{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:35:54Z","timestamp":1774697754275,"version":"3.50.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T00:00:00Z","timestamp":1591315200000},"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":["BMC Pharmacol Toxicol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Progressive bone pain and fracture and abnormal positron emission tomography combined with a computed tomography are main reasons for the oncologists suspecting bone tumor. During the patient\u2019s medical treatment, the oncologists\u2019 unfamiliarity with adverse reactions to anti-HBV drugs were main reason for the long-term exposure to the drug and the adverse reaction (ADR) experienced by the patient.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>A 63-year-old Chinese man had a 27-month history of progressive generalized bone pain combined with spontaneous fractures. Positron emission tomography combined with a computed tomography, revealed an abnormal increase in ribose metabolism and low positron serum inorganic phosphorus concentration (0.7; 0.78\u20131.65\u2009mmol\/L). Serum creatinine level was 252\u2009\u03bcmol\/L (53\u201397) \u03bcmol\/L, and glomerular filtration rate was 22.79\u2009mL\/min\/1.73\u2009m<jats:sup>2<\/jats:sup>. The patient was referred to a multidisciplinary clinic to clarify the diagnosis of myeloma or bone tumor for further treatment in 2017. His medical history revealed that he had a 30-year history of chronic hepatitis B infection. He had received lamivudine at a daily dose of 100\u2009mg for 19\u2009years (1990 to 2009), which had been changed to adefovir (10\u2009mg\/day) owing to lamivudine resistance in 2009. Based on the changes in the patient\u2019s laboratory markers and the results of emission computed tomography and other radiographic findings, adefovir-induced hypophosphatemic osteomalacia due to acquired renal Fanconi syndrome was suspected by the clinical pharmacist. Considerable clinical improvement was observed after adefovir discontinuation and the administration of entecavir (1.0\u2009mg, every other day).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Fanconi syndrome with osteomalacia can develop in patients with chronic hepatitis B infection being treated with adefovir at a conventional low dosage of 10\u2009mg\/day. This case highlights the importance of ADR as a differential diagnosis and the need of pharmacists with drug safety expertise expert in the patient management.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s40360-020-00421-6","type":"journal-article","created":{"date-parts":[[2020,6,5]],"date-time":"2020-06-05T19:02:50Z","timestamp":1591383770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Osteomalacia and renal failure due to Fanconi syndrome caused by long-term low-dose Adefovir Dipivoxil: a case report"],"prefix":"10.1186","volume":"21","author":[{"given":"Qian","family":"Xiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanxu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiufen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyan","family":"Mu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinan","family":"Cen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4186-1005","authenticated-orcid":false,"given":"Yimin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,5]]},"reference":[{"key":"421_CR1","volume-title":"Global hepatitis report, 2017","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. Global hepatitis report, 2017. Geneva: World Health Organization; 2017."},{"key":"421_CR2","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","volume":"67","author":"European Association for the Study of the Liver","year":"2017","unstructured":"European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370\u201398.","journal-title":"J Hepatol"},{"key":"421_CR3","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1038\/ki.2014.363","volume":"87","author":"YC Chen","year":"2015","unstructured":"Chen YC, Su YC, Li CY, Wu CP, Lee MS. A nationwide cohort study suggests chronic hepatitis B virus infection increases the risk of end-stage renal disease among patients in Taiwan. Kidney Int. 2015;87:1030\u20138.","journal-title":"Kidney Int"},{"key":"421_CR4","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1111\/j.1440-1746.2011.06852.x","volume":"27","author":"YJ Kim","year":"2012","unstructured":"Kim YJ, Cho HC, Sinn DH, Gwak GY, Choi MS, Koh KC, et al. Frequency and risk factors of renal impairment during long-term adefovir dipivoxil treatment in chronic hepatitis B patients. J Gastroenterol Hepatol. 2012;27:306\u201312.","journal-title":"J Gastroenterol Hepatol"},{"issue":"1","key":"421_CR5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40360-018-0212-7","volume":"19","author":"N Chen","year":"2018","unstructured":"Chen N, Zhang JB, Zhang Q, Zhao YP, Li LY, Liu LW, et al. Adefovir dipivoxil induced hypophosphatemic osteomalacia in chronic hepatitis B: a comparative study of Chinese and foreign case series. BMC Pharmacol Toxicol. 2018;19(1):23.","journal-title":"BMC Pharmacol Toxicol"},{"key":"421_CR6","doi-asserted-by":"publisher","first-page":"442","DOI":"10.4254\/wjh.v2.i12.442","volume":"2","author":"M Minemura","year":"2010","unstructured":"Minemura M, Tokimitsu Y, Tajiri K, Nakayama Y, Kawai K, Kudo H, et al. Development of osteomalacia in a post-liver transplant patient receiving adefovir dipivoxil. World J Hepatol. 2010;2:442\u20136.","journal-title":"World J Hepatol"},{"key":"421_CR7","doi-asserted-by":"publisher","first-page":"990","DOI":"10.3109\/00365548.2011.581307","volume":"43","author":"G Fabbriciani","year":"2011","unstructured":"Fabbriciani G, de Socio GV, Massarotti M, Ceriani R, Marasini B. Adefovir induced hypophosphatemic osteomalacia. Scand J Infect Dis. 2011;43:990\u20132.","journal-title":"Scand J Infect Dis"},{"issue":"1","key":"421_CR8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s13256-019-2018-7","volume":"13","author":"T Kunii","year":"2019","unstructured":"Kunii T, Iijima T, Jojima T, Shimizu M, Kase M, Sakurai S, et al. Denosumab improves clinical manifestations of hypophosphatemic osteomalacia by adefovir-induced Fanconi syndrome: a case report. J Med Case Rep. 2019;13(1):99.","journal-title":"J Med Case Rep"},{"issue":"3","key":"421_CR9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.3350\/cmh.2017.0009","volume":"24","author":"S Park","year":"2017","unstructured":"Park S, Kim WI, Cho DH, Kim YJ, Kim HS, Kim JH, et al. Adefovir-induced Fanconi syndrome associated with osteomalacia. Clin Mol Hepatol. 2017;24(3):339\u201344.","journal-title":"Clin Mol Hepatol"},{"key":"421_CR10","unstructured":"The Uppsala Monitoring Centre (the UMC). The use of the WHO-UMC system for standardized case causality assessment. https:\/\/www.whoumc.org\/media\/164200\/who-umc-causality-assessment_new-logo.pdf, 2018-4-6\/2018-12-11."},{"issue":"2","key":"421_CR11","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1038\/clpt.1981.154","volume":"30","author":"CA Naranjo","year":"1981","unstructured":"Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239\u201345.","journal-title":"Clin Pharmacol Ther"},{"issue":"2","key":"421_CR12","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1365-2796.1990.tb00199.x","volume":"228","author":"J Hallas","year":"1990","unstructured":"Hallas J, Harvald B, Gram LF, Grodum E, Brosen K, Haghfelt T, et al. Drug related hospital admissions: the role of definitions and intensity of data collection, and the possibility of prevention. J Intern Med. 1990;228(2):83\u201390.","journal-title":"J Intern Med"},{"key":"421_CR13","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/jcpt.12050","volume":"38","author":"C Wu","year":"2013","unstructured":"Wu C, Zhang H, Qian Y, Wang L, Gu X, Dai Z. Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition. J Clin Pharm Ther. 2013;38:321\u20136.","journal-title":"J Clin Pharm Ther"},{"key":"421_CR14","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.nephro.2005.06.011","volume":"1","author":"A Servais","year":"2005","unstructured":"Servais A, Lechat P, Zahr N, Urien S, Aymard G, Jaudon MC, et al. Tubular transporters OAT1 and MRP2 and clearance of adefovir. Nephrol Ther. 2005;1:296\u2013300.","journal-title":"Nephrol Ther"},{"key":"421_CR15","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1517\/14740338.2011.593507","volume":"10","author":"M Vigano","year":"2011","unstructured":"Vigano M, Lampertico P, Colombo M. Drug safety evaluation of adefovir in HBV infection. Expert Opin Drug Saf. 2011;10:809\u201318.","journal-title":"Expert Opin Drug Saf"},{"issue":"2","key":"421_CR16","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1007\/s00774-012-0384-y","volume":"31","author":"H Kimdu","year":"2013","unstructured":"Kimdu H, Sung DH, Min YK. Hypophosphatemic osteomalacia induced by low-dose adefovir therapy: focus on manifestations in the skeletal system and literature review. J Bone Miner Metab. 2013;31(2):240\u20136.","journal-title":"J Bone Miner Metab"},{"issue":"1","key":"421_CR17","doi-asserted-by":"publisher","first-page":"307","DOI":"10.3892\/ol.2016.5393","volume":"13","author":"Y Lin","year":"2017","unstructured":"Lin Y, Pan F, Wang Y, Chen Z, Lin C, Yao L, et al. Adefovir dipivoxil-induced Fanconi syndrome and its predictive factors: a study of 28 cases. Oncol Lett. 2017;13(1):307\u201314.","journal-title":"Oncol Lett"},{"issue":"1","key":"421_CR18","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1186\/s12882-017-0693-4","volume":"18","author":"J Lin","year":"2017","unstructured":"Lin J, Zhuo Y, Zhang D. Nephrolithiasis and Osteomalacia associated with adefovir-induced Fanconi syndrome in a patient with hepatitis B. BMC Nephrol. 2017;18(1):275.","journal-title":"BMC Nephrol"},{"key":"421_CR19","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.2147\/DDDT.S192632","volume":"13","author":"YY Qian","year":"2019","unstructured":"Qian YY, Dai ZJ, Ruan LY, Pan YJ, Jin J, Shi MT, et al. Low-dose adefovir dipivoxil-induced hypophosphatemia osteomalacia in five chronic hepatitis B virus-infected patients. Is low-dose adefovir dipivoxil-induced nephrotoxicity completely reversible? Drug Des Devel Ther. 2019;13:1127\u201333.","journal-title":"Drug Des Devel Ther"},{"issue":"12","key":"421_CR20","doi-asserted-by":"publisher","first-page":"3657","DOI":"10.3748\/wjg.v21.i12.3657","volume":"21","author":"HY Jia","year":"2015","unstructured":"Jia HY, Ding F, Chen JY, Lian JS, Zhang YM, Zeng LY, et al. Early kidney injury during long-term adefovir dipivoxil therapy for chronic hepatitis B. World J Gastroenterol. 2015;21(12):3657\u201362.","journal-title":"World J Gastroenterol"},{"key":"421_CR21","doi-asserted-by":"publisher","first-page":"c951","DOI":"10.1136\/bmj.c951","volume":"340","author":"C Taylor","year":"2010","unstructured":"Taylor C, Munro AJ, Glynne-Jones R, Griffith C, Trevatt P, Richards M, et al. Multidisciplinary team working in cancer: what is the evidence? BMJ. 2010;340:c951.","journal-title":"BMJ."},{"issue":"4","key":"421_CR22","first-page":"378","volume":"29","author":"R Kurpad","year":"2011","unstructured":"Kurpad R, Kim W, Rathmell WK, Godley P, Whang Y, Fielding J, et al. A multidisciplinary approach to the management of urologic malignancies: does it influence diagnostic and treatment decisions? Urol Oncol Semin Orig Invest. 2011;29(4):378\u201382.","journal-title":"Urol Oncol Semin Orig Invest"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00421-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-020-00421-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00421-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T23:11:06Z","timestamp":1622848266000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-020-00421-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,5]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["421"],"URL":"https:\/\/doi.org\/10.1186\/s40360-020-00421-6","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,5]]},"assertion":[{"value":"3 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43"}}