Osteoporosis International

, Volume 26, Issue 2, pp 499–503 | Cite as

Incidence of ocular side effects with intravenous zoledronate: secondary analysis of a randomized controlled trial

  • D. V. Patel
  • M. Bolland
  • Z. Nisa
  • F. Al-Abuwsi
  • M. Singh
  • A. Horne
  • I. R. Reid
  • C. N. J. McGhee
Original Article



This prospective study showed that the incidence of acute anterior uveitis, confirmed by ophthalmic examination, in patients receiving intravenous zoledronate infusions as part of a randomized controlled trial for fracture prevention is 1.1 %.


We prospectively investigated the incidence of ocular side effects after a single intravenous zoledronate infusion.


In a secondary analysis of a double-blind, placebo-controlled trial in which early post-menopausal women (N = 1054) with normal bone density or osteopenia were randomized to infusion of zoledronate 5 mg (N = 703) or placebo (N = 351), we analyzed significant adverse ocular events occurring within 3 months.


Fourteen participants reported ocular symptoms after the infusion. All were examined by an ophthalmologist and eight were diagnosed with acute anterior uveitis (AAU) and one with sectoral episcleritis. The incidence of AAU and episcleritis was 1.1 % (95 % CI 0.5–2.1) and 0.1 % (95 % CI 0.0–0.7), respectively, in the zoledronate group and 0 % for both conditions in the placebo group (95 % CI 0.0–0.8). The mean time from infusion to symptom onset for AAU was 3 days (range 2–4). Three cases were bilateral. AAU was mild-moderate in seven participants and severe in one. All affected eyes were treated with topical cyclopentolate 1 % (to break, or minimize, posterior synechiae), and intensive, potent, topical corticosteroids with a tapering regime based on treatment response. The mean duration of topical corticosteroid was 26 ± 10 days (range 17–44). The mean, best corrected visual acuity was 20/20 (range 20/20–20/40) at presentation, which remained unchanged after AAU resolution. None of the participants lost vision, and no long-term sequelae were reported at last follow-up (range 3–13 months post-infusion).


Prescribers should inform patients about the possibility of ocular side effects with zoledronate infusions and refer promptly to an ophthalmologist if symptoms develop.


Acute anterior uveitis Bisphosphonate Osteoporosis Zoledronate 


  1. 1.
    Black DM, Delmas PD, Eastell R et al (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–22PubMedCrossRefGoogle Scholar
  2. 2.
    Hosking D, Lyles K, Brown JP et al (2007) Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate. J Bone Miner Res 22:142–8PubMedCrossRefGoogle Scholar
  3. 3.
    Lyles KW, Colon-Emeric CS, Magaziner JS et al (2007) Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 357:1799–809PubMedCrossRefGoogle Scholar
  4. 4.
    Reid IR, Gamble GD, Mesenbrink P et al (2010) Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab 95:4380–7PubMedCrossRefGoogle Scholar
  5. 5.
    Sauty A, Pecherstorfer M, Zimmer-Roth I et al (1996) Interleukin-6 and tumor necrosis factor alpha levels after bisphosphonates treatment in vitro and in patients with malignancy. Bone 18:133–9PubMedCrossRefGoogle Scholar
  6. 6.
    Kunzmann V, Bauer E, Wilhelm M (1999) Gamma/delta T-cell stimulation by pamidronate. N Engl J Med 340:737–8PubMedCrossRefGoogle Scholar
  7. 7.
    Durnian JM, Olujohungbe A, Kyle G (2005) Bilateral acute uveitis and conjunctivitis after zoledronic acid therapy. Eye 19:221–2PubMedCrossRefGoogle Scholar
  8. 8.
    Woo TCS, Joseph DJ, Wilkinson R (2006) Serious ocular complications of zoledronate. Clin Oncol R Coll Radiol 18:545–6PubMedCrossRefGoogle Scholar
  9. 9.
    Kaur H, Uy C, Kelly J et al (2011) Orbital inflammatory disease in a patient treated with zoledronate. Endocr Pract 17:e101–3PubMedCrossRefGoogle Scholar
  10. 10.
    Patel DV, Horne A, House M et al (2013) The incidence of acute anterior uveitis after intravenous zoledronate. Ophthalmology 120:773–6PubMedCrossRefGoogle Scholar
  11. 11.
    Jabs DA, Nussenblatt RB, Rosenbaum JT et al (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol 140(3):509–16PubMedCrossRefGoogle Scholar
  12. 12.
    Aurich-Barrera B, Wilton L, Harris S et al (2006) Ophthalmological events in patients receiving risedronate: summary of information gained through follow-up in a prescription-event monitoring study in England. Drug Saf 29:151–60PubMedCrossRefGoogle Scholar
  13. 13.
    French DD, Margo CE (2008) Postmarketing surveillance rates of uveitis and scleritis with bisphosphonates among a national veteran cohort. Retina 28:889–93PubMedCrossRefGoogle Scholar
  14. 14.
    Fietta P, Manganelli P, Lodigiani L (2003) Clodronate induced uveitis. Ann Rheum Dis 62:378PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    El Saghir NS, Otrock ZK, Bleik JH (2005) Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer. BMC Cancer 5:156PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Richards JC, Wiffen SJ (2006) Corneal graft rejection precipitated by uveitis secondary to alendronate sodium therapy. Cornea 25:1100–1PubMedCrossRefGoogle Scholar
  17. 17.
    Macarol V, Fraunfelder FT (1994) Pamidronate disodium and possible ocular adverse drug reactions. Am J Ophthalmol 118:220–4PubMedCrossRefGoogle Scholar
  18. 18.
    Fraunfelder FW, Fraunfelder FT (2003) Bisphosphonates and ocular inflammation. N Engl J Med 348:1187–8PubMedCrossRefGoogle Scholar
  19. 19.
    Wakefield D, Gray P, Chang J et al (2010) The role of PAMPs and DAMPs in the pathogenesis of acute and recurrent anterior uveitis. Br J Ophthalmol 94:271–4PubMedCrossRefGoogle Scholar
  20. 20.
    Roelofs AJ, Jauhiainen M, Monkkonen H et al (2009) Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. Br J Haematol 144:245–50PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version. www.OpenEpi.com, updated 2013/04/06. Accessed 13 Jan 2014
  22. 22.
    Graphpad Quickcalcs http://graphpad.com/quickcalcs/NNT1.cfm. Accessed 14 Jan 2014

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2014

Authors and Affiliations

  • D. V. Patel
    • 1
  • M. Bolland
    • 2
  • Z. Nisa
    • 2
  • F. Al-Abuwsi
    • 2
  • M. Singh
    • 2
  • A. Horne
    • 2
  • I. R. Reid
    • 2
  • C. N. J. McGhee
    • 1
  1. 1.Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Medicine, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand

Personalised recommendations