Yes, Prolia (denosumab) does appear to weaken your immune system. Research has shown people who take Prolia are at an increased risk of serious infections leading to hospitalizations, including serious infections of the skin, abdominal, urinary tract, and ear. People taking Prolia are also at increased risk of endocarditis (an infection of the heart’s inner lining, usually involving the heart valves). People administered concomitant immunosuppressant agents (such as prednisone or cyclosporine) or with impaired immune systems may be at an even higher risk.

Doctors may need to consider discontinuing Prolia in people who develop serious infections.

How does Prolia weaken the immune system?

Experts aren’t exactly sure how Prolia weakens the immune system but suspect it has to do with the way it works, which is by inhibiting RANKL. RANKL is a protein that osteoclasts need to work. Prolia stops RANKL from binding to its receptor RANK so reduces the development of new osteoclasts and reduces bone breakdown, bone loss, bone pain, and other bone complications.

RANKL and RANK are also expressed in cells of the immune system, including activated T lymphocytes, B cells, and dendritic cells. RANK activation by RANKL is thought to play a key role in the development of lymph nodes and is also essential for the growth of T cells and the function of dendritic cells. RANKL also enhances the survival of dendritic cells and the presentation of antigens.

This implies that inhibition of RANKL by Prolia might alter a person’s immune function and increase their susceptibility to infections.