How Common Is Osteonecrosis of the Jaw With Prolia?

Osteonecrosis of the jaw (ONJ) with Prolia, the brand name for denosumab used to treat osteoporosis, is rare. The most commonly cited figure in osteoporosis patients is about 4 cases per 10,000 treated, or roughly 0.04%.¹ That number sounds reassuring, and for most people it should be. But the real picture depends on how long you take the drug, what dental work you need, and whether you have certain other health conditions. And in cancer patients receiving higher doses, the risk is dramatically higher.

Osteoporosis Doses Versus Cancer Doses

One of the biggest sources of confusion around ONJ and denosumab is that the drug is used at very different doses depending on the condition. For osteoporosis, Prolia is given as a 60 mg injection every six months. For cancer patients with bone metastases, the same drug is marketed as Xgeva and given at 120 mg every four weeks, which works out to roughly twelve times the annual dose. That difference in exposure matters enormously for jaw risk.

In cancer patients receiving high-dose denosumab, the incidence of ONJ has been reported between roughly 1% and 9%.¹ That is orders of magnitude above the osteoporosis figure. Much of the alarming data you may encounter online comes from cancer studies, and it gets applied, incorrectly, to people taking the lower osteoporosis dose. If your prescription is Prolia for bone density, the cancer numbers do not apply to you.

Risk Climbs With Time on the Drug

The 0.04% figure is a snapshot. ONJ risk is not static; it accumulates the longer you stay on denosumab. A study of patients on long-term denosumab found that the probability of developing ONJ rose from under 1% in the first year to about 6% in the second year and over 13% by the third year.² Those numbers are considerably higher than the overall average, partly because this particular cohort was not limited to osteoporosis patients and included people on higher-intensity regimens.

The pattern is even more striking in prostate cancer patients receiving bone-modifying agents over many years. In one long-term study, the cumulative incidence of ONJ reached 8% at two years, 18% at five years, and 27% at ten years.³ These are high-dose cancer regimens, not the osteoporosis schedule, but they illustrate the consistent pattern: the longer the exposure, the higher the risk. For osteoporosis patients, the absolute numbers are much lower, but the upward drift with duration still applies, which is relevant because Prolia is often prescribed for years or even indefinitely.

How Prolia Compares to Bisphosphonates

Bisphosphonates, the older class of bone-protecting drugs, have been linked to ONJ for decades. An obvious question is whether switching to denosumab makes jaw problems more or less likely. The honest answer is that studies disagree, and the comparison is more complicated than it first appears.

A European cohort study found the rate of ONJ was substantially higher in patients receiving denosumab than in those on bisphosphonates, with roughly 28 cases per 10,000 patient-years on denosumab compared to about 5 per 10,000 patient-years on bisphosphonates. That translated to a hazard ratio of about 3.5, meaning denosumab users were more than three times as likely to develop ONJ. An important detail: nine of the twelve denosumab patients who developed ONJ had previously taken bisphosphonates before switching, which may have loaded additional risk.⁴

A large Taiwanese study found the opposite pattern. In that cohort, the rate of ONJ was actually lower in denosumab users than bisphosphonate users (about 1.5 versus 2.5 events per 1,000 person-years), and the difference became significant from the third year of use onward, favoring denosumab.⁵ The conflicting results likely reflect differences in patient populations, how many people had been on bisphosphonates before switching to denosumab, and how carefully cases were detected. The European study’s warning about prior bisphosphonate use as an added risk factor matters a lot here, because many patients starting Prolia have already spent years on oral bisphosphonates.

Dental Extractions Are the Biggest Trigger

ONJ rarely appears out of nowhere. In most cases, there is an identifiable trigger, and the single most common one is tooth extraction. A study of 427 osteoporosis patients on denosumab who underwent dental extractions found that about 2.3% developed ONJ afterward, compared to zero cases in a control group of 299 patients not on the drug. The more teeth extracted, the higher the risk: each additional extraction increased the odds by about 35%.⁶

A separate retrospective study of patients who had dental extractions while on antiresorptive drugs found an ONJ incidence of about 2.7% per person-year among osteoporosis patients. Among cancer patients receiving higher doses, the figure jumped to over 26% per person-year. Critically, the reason the tooth was being pulled mattered: when the extraction was done because of a dental infection, the risk of ONJ was dramatically higher compared to extractions for other reasons.⁷ This points to infection, rather than the extraction itself, as the deeper culprit. Some researchers have argued that getting an infected tooth out may actually be protective, because letting the infection linger beside suppressed bone creates the conditions ONJ needs to develop.⁸

This finding is practically useful. The risk from dental extractions on Prolia is real but low, and letting an infection fester to avoid pulling a tooth is not necessarily the safer bet. Coordination between your dentist and your prescribing physician is what reduces risk most, not avoidance of dental care entirely.

Who Faces Higher Risk

Several patient-level factors have been linked to greater ONJ risk during denosumab treatment. A study that examined a range of potential predictors identified the following as significantly increasing the chances of developing ONJ: concurrent chemotherapy or hormonal therapy, higher denosumab doses (the cancer-level regimen), corticosteroid use, diabetes, high blood pressure, periodontal disease, dental root infections, and wearing dentures.⁹

A few of those deserve emphasis. Diabetes and periodontal disease both impair the jaw’s ability to heal after minor injuries. Denture use creates chronic low-grade pressure on gum tissue, which can lead to small sores that then fail to heal properly when bone turnover is suppressed. Corticosteroids, which many patients with chronic conditions take alongside their bone-protecting drugs, independently weaken bone and slow healing. If you carry several of these risk factors, your personal odds may be meaningfully higher than the overall 0.04% average, even at the osteoporosis dose.

The Problem With Stopping Prolia

A natural reaction to learning about ONJ risk is to want to stop the drug, especially if dental work is coming up. But denosumab creates a difficult catch-22 that bisphosphonates do not. Bisphosphonates embed themselves in bone and their effects linger for years after you stop. Denosumab works differently: it blocks a signaling molecule in the bloodstream, and when you stop injecting it, the effect wears off within months. That sounds like a good thing, and in some ways it is (more on that below). But the rapid reversal comes with a serious downside.

When denosumab is discontinued, bone turnover doesn’t just return to baseline. It rebounds above where it started, leading to a burst of accelerated bone loss. A case report described a 69-year-old woman who stopped denosumab for dental treatment after three years on the drug. Ten months after her last injection, she developed five acute vertebral fractures without any trauma, the kind of rebound event that has been reported repeatedly in the medical literature.¹⁰ This means pausing Prolia for a dental procedure is not a simple or risk-free choice. The fracture risk from stopping may outweigh the jaw risk from continuing, depending on your spine health, age, and how long you have been on the drug.

For this reason, guidelines generally recommend that if you need dental surgery while on Prolia, you work with your providers to time the procedure and manage risk, rather than simply discontinuing the drug. The decision requires balancing two low-probability but serious outcomes against each other.

Why Denosumab-Related ONJ May Heal Faster

The same reversibility that makes stopping Prolia risky for fractures may actually be a silver lining when ONJ develops. Because denosumab’s effect on bone turnover wears off within roughly six months of the last dose, the jaw’s ability to remodel and heal can potentially return faster than it would after years of bisphosphonate use, where the drug remains locked in bone tissue for a very long time.¹¹ In theory, a carefully managed drug holiday could give the jaw a window to recover. In practice, though, any drug holiday has to be weighed against the rebound fracture problem discussed above, so this is not a decision to make on your own.

What Happens if ONJ Develops

ONJ can range from mild (a small area of exposed bone with no pain) to severe (large areas of dead bone with infection, pus drainage, and sometimes pathologic jaw fractures). Treatment options range from conservative management, such as antimicrobial rinses and antibiotics, to surgical removal of dead bone. The evidence increasingly favors surgical approaches for anything beyond the mildest cases.

One study found that surgically treated ONJ lesions healed completely in about 86% of cases, and even the ones that did not fully heal were reduced in severity. By contrast, lesions managed without surgery generally remained stable or worsened, with complete healing essentially absent.¹² Another study of patients with denosumab-related ONJ specifically found that nine out of eleven patients healed within four weeks of surgery, though two patients died from their underlying cancer, which underscores how outcomes depend heavily on the patient’s overall health.¹³

For osteoporosis patients who are otherwise healthy, surgical treatment of ONJ tends to have good results. The condition is treatable and not a death sentence for the jawbone, which is worth remembering when the initial diagnosis feels alarming.

Managing Osteoporosis After ONJ

A particularly tricky clinical question arises once ONJ has occurred: how do you continue treating osteoporosis without making the jaw worse? Restarting denosumab or switching to a bisphosphonate carries the risk of triggering a recurrence. One approach that has shown promise is using teriparatide, a bone-building drug that works through a completely different mechanism. Rather than suppressing bone breakdown, teriparatide stimulates new bone formation. A tertiary center that managed ONJ cases over thirteen years found that teriparatide followed by raloxifene appeared to be a workable approach, since both drugs act differently from the antiresorptive drugs that caused the problem.¹⁴

This is not a one-size-fits-all solution. Teriparatide is injectable, expensive, and limited to about two years of use. But it represents an option for patients caught between needing bone protection and fearing jaw complications, and it is the kind of conversation worth raising with an endocrinologist if ONJ occurs.

Preventing ONJ Before It Starts

The strongest protective measure is dental health. If you are about to start Prolia, getting a thorough dental exam beforehand and resolving any infections, cracked teeth, or needed extractions reduces the risk of an invasive procedure being necessary later. Ongoing periodontal care while on the drug matters too, because chronic gum disease is both a risk factor for ONJ and a common reason extractions become necessary down the line.

Some practical steps that clinicians recommend include:

Baseline dental exam: Before starting denosumab, get a comprehensive oral evaluation and complete any needed extractions or surgical work in advance.
Regular cleanings: Maintain routine dental visits every six months, ideally timed around your Prolia injection schedule.
Infection control: Treat gum disease, cavities, and dental abscesses promptly rather than waiting.
Inform your dentist: Make sure every dental provider you see knows you are on denosumab. This affects how they plan extractions and other procedures.
Implants and dentures: Discuss the added risk with both your dentist and prescribing doctor, since both dental implant placement and denture use have been flagged as risk factors.

The goal is not to avoid dental care but to make it as low-risk as possible. Skipping the dentist out of fear of ONJ is counterproductive: the infections that develop from neglected teeth are themselves among the biggest ONJ triggers.

Genetic Susceptibility Is Still an Open Question

Researchers have been hunting for genetic markers that could predict who is likely to develop ONJ, hoping to identify high-risk patients before they start treatment. A systematic review examining this question catalogued 136 genetic variants across 58 genes that had been studied for possible links to ONJ. These genes are involved in immune response, inflammation, blood vessel formation, and bone remodeling. Despite this extensive catalog, the review concluded that no definitive genetic risk factors could be identified, because findings were inconsistent across studies and rarely replicated.¹⁵

The takeaway is that ONJ susceptibility is probably shaped by many small genetic influences interacting with the clinical risk factors already discussed, not by a single gene you could test for. This also helps explain why ONJ is hard to predict: two patients with seemingly identical risk profiles can have very different outcomes, and we do not yet have the tools to tell them apart in advance.

Fear of ONJ and Treatment Avoidance

The rarity of ONJ in osteoporosis patients stands in stark contrast to how much patients worry about it. A qualitative study of people managing osteoporosis found that fears about drug safety were the main driver of not taking prescribed treatment, and that negative information had the most impact on their decisions, even when it came from unreliable sources like social media.¹⁶ ONJ is one of the complications that comes up most often in these conversations, despite being far less common than the fractures that untreated osteoporosis causes.

Osteoporotic fractures are not minor events. A hip fracture in an older adult carries roughly a 20-30% one-year mortality rate, and vertebral fractures can cause chronic pain and disability. The risk of these fractures without treatment is often many times higher than the risk of ONJ with treatment. That does not make ONJ risk negligible or unworthy of discussion, but it does mean that refusing Prolia based on jaw fears alone often trades a small risk for a much larger one. A frank conversation with your prescriber about your specific fracture risk versus your specific ONJ risk, given your dental health and other factors, is more useful than blanket fear of either outcome.