{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:14:12Z","timestamp":1791828852199,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Tumor necrosis factor alpha (TNF-\u03b1), which enhances osteoclast activity and bone resorption, is one of the key inflammation mediators in rheumatoid arthritis (RA). The aim of this study was to assess the influence of yearlong TNF-\u03b1 inhibitor application on bone metabolism. The study sample comprised 50 female patients with RA. Analyses involved the osteodensitometry measurements obtained using a \u201cLunar\u201d type apparatus and the following biochemical markers from serum: procollagen type 1 N-terminal propeptide (P1NP), beta crosslaps C-terminal telopeptide of collagen type I (b-CTX) by ECLIA method, total and ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone and vitamin D. Analyses revealed changes in bone mineral density (BMD) at L1\u2013L4 and the femoral neck, with the difference in mean BMD (g\/cm2) not exceeding the threshold of statistical significance (p = 0.180; p = 0.502). Upon completion of 12-month therapy, a significant increase (p &lt; 0.001) in P1NP was observed relative to b-CTX, with mean total calcium and phosphorus values following a decreasing trend, while vitamin D levels increased. These results suggest that yearlong application of TNF inhibitors has the capacity to positively impact bone metabolism, as indicated by an increase in bone-forming markers and relatively stable BMD (g\/cm2).<\/jats:p>","DOI":"10.3390\/jcm12051901","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:02:32Z","timestamp":1678071752000},"page":"1901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Changes in Bone Metabolism in Patients with Rheumatoid Arthritis during Tumor Necrosis Factor Inhibitor Therapy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-1794","authenticated-orcid":false,"given":"Tanja","family":"Jankovi\u0107","sequence":"first","affiliation":[{"name":"Medical Faculty, University of Novi Sad, Special Hospital for Rheumatic Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momir","family":"Mikov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical Faculty, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Zveki\u0107 Svorcan","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Novi Sad, Special Hospital for Rheumatic Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-8618","authenticated-orcid":false,"given":"Ivana","family":"Minakovi\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Novi Sad, Health Center \u201cNovi Sad\u201d, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mikov","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenija","family":"Bo\u0161kovi\u0107","sequence":"additional","affiliation":[{"name":"Medical Faculty, University of Novi Sad, Special Hospital for Rheumatic Diseases, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darko","family":"Miki\u0107","sequence":"additional","affiliation":[{"name":"Pathology and Forensic Medicine Institute, Medical Faculty of the Military Medical Academy, University of Defence, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, T.L., Chang, K.H., and Su, K.Y. (2022). Effects of Biological\/Targeted Therapies on Bone Mineral Density in Inflammatory Arthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084111"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.3346\/jkms.2013.28.2.287","article-title":"Periarticular Osteoporosis Is a Prominent Feature in Early Rheumatoid Arthritis: Estimation Using Shaft to Periarticular Bone Mineral Density Ratio","volume":"28","author":"Moon","year":"2013","journal-title":"J. Korean Med. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.0105-2896.2005.00338.x","article-title":"Rheumatic diseases: The effects of inflammation on bone","volume":"208","author":"Walsh","year":"2005","journal-title":"Immunol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s11914-012-0104-5","article-title":"Pathways for Bone Loss in Inflammatory Disease","volume":"10","author":"Braun","year":"2012","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cca.2016.06.036","article-title":"Clinical Usefulness of Bone Turnover Marker Concentrations in Osteoporosis","volume":"467","author":"Morris","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6910312","DOI":"10.1155\/2020\/6910312","article-title":"RANKL\/RANK\/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling","volume":"2020","author":"Tobeiha","year":"2020","journal-title":"Biomed Res. Int."},{"key":"ref_7","unstructured":"Wysocki, T. (2023, February 16). Tumor Necrosis Factor in Rheumatoid Arthritis. Encyclopedia. Available online: https:\/\/encyclopedia.pub\/entry\/20537."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yi, S.-J., Lee, H., Lee, J., Lee, K., Kim, J., Kim, Y., Park, J.-I., and Kim, K. (2019). Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20133147"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e13309","DOI":"10.1111\/cpr.13309","article-title":"The Role of the Wnt Signalling Pathway in the Energy Metabolism of Bone Remodelling","volume":"55","author":"Zhu","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1210\/en.2006-1372","article-title":"In Vivo Analysis of Wnt Signaling in Bone","volume":"148","author":"Glass","year":"2007","journal-title":"Endocrinology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1007\/s11914-017-0358-z","article-title":"TNF and Bone Remodeling","volume":"15","author":"Zhao","year":"2017","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"v3","DOI":"10.1093\/rheumatology\/kes113","article-title":"Understanding the Dynamics: Pathways Involved in the Pathogenesis of Rheumatoid Arthritis","volume":"51","author":"Choy","year":"2012","journal-title":"Rheumatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s00393-007-0182-4","article-title":"Bone Metabolism: Molecular Mechanisms","volume":"66","author":"Neumann","year":"2007","journal-title":"Z. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40364-017-0097-4","article-title":"Bone Biomarker for the Clinical Assessment of Osteoporosis: Recent Developments and Future Perspectives","volume":"5","author":"Kuo","year":"2017","journal-title":"Biomark. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4103\/2230-8210.192914","article-title":"Bone Turnover Markers: Emerging Tool in the Management of Osteoporosis","volume":"20","author":"Shetty","year":"2016","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1093\/rheumatology\/kez655","article-title":"The Impact of Long-Term Biologics\/Target Therapy on Bone Mineral Density in Rheumatoid Arthritis: A Propensity Score-Matched Analysis","volume":"59","author":"Chen","year":"2020","journal-title":"Rheumatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s00198-021-05900-y","article-title":"The Clinician\u2019s Guide to Prevention and Treatment of Osteoporosis","volume":"3","author":"LeBoff","year":"2022","journal-title":"Osteoporos. Int."},{"key":"ref_19","unstructured":"Gerriets, V., Bansal, P., and Khaddour, K. (2022, May 20). Tumor Necrosis Factor (TNF) Inhibitors, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482425\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41584-022-00764-w","article-title":"Effects of Targeted Therapies on Bone in Rheumatic and Musculoskeletal Diseases","volume":"18","author":"Raterman","year":"2022","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1002\/1529-0131(200003)43:3<522::AID-ANR7>3.0.CO;2-Y","article-title":"Bone Mineral Density and Frequency of Osteoporosis in Female Patients with Rheumatoid Arthritis: Results from 394 Patients in the Oslo County Rheumatoid Arthritis Register","volume":"43","author":"Haugeberg","year":"2000","journal-title":"Arthritis Rheum."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1136\/ard.2007.076604","article-title":"Long-Term Effects of Infliximab on Bone and Cartilage Turnover Markers in Patients with Rheumatoid Arthritis","volume":"67","author":"Chopin","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s00223-016-0114-x","article-title":"Short-Term Effects of TNF Inhibitors on Bone Turnover Markers and Bone Mineral Density in Rheumatoid Arthritis","volume":"98","author":"Orsolini","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology\/European League against Rheumatism Collaborative Initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/art.1780230202","article-title":"Measurement of Patient Outcome in Arthritis","volume":"23","author":"Fries","year":"1980","journal-title":"Arthritis Rheum."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/acr2.11171","article-title":"DAS28-CRP Cutoffs for High Disease Activity and Remission Are Lower than DAS28-ESR in Rheumatoid Arthritis","volume":"2","author":"Greenmyer","year":"2020","journal-title":"ACR Open Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1007\/s00198-014-2794-2","article-title":"Clinician\u2019s Guide to Prevention and Treatment of Osteoporosis","volume":"25","author":"Cosman","year":"2014","journal-title":"Osteoporos. Int."},{"key":"ref_28","unstructured":"Weir, C.B., and Jan, A. (2022, September 24). BMI Classification Percentile and Cut Off Points, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK541070\/."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"484280","DOI":"10.1155\/2014\/484280","article-title":"Bone Remodelling Markers in Rheumatoid Arthritis","volume":"2014","author":"Fardellone","year":"2014","journal-title":"Mediators Inflamm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e000065","DOI":"10.1136\/rmdopen-2015-000065","article-title":"Bone and TNF in Rheumatoid Arthritis: Clinical Implications","volume":"1","author":"Manara","year":"2015","journal-title":"RMD Open"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1007\/s00198-021-05871-0","article-title":"Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis","volume":"32","author":"Hamar","year":"2021","journal-title":"Osteoporos. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/ar4180","article-title":"Cortical Remodeling during Menopause, Rheumatoid Arthritis, Glucocorticoid and Bisphosphonate Therapy","volume":"15","author":"Aeberli","year":"2013","journal-title":"Arthritis Res. Ther."},{"key":"ref_33","unstructured":"Nut, A., Duny, Y., Barnetche, T., Morel, J., Combe, B., and Daien, C. (2014, January 14\u201319). Can tumor necrosis factor inhibitors protect rheumatoid arthritis patients from osteoporosis? Impact of tumor necrosis factor inhibitors on bone mineral density and bone remodeling markers. Proceedings of the ACR\/ARHP Annual Meeting, Boston, MA, USA."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00198-016-3769-2","article-title":"Biologic Therapies and Bone Loss in Rheumatoid Arthritis","volume":"28","author":"Zerbini","year":"2016","journal-title":"Osteoporos. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.2174\/13894501113149990176","article-title":"The Effects of TNF \u03b1 Antagonist Therapy on Bone Metabolism in Rheumatoid Arthritis: A Systematic Review","volume":"14","author":"Sakthiswary","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0140-6736(04)15640-7","article-title":"TEMPO (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) study investigators. Therapeutic Effect of the Combination of Etanercept and Methotrexate Compared with Each Treatment Alone in Patients with Rheumatoid Arthritis: Double-Blind Randomised Controlled Trial","volume":"363","author":"Klareskog","year":"2004","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"601618","DOI":"10.3389\/fmed.2020.601618","article-title":"Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons","volume":"7","author":"Llorente","year":"2020","journal-title":"Front. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1002\/art.11292","article-title":"Early Changes in Bone Metabolism in Rheumatoid Arthritis Patients Treated with Infliximab","volume":"48","author":"Vis","year":"2003","journal-title":"Arthritis Rheum."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jura-P\u00f3\u0142torak, A., Szeremeta, A., Olczyk, K., Zo\u0144-Giebel, A., and Komosi\u0144ska-Vassev, K. (2021). Bone Metabolism and RANKL\/OPG Ratio in Rheumatoid Arthritis Women Treated with TNF-\u03b1 Inhibitors. J. Clin. Med., 10.","DOI":"10.3390\/jcm10132905"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Szulc, P., Bauer, D.C., and Eastell, R. (2013). Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Academic Press.","DOI":"10.1002\/9781118453926.part4"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1749-799X-6-30","article-title":"Effects of Obesity on Bone Metabolism","volume":"6","author":"Cao","year":"2011","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Turcotte, A.F., O\u2019Connor, S., Morin, S.N., Gibbs, J.C., Willie, B.M., Jean, S., and Gagnon, C. (2021). Association between Obesity and Risk of Fracture, Bone Mineral Density and Bone Quality in Adults: A Systematic Review and Meta-Analysis. PLOS ONE, 16.","DOI":"10.1371\/journal.pone.0252487"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Takahashi, K., Setoguchi, T., Tawaratsumida, H., Arishima, Y., Tominaga, H., Ishidou, Y., Nagano, S., Shigemizu, S., Aoki, N., and Akimoto, M. (2015). Risk of Low Bone Mineral Density in Patients with Rheumatoid Arthritis Treated with Biologics. BMC Musculoskelet. Disord., 16.","DOI":"10.1186\/s12891-015-0732-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s002239900416","article-title":"Relationship between Disease Activity and Serum Levels of Vitamin D Metabolites and PTH in Rheumatoid Arthritis","volume":"62","author":"Oelzner","year":"1998","journal-title":"Calcif. Tissue Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1136\/ard.40.6.580","article-title":"Serum Calcium Levels in Rheumatoid Arthritis","volume":"40","author":"Scott","year":"1981","journal-title":"Ann. Rheum. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lin, J., Liu, J., Davies, M.L., and Chen, W. (2016). Serum Vitamin D Level and Rheumatoid Arthritis Disease Activity: Review and Meta-Analysis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146351"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"300","DOI":"10.2174\/1874312901812010300","article-title":"Vitamin D, Inflammation and Osteoporosis in Rheumatoid Arthritis","volume":"12","author":"Sainaghi","year":"2018","journal-title":"Open Rheumatol. J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/5\/1901\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:43:42Z","timestamp":1760121822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/5\/1901"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,28]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["jcm12051901"],"URL":"https:\/\/doi.org\/10.3390\/jcm12051901","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,28]]}}}