Correspondence
Bisphosphonates and Ocular Inflammation
N Engl J Med 2003; 348:1187-1188March 20, 2003
- Article
To the Editor:
Bisphosphonates are used to inhibit bone resorption in postmenopausal women and to manage hypercalcemia associated with osteolytic bone cancer, metastases of breast cancer, multiple myeloma, and Paget's disease of bone. Pamidronate disodium can cause uveitis, nonspecific conjunctivitis, episcleritis, or scleritis.1,2 The drug must be discontinued to resolve the scleritis. Other bisphosphonates available in the United States include alendronate sodium (Fosamax, Merck), risedronate sodium (Actonel, Procter & Gamble), zoledronic acid (Zometa, Novartis), etidronate disodium (Didronel, Procter & Gamble), and tiludronate disodium (Skelid, Sanofi Winthrop). Bisphosphonates not approved by the Food and Drug Administration (FDA) include clodronate disodium (Ostac, Roche, and Bonefos, Aventis Pharma), ibandronate (Roche and GlaxoSmithKline), and olpadronate (Gador Pharmaceuticals). The Physicians' Desk Reference for Ophthalmology 3 does not list ocular inflammation as a potential side effect of the bisphosphonates marketed in the United States.
Because of the uniqueness of the reported reactions of the visual system to pamidronate disodium, we reviewed the data on other bisphosphonates available in the United States and abroad (Table 1Table 1
Bisphosphonates and Adverse Ocular Effects.).4 These data suggest that, in rare instances, this class of medicine can cause serious ocular side effects. The variance in the number of ocular side effects reported for the different bisphosphonates probably reflects the individual popularity of each medication as well as the timing of the FDA's approval of the medication for marketing. A finding of particular importance to clinicians is that no case of unilateral or bilateral scleritis that developed in a person receiving bisphosphonates resolved, regardless of therapy, until the bisphosphonate was discontinued.Data from spontaneous reporting systems can be suspect; nevertheless, the temporal relation and overall pattern of ocular side effects in patients receiving other bisphosphonates were very similar to those reported for pamidronate. In addition, we are unaware of any reports of scleritis caused by any other class of medication.5
We suggest the following guidelines for the care of patients receiving bisphosphonates. First, patients with vision loss or ocular pain should be referred to an ophthalmologist. Second, nonspecific conjunctivitis seldom requires treatment and usually decreases in intensity during subsequent exposure to a bisphosphonate. Third, more than one ocular side effect can occur at the same time; for instance, episcleritis may occur in conjunction with uveitis. In some instances, the drug may need to be discontinued in order for the ocular inflammation to resolve. Finally, for scleritis to resolve, even during full medical therapy, the bisphosphonate must be discontinued.
5 ReferencesFrederick W. Fraunfelder, M.D.
Frederick T. Fraunfelder, M.D.
Casey Eye Institute, Portland, OR 97201-4197
fraunfer@ohsu.edu 1
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Fraunfelder FW ,Fraunfelder FT ,Jensvold B . Scleritis and other ocular side effects associated with pamidronate disodium. Am J Ophthalmol 2003;135:219-222
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Physicians' desk reference for ophthalmology. 54th ed. Montvale, N.J.: Medical Economics, 2002:1798-802.
4
Mbekeani JN ,Slamovits TL ,Schwartz BH ,Sauer HL . Ocular inflammation associated with alendronate therapy. Arch Ophthalmol 1999;117:837-838
Web of Science | Medline5
Fraunfelder FT, Fraunfelder FW. Drug-induced ocular side effects. 5th ed. Boston: Butterworth–Heinemann, 2001.
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2012. 1-Hydroxyethan-1,1-diphosphonsäure und ihre Natrium- und Kaliumsalze [MAK Value Documentation in German language, 2010]. .
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A. John Camm. (2010) Review of the cardiovascular safety of zoledronic acid and other bisphosphonates for the treatment of osteoporosis. Clinical Therapeutics 32:3, 426-436
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Veena Rao Raiji, Alan Gary Palestine, David Leland Parver. (2009) Scleritis and Systemic Disease Association in a Community-Based Referral Practice. American Journal of Ophthalmology 148:6, 946-950
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Frederick W. Fraunfelder, Kevin Winthrop, Eric Suhler, Dongseok Choi, Frederick T. Fraunfelder. (2009) Correspondence. Retina 29:2, 285-286
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DUSTIN D. FRENCH, CURTIS E. MARGO. (2008) POSTMARKETING SURVEILLANCE RATES OF UVEITIS AND SCLERITIS WITH BISPHOSPHONATES AMONG A NATIONAL VETERAN COHORT. Retina 28:6, 889-893
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Colin R Dunstan, Dieter Felsenberg, Markus J Seibel. (2007) Therapy Insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nature Clinical Practice Oncology 4:1, 42-55
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F.W. Fraunfelder, F.T. Fraunfelder. (2004) Adverse ocular drug reactions recently identified by the National Registry of Drug-Induced Ocular Side Effects. Ophthalmology 111:7, 1275-1279
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