Acute effects of intravenous administration of pamidronate in patients with osteoporosis

Abstract

We investigated acute effects of intermittent large dose bisphosphonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 microM) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.

Keywords: Acute-Phase Reaction; Diphosphonates; Osteoporosis; Pamidronate.

Fig. 1

The acute effect of pamidronate on CRP (A) and ESR (B). CRP increased significantly for three consecutive days (P=0.026) whereas ESR increased only marginally (P=0.312). Statistical analysis was carried out using repeated measure ANOVA.

Fig. 2

Effects of pamidronate on serum level of TNF-α (A), IL-6 (B) and IFN-γ (C). All serum levels of cytokines were elevated at 48 hr after infusion of pamidronate (30 mg). ^*P=0.009; ^†P=0.014; ^‡P=0.035.