Acute phase response after administration of intravenous phamidronate

초록

The acute phase response of bisphonate is notorious. Increase of cytokines in acute phase response to bisphosphonate was reported mostly in the treatment for cancer and only few studies were for the osteoporosis.The aim of this study is to evaluate cytokine change in acute phase response and bone metabolism shortly after single dose of intravenous pamidronate. Twenty-one patients with osteoporosis and rheumatism without prior bisphosphonate or immunosuppressant use were selected. They were given 30 mg of IV pamidronate and the venous blood samples were taken before and 48 hours after the infusion. Serum level of IL-6, TNF-α and c-telopeptide (CTX) were measured with an immunoenzymetric assay (serum IL-6 and TNF-α: R&D Systems, Minneapolis, Minn., USA; serum CTX: Nordic Bioscience Diagnostics, Bolden, UK). The real-time RT-PCR quantified the expression of the IL-6, TNF-α and interferon (IFN)- in cDNA from peripheral blood mononuclear cells. There was a continued increase in the mean level of CRP after the treatment and each rise for 3 consecutive days were all significant (p = 0.000). ESR seemed to increase at 48 hours but its rise was not so significant (p = 0.057). The leukocyte count slightly decreased from 6,763 /㎕ ± 1778 at baseline to 6,352 /㎕ ± 2212 at 48 hours (p = 0.31). Serum calcium level also tended to decrease after the treatment (9.26 mg/dL ± 0.38 at baseline, 9.04 mg/dL ± 0.48 at 48 hours, p = 0.2). Serum TNF- α increased significantly (p = 0.031) and its increment strongly correlated with that of CRP (p=0.023). Serum IL-6 increased marginally. Serum CTX decreased rapidly after the treatment (p = 0.009). This study showed that acute phase response occurred in intermittent large dose for osteoporosis. The rapid decrease of serum CTX implies that osteoclastic activity is suppressed as early as 48 hours after the treatment.