Q. How does the drug Prolia work and what are the side effects?


Denosumab is a relatively recent drug on the market, approved by the US Food and Drug Administration (FDA) under the trade name of Prolia for postmenopausal women with risk for osteoporosis in June, 2010. As well as under the trade name of Xgeva for the prevention of bone events in patients with bone metastases from tumors in November, 2010.

To understand it’s mechanism of action, let us look at some physiology. Bone remodeling is the process where the body continuously builds new bone and removes old bone material. This work is accomplished by several types of cells, most simply osteoblasts, which secrete new bone, and osteoclasts, which break it down.

Precursors to osteoclasts secrete RANK (receptor activator of nuclear-kappa B). RANK is activated by RANKL (RANK-Ligand), which is produced by osteoblasts. Activation of RANK promotes the maturation of osteoclasts.

Denosumab inhibits this maturation of bone-destroying osteoclasts by binding to and inhibiting RANKL. This helps counter the progression of osteoporosis. The drug therefore mimics the body’s own mechanism of osteoprotegerin, another receptor produced by osteoblasts which can bind RANKL, thus reducing its effect on RANK and helping to modulate bone production.

So far, common side effects include infections of the urinary and respiratory tract, osteonecrosis of the jaw, back pain, pain in the extremities, musculoskeletal pain, high cholesterol levels, cataracts, constipation and rashes.

As more people take this medication and increasing research is done, it will probably be discovered once again, that taking this medication in conjunction with a lifestyle that promotes healthy bones, will receive the greatest benefit. For more information on what this lifestyle may entail, click here.

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