Long-term effects of amino-bisphosphonates on circulating γδ T cells.
The aim of this study was to explore whether desensitization to the occurrence of the acute-phase response (APR) in patients previously treated with amino-bisphosphonates (N-BPs) is due to a long-lasting reduction in the number of circulating γδ T cells. Circulating lymphocyte subpopulation counts were obtained from 63 patients with postmenopausal or senile osteoporosis at baseline and after 2 days and 12 months of the first intravenous (IV) 5 mg zoledronic acid (ZOL) infusion. At baseline both the proportion and absolute number of circulating γδ T cells were significantly higher in patients who had never used N-BPs vs. previous users, either oral or IV. A typical APR was observed in none of the patients given IV ZOL a year earlier, in 6 (22 %) of the patients previously treated with oral N-BPs, and in 13 (57 %) of the patients naive to any N-BP treatment. In patients naive to N-BPs, a significant reduction in both total lymphocytes and their subsets was observed 2 days after ZOL infusion; all these changes returned to baseline values 1 year later with the exception of γδ T cells, which remained significantly lower in terms of both proportion and absolute number. These results indicate for the first time that both IV and oral N-BP treatments are associated with a long-lasting decrease in circulating γδ T cells, and this may explain the lower incidence of APR in patients previously exposed to N-BPs. Other clinical implications of this sustained effect of N-BPs on immune-regulatory cells might be important.
Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy. maurizio.rossini@univr.it
Maurizio
M
Rossini
Silvano
S
Adami
Ombretta
O
Viapiana
Elena
E
Fracassi
Riccardo
R
Ortolani
Antonio
A
Vella
Roberta
R
Zanotti
Gaia
G
Tripi
Luca
L
Idolazzi
Davide
D
Gatti
D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D000077211:Zoledronic Acid
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid