Correspondence
Zoledronic Acid Infusion and Orbital Inflammatory Disease
N Engl J Med 2008; 359:1410-1411September 25, 2008
- Article
To the Editor:
Bisphosphonates are being used increasingly for the prevention and treatment of osteoporosis, hypercalcemia of malignant disease, and other disorders of bone metabolism. Known ocular complications of bisphosphonates include conjunctivitis, anterior uveitis, episcleritis, and scleritis.1
A 57-year-old man presented with a 4-day history of increasing orbital pain and swelling in the right eye. Three days before the onset of symptoms, he had received an infusion of zoledronic acid bisphosphonate for spontaneous osteonecrosis of the knee. His medical history was otherwise unremarkable.
On examination, his visual acuity was 20/60 in his right eye (corrected to 20/16 with the use of a pinhole occluder) and 20/16 in his left eye. There was marked orbital swelling and 2 mm of proptosis in the right eye on Luedde proptometry.2 His right-eye movements were reduced in all directions. He had conjunctival chemosis and inferior corneal punctate erosions in the right eye (Figure 1Figure 1
Conjunctival Chemosis and Proptosis of the Right Eye on Initial Presentation.), with a subtle, relative afferent pupillary defect.An orbital computed tomographic scan showed extensive preseptal and postseptal fat stranding with proptosis in the right eye (Figure 2Figure 2
Orbital CT Scan Showing Extensive Preseptal and Postseptal Fat Stranding and Proptosis in the Right Eye.). There was no orbital collection or sinus disease. Despite high-dose intravenous antibiotic therapy for 5 days, there was no improvement.A diagnosis of orbital inflammatory disease due to bisphosphonate infusion was made. Treatment with intravenous pulse methylprednisolone was initiated, with immediate improvement. After three doses, the patient's pain had resolved completely and the swelling had improved markedly. He was discharged while receiving decreasing doses of oral prednisone, and his condition continued to improve.
To our knowledge, there have been only three previously reported cases of orbital inflammatory disease due to bisphosphonates, and in each case, the associated agent was intravenous pamidronate.3,4 In all cases, the onset of ocular pain and swelling occurred within 6 days after the bisphosphonate infusion, and these symptoms responded rapidly to corticosteroid therapy.
The mechanisms of orbital inflammatory disease due to bisphosphonates are uncertain. Bisphosphonates may stimulate the release of acute-phase reactants and cytokines, including interleukin-1 and interleukin-6.5 The release of these cytokines with extraocular muscle inflammation might be the mechanism in orbital inflammatory disease.3
Physicians should be aware of this rare complication of bisphosphonates. We recommend taking a thorough history, with specific questions about recent bisphosphonate therapy, for all patients presenting with symptoms of orbital inflammatory disease. Bisphosphonate infusions should be used with caution, or avoided altogether, in patients with acute ocular inflammation or a history of inflammatory eye disease or uveitis.
Neil S. Sharma, M.B., B.S., M.P.H.
Ju-Lee Ooi, M.B., B.S., M.P.H.
Sydney Eye Hospital, Sydney, NSW 2000, AustraliaKatherine Masselos, M.B., B.S.
University of New South Wales, Sydney, NSW 2033, AustraliaMichael J. Hooper, M.D.
University of Sydney, Sydney, NSW 2006, AustraliaIan C. Francis, M.B., B.S., Ph.D.
Prince of Wales Hospital, Sydney, NSW 2031, Australia
iancfrancis@gmail.com Dr. Hooper reports receiving consulting and lecture fees from Merck, Novartis, and AstraZeneca and lecture fees from Servier. No other potential conflict of interest relevant to this letter was reported.
5 References1
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Full Text | Web of Science | Medline
- Citing Articles (8)
Citing Articles
1
Kory H. Kitagawa, Marcelle Grassi. (2011) Zoledronic acid–induced cutaneous B-cell pseudolymphoma. Journal of the American Academy of Dermatology 65:6, 1238-1240
CrossRef2
Harpreet Kaur, Christine Uy, Jennifer Kelly, Arnold M. Moses. (2011) Orbital Inflammatory Disease in a Patient Treated with Zoledronate. Endocrine Practice 17:4, e101-e103
CrossRef3
P. Hadji. (2011) Managing bone health with zoledronic acid: a review of randomized clinical study results. Climacteric 14:3, 321-332
CrossRef4
E. Michael Lewiecki. (2011) Safety of Long-Term Bisphosphonate Therapy for the Management of Osteoporosis. Drugs 71:6, 791-814
CrossRef5
Santiago Ortiz-Perez, Estrella Fernandez, Juan Jose Molina, Bernardo Sanchez-Dalmau, Manuel Navarro, Xavier Corretger, Jane M. Olver. (2011) Two Cases of Drug-Induced Orbital Inflammatory Disease. Orbit 30:1, 37-39
CrossRef6
F. Procianoy, E. Procianoy. (2010) Orbital inflammatory disease secondary to a single-dose administration of zoledronic acid for treatment of postmenopausal osteoporosis. Osteoporosis International 21:6, 1057-1058
CrossRef7
E Bo Yang, Emily S Birkholz, Andrew G Lee. (2010) Another Case of Bisphosphonate-Induced Orbital Inflammation. Journal of Neuro-Ophthalmology 30:1, 94-95
CrossRef8
Atul F. Kamath. (2009) Current Controversies in Bisphosphonate Therapy. Orthopedics 32:7, 473-475
CrossRef
