Study dates
- 22 May 2025to 1 Jun 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: Study Population Age Range: 18 to 60 years Sex: Male and Female HBV Status: HBV-positive patients Treatment Duration: Long-term use of Tenofovir (TDF) for more than five years Sampling Method: Non-Probability Sampling Healthy Volunteers: Not Accepted
Who may be able to join
- -
- 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.
Who cannot join
- 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.
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
NOUR SHAABAN MOHAMED, RESIDENT contact
Egypt1 site
Faculty of Medicine, Assuit
Asyut
NOUR SHAABAN MOHAMED, RESIDENT, +0201122193390 ext. +0201116123320, NOUR.20124438@MED.AUN.EDU.EG
About this study
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.
Read the 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
- Being tested
- TDF (Tenofovir)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDF (Tenofovir)Drug
ANTIVIRAL TREATMENT FOR CHRONIC HEPATITIS B VIRUS INFECTION
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Bone Mineral Density (BMD)
Change in BMD measured by dual-energy X-ray absorptiometry (DEXA), expressed as percentage change from baseline.
Measured: Baseline to 5 years post-TDF initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start22 May 2025 (estimated)
- Primary completion1 May 2026 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Tenofovir Disoproxil FumarateStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 172 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nour shaaban Mohamed Abd elrasoul, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06990438
- Sponsor's protocol ID
- TDF ON BONE HEALTH
- Status last verified
- May 2025
- First submitted
- 17 May 2025
- Last updated
- 25 May 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 27915131Kara 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.
PubMed 31314188Perazella MA. Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney Int. 2010 Dec;78(11):1060-3. doi: 10.1038/ki.2010.344.
PubMed 21076445Jeong 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.
PubMed 34731856Trepo 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.
PubMed 24954675Nguyen 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.
PubMed 32102898Chien RN, Liaw YF. Current Trend in Antiviral Therapy for Chronic Hepatitis B. Viruses. 2022 Feb 21;14(2):434. doi: 10.3390/v14020434.
PubMed 35216027Castillo 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.
PubMed 12472227Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
PubMed 26563120Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261-83. doi: 10.1002/hep.28156. Epub 2015 Nov 13. No abstract available.
PubMed 26566064
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Long-Term Use of Tenofovir (TDF) on Bone Density in Patients With Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT06990438
- Acronym / sponsor ID
- TDF ON BONE HEALTH
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 22 May 2025 (estimated)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 25 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Study Population Age Range: 18 to 60 years Sex: Male and Female HBV Status: HBV-positive patients Treatment Duration: Long-term use of Tenofovir (TDF) for more than five years Sampling Method: Non-Probability Sampling Healthy Volunteers: Not Accepted
Key inclusion criteria (4 listed)
- -
- 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.
Key exclusion criteria (7 listed)
- Presence of other chronic liver diseases.
- Diagnosed with Chronic Kidney Disease (CKD), regardless of etiology.
- Patients who refuse to participate in the study.
- Interferon and Nucleoside analogue combination therapy.
- Multiple nucleoside analogue combination therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDF (Tenofovir)ANTIVIRAL TREATMENT FOR CHRONIC HEPATITIS B VIRUS INFECTION | Drug | – |
Primary outcome
Percent Change in Bone Mineral Density (BMD)
Time frame: Baseline to 5 years post-TDF initiation
Change in BMD measured by dual-energy X-ray absorptiometry (DEXA), expressed as percentage change from baseline.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Results publication: PubMed 27915131Han 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.
- Results publication: PubMed 31314188Kara 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.
- Results publication: PubMed 21076445Perazella MA. Tenofovir-induced kidney disease: an acquired renal tubular mitochondriopathy. Kidney Int. 2010 Dec;78(11):1060-3. doi: 10.1038/ki.2010.344.
- Results publication: PubMed 34731856Jeong 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.
- Results publication: PubMed 24954675Trepo 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.
- Results publication: PubMed 32102898Nguyen 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.
- Results publication: PubMed 35216027Chien RN, Liaw YF. Current Trend in Antiviral Therapy for Chronic Hepatitis B. Viruses. 2022 Feb 21;14(2):434. doi: 10.3390/v14020434.
- Results publication: PubMed 12472227Castillo 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.
- Results publication: PubMed 26563120Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016 Jan;10(1):1-98. doi: 10.1007/s12072-015-9675-4. Epub 2015 Nov 13.
- Results publication: PubMed 26566064Terrault NA, Bzowej NH, Chang KM, Hwang JP, Jonas MM, Murad MH; American Association for the Study of Liver Diseases. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261-83. doi: 10.1002/hep.28156. Epub 2015 Nov 13. No abstract available.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
NOUR SHAABAN MOHAMED, RESIDENT contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tenofovir Disoproxil Fumarate and Bone Density, run by Assiut University at 1 site in Egypt.
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 7 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: opening soon, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact NOUR SHAABAN MOHAMED, RESIDENT (+0201122193390 ext. +0201116123320, NOUR.20124438@MED.AUN.EDU.EG), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Bone Mineral Density (BMD) (time frame: Baseline to 5 years post-TDF initiation). 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 NCT06990438, which also lists 10 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 25 May 2025.