International Journal of Clinical Pharmacy

, Volume 36, Issue 6, pp 1277–1281 | Cite as

Effect of intravenous hydration in patients receiving bisphosphonate therapy

  • David Attivi
  • Gaétan Kosmalski
  • Claire Zeghmouli
  • Stéphane GibaudEmail author
Research Article


Background Patients with advanced cancers are at high risk for bone metastases, which accelerate bone resorption and skeletal complications. Therefore, bisphosphonates, which are strong inhibitors of bone resorption, are widely used to prevent pathological fractures, pain and tumour-induced hypercalcaemia. Intravenous infusion of bisphosphonate is associated with dose- and infusion rate-dependent adverse renal effects. Objective The present study investigated the effect of hydration on bisphosphonate efficacy and safety. Settings The 600-bed CHOV Hospital (Neufchâteau, France) and the Université de Lorraine (Nancy, France). Methods Patients who received pamidronate or zoledronic acid treatments were identified: 50 patients [16 of whom were hydrated and 34 of whom were non-hydrated]. Data on serum calcium levels, creatinine clearance and clinical tolerance were collected. Main outcome measure The impact of hydration on these parameters was analysed between day 1 and day 7. Results Bisphosphonate normalized calcaemia and hydration did not induce further reduction of calcium levels. Patient kidneys were significantly preserved by hydration in both groups (median clearance: +6.2 %), whereas dehydrated patients had lower creatinine clearance (median clearance: −1.1 %). Hydration did not influence other clinical or biological parameters tested. Conclusion Hydration plays an important role in the treatment of hypercalcaemia by pamidronate and zoledronic acid: it enhances kidney protection (i.e., creatinine clearance).


Biphosphonate Cancer Hypercalcaemia Renal toxicity Side effect 



We thank all physicians and nurses who helped us for this study.



Conflicts of interest



  1. 1.
    Stewart A. Hypercalcemia associated with cancer. N Engl J Med. 2005;352:373–9.PubMedCrossRefGoogle Scholar
  2. 2.
    U.S. Food and Drug Administration. Zoledronic acid for osteoporosis (marketed as reclast). In: FDA editor. Drug safety newsletter, vol 2(2). Silver Spring: FDA; 2009. p. 16–8.Google Scholar
  3. 3.
    Actonel®—Prescribing information. 2013. Accessed 10 April 2014.
  4. 4.
    Boniva®—Prescribing information. 2010. Accessed 10 April 2014.
  5. 5.
    Fosamax®—Prescribing information. 2013. Accessed 10 April 2014.
  6. 6.
    Reclast®—Prescribing information. 2013. Accessed 10 April 2014.
  7. 7.
    Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, et al. Collapsing focal segmental glomerulosclerosis following treatment with high dose pamidronate. J Am Soc Nephrol. 2001;12:1164–72.PubMedGoogle Scholar
  8. 8.
    Tralongo P, Repetto L, Di Mari A, Mauceri G, Bollina R, Ferrau F, et al. Safety of long-term administration of bisphosphonates in elderly cancer patients. Oncology. 2004;67:112–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Ali SM, Esteva FJ, Hortobagyi G, Harvey H, Seaman J, Knight R, et al. Safety and efficacy of bisphosphonates beyond 24 months in cancer patients. J Clin Oncol. 2001;19:3434–7.PubMedGoogle Scholar
  10. 10.
    Lumachi F, Brunello A, Roma A, Basso U. Cancer-induced hypercalcemia. Anticancer Res. 2009;29:1551–5.PubMedGoogle Scholar
  11. 11.
    LeGrand SB. Narrative review: furosemide for hypercalcemia: an unproven yet common practice. Ann Intern Med. 2008;149:259–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Fisken RA, Heath DA, Bold AM. Hypercalcaemia—a hospital survey. QJM-Int J Med. 1980;49:405–18.Google Scholar
  13. 13.
    Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int. 2008;19:733–59.PubMedCrossRefGoogle Scholar
  14. 14.
    Luhe A, Kunkele KP, Haiker M, Schad K, Zihlmann C, Bauss F, et al. Preclinical evidence for nitrogen-containing bisphosphonate inhibition of farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety. Toxicol In Vitro. 2008;22:899–909.PubMedCrossRefGoogle Scholar
  15. 15.
    Bounameaux HM, Schifferli J, Montani JP, Jung A, Chatelanat F. Renal failure associated with intravenous diphosphonates. Lancet. 1983;1:471.PubMedCrossRefGoogle Scholar
  16. 16.
    Fleisch H. Bisphosphonates: mechanisms of action. Endocr Rev. 1998;19:80–100.PubMedCrossRefGoogle Scholar
  17. 17.
    Green JR, Seltenmeyer Y, Jaeggi KA, Widler L. Renal tolerability profile of novel, potent bisphosphonates in two short-term rat models. Pharmacol Toxicol. 1997;80:225–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Markowitz GS, Fine PL, Stack JI, Kunis CL, Radhakrishnan J, Palecki W, et al. Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Kidney Int. 2003;64:281–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Bodmer M, Amico P, Mihatsch MJ, Haschke M, Kummer O, Krahenbuhl S, et al. Focal segmental glomerulosclerosis associated with long-term treatment with zoledronate in a myeloma patient. Nephrol Dial Transplant. 2007;22:2366–70.PubMedCrossRefGoogle Scholar
  20. 20.
    Henley D, Kaye J, Walsh J, Cull G. Symptomatic hypocalcaemia and renal impairment associated with bisphosphonate treatment in patients with multiple myeloma. Intern Med J. 2005;35:726–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Solomon R, Werner C, Mann D, D’Elia J, Silva P. Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med. 1994;331:1416–20.PubMedCrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Authors and Affiliations

  • David Attivi
    • 1
  • Gaétan Kosmalski
    • 1
  • Claire Zeghmouli
    • 1
  • Stéphane Gibaud
    • 1
    • 2
    • 3
    Email author
  1. 1.CHOV, Site de Neufchâteau, PharmacieNeufchâteauFrance
  2. 2.Faculté de Pharmacie, Equipe CITHEFOR (EA3452)Université de LorraineNancyFrance
  3. 3.Faculté de Pharmacie, Pharmacie CliniqueUniversité de LorraineNancyFrance

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