Can Peripheral Blood gamma delta T Cells Predict Osteonecrosis of the Jaw? An Immunological Perspective on the Adverse Drug Effects of Aminobisphosphonate Therapy

• Published in: Journal of bone and mineral research 2013-04, Vol.28 (4), p.728-735
• Main Authors: Kalyan, S, Quabius, E S, Wiltfang, J, Moenig, H, Kabelitz, D
• Format: Article
• Language: English
• ISSN: 0884-0431
• DOI: 10.1002/jbmr.1769

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 gamma 9V delta 2 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 gamma 9V delta 2 T cells in osteoporotic patients on n-BP therapy as a function of time and type of therapy; 2) evaluate the proportion of V gamma 9V delta 2 T cells in patients who had recently experienced n-BP-associated ONJ. We found there is a notable loss of V gamma 9V delta 2 T cells over time in osteoporotic patients on n-BP therapy, particularly those on intravenous (iv) therapy (Spearman r = -0.55, p < 0.0001 iv; r = -0.3, p < 0.03 oral) (n = 68); no difference was observed in total T cells, monocytes, or granulocytes. Importantly, the observed negative effect on V gamma 9V delta 2 T cells coincides with the reported route of administration and timing of the rare occurrence of BAONJ. Patients (n = 6) who had experienced BAONJ were all found to be significantly deficient in V gamma 9V delta 2 T cells (median = 0.07%) in comparison to age- and sex-matched treatment-naive controls (N = 11; median = 2.40%), U = 0, p = 0.001; 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 gamma 9V delta 2 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.