Bisphosphonate-induced orbital inflammation: more common than once thought?

  • L.K. ChehadeEmail author
  • D. Curragh
  • D. Selva
Case Report


To report two cases of bisphosphonate-induced orbital inflammation, discuss the clinic-radiological features and management options, and highlight the increasing frequency of an association previously considered extremely rare. A retrospective review of two cases presenting to our department, and review of the literature reporting this association. Two new cases of bisphosphonate-induced orbital inflammation were added to the literature. The first occurred in the context of a risedronate re-challenge, and the second with zoledronic acid. Both cases were managed successfully with topical steroids. Clinicians prescribing bisphosphonates, particularly for the first time, should be aware of the increasingly reported association with orbital inflammation. The presence of suggestive clinical features should prompt urgent referral to an ophthalmologist for appropriate management.


Bisphosphonate Orbital inflammation Risedronate Zoledronic acid 


Compliance with ethical standards

Conflict of interest



The content of this submission has not been published or submitted for publication elsewhere.

Declaration of Helsinki

The report adhered to the ethical principles outlined in the 2013 amended Declaration of Helsinki.


  1. 1.
    NICE (2017) TA464: bisphosphonates for treating osteoporosis. National Institute for Health and Care Excellence, LondonGoogle Scholar
  2. 2.
    Mbekeani JN, Slamovits TL, Schwartz BH, Sauer HL (1999) Ocular inflammation associated with alendronate therapy. Arch Ophthalmol 117(6):837–838Google Scholar
  3. 3.
    Umunakwe OC, Herren D, Kim SJ, Kohanim S (2017) Diffuse ocular and orbital inflammation after zoledronate infusion-case report and review of the literature. Digit J Ophthalmol 23(4):18–21CrossRefGoogle Scholar
  4. 4.
    Lefebvre DR, Mandeville JT, Yonekawa Y, Arroyo JG, Torun N, Case Series FSKA (2016) Review of bisphosphonate-associated orbital inflammation. Ocul Immunol Inflamm 24(2):134–139Google Scholar
  5. 5.
    Pirbhai A, Rajak SN, Goold LA, Cunneen TS, Wilcsek G, Martin P et al (2015) Bisphosphonate-induced orbital inflammation: a case series and review. Orbit (Amsterdam, Netherlands) 34(6):331–335Google Scholar
  6. 6.
    Ryan PJ, Sampath R (2001) Idiopathic orbital inflammation following intravenous pamidronate. Rheumatology (Oxford, England) 40(8):956–957CrossRefGoogle Scholar
  7. 7.
    Subramanian PS, Kerrison JB, Calvert PC, Miller NR (2003) Orbital inflammatory disease after pamidronate treatment for metastatic prostate cancer. Arch Ophthalmol 121(9):1335–1336CrossRefGoogle Scholar
  8. 8.
    Phillips PM, Newman SA (2008) Orbital inflammatory disease after intravenous infusion of zoledronate for treatment of metastatic renal cell carcinoma. Arch Ophthalmol (Chicago, Ill : 1960) 126(1):137–139CrossRefGoogle Scholar
  9. 9.
    Sharma NS, Ooi JL, Masselos K, Hooper MJ, Francis IC (2008) Zoledronic acid infusion and orbital inflammatory disease. N Engl J Med 359(13):1410–1411CrossRefGoogle Scholar
  10. 10.
    Seth A, Anderson DP, Albiani DA, Barton JJ (2009) Orbital inflammation and optic neuropathy with zoledronic acid for metastatic prostate cancer. Can J Ophthalmol 44(4):467–468CrossRefGoogle Scholar
  11. 11.
    Missotten G, Verheezen Y (2010) Orbital inflammation after use of zoledronic acid for metastasized prostate carcinoma. Bull Soc Belge Ophtalmol 315:23–24Google Scholar
  12. 12.
    Procianoy F, Procianoy E (2010) Orbital inflammatory disease secondary to a single-dose administration of zoledronic acid for treatment of postmenopausal osteoporosis. Osteoporos Int 21(6):1057–1058CrossRefGoogle Scholar
  13. 13.
    Yang EB, Birkholz ES, Lee AG (2010) Another case of bisphosphonate-induced orbital inflammation. J Neuroophthalmol 30(1):94–95CrossRefGoogle Scholar
  14. 14.
    Yeo J, Jafer AK (2010) Zolendronate associated inflammatory orbital disease. N Z Med J 123(1323):50–52Google Scholar
  15. 15.
    Kaur H, Uy C, Kelly J, Moses AM (2011) Orbital inflammatory disease in a patient treated with zoledronate. Endocr Pract 17(4):e101–e103CrossRefGoogle Scholar
  16. 16.
    Ortiz-Perez S, Fernandez E, Molina JJ, Sanchez-Dalmau B, Navarro M, Corretger X et al (2011) Two cases of drug-induced orbital inflammatory disease. Orbit (Amsterdam, Netherlands) 30(1):37–39Google Scholar
  17. 17.
    Schwab P, Harmon D, Bruno R, Fraunfelder FW, Hyunchung Kim D (2012) A 55-year-old woman with orbital inflammation. Arthritis Care Res 64(11):1776–1782CrossRefGoogle Scholar
  18. 18.
    Boni C, Kordic H, Chaloupka K (2013) Bisphosphonate-associated orbital inflammatory disease and uveitis anterior--a case report and review. Klin Monbl Augenheilkd 230(4):367–369CrossRefGoogle Scholar
  19. 19.
    Peterson JD, Bedrossian EH Jr (2012) Bisphosphonate-associated orbital inflammation--a case report and review. Orbit (Amsterdam, Netherlands) 31(2):119–123Google Scholar
  20. 20.
    Vora MM, Rodgers IR, Uretsky S (2014) Nitrogen bisphosphonate-induced orbital inflammatory disease: gamma delta T cells--a report and review of 2 cases. Ophthalmic Plast Reconstr Surg 30(4):e84–e85CrossRefGoogle Scholar
  21. 21.
    Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M (2000) Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma. Blood 96(2):384–392Google Scholar
  22. 22.
    Mbekeani JN, Slamovits TL, Schwartz BH, Sauer HL (1999) Ocular inflammation associated with alendronate therapy. Arch Ophthalmol 117(6):837–838Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2019

Authors and Affiliations

  1. 1.South Australian Institute of OphthalmologyUniversity of AdelaideAdelaideAustralia
  2. 2.Department of OphthalmologyThe Royal Adelaide HospitalAdelaideAustralia

Personalised recommendations