Inflammopharmacology

, Volume 25, Issue 6, pp 665–671 | Cite as

Immune-mediated syndromes following intravenous bisphosphonate therapy

Original Article
First Online:
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Accepted:

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.

Keywords

γδ T cells Vγ9δ2 T cells Aminobisphosphonates Zoledronic acid 
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Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Noa Markovits
    • 2
    • 5
  • Ronen Loebstein
    • 2
    • 5
  • Ilan Bank
    • 1
    • 3
    • 4
    • 5
  1. 1.Autoimmunity Institute and Laboratory for ImmunoregulationChaim Sheba Medical CenterTel HashomerIsrael
  2. 2.Institute of Clinical PharmacologyChaim Sheba Medical CenterTel HashomerIsrael
  3. 3.Department of MedicineMaayenei Hayeshuah Medical CenterBnei BrakIsrael
  4. 4.Meuhedet Health ServicesTel AvivIsrael
  5. 5.Sackler School of MedicineTel Aviv UniversityTel AvivIsrael

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