Prolia, generic denosumab, is a new treatment for prevention of osteoporosis and bone related disease. It is a monoclonal antibody to RANKL and acts by preventing it from activating its target receptors. Since RANKL promotes cells to grow that digest your bone, preventing its action has important protective effects.
Studies have shown that Prolia works to improve bone mineral density and reduce different types of fractures.
This is an extremely important function in older women. After menopause, low levels of estrogen result in bones becoming weaker. 30% of women after menopause will have osteoporosis, and 40% of those will have some sort of fragility fracture.
There are some very promising aspects to Prolia. It works well and can be delivered subcutaneously, or just under your skin. Importantly, it lasts for a very long time in your body, which means that Prolia can be given infrequently, possibly just once every six months.
To get a sense for how well Prolia works, take a look at some of the data.
The FREEDOM study lasted for 3 years and followed 7868 women with osteoporosis and gave either placebo or 60mg of Prolia. A solid 83% of participants finished the study which is a fairly good rate. In that study, 2.3% had a new vertebral fracture – compared to a much higher 7.2% rate of fracture in the placebo group. And 0.7% of those on Prolia had a new hip fracture as oppose to 1.2% of those on placebo.
Other studies have also shown that Prolia is fairly effective at improving bone health and reducing risk of fractures.
Prolia Side effects
After how well something works, the next thing you want to know about a treatment is – what potential side effects does it have?
The studies have shown different side effects from Prolia. In general, it was shown to have similar rates of adverse effect as placebo regards cardiovascular incidents, infections, and cancer. Getting Prolia in general seems to not be much different from getting placebo – regarding side effects.
That said, we found some data that hint at potential issues. One study over 4 years showed that 3.2% of those on Prolia had a serious infection that required hospitalization as compared to none on placebo or a competing medication. All the infections responded to treatment, and other studies have shown no increase in risk for infection on Prolia.
Another study hinted at a slight increase in eczema and cellulitis from those using Prolia: 0.3% of those on it had it versus 0.1% of those on placebo.
It is important to note that overall, Prolia has shown general safety and low incidence of side effects, while appreciating that the issues raised in clinical trials may mean something.
Osteonecrosis of the Jaw
It is highly likely that Prolia will be considered for use in certain types of cancer, particularly when there is bone metastases. This raises the potential for osteonecrosis of the jaw (ONJ). It is important to note that in the cancer setting, Prolia has been used at much higher doses than for osteoporosis, possibly 120mg per month.
We looked at two studies. In one study of 1026 patients, 2% of those on Prolia had ONJ compared to 1.4% of those on zoledronate. Another study of 888 patients had 1.1% on Prolia have ONJ compared to 1.3% on zoledronate.
If you want to learn about other new drugs, see here.
1) Denosumab update
2) Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis
3) Denosumab-related osteonecrosis of the jaws