{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:22:34Z","timestamp":1771464154437,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nucleoside\/nucleotide analogs such as tenofovir, have been used as long-term therapy for the treatment of hepatitis B and side effects such as the reduction in bone mineral density have been associated with their use. To determine the relationships between bone, hormonal, biochemical, and mineral parameters in patients with hepatitis B treated with nucleoside\/nucleotide antiviral. A cross-sectional study was conducted with 81 adult patients with chronic hepatitis B infection. Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density. Biochemical analyses were performed for osteocalcin, deoxypyridinoline, parathyroid hormone, vitamin D, IGF-1, TSH, testosterone, estradiol, FSH, transaminases, urea, creatinine, calcium, serum and urinary phosphorus, magnesium, and FGF-23, body composition was performed by DXA. Participants, both gender, were divided according to the use of antiretrovirals: Group1: 27 inactive virus carriers without medication; Group2: 27 patients using tenofovir; and Group3: 27 patients using lamivudine or entecavir. DXA readings diagnosed osteopenia in the lumbar spine for 7.4% of individuals in Group1, 15% in Group2, and 3.7% in Group3. For all groups, we observed normal values in bone formation markers, osteocalcin levels as well as parathyroid hormone, insulin growth factor 1, and FGF-23. In all groups, we found increased levels of urinary deoxypyridinoline, a bone resorption marker. Increased levels in the bone resorption markers indicated a high resorptive activity of bone tissue. These data suggested high resorption activity of bone tissue in hepatitis B virus-infected patients independent of the use of antiretrovirals.<\/jats:p>","DOI":"10.1038\/s41598-021-89486-9","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T10:03:16Z","timestamp":1620900196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bone loss in hepatitis B virus-infected patients can be associated with greater osteoclastic activity independently of the retroviral use"],"prefix":"10.1038","volume":"11","author":[{"given":"Renata","family":"Dessordi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ligia Moriguchi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Palma","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elen Almeida","family":"Rom\u00e3o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"de Lourdes Candolo Martinelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"de Carvalho Santana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anderson Marliere","family":"Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"issue":"2","key":"89486_CR1","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1172\/JCI92812","volume":"128","author":"L Rivino","year":"2018","unstructured":"Rivino, L. et al. Hepatitis B virus\u2013specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation. J. Clin. Invest. 128(2), 668\u2013681 (2018).","journal-title":"J. Clin. Invest."},{"issue":"1","key":"89486_CR2","doi-asserted-by":"publisher","first-page":"S64","DOI":"10.1016\/S0168-8278(03)00141-7","volume":"39","author":"MJ Alter","year":"2003","unstructured":"Alter, M. J. Epidemiology of hepatitis B in Europe and worldwide. J. Hepatol. 39(1), S64\u2013S69 (2003).","journal-title":"J. Hepatol."},{"key":"89486_CR3","unstructured":"Global hepatitis report, 2017. USA: World Health Organization. Hepatitis B. [update 2017 Apr]. Available from: http:\/\/apps.who.int\/iris\/bitstream\/10665\/255016\/1\/9789241565455-eng.pdf?ua=1 (2017)."},{"key":"89486_CR4","unstructured":"Ministry of Health. Clinical Protocol and Therapeutic Guidelines for Hepatitis B and Coinfections. [Update 2017 Sep 27]. Available from: http:\/\/www.aids.gov.br\/pt-br\/pub\/2016\/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes (2017)."},{"issue":"1","key":"89486_CR5","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.cgh.2012.10.003","volume":"11","author":"S K\u00f6kl\u00fc","year":"2013","unstructured":"K\u00f6kl\u00fc, S. et al. Long-term efficacy and safety of lamivudine, entecavir, and tenofovor for treatment of hepatitis B virus-related cirrhosis. Clin. Gastroenterol. Hepatol. 11(1), 88\u201394 (2013).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"89486_CR6","doi-asserted-by":"publisher","first-page":"S185","DOI":"10.1002\/hep.22885","volume":"49","author":"RJ Fontana","year":"2009","unstructured":"Fontana, R. J. Side effects os long-term oral antiviral therapy for hepatitis B. Hepatology 49, S185\u2013S195 (2009).","journal-title":"Hepatology"},{"issue":"6","key":"89486_CR7","first-page":"41","volume":"2","author":"IF Grigby","year":"2010","unstructured":"Grigby, I. F., Pham, L., Mansky, L. M., Gopalakrishan, R. & Mansky, K. C. Tenofovir-associated bone density loss. Ther. Clin. Risk Manag. 2(6), 41\u201347 (2010).","journal-title":"Ther. Clin. Risk Manag."},{"issue":"Suppl 2","key":"89486_CR8","doi-asserted-by":"publisher","first-page":"A28","DOI":"10.1136\/gutjnl-2011-300857a.61","volume":"60","author":"US Gill","year":"2011","unstructured":"Gill, U. S. et al. P61Bone mineral density loss in tenofovir treated Chronic Hepatitis B Virus (HBV) patients is a consequence of Vitamin D deficiency and not Tenofovir therapy. Gut 60(Suppl 2), A28 (2011).","journal-title":"Gut"},{"issue":"1","key":"89486_CR9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.cgh.2013.04.036","volume":"12","author":"S Yapali","year":"2014","unstructured":"Yapali, S., Talaat, N. & Lok, A. S. Management of hepatitis B: Our practice and how it relates to the guidelines. Clin. Gastroenterol. Hepatol. 12(1), 16\u201326 (2014).","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"89486_CR10","first-page":"S189","volume":"7","author":"MFG Elkashab","year":"2013","unstructured":"Elkashab, M. F. G. et al. High prevalence of vitamin D deficiency among chronic hepatitis B patients entering a large global prospective trial (Study GS-US-174-0149). Hepatol. Int. 7, S189 (2013).","journal-title":"Hepatol. Int."},{"issue":"1","key":"89486_CR11","first-page":"67","volume":"150","author":"JM Fakruddin","year":"2005","unstructured":"Fakruddin, J. M. & Laurence, J. HIV-1 Vpr enhances production of receptor of activated NF-kappaB ligand (RANKL) via potentiation of glucocorticoid receptor activity. Adv. Virol. 150(1), 67\u201378 (2005).","journal-title":"Adv. Virol."},{"issue":"7","key":"89486_CR12","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1002\/sim.722","volume":"20","author":"J Singer","year":"2001","unstructured":"Singer, J. A simple procedure to compute the sample size needed to compare two independent groups when the population variances are unequal. Stat. Med. 20(7), 1089\u20131095 (2001).","journal-title":"Stat. Med."},{"issue":"2","key":"89486_CR13","doi-asserted-by":"publisher","first-page":"207","DOI":"10.5604\/16652681.1231577","volume":"16","author":"R Saeedi","year":"2017","unstructured":"Saeedi, R. et al. Lamivudine, Entecavir, or Tenofovir treatment of hepatitis B infection: Effects on calcium, phosphate, FGF23 and Indicators of bone metabolism. Ann. Hepatol. 16(2), 207\u2013214. https:\/\/doi.org\/10.5604\/16652681.1231577 (2017).","journal-title":"Ann. Hepatol."},{"key":"89486_CR14","unstructured":"WHO\u2014World Health Organization. Assessment of fracture risk and Itsapplication to screening for postmenopausal osteoporosis. WHO Technical ReportSeries G, 853 (1994)."},{"issue":"Pt 1","key":"89486_CR15","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1258\/0004563001901371","volume":"37","author":"JH Barth","year":"2000","unstructured":"Barth, J. H., Jones, R. G. & Payne, R. B. Calculation of renal tubular reabsorption of phosphate: The algorithm performs better than the nomogram. Ann. Clin. Biochem. 37(Pt 1), 79\u201381 (2000).","journal-title":"Ann. Clin. Biochem."},{"key":"89486_CR16","doi-asserted-by":"publisher","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","volume":"150","author":"AS Levey","year":"2009","unstructured":"Levey, A. S. et al. A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 150, 604\u2013612 (2009).","journal-title":"Ann. Intern. Med."},{"key":"89486_CR17","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1093\/ndt\/gfr657","volume":"27","author":"F Ibrahim","year":"2012","unstructured":"Ibrahim, F. et al. Comparison of CKD-EPI and MDRD to estimate baseline renal function in HIV-positive patients. Nephrol. Dial. Transplant. 27, 2291\u20132297 (2012).","journal-title":"Nephrol. Dial. Transplant."},{"issue":"3","key":"89486_CR18","first-page":"7","volume":"22","author":"D Garriguet","year":"2011","unstructured":"Garriguet, D. Bone health: Osteoporosis, calcium and vitamin D. Health Rep. 22(3), 7\u201314 (2011).","journal-title":"Health Rep."},{"key":"89486_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.23970\/AHRQEPCERTA217","volume":"217","author":"SJ Newberry","year":"2014","unstructured":"Newberry, S. J. et al. Vitamin D and calcium: A systematic review of health outcomes (Update). Evid. Rep. Technol. Assess. (Full Rep) 217, 1\u2013929. https:\/\/doi.org\/10.23970\/AHRQEPCERTA217 (2014).","journal-title":"Evid. Rep. Technol. Assess. (Full Rep)"},{"key":"89486_CR20","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1086\/644785","volume":"200","author":"A Calmy","year":"2009","unstructured":"Calmy, A. et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: A cross-sectional study. J. Infect. Dis. 200, 1746\u20131754 (2009).","journal-title":"J. Infect. Dis."},{"issue":"3","key":"89486_CR21","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1093\/infdis\/jiu471","volume":"211","author":"US Gill","year":"2015","unstructured":"Gill, U. S. et al. Assessment of bone mineral density in Tenofovir-Treated patients with chronic Hepatitis B: Can the fracture risk assessment tool identify those at greatest risk?. J. Infect. Dis. 211(3), 374\u2013382 (2015).","journal-title":"J. Infect. Dis."},{"key":"89486_CR22","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1001\/jama.292.2.191","volume":"292","author":"J Gallant","year":"2004","unstructured":"Gallant, J. et al. Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-na\u0131\u00a8ve patients: A randomized trial. JAMA 292, 191\u2013201 (2004).","journal-title":"JAMA"},{"key":"89486_CR23","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1089\/aid.2007.0107","volume":"23","author":"J Molina","year":"2007","unstructured":"Molina, J. et al. A lopinavir\/ritonavir based oncedaily regimen results in better compliance and is noninferior to a twicedaily regimen through 96 weeks. AIDS Res. Hum. Retrovir. 23, 1505\u20131514 (2007).","journal-title":"AIDS Res. Hum. Retrovir."},{"issue":"2","key":"89486_CR24","doi-asserted-by":"publisher","first-page":"457","DOI":"10.12669\/pjms.332.12099","volume":"33","author":"Z Huang","year":"2017","unstructured":"Huang, Z. et al. Low bone mineral density in chronic hepatitis B virus infection: A case-control study. Pak. J. Med. Sci. 33(2), 457\u2013461 (2017).","journal-title":"Pak. J. Med. Sci."},{"key":"89486_CR25","doi-asserted-by":"publisher","first-page":"i1","DOI":"10.1136\/gut.50.suppl_1.i1","volume":"50","author":"J Collier","year":"2002","unstructured":"Collier, J., Ninkovic, M. & Comstom, J. E. Guidelines on the management of osteoporosis associated chronic liver disease. Gut 50, i1-9 (2002).","journal-title":"Gut"},{"issue":"11","key":"89486_CR26","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1086\/644785","volume":"200","author":"A Calmy","year":"2009","unstructured":"Calmy, A. et al. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: A cross-sectional study. J. Infect. Dis. 200(11), 1746\u20131754. https:\/\/doi.org\/10.1086\/644785 (2009).","journal-title":"J. Infect. Dis."},{"issue":"12","key":"89486_CR27","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1097\/QAD.0b013e32832c1792","volume":"23","author":"B Grund","year":"2009","unstructured":"Grund, B. et al. Continuous antiretroviral therapy decreases bone mineral density. AIDS 23(12), 1519\u20131529. https:\/\/doi.org\/10.1097\/QAD.0b013e32832c1792 (2009).","journal-title":"AIDS"},{"issue":"1","key":"89486_CR28","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1177\/1759720X16671927","volume":"9","author":"E Biver","year":"2017","unstructured":"Biver, E., Calmy, A. & Rizzoli, R. Bone health in HIV and hepatitis B or C infections. Adv. Musculoskelet. Dis. 9(1), 22\u201334 (2017).","journal-title":"Adv. Musculoskelet. Dis."},{"issue":"12","key":"89486_CR29","doi-asserted-by":"publisher","first-page":"815","DOI":"10.7326\/M14-1409","volume":"162","author":"ET Overton","year":"2015","unstructured":"Overton, E. T. et al. High-dose vitamin D and calcium attenuates bone loss with antiretroviral therapy initiation: A prospective, randomized placebo-controlled trial for bone health in HIV-infected individuals. Ann. Intern. Med. 162(12), 815\u2013824. https:\/\/doi.org\/10.7326\/M14-1409 (2015).","journal-title":"Ann. Intern. Med."},{"key":"89486_CR30","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-018-1583-8","author":"E Gaffney-Stomberg","year":"2018","unstructured":"Gaffney-Stomberg, E. The impact of trace minerals on bone metabolism. Biol. Trace Elem. Res. https:\/\/doi.org\/10.1007\/s12011-018-1583-8 (2018).","journal-title":"Biol. Trace Elem. Res."},{"issue":"5","key":"89486_CR31","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1097\/QAI.0b013e3181caebaa","volume":"54","author":"MM Rosenvinge","year":"2010","unstructured":"Rosenvinge, M. M. et al. Tenofovir-linked hyperparathyroidism is independently associated with the presence of vitamin D deficiency. J. Acquir. Immune Defic. Syndr. 54(5), 496\u2013499 (2010).","journal-title":"J. Acquir. Immune Defic. Syndr."},{"issue":"6","key":"89486_CR32","doi-asserted-by":"publisher","first-page":"e38377","DOI":"10.1371\/journal.pone.0038377","volume":"7","author":"H Haskelberg","year":"2012","unstructured":"Haskelberg, H. et al. Changes in bone turnover and bone loss in HIV-infected patients changing treatment to tenofovir-emtricitabine or abacavir-lamivudine. PLoS ONE 7(6), e38377. https:\/\/doi.org\/10.1371\/journal.pone.0038377 (2012).","journal-title":"PLoS ONE"},{"key":"89486_CR33","first-page":"610A","volume":"54","author":"HL Nguyen","year":"2011","unstructured":"Nguyen, H. L. et al. No effect of tenofovir or entecavir on vitamin D levels in chronic hepatitis B mono-infected patients single centre \u201creal life\u201d cohort experience. Hepatology 54, 610A (2011).","journal-title":"Hepatology"},{"issue":"2","key":"89486_CR34","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1007\/s11914-017-0353-4","volume":"15","author":"BZ Leder","year":"2017","unstructured":"Leder, B. Z. Parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis therapy. Curr. Osteoporos. Rep. 15(2), 110\u2013119. https:\/\/doi.org\/10.1007\/s11914-017-0353-4 (2017).","journal-title":"Curr. Osteoporos. Rep."},{"issue":"4","key":"89486_CR35","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1093\/jac\/dku502","volume":"70","author":"P Maggi","year":"2015","unstructured":"Maggi, P. et al. Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: A longitudinal study. J. Antimicrob. Chemother. 70(4), 1150\u20131154 (2015).","journal-title":"J. Antimicrob. Chemother."},{"issue":"6","key":"89486_CR36","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s00223-014-9854-7","volume":"94","author":"R Saeedi","year":"2014","unstructured":"Saeedi, R., Jiang, S. Y., Holmes, D. T. & Kendler, D. L. Fibroblast growth factor 23 is elevated in tenofovir-related hypophosphatemia. Calcif. Tissue Int. 94(6), 665\u2013668 (2014).","journal-title":"Calcif. Tissue Int."},{"issue":"1","key":"89486_CR37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1530\/EJE-09-0597","volume":"162","author":"I Ramon","year":"2010","unstructured":"Ramon, I., Kleynen, P., Body, J. J. & Karmali, R. Fibroblast growth factor 23 and its role in phosphate homeostasis. Eur. J. Endocrinol. 162(1), 1\u201310 (2010).","journal-title":"Eur. J. Endocrinol."},{"key":"89486_CR38","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1359\/JBMR.0301264","volume":"19","author":"T Shimada","year":"2004","unstructured":"Shimada, T. et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphonate homeostasis. J. Bone Miner. Res. 19, 429\u2013435 (2004).","journal-title":"J. Bone Miner. Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89486-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89486-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89486-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T08:11:47Z","timestamp":1670055107000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89486-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,13]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["89486"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-89486-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,13]]},"assertion":[{"value":"14 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10162"}}