Denosumab (sold as Prolia) works differently to bisphosphonates. Rather than binding to bone directly, it is a biological medicine that blocks a protein called RANKL, which normally activates osteoclasts. By intercepting that signal, it significantly reduces bone breakdown. The result is often meaningful improvements in bone density at both the spine and hip and substantial reductions in fracture risk.
CALLOUT: Prolia is particularly effective for women with a high fracture risk, those who cannot tolerate oral bisphosphonates, or those with reduced kidney function. This is because unlike bisphosphonates, it does not require the kidneys to process it.
How treatment works
Prolia is given as an injection under the skin of the abdomen, upper arm, or thigh every six months. The injection is administered by your doctor or nurse at a clinic appointment. You do not take anything at home between injections.
Each injection provides approximately six months of protection. After that, the effect begins to wear off. This is why the timing of your next injection matters more with Prolia than with most other osteoporosis medications.
QUOTE: "Missing or significantly delaying a Prolia injection is not like missing a tablet. The protection it provides has a defined window. Beyond six months, bone loss can begin to accelerate."
The most important thing to understand about stopping Prolia
This is the single most critical piece of information for any woman on Prolia and it is not communicated clearly often enough.
If Prolia is stopped without transitioning to another medication, bone density can decline rapidly. In some women, this rebound bone loss occurs faster than the original rate of loss before treatment began. Multiple vertebral fractures have been reported in women who stopped Prolia without a transition plan.
This does not mean Prolia is dangerous. It means stopping it requires careful management. If you are on Prolia and considering stopping for any reason - side effects, cost, personal choice - this must be discussed with your doctor first. A transition to another medication, typically a bisphosphonate, is almost always recommended to protect the gains made during treatment.
CALLOUT: Never stop Prolia without speaking to your doctor first. This is one of the most important safety messages in osteoporosis treatment and one of the most frequently overlooked.
Dental considerations
As with bisphosphonates, ONJ is a rare but recognised risk with Prolia and the risk increases with longer duration of treatment. Before starting, your doctor should ask about your dental health. If you have significant dental work planned, it is worth discussing timing with both your doctor and dentist. This is ideally completing it before you begin, if your fracture risk allows time for that.
During treatment, inform any dentist you see that you are on Prolia. Routine dental care, fillings, and hygiene appointments are generally safe and should continue as normal.
CALLOUT: Never delay or skip a Prolia injection to prepare for dental work without speaking to your doctor first. Unlike bisphosphonates, stopping Prolia abruptly, even briefly, carries a real risk of rapid bone loss and fracture. This is a decision that requires a conversation, not an independent choice. Our article on side-effects covers ONJ and dental considerations in full.
Calcium and vitamin D
Prolia can cause low calcium levels in the blood, particularly in women who are already deficient. This is why your doctor will almost always recommend calcium and vitamin D supplements alongside treatment, and may check your blood calcium levels before and during treatment.
Do not skip your supplements while on Prolia. They are not optional extras, they are part of the treatment plan.
Monitoring over time
Most women on Prolia have a DEXA scan every one to two years to monitor their response. Blood tests may be done periodically to check calcium levels. Your six-monthly injection appointment is also an opportunity to check in with your doctor about how treatment is progressing and whether anything has changed in your health that might affect the plan.
CALLOUT: If you're on Prolia or considering it, Lenari's Prolia explainer covers everything in this article and more, including the questions worth raising with your doctor before you start. [Read the Prolia guide →]