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No Effect of Rosuvastatin in the Zoledronate-Induced Acute-Phase Response

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The acute-phase response (APR) is frequently observed in patients treated with intravenous (iv) zoledronate (ZOL). We investigated whether a short course of rosuvastatin (ROSU) could attenuate the ZOL-induced APR through blocking the mevalonate pathway at a proximal level. Twenty-eight osteoporotic postmenopausal women with no prior bisphosphonate use (mean age 65.3 ± 1.9 years) were subjected to ZOL iv infusion. Patients were randomly assigned into either a ROSU+ group (n = 12), which received ROSU 10 mg/day starting 5 days before the infusion of ZOL for a total period of 11 days, or a ROSU− group (n = 16), which did not receive ROSU. The visual analog pain scale (VAS) for musculoskeletal symptoms and body temperature was used to define clinically APR. In addition, white blood cell (WBC) count, leukocytic subpopulations, and C-reactive protein (CRP) were obtained before and 48 h following the infusion. Seven (58.3%) patients in the ROSU+ group and 13 (81.3%) in the ROSU− group experienced APR (P = not significant). No difference was found in fever and VAS measurements. CRP and granulocytes increased significantly in both groups; WBC count increased, while lymphocytes and eosinophils decreased significantly only in the ROSU− group. In a post hoc analysis of only patients with an APR, all laboratory parameters exhibited a similar significant change solely within the ROSU− group. In conclusion, our data suggest that a short course of ROS at this dose cannot prevent the ZOL-induced APR among osteoporotic women. Milder changes in acute-phase laboratory parameters in ROSU+ patients suggest that studies with higher doses may be warranted.

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References

  1. Reid IR, Gamble GD, Mesenbrink P, Lakatos P, Black DM (2010) Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab 95:4380–4387

    Article  PubMed  CAS  Google Scholar 

  2. Adami S, Bhalla A, Dorizzi R, Montesanti F, Rosini S, Salvagno G, Lo Cascio V (1987) The acute-phase response after bisphosphonate administration. Calcif Tissue Int 41:326–331

    Article  PubMed  CAS  Google Scholar 

  3. Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Lowik CW, Papapoulos SE (1995) Interleukin-6 and the acute phase response during treatment of patients with Paget’s disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate. J Bone Miner Res 10:956–962

    Article  PubMed  CAS  Google Scholar 

  4. Thiebaud D, Sauty A, Burckhardt P, Leuenberger P, Sitzler L, Green JR, Kandra A, Zieschang J, Ibarra de Palacios P (1997) An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int 61:386–392

    Article  PubMed  CAS  Google Scholar 

  5. Harinck HI, Papapoulos SE, Blanksma HJ, Moolenaar AJ, Vermeij P, Bijvoet OL (1987) Paget’s disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). Br Med J (Clin Res Ed) 295:1301–1305

    Article  CAS  Google Scholar 

  6. van Beek E, Pieterman E, Cohen L, Löwik C, Papapoulos S (1999) Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun 264:108–111

    Article  PubMed  Google Scholar 

  7. van Beek E, Löwik C, van der Pluijm G, Papapoulos S (1999) The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants in vitro: a clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res 14:722–729

    Article  Google Scholar 

  8. Roelofs AJ, Thompson K, Gordon S, Rogers MJ (2006) Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res 12:6222–6230

    Article  Google Scholar 

  9. Roelofs AJ, Jauhiainen M, Mönkkönen H, Rogers MJ, Mönkkönen J, Thompson K (2009) Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. Br J Haematol 144:245–250

    Article  PubMed  Google Scholar 

  10. Thompson K, Rogers MJ (2004) Statins prevent bisphosphonate-induced gdT-cell proliferation and activation in vitro. J Bone Miner Res 19:278–288

    Article  PubMed  CAS  Google Scholar 

  11. Srivastava T, Haney CJ, Alon US (2009) Atorvastatin may have no effect on acute phase reaction in children after intravenous bisphosphonate Infusion. J Bone Miner Res 24:334–337

    Article  PubMed  Google Scholar 

  12. Bijvoet OL, Frijlink WB, Jie K, van der Linden H, Meijer CJ, Mulder H, van Paassen HC, Reitsma PH, te Velde J, de Vries E, van der Wey JP (1980) APD in Paget’s disease of bone. Role of the mononuclear phagocyte system? Arthritis Rheum 23:1193–1204

    Article  PubMed  CAS  Google Scholar 

  13. Bertoldo F, Pancheri S, Zenari S, Boldini S, Giovanazzi B, Zanatta M, Valenti MT, Carbonare LD, Lo Cascio V (2010) Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion. J Bone Miner Res 25:447–454

    Article  PubMed  CAS  Google Scholar 

  14. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822

    Article  PubMed  CAS  Google Scholar 

  15. Saag K, Lindsay R, Kriegman A, Beamer E, Zhou W (2007) A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone 40:1238–1243

    Article  PubMed  CAS  Google Scholar 

  16. Dunford JE, Thompson K, Coxon FP, Luckman SP, Hahn FM, Poulter CD, Ebetino FH, Rogers MJ (2001) Structure–activity relationships for inhibition of farnesyl diphosphate synthase in vitro and inhibition of bone resorption in vivo by nitrogen-containing bisphosphonates. J Pharmacol Exp Ther 296:235–242

    PubMed  CAS  Google Scholar 

  17. Pérez-Castrillón JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Dueñas A (2007) Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 99:903–905

    Article  PubMed  Google Scholar 

  18. Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, Kucukazman M, Dal K, Hokkaomeroglu MS, Yavuz BB, Tutal E (2009) Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther 23:295–299

    Article  PubMed  CAS  Google Scholar 

  19. Yoon SS, Dillon CF, Carroll M, Illoh K, Ostchega Y (2010) Effects of statins on serum inflammatory markers: the U.S. National Health and Nutrition Examination Survey 1999–2004. J Atheroscler Thromb 17:1176–1182

    PubMed  CAS  Google Scholar 

  20. Thompson K, Keech F, McLernon DJ, Vinod K, May RJ, Simpson WG, Rogers MJ, Reid DM (2010) Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women. Bone. doi:10.1016/j.bone.2010.10.177

  21. Staal A, Frith JC, French MH, Swartz J, Güngör T, Harrity TW, Tamasi J, Rogers MJ, Feyen JH (2003) The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity. J Bone Miner Res 18:88–96

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, 3 Kanellopoulou St, 115 25, Athens, Greece

    Polyzois Makras

  2. Department of Endocrinology, 424 Military Hospital, Thessaloniki, Greece

    Athanasios D. Anastasilakis

  3. Second Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece

    Stergios A. Polyzos

  4. First Department of Orthopaedics, 424 Military Hospital, Thessaloniki, Greece

    Ilias Bisbinas

  5. Department of Rheumatology, 424 Military Hospital, Thessaloniki, Greece

    Grigorios T. Sakellariou

  6. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands

    Socrates E. Papapoulos

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  1. Polyzois Makras
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  2. Athanasios D. Anastasilakis
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  3. Stergios A. Polyzos
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  4. Ilias Bisbinas
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  5. Grigorios T. Sakellariou
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  6. Socrates E. Papapoulos
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Correspondence to Polyzois Makras.

Additional information

S. Papapoulos has received consulting fees from the Alliance for Better Bone Health, Amgen, Merck & Co., Novartis, and Roche/GSK.

All other authors have stated that they have no conflict of interest.

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Makras, P., Anastasilakis, A.D., Polyzos, S.A. et al. No Effect of Rosuvastatin in the Zoledronate-Induced Acute-Phase Response. Calcif Tissue Int 88, 402–408 (2011). https://doi.org/10.1007/s00223-011-9468-2

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  • DOI: https://doi.org/10.1007/s00223-011-9468-2

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