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J Bone Miner Metab (2014) 32:7277 DOI 10.1007/s00774-013-0467-4
ORIGINAL ARTICLE
Markers of inammation after zoledronic acid redosing
Antonis Sykiotis Garyphallia Papaioannou Jordan Mavropoulos
Maria Triantaphyllopoulou Fotini Papandroulaki Vassiliki Ktena
Stavroula Thanou Argyris Pardalakis Aikaterini Kaltsa Helen Karga
Received: 5 November 2012 / Accepted: 26 March 2013 / Published online: 21 May 2013 The Japanese Society for Bone and Mineral Research and Springer Japan 2013
Abstract The symptoms of acute phase response (APR) following the rst infusion of zoledronic acid (ZA) are attenuated after re-administration. We investigated the reasons for this attenuation, focusing on the changes in several hormones, bone markers and markers of inammation occurring after the second ZA injection in patients who had experienced a severe APR after their rst ZA infusion. Twenty-two postmenopausal women with osteoporosis and severe symptoms of APR following the rst ZA infusion were included in the study (group A1). A year later, the same women (possibly with a residual activity of ZA) were subjected to ZA re-administration (group A2). Urine NTx (uNTx), white blood cells, parathyroid hormone, serum calcium, phosphorus and several serum markers of inammation were measured before (0) and at 1 and 2 days following the rst as well as the second infusion. In group A1, the APR was associated with a signicant increase in serum C-reactive protein (CRP), high-sensitive interleukin 6 (hsIL-6), high-sensitive tumor necrosis factor alpha (hsTNF-a) and cortisol within 24 h after the infusion. The majority of the patients in group A2 did not experience an APR and serum calcium, phosphorus, CRP, hsIL-6, hsTNF-a, and cortisol remained essentially unchanged throughout the study. In group A2, on day 0, the uNTx were signicantly lower than in group A1. In group A1 the uNTx decreased by 69 and 78 % from baseline on days 1 and 2, whereas in group A2, they decreased by 48 and 53 % (p \ 0.01), respectively. A positive correlation
was found between the degree of uNTx decline from the baseline levels (D-uNTx) and hsTNF-a and between D-uNTx and CRP. The D-uNTx, reecting the osteoclast-mediated bone resorption, may play some role in the APR appearance, although it must be excluded if the relationships of the changes between uNTx and hsTNF-a/CRP are coincidental effects and not causal.
Keywords Zoledronic acid Redosing Cytokines