Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women.

摘要

The acute-phase response (APR) to aminobisphosphonates is triggered by activation of gammadelta T cells, resulting in pro-inflammatory cytokine release. Statins prevent aminobisphosphonate-induced gammadelta T cell activation in vitro, raising the possibility that statins might prevent the APR in vivo. The objective of this study was to determine whether fluvastatin prevents the APR to zoledronic acid in post-menopausal women. A double-blind, randomised, placebo-controlled study was conducted in 60 healthy, post-menopausal, female volunteers (mean age 60.6 +/- 4.0). Volunteers received 5 mg zoledronic acid by intravenous infusion, and either three times 40 mg fluvastatin (0 hr, 24 hr and 48 hr), 40 mg fluvastatin (0 hr) plus placebo (24 hr and 48 hr), or placebo (0 hr, 24 hr and 48 hr), orally. Post-infusion symptoms were assessed by questionnaire. Changes in gammadelta T cell levels, pro-inflammatory cytokines (TNFalpha, IFNgamma, IL-6) and C-reactive protein (CRP) were measured in peripheral blood at various time-points post-infusion. Zoledronic acid administration triggered increased serum levels of TNFalpha, IFNgamma, IL-6 and CRP in >/=70% of study volunteers, whilst characteristic APR symptoms were observed in >50% of participants. Zoledronic acid also induced a transient fall in circulating Vgamma9Vdelta2 T cell levels at 48 hr, consistent with Vgamma9Vdelta2 T cell activation. Concurrent fluvastatin administration did not prevent zoledronic acid-induced cytokine release, alter circulating Vgamma9Vdelta2 T cell levels, nor diminish the frequency or severity of APR symptoms. In conclusion, intravenous zoledronic acid induced pro-inflammatory cytokine release and APR symptoms in the majority of study participants, which was not prevented by co-administration of fluvastatin.