April 2012

A number of medications in use have side-effects in the eye. Perhaps the best known of these is Hydroxychloroquine (sold as Plaquenil [Sanofi]), used to treat rheumatoid arthritis and systemic lupus erythematosus (lupus), which can cause macular toxicity when a large enough cumulative dose is received.

This month a Canadian cohort study presented perhaps the best evidence yet that bisphosphonates can increase the risk of inflammation in the eye. Bisphonates (eg Alendronate, sold as Fosamax [Merck]) are  used for the treatment of osteoporosis and other pathological causes of bone fracture (such as multiple myeloma, Paget’s disease, hyperparathyroidism, bone metastasis). 

Bone undergoes constant turnover and there is a dynamic balance between creation and destruction of bone. Osteoblasts are cells that lay down and mineralize bone, and osteoclasts are cells that break it down, or resorb it. Bisphosponate therapy has been shown to interfere with osteoclast metabolism and thus inhibit bone resorption.

In the Canadian study bisposphonate use was associated with an increase in the risk of scleritis and uveitis, two inflammatory eye conditions that can be associated with loss of vision. Etminan and colleagues looked at data for all 934,147 patients in British Columbia that visited an ophthalmologist from 2000 to 2007. 10,827 were first time uses of bisphosphonates. The risk of scleritis was 63 per 10,000 person-years in bisposphonate users compared to 36 in non-users, and the risk of uveitis was 29 per 10,000 person-years in bisposphonate users compared to 20 in non-users.

Although the increase in risk is significant, the total risk remains quite low and this is certainly not a reason to avoid bisphosphonates. Bisphosphonate therapy can save lives by preventing fractures that ultimately limit mobility, and based on this study there would be one case of uveitis for every 1100 patients taking bisphosphonates and one case of scleritis for every 370 patients. But it does mean that doctors prescribing Fosamax and other bisphosphonates, and patients taking them, should be aware of the association and seek urgent advice and assessment from their ophthalmologist if there is a suspicion of eye inflammation. There were 1.5 million scripts written for Alendrolate alone in Australia last financial year.

The good news is that early specialist intervention for both uveitis and scleritis can lead to good outcomes and can avoid any impact on vision.