From the Research
Denosumab can cause ankle swelling or edema as a potential side effect, although it is not among the most common side effects. Denosumab (brand names Prolia and Xgeva) is a monoclonal antibody medication used to treat osteoporosis and prevent skeletal-related events in certain cancers. The mechanism behind this edema may relate to denosumab's effects on RANK ligand inhibition, which can influence vascular permeability and fluid balance in some patients 1. If you experience ankle swelling while taking denosumab, you should report this to your healthcare provider, as they may want to evaluate whether the edema is related to the medication or has another cause. They can help determine if you should continue the treatment or consider alternatives. While mild edema might be manageable with elevation and monitoring, more severe or persistent swelling may require medical attention or medication adjustment. It is essential to note that denosumab has been shown to be effective in treating bone marrow oedema syndrome, which can cause ankle swelling, as demonstrated in a study published in 2017 1. However, the most recent and highest quality study, published in 2025, found that denosumab may increase the risk of major adverse cardiac events (MACE) by 36% compared to oral bisphosphonates, although it also lowered the risk of fractures by 45% 2. Therefore, it is crucial to weigh the benefits and risks of denosumab treatment and closely monitor patients for any potential side effects, including ankle swelling or edema. Some key points to consider when evaluating the risk of ankle swelling or edema with denosumab include:
- The patient's underlying medical conditions, such as renal insufficiency or cardiorenal insufficiency 3, 4
- The patient's concomitant medications, such as immunosuppressive agents or steroids 4
- The patient's calcium and vitamin D levels, as hypocalcemia can increase the risk of edema 5
- The patient's response to denosumab treatment, including any changes in ankle swelling or edema 1, 2