Zoledronic acid is commonly used in cancer patients for the management of hypercalcemia or to help prevent bone pain/fractures in the setting of bone metastasis [3]. In women with breast cancer, bisphosphonates are used as adjuvant treatment given the evidence demonstrating improvement in recurrence, distant recurrence, and breast cancer mortality [1]. Current ASCO (American Society of Clinical oncology) guidelines recommend that adjuvant bisphosphonate therapy be discussed with all post-menopausal women irregardless of their hormone receptor status. The decision as to whether or not to pursue adjuvant bisphosphonates will depend on several factors such as patient’s risk of recurrence, risk of side-effects, comorbidities, and life expectancy. Current options for adjuvant bisphosphonates apart from Zoledronic acid, also include oral clodronate and ibandronate [1].
The most common site of breast cancer metastasis is the bone [4]. Cancer cells are attracted to the sites of bone resorption, these malignant cells then release cytokines that uncouple the delicate balance between osteoclasts and osteoblasts which in turns leads to increased bone resorption [4]. The increased bone resorption allows for increased cytokines thus creating an environment favoring survival for cancer cells [3]. Bisphosphonates are fundamental in halting this process by binding to bone resorption sites, become internalized by osteoclasts and thereby prevent osteoclast function [4, 5]. For this reason, bisphosphonates, such as Zoledronic acid remains a vital and important tool in cancer treatment. In this particular case, we illustrate the importance of a rare side effect associated with the use of Zoledronic acid. Within a few days of the initial dose, the patient developed the classical symptoms of blurry vision and ocular pain.
Bisphosphonates are a rare but known cause of drug induced uveitis, especially when administered intravenously [6]. Anterior uveitis is typically more common, often presenting with vision loss, pain and redness. Our patient was evaluated by an ophthalmologist which is vital to ensure early recognition and prevention of complications. Diagnosis entails slit lamp and dilated fundus exam.[7] Slit lamp exam might show leukocytes in the anterior chamber of the eye. Active inflammation can be visualized directly. Treatment for non-infectious etiologies involves cessation of the inflicting drug and application of topical glucocorticoids such as in our patient.[7] Literature search shows several other case reports in which acute uveitis resulted with the first infusion of Zoledronic acid [8]. Interestingly in our patient, she initially developed flu like symptoms, which may have been part of the acute phase reaction. The common adverse events listed in the package insert include occurring in > 25% listed included nausea, fatigue, anemia, bone pain, constipation, fever, vomiting, and dyspnea [9]. The package insert does make a special note to include recommendations to hydrate patients, watch for renal dysfunction, electrolyte abnormalities, severe bone, joint and muscle pain, osteonecrosis [9]. Post-marketing research for zoledronic acid reports ocular inflammation such as uveitis and scleritis in patients.
This further validates the need for both providers and patients to be educated on the clinical presentation of uveitis and encourages early ophthalmologic evaluation. Providers need to be wary of the use of adjuvant zoledronic acid in patients with history of ocular inflammation.