Circulating γδ T cells and the risk of acute-phase response after zoledronic acid administration

Abstract

The use of intravenous nitrogen-containing bisphosphonates (N-BPs) is associated with the appearance of an acute phase response (APR) in a proportion of the patients for reasons that are poorly understood. The APR was attributed to the indirect activation of gd T cells with the release of interferon-g and tumor necrosis factor (TNF). Forty patients with postmenopausal or senile osteoporosis (age range ¼ 53-91 years) never previously treated with intravenous (iv) bisphosphonate, received a single 5-mg zoledronic acid (ZOL) iv infusion over 15 minutes. White blood cells were counted and analyzed with an automated hematology analyzer (ADVIA 2120i Siemens, New York, USA) and by flow cytometer (BD FACSCanto, Becton Dickinson). The occurrence of APR was defined by the occurrence of fever (>37 8C) during the next 2 days. Forty-two percent of patients (17 of 40) receiving the infusion of ZOL experienced an APR. Compared with the others they were younger (69 AE 7 years versus 74 AE 8 years; p ¼ 0.06), and both the proportion and absolute number of gd T cells were significant higher ( p ¼ 0.02 and p ¼ 0.013, respectively). Nonsignificant differences were found between the two groups for white blood cells and for the other circulating lymphocyte subpopulations. Age was inversely correlated with circulating gd T cells (p ¼ 0.003) but the difference between the two groups in circulating gd T cells persisted for age-adjusted values and vice versa. In conclusion, the results of this study indicate that the number of circulating gd T cells, together with age, are important determinant of the occurrence of APR after intravenous infusion of ZOL and possibly of any other N-BPs. ß

Safety issues and adverse reactions with osteoporosis management

“…The incidence and severity of APR decreases after the subsequent infusions and are clearly related to age and possibly vitamin D deficiency [14] Recently, it was proposed that nitrogencontaining BPs might act as non-peptide phosphoantigens, capable of binding to γδT cells [15] with subsequent release of pro-inflammatory cytokines such IL-6, TNF-α, and IFN-γ [16]. The lower incidence of APR with advancing age was clearly associated with an age-related decrease in γδT cells as low as 3% below threshold where the appearance of APR is quite unlikely [17].…”

Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis

“…Knowing that ZA is myelotoxic 12 and has effects on the number of circulating leukocytes (acutely and chronically) 20,21 we performed haematological analysis throughout the experimental protocol. Each week, beginning on the 6th day of the first dose of ZA, 2 mL of blood (retro-orbital plexus) was collected.…”

The Association between Fever and Prognosis in Lung Cancer Patients with Bone Metastases Receiving Zoledronic Acid

“…In this pathway, isopentenyl diphosphate and dimethylallyl diphosphate accumulate in monocytes when this enzyme is blocked, resulting in the activation of adjacent γδ T cells with the release of interferon-γ and TNF. In patients treated with zoledronic acid, the proportion and absolute numbers of γδ T cells were significantly higher in those who experienced APR than in those who did not [21]. …”