Change in tartrate‑resistant acid phosphatase isoform 5b levels, a marker of bone metabolism, in patients with chronic hepatitis B treated with tenofovir alafenamide

Okamura,Takuma; Ichikawa,Tatsuki; Miyaaki,Hisamitsu; Miuma,Satoshi; Motoyoshi,Yasuhide; Yamashima,Mio; Yamamichi,Shinobu; Koike,Makiko; Nakano,Yusuke; Honda,Tetsurou; Yajima,Hiroyuki; Miyazaki,Osamu; Kuribayashi,Yasutaka; Ikeda,Tomonari; Taura,Naota; Nakao,Kazuhiko

doi:10.3892/br.2021.1489

Change in tartrate‑resistant acid phosphatase isoform 5b levels, a marker of bone metabolism, in patients with chronic hepatitis B treated with tenofovir alafenamide

Authors:
- Takuma Okamura
- Tatsuki Ichikawa
- Hisamitsu Miyaaki
- Satoshi Miuma
- Yasuhide Motoyoshi
- Mio Yamashima
- Shinobu Yamamichi
- Makiko Koike
- Yusuke Nakano
- Tetsurou Honda
- Hiroyuki Yajima
- Osamu Miyazaki
- Yasutaka Kuribayashi
- Tomonari Ikeda
- Naota Taura
- Kazuhiko Nakao
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Affiliations: Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki 850‑8555, Japan, Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852‑8501, Japan, Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Nagasaki 850‑8555, Japan
Published online on: November 24, 2021 https://doi.org/10.3892/br.2021.1489
Article Number: 6
Copyright: © Okamura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hepatitis B virus (HBV) infection is associated with the risk of osteoporosis and bone mineral density (BMD) loss. Tenofovir alafenamide (TAF) is associated with a slightly lower degree of BMD loss compared with tenofovir disoproxil, without loss of the excellent anti‑HBV effects. The aim of the present study was to verify the effect of bone metabolism in patients with HBV treated with TAF. A total of 87 patients were treated with TAF. Of these, 32 patients were treatment naïve, and 55 patients were treated with entecavir (ETV) for at least 1 year, after which ETV was switched to TAF. At the start of TAF and after 1 year, BMD in the lumbar and neck of the femur, tartrate‑resistant acid phosphatase isoform 5b (TRACP‑5b) levels as a marker of bone metabolism and serum inorganic phosphorus (P) were compared to estimate bone metabolism. Serum creatinine (Cr), cystatin C, urine protein and β2 microglobulin levels were evaluated to estimate kidney function. Treatment with TAF for 1 year decreased TRACP‑5b levels, particularly in patients with bone disease, except for a minimal significant change (MSC; decrease of 12.4%) in TRACP‑5b levels. The change in rate of TRACP‑5b levels were positively associated with changes in P, Cr‑estimated glomerular filtration rate and TRACP‑5b levels at the start of TAF. Logistic regression analysis showed that increased BMD in the lumbar region contributed to the switch from ETV to TAF. TAF induced a decrease in TRACP‑5b levels in patients with HBV. Bone disease was a contributing factor for MSC. Since TRACP‑5b can be used as a marker of bone metabolism and fractures, TAF may exhibit potential in preventing fractures in patients with HBV.

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1	Papatheodoridis G, Buti M, Cornberg M, Janssen H, Mutimer D, Pol S and Raimondo G: EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 57:167–185. 2012.PubMed/NCBI View Article : Google Scholar
2	Raffetti E, Fattovich G and Donato F: Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: A systematic review and meta-analysis. Liver Int. 36:1239–1251. 2016.PubMed/NCBI View Article : Google Scholar
3	Lampertico P, Agarwal K, Berg T, Buti M, Janssen HLA, Papatheodoridis G, Zoulim F and Tacke F: EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 67:370–398. 2017.PubMed/NCBI View Article : Google Scholar
4	Si J, Yu C, Guo Y, Bian Z, Qin C, Yang L, Chen Y, Yin L, Li H, Lan J, et al: Chronic hepatitis B virus infection and risk of chronic kidney disease: A population-based prospective cohort study of 0.5 million Chinese adults. BMC Med. 16(93)2018.PubMed/NCBI View Article : Google Scholar
5	Rouillard S and Lane NE: Hepatic osteodystrophy. Hepatology. 33:301–307. 2001.PubMed/NCBI View Article : Google Scholar
6	Ehnert S, Aspera-Werz RH, Ruoß M, Dooley S, Hengstler JG, Nadalin S, Relja B, Badke A and Nussler AK: Hepatic osteodystrophy-molecular mechanisms proposed to favor its development. Int J Mol Sci. 20(2555)2019.PubMed/NCBI View Article : Google Scholar
7	Leslie WD, Bernstein CN and Leboff MS: American Gastroenterological Association Clinical Practice Commitee. AGA technical review on osteoporosis in hepatic disorders. Gastroenterology. 125:941–966. 2003.PubMed/NCBI View Article : Google Scholar
8	Chen CH, Lin CL and Kao CH: Association between chronic hepatitis B virus infection and risk of osteoporosis: A nationwide population-based study. Medicine (Baltimore). 94(e2276)2015.PubMed/NCBI View Article : Google Scholar
9	Baeg MK, Yoon SK, Ko SH, Han KD, Choi HJ, Bae SH, Choi JY and Choi MG: Males seropositive for hepatitis B surface antigen are at risk of lower bone mineral density: The 2008-2010 Korea national health and nutrition examination surveys. Hepatol Int. 10:470–477. 2016.PubMed/NCBI View Article : Google Scholar
10	Shimizu T, Arita K, Murota E, Hiratsuka S, Fujita R, Ishizu H, Asano T, Takahashi D, Takahata M and Iwasaki N: Effects after starting or switching from bisphosphonate to romosozumab or denosumab in Japanese postmenopausal patients. J Bone Miner Metab. 39:868–875. 2021.PubMed/NCBI View Article : Google Scholar
11	Miller PD, Hochberg MC, Wehren LE, Ross PD and Wasnich RD: How useful are measures of BMD and bone turnover? Curr Med Res Opin. 21:545–554. 2005.PubMed/NCBI View Article : Google Scholar
12	Agarwal K, Brunetto M, Seto WK, Lim YS, Fung S, Marcellin P, Ahn SH, Izumi N, Chuang WL, Bae H, et al: 96 weeks treatment of tenofovir alafenamide vs tenofovir disoproxil fumarate for hepatitis B virus infection. J Hepatol. 68:672–681. 2018.PubMed/NCBI View Article : Google Scholar
13	Seto WK, Asahina Y, Brown TT, Peng CY, Stanciu C, Abdurakhmanov D, Tabak F, Nguyen TT, Chuang WL, Inokuma T, et al: Improved bone safety of tenofovir alafenamide compared to tenofovir disoproxil fumarate over 2 years in patients with chronic HBV infection. Clin Gastroenterol Hepatol, Jun 20, 2018 (Online ahead of print).
14	Chan HL, Fung S, Seto WK, Chuang WL, Chen CY, Kim HJ, Hui AJ, Janssen HL, Chowdhury A, Tsang TY, et al: Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-positive chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol. 1:185–195. 2016.PubMed/NCBI View Article : Google Scholar
15	Ogawa E, Nomura H, Nakamuta M, Furusyo N, Koyanagi T, Dohmen K, Ooho A, Satoh T, Kawano A, Kajiwara E, et al: Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. Liver Int. 40:1578–1589. 2020.PubMed/NCBI View Article : Google Scholar
16	Notsumata K, Nomura Y, Tanaka A, Ueda T, Sanada T, Watanabe H and Toya D: Early changes in tubular dysfunction markers and phosphorus metabolism regulators as a result of switching from entecavir to tenofovir alafenamide fumarate nucleoside analog therapy for chronic hepatitis B patients. Hepatol Res. 50:402–404. 2020.PubMed/NCBI View Article : Google Scholar
17	Hagiwara S, Nishida N, Ida H, Ueshima K, Minami Y, Takita M, Komeda Y and Kudo M: Switching from entecavir to tenofovir alafenamide versus maintaining entecavir for chronic hepatitis B. J Med Virol. 91:18040–1810. 2019.PubMed/NCBI View Article : Google Scholar
18	Uchida Y, Nakao M, Tsuji S, Uemura H, Kouyama JI, Naiki K, Motoya D, Sugawara K, Nakayama N, Imai Y, et al: Significance of switching of the nucleos(t)ide analog used to treat Japanese patients with chronic hepatitis B virus infection from entecavir to tenofovir alafenamide fumarate. J Med Virol. 92:329–338. 2020.PubMed/NCBI View Article : Google Scholar
19	Tamaki N, Kurosaki M, Nakanishi H, Itakura J, Inada K, Kirino S, Kirino S, Yamashita K, Osawa L, Sekiguchi S, et al: Comparison of medication adherence and satisfaction between entecavir and tenofovir alafenamide therapy in chronic hepatitis B. J Med Virol. 92:1355–1358. 2020.PubMed/NCBI View Article : Google Scholar
20	Shephard DA: The 1975 declaration of Helsinki and consent. Can Med Assoc J. 115:1191–1192. 1976.PubMed/NCBI
21	Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO study group. World Health Organ Tech Rep Ser. 843:1–129. 1994.PubMed/NCBI
22	Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H and Hishida A: Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 53:982–992. 2009.PubMed/NCBI View Article : Google Scholar
23	Kashani KB, Frazee EN, Kukrálová L, Sarvottam K, Herasevich V, Young PM, Kashyap R and Lieske JC: Evaluating muscle mass by using markers of kidney function: Development of the sarcopenia index. Crit Care Med. 45:e23–e29. 2017.PubMed/NCBI View Article : Google Scholar
24	Kim SW, Jung HW, Kim CH, Kim K, Chin HJ and Lee H: A new equation to estimate muscle mass from creatinine and cystatin C. PLoS One. 11(e0148495)2016.PubMed/NCBI View Article : Google Scholar
25	Spirlandeli AL, Dick-de-paula I, Zamarioli A, Jorgetti V, Ramalho LNZ, Nogueira-Barbosa MH, Volpon JB, Jordão AA, Cunha FQ, Fukada SY and de Paula FJA: Hepatic osteodystrophy: The mechanism of bone loss in hepatocellular disease and the effects of pamidronate treatment. Clinics (Sao Paulo). 72:231–237. 2017.PubMed/NCBI View Article : Google Scholar
26	Lv Y, Wang G, Xu W, Tao P, Lv X and Wang Y: Tartrate-resistant acid phosphatase 5b is a marker of osteoclast number and volume in RAW 264.7 cells treated with receptor-activated nuclear κB ligand. Exp Ther Med. 9:143–146. 2015.PubMed/NCBI View Article : Google Scholar
27	Ivaska KK, Gerdhem P, Väänänen HK, Akesson K and Obrant KJ: Bone turnover markers and prediction of fracture: A prospective follow-up study of 1040 elderly women for a mean of 9 years. J Bone Miner Res. 25:393–403. 2010.PubMed/NCBI View Article : Google Scholar
28	Kasai H, Mori Y, Ose A, Shiraki M and Tanigawara Y: Prediction of fracture risk from early-stage bone markers in patients with osteoporosis treated with once-yearly administered zoledronic acid. J Clin Pharmacol. 61:606–613. 2021.PubMed/NCBI View Article : Google Scholar
29	Wei MT, Le AK, Chang MS, Hsu H, Nguyen P, Zhang JQ, Wong C, Wong C, Cheung R and Nguyen MH: Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B. J Med Virol. 91:1288–1294. 2019.PubMed/NCBI View Article : Google Scholar
30	Fung J, Seto W, Lai C and Yuen M: Extrahepatic effects of nucleoside and nucleotide analogues in chronic hepatitis B treatment. J Gastroenterol Hepatol. 29:428–434. 2014.PubMed/NCBI View Article : Google Scholar