{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:13:31Z","timestamp":1790874811390,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T00:00:00Z","timestamp":1347926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nitrogen-bisphosphonates (n-BP), often referred to as aminobisphosphonates, are the most commonly prescribed drugs for the treatment of disorders of bone fragility. However, long-term continuous treatment predisposes certain individuals to serious rare side effects, such as bisphosphonate-associated osteonecrosis of the jaw (BAONJ). n-BP use is known to unintentionally activate a subset of innate T cells called V\u03b39V\u03b42 T cells, but the consequence of this chronic immune stimulation has remained unexplored. The primary objectives of this study were to 1) determine the fate of V\u03b39V\u03b42 T cells in osteoporotic patients on n-BP therapy as a function of time and type of therapy; 2) evaluate the proportion of V\u03b39V\u03b42 T cells in patients who had recently experienced n-BP\u2013associated ONJ. We found there is a notable loss of V\u03b39V\u03b42 T cells over time in osteoporotic patients on n-BP therapy, particularly those on intravenous (iv) therapy (Spearman r\u2009=\u2009\u22120.55, p\u2009&amp;lt;\u20090.0001 iv; r\u2009=\u2009\u22120.3, p\u2009&amp;lt;\u20090.03 oral) (n\u2009=\u200968); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on V\u03b39V\u03b42 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n\u2009=\u20096) who had experienced BAONJ were all found to be significantly deficient in V\u03b39V\u03b42 T cells (median\u2009=\u20090.07%) in comparison to age- and sex-matched treatment-na\u00efve controls (N\u2009=\u200911; median\u2009=\u20092.40%), U\u2009=\u20090, p\u2009=\u20090.001; this was the only consistent difference in the leukocytes assessed. All BAONJ cases had an underlying condition that further contributed to impaired immunity. We propose V\u03b39V\u03b42 T cells show a strong potential to serve as harbingers of possible adverse immune effects of n-BP therapy, particularly in those patients already having a compromised immune system as they may be most vulnerable to the development of conditions such as BAONJ. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1769","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T12:15:16Z","timestamp":1347970516000},"page":"728-735","source":"Crossref","is-referenced-by-count":66,"title":["Can peripheral blood\n                    <b>\u03b3\u03b4<\/b>\n                    T cells predict osteonecrosis of the jaw? An immunological perspective on the adverse drug effects of aminobisphosphonate therapy"],"prefix":"10.1093","volume":"28","author":[{"given":"Shirin","family":"Kalyan","sequence":"first","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts University Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elgar Susanne","family":"Quabius","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts University Kiel, Kiel, Germany"},{"name":"Institute of Immunology, Christian-Albrechts University Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Wiltfang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Christian-Albrechts University Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"M\u00f6nig","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Christian-Albrechts University Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Kabelitz","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Christian-Albrechts University Kiel, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,9,18]]},"reference":[{"key":"2024020318410127700_bib1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1517\/14740338.7.4.491","article-title":"Insight into bisphosphonate-associated osteomyelitis of the jaw: pathophysiology, mechanisms and clinical management","volume":"7","author":"Wimalawansa","year":"2008","journal-title":"Expert Opin Drug 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