The Effect of Entecavir and Tenofovir Disoproxil on Bone Mineral Density in Chronic Hepatitis B Treatment
Abstract
Background/Aim:Evaluation of the relationship between drugs and osteoporosis in patients receiving entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B infection (CHB).
Material and Method: The study included patients who received ETV or TDF treatment for at least 12 months between 2016 and 2021 and underwent bone mineral densitometry (BMD) measurement within 12 months after treatment. Demographic characteristics of the patients and the association of antiviral drug use with osteopenia/osteoporosis were retrospectively.
Results: The study included 170 patients, 92 (54.1%) of whom were male, with a mean age at diagnosis of 36.57 ± 14.88 years. Of the patients, 24 (14.1%) were on ETV and 146 (85.9%) were on TDF. The mean age at BMD measurement was 48.62 ± 13.4 years. The median time from diagnosis to BMD was 138.5 (15-373) months. Osteopenia/osteoporosis was found in 14 (15.2%) of male patients and 25 (32.1%) of female patients. The frequency of osteopenia/osteoporosis was significantly higher in women (p=0.011). There was no significant difference in the frequency of osteopenia/osteoporosis between ETV and TDF (p=0.112). Lumbar spine (LS) BMD was significantly higher in TDF users (p=0.043). While no patient had a BMD within 12 months of treatment initiation, 6 (3.5%) of the patients had a BMD within 24 months, 8 (4.7%) within 36 months and 25 (14.7%) within 60 months of treatment initiation.
Conclusion: There was no significant difference in the development of osteopenia/osteoporosis in patients using TDF and ETV. It was found that bone mineral measurements of patients with CHB were not performed regularly and appropriately.
Ethical Statement
The study was carried out with the permission of Karadeniz Technical University Faculty of Medicine Ethics Committee (Date:13.01.2022 Decision no:315). All procedures were carried out in accordance with the ethical rules and the principles of the Declaration of Helsinki.
Supporting Institution
None
Thanks
I would like to thank Associate Professor Dr. Serdar DURAK for his support at every stage of the article.
References
- 1. World Health Organization. Hepatitis B. 2023.
- 2. Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.
- 3. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.
- 4. Terrault NA, Lok ASF, McMahon BJ, Chang K, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99.
- 5. KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol [Internet]. 2019;25(2):93–159. Available from: http://e-cmh.org/journal/view.php?doi=10.3350/cmh.2019.1002
- 6. Collier J. Bone disorders in chronic liver disease. Hepatology. 2007;46(4):1271–8.
- 7. Castillo AB, Tarantal AF, Watnik MR, Bruce Martin R. Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). Journal of Orthopaedic Research. 2002;20(6):1185–9.
- 8. Van Rompay KKA, Brignolo LL, Meyer DJ, Jerome C, Tarara R, Spinner A, et al. Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques. Antimicrob Agents Chemother. 2004;48(5):1469–87.
- 9. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1–129.
- 10. Grossi G, Viganò M, Loglio A, Lampertico P. Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs). Liver International. 2017 ;37:45–51.
- 11. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. The Lancet. 2013;381(9865):468–75.
- 12. Rodríguez‐Nóvoa S, Labarga P, Soriano V, Egan D, Albalater M, Morello J, et al. Predictors of Kidney Tubular Dysfunction in HIV‐Infected Patients Treated with Tenofovir: A Pharmacogenetic Study. Clinical Infectious Diseases. 2009;48(11):e108–16.
- 13. Lucey JM, Hsu P, Ziegler JB. Tenofovir-related Fanconi’s syndrome and osteomalacia in a teenager with HIV. Case Reports. 2013; bcr2013008674.
- 14. Grigsby IF, Pham L, Mansky LM, Gopalakrishnan R, Mansky KC. Tenofovir-associated bone density loss. Ther Clin Risk Manag. 2010;6:41–7.
- 15. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, et al. Randomized Comparison of Tenofovir Disoproxil Fumarate vs Emtricitabine and Tenofovir Disoproxil Fumarate in Patients With Lamivudine-Resistant Chronic Hepatitis B. Gastroenterology. 2014;146(4):980-988.e1.
- 16. Wong GL, Tse Y, Wong VW, Yip TC, Tsoi KK, Chan HL. Long‐term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: A cohort study of 53,500 subjects. Hepatology. 2015;62(3):684–93.
- 17. Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic Review and Meta‐analysis: Renal Safety of Tenofovir Disoproxil Fumarate in HIV‐Infected Patients. Clinical Infectious Diseases. 2010;51(5):496–505.
- 18. Wei MT, Le AK, Chang MS, Hsu H, Nguyen P, Zhang JQ, et al. Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B. J Med Virol. 2019;91(7):1288–94.
- 19. Yang X, Yan H, Zhang X, Qin X, Guo P. Comparison of renal safety and bone mineral density of tenofovir and entecavir in patients with chronic hepatitis B: a systematic review and meta-analysis. International Journal of Infectious Diseases. 2022;124:133–42.
- 20. Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, et al. RETRACTION: Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients with Chronic HBV Infection. Clinical Gastroenterology and Hepatology. 2018; S1542-3565(18)30633-5.
- 21. Türkiye Endokrinoloji ve Metabolizma Derneği. Osteoporoz ve Metabolik Kemik Hastalıkları Tanı ve Tedavi Kılavuzu. 2023. 79–82 p.
Abstract
Öz
Amaç:Kronik hepatit B enfeksiyonu (KHB) olması nedeniyle entekavir(ETV) veya tenofovir disoproksil fumarat (TDF) tedavisi alan hastalarda ilaçların osteoporoz ile ilişkisinin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: 2016-2021 yılları arasında en az 12 ay boyunca ETV veya TDF tedavisi başlanan ve sonraki 12 ay içinde kemik mineral dansitometri (KMD) ölçümü yapılan hastaların demografik özellikleri ile antiviral ilaç kullanımının osteopeni/ osteoporoz ile ilişkisi retrospektif olarak değerlendirildi.
Bulgular: Çalışmaya 92’si (%54,1) erkek, ortalama tanı yaşı 36,57 ± 14,88 yıl olan 170 hasta dâhil edildi. Hastaların 24’ü (%14,1) ETV, 146’sı (%85,9) ise TDF kullanıyordu. Ortalama KMD ölçüm yaşı 48,62 ± 13,4 yıl idi. Tanıdan itibaren KMD’ye kadar geçen süre ortanca 138,5 (15-373) ay idi. Erkek hastaların 14’ünde (%15,2), kadın hastaların ise 25’inde (%32,1) osteopeni/osteoporoz saptanırken, kadınlarda osteopeni/osteoporoz sıklığı anlamlı olarak daha yüksek idi (p=0,011). ETV ve TDF arasında osteopeni/osteoporoz sıklığı açısından anlamlı farklılık izlenmedi (p=0,112). KMD parametrelerinde Lomber spine(LS) KMD TDF kullananlarda anlamlı olarak daha yüksek idi (p=0,043). Tedavi başlandıktan sonra 12 ay içinde hiçbir hastaya KMD istenmezken, hastaların 6 ’sına (%3,5) tedavi başlandıktan sonraki 24 ay içinde, 8’ine (%4,7) 36 ay içinde, 25’ine de (%14,7) 60 ay içinde KMD istenmişti.
Sonuç: TDF ve ETV kullanan hastalarda osteopeni/osteoporoz gelişimi açısından anlamlı farklılık saptanmadı. KHB’si olan hastaların kemik mineral ölçümlerinin düzenli ve uygun bir şekilde yapılmadığı saptandı.
References
- 1. World Health Organization. Hepatitis B. 2023.
- 2. Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, et al. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.
- 3. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10(1):1–98.
- 4. Terrault NA, Lok ASF, McMahon BJ, Chang K, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67(4):1560–99.
- 5. KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol [Internet]. 2019;25(2):93–159. Available from: http://e-cmh.org/journal/view.php?doi=10.3350/cmh.2019.1002
- 6. Collier J. Bone disorders in chronic liver disease. Hepatology. 2007;46(4):1271–8.
- 7. Castillo AB, Tarantal AF, Watnik MR, Bruce Martin R. Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta). Journal of Orthopaedic Research. 2002;20(6):1185–9.
- 8. Van Rompay KKA, Brignolo LL, Meyer DJ, Jerome C, Tarara R, Spinner A, et al. Biological Effects of Short-Term or Prolonged Administration of 9-[2-(Phosphonomethoxy)Propyl]Adenine (Tenofovir) to Newborn and Infant Rhesus Macaques. Antimicrob Agents Chemother. 2004;48(5):1469–87.
- 9. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;843:1–129.
- 10. Grossi G, Viganò M, Loglio A, Lampertico P. Hepatitis B virus long-term impact of antiviral therapy nucleot(s)ide analogues (NUCs). Liver International. 2017 ;37:45–51.
- 11. Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. The Lancet. 2013;381(9865):468–75.
- 12. Rodríguez‐Nóvoa S, Labarga P, Soriano V, Egan D, Albalater M, Morello J, et al. Predictors of Kidney Tubular Dysfunction in HIV‐Infected Patients Treated with Tenofovir: A Pharmacogenetic Study. Clinical Infectious Diseases. 2009;48(11):e108–16.
- 13. Lucey JM, Hsu P, Ziegler JB. Tenofovir-related Fanconi’s syndrome and osteomalacia in a teenager with HIV. Case Reports. 2013; bcr2013008674.
- 14. Grigsby IF, Pham L, Mansky LM, Gopalakrishnan R, Mansky KC. Tenofovir-associated bone density loss. Ther Clin Risk Manag. 2010;6:41–7.
- 15. Fung S, Kwan P, Fabri M, Horban A, Pelemis M, Hann HW, et al. Randomized Comparison of Tenofovir Disoproxil Fumarate vs Emtricitabine and Tenofovir Disoproxil Fumarate in Patients With Lamivudine-Resistant Chronic Hepatitis B. Gastroenterology. 2014;146(4):980-988.e1.
- 16. Wong GL, Tse Y, Wong VW, Yip TC, Tsoi KK, Chan HL. Long‐term safety of oral nucleos(t)ide analogs for patients with chronic hepatitis B: A cohort study of 53,500 subjects. Hepatology. 2015;62(3):684–93.
- 17. Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic Review and Meta‐analysis: Renal Safety of Tenofovir Disoproxil Fumarate in HIV‐Infected Patients. Clinical Infectious Diseases. 2010;51(5):496–505.
- 18. Wei MT, Le AK, Chang MS, Hsu H, Nguyen P, Zhang JQ, et al. Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B. J Med Virol. 2019;91(7):1288–94.
- 19. Yang X, Yan H, Zhang X, Qin X, Guo P. Comparison of renal safety and bone mineral density of tenofovir and entecavir in patients with chronic hepatitis B: a systematic review and meta-analysis. International Journal of Infectious Diseases. 2022;124:133–42.
- 20. Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, et al. RETRACTION: Improved Bone Safety of Tenofovir Alafenamide Compared to Tenofovir Disoproxil Fumarate Over 2 Years in Patients with Chronic HBV Infection. Clinical Gastroenterology and Hepatology. 2018; S1542-3565(18)30633-5.
- 21. Türkiye Endokrinoloji ve Metabolizma Derneği. Osteoporoz ve Metabolik Kemik Hastalıkları Tanı ve Tedavi Kılavuzu. 2023. 79–82 p.
Details
| Primary Language | English |
|---|---|
| Subjects | Endocrinology, Gastroenterology and Hepatology |
| Journal Section | Original Research |
| Authors | |
| Publication Date | September 30, 2023 |
| Acceptance Date | September 26, 2023 |
| Published in Issue | Year 2023 Volume: 13 Issue: 5 |
