Bisphosphonates can have ocular side effects

Issue: November 2003

ByMichael J. Trad, OD

The class of systemic medications known as bisphosphonates is used to increase bone density in patients with osteoporosis, myeloma bone disease, Paget’s disease, metastatic cancer to bone, hypercalcemia of malignancy (also known as tumor-induced hypercalcemia) and total hip replacement or spinal cord injury (for the prevention and treatment of secondary heterotopic ossification).

Ocular Side Effects of the Bisphosphonates
Medication	Reported potential ocular side effects
Aredia	Scleritis, episcleritis, anterior uveitis, eye pain, blurred vision
Actonel	Conjunctivitis, cataract
Skelid	Conjunctivitis, cataract, glaucoma
Fosamax	Anterior uveitis
Zometa	None
Didronel	None

Bisphosphonates exhibit strong chemical affinity for hydroxyapatite — a major inorganic bone component — thereby inhibiting osteoclasts, or bone-destroying cells. The various bisphosphonates inhibit osteoclasts by different means, such as preventing osteoclast attachment to bone surface, limiting production of osteoclast-stimulating factors, altering actual osteoclast cell development or performing multiple tasks.

In early 2003, researchers at the Casey Eye Institute, Oregon Health Sciences University in Portland, alerted health professionals and the public to rare but potentially harmful ocular side effects associated with these drugs through publications in the American Journal of Ophthalmology (Fraunfelder FW, Fraunfelder FT, Jensvold B. Scleritis and other ocular side effects associated with pamidronate disodium. Am J Ophthalmol. 2003;135(2):219-222) and the New England Journal of Medicine (Fraunfelder FW, Fraunfelder FT. Bisphosphonates and ocular inflammation. N Engl J Med. 2003;348(12):1187-1188).

Of particular interest in the AJO article was the observation that 18 of 314 subjects taking pamidronate developed scleritis within 6 to 48 hours after starting therapy. In addition, other patients taking the medication experienced blurred vision, ocular pain, conjunctivitis and bilateral anterior uveitis. Although all cases of blurred vision, ocular pain, conjunctivitis and uveitis resolved during treatment, no instances of scleritis abated unless the medication was discontinued. Other bisphosphonates include Fosamax (alendronate sodium, Merck), Actonel (risedronate sodium, Procter & Gamble), Skelid (tiludronate disodium, Sanofi-Synthelabo), Zometa (zoledronic acid, Novartis) and Didronel (etidronate disodium, Procter & Gamble).

While patients taking these medications are evaluated every 3 to 6 months for kidney function through blood and urine testing by their physicians, the accepted protocol for ophthalmic evaluation is not as clear. A prudent approach may be for the prescribing physician to provide thorough verbal education to the patient regarding the symptoms of scleritis and uveitis (red eye, ocular pain and perhaps blurred vision). Patients experiencing these symptoms should then be instructed to notify their prescribing physician to ensure appropriate ophthalmic referral.