Noa Markovits1,2, Ronen Loebstein3,4, Ilan Bank5,6,7,4. 1. Institute of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer, Israel. noamarkovits@gmail.com. 2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. noamarkovits@gmail.com. 3. Institute of Clinical Pharmacology, Chaim Sheba Medical Center, Tel Hashomer, Israel. 4. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Autoimmunity Institute and Laboratory for Immunoregulation, Chaim Sheba Medical Center, Tel Hashomer, Israel. 6. Department of Medicine, Maayenei Hayeshuah Medical Center, Bnei Brak, Israel. 7. Meuhedet Health Services, Tel Aviv, Israel.
Abstract
OBJECTIVES: Intravenous (IV) infusion of aminobisphosphonates (ABP) induces cytokine release by peripheral blood Vγ9δ2 T cells, resulting in an immediate short-term inflammatory response in up to 50% of patients. We evaluated possible long-term pro-inflammatory effects of IV ABP. METHODS: Retrospective case-series study from one rheumatology specialist's clinic. 2261 electronic charts were reviewed for administration of 'zoledronate' or different brand names of zoledronic acid, and relevant clinical data was retrieved for patients who had received the infusion. RESULTS: Thirteen patients had recieved zoledronate. In six, new-onset or exacerbation of a previous inflammatory/autoimmune disorder was diagnosed within 3 months following infusion. Of these, one patient developed new-onset rheumatoid arthritis (RA), two polymyalgia rheumatica (PMR), two suffered a flare of Crohn's disease-related and aromatase inhibitor-induced arthralgias, and one patient acquired autoimmune hemophilia. Pre-existing malignancy and immediate inflammatory response following zoledronate were more frequent in patients experiencing new or worsening immunologic manifestations (3/6 vs. 0/7, and 5/6 vs. 2/7, respectively). CONCLUSIONS: Intravenous ABP may trigger induction of persistent autoimmune syndromes, especially when accompanied by an immediate adverse reaction or pre-existing malignancy.
OBJECTIVES: Intravenous (IV) infusion of aminobisphosphonates (ABP) induces cytokine release by peripheral blood Vγ9δ2 T cells, resulting in an immediate short-term inflammatory response in up to 50% of patients. We evaluated possible long-term pro-inflammatory effects of IV ABP. METHODS: Retrospective case-series study from one rheumatology specialist's clinic. 2261 electronic charts were reviewed for administration of 'zoledronate' or different brand names of zoledronic acid, and relevant clinical data was retrieved for patients who had received the infusion. RESULTS: Thirteen patients had recieved zoledronate. In six, new-onset or exacerbation of a previous inflammatory/autoimmune disorder was diagnosed within 3 months following infusion. Of these, one patient developed new-onset rheumatoid arthritis (RA), two polymyalgia rheumatica (PMR), two suffered a flare of Crohn's disease-related and aromatase inhibitor-induced arthralgias, and one patient acquired autoimmune hemophilia. Pre-existing malignancy and immediate inflammatory response following zoledronate were more frequent in patients experiencing new or worsening immunologic manifestations (3/6 vs. 0/7, and 5/6 vs. 2/7, respectively). CONCLUSIONS: Intravenous ABP may trigger induction of persistent autoimmune syndromes, especially when accompanied by an immediate adverse reaction or pre-existing malignancy.
Entities:
Keywords:
Aminobisphosphonates; Vγ9δ2 T cells; Zoledronic acid; γδ T cells
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