What Is the Risk of MRONJ and Atypical Femur Fractures?

It is completely normal to feel anxious about starting osteoporosis medications, such as bisphosphonates (like alendronate) or denosumab, especially after hearing about rare side effects like jaw bone necrosis (MRONJ) and unusual thigh breaks (atypical femur fractures). The direct answer is that while these side effects are real, they are very rare when these drugs are used at standard osteoporosis doses. For most patients, the absolute risk of experiencing these side effects is a fraction of a percent per year. When you compare this to the danger of leaving severe osteoporosis untreated, the expected benefit of preventing life-altering hip and spine fractures generally outweighs the small risk of these rare complications. Your personal decision should be based on your individual fracture risk, which depends on your age, bone density, and medical history.

Medication-Related Osteonecrosis of the Jaw (MRONJ)

MRONJ is a condition where a small section of the jaw bone becomes exposed and is slow to heal. It can sometimes occur spontaneously, but it most often develops after an invasive dental procedure, such as a tooth extraction, especially in patients with poor oral hygiene, active dental infections, or those who smoke ^[1][2].

• The Actual Risk: For patients taking standard osteoporosis doses, the risk of MRONJ is exceptionally low. Consensus estimates show the incidence ranges from roughly 21 to 283 cases per 100,000 patient-years (0.021% to 0.28% annually) ^[3]. A large Japanese study similarly found a rate of about 2.3 cases per 10,000 patient-years ^[4].
• The “Cancer Dose” Confusion: Much of the fear surrounding MRONJ comes from cancer treatments. Patients receiving these exact same medications at vastly higher doses for cancer have a significantly higher risk of jaw issues than osteoporosis patients ^[5][6].
• Dental Considerations: Maintaining routine dental hygiene and treating active oral infections is important ^[2]. However, you generally do not need to delay starting crucial bone medication just to get routine “dental clearance,” and any invasive procedures should be coordinated between your dentist and your prescribing doctor ^[7].

Atypical Femur Fractures (AFF)

An atypical femur fracture is an unusual break that occurs straight across the shaft of the thigh bone, often with little to no trauma.

• The Actual Risk: AFFs are strongly linked to long-term use of bisphosphonates, but the absolute numbers are very small. In the first 2 to 4 years of taking an oral bisphosphonate, the risk is roughly 9 cases per 100,000 patient-years ^[8].
• The Role of Time: The risk of AFF increases the longer you stay on the medication. After 8 or more years of continuous use, the risk rises to about 112 per 100,000 patient-years (roughly 1 in 1,000) ^[8]. Reassuringly, the risk appears to drop rapidly once the bisphosphonate is stopped ^[9].
• Warning Signs and Action Plan: AFF is often preceded by a warning sign: new, unexplained aching pain in the thigh or groin ^[10]. If you experience this symptom, contact your prescriber immediately. Do not stop taking your medication on your own. Your doctor will likely order X-rays or other imaging of both of your thigh bones to check for early signs of stress ^[11].

The Danger of “Drug Holidays” with Denosumab

Because the risk of AFF increases over time with bisphosphonates (such as alendronate or zoledronic acid), doctors often evaluate whether a patient can take a “drug holiday”—a planned, supervised pause from the medication—after 3 to 5 years ^[12].

However, denosumab (Prolia) requires an entirely different approach. You must never skip, delay, or take a “holiday” from a denosumab injection on your own. Stopping denosumab causes a rapid rebound effect in bone turnover, which can lead to rapid bone loss and a high risk of suffering multiple spinal fractures. If denosumab must be stopped, your doctor must actively transition you to another antiresorptive medication.

Weighing the Trade-Offs

To truly understand these risks, they must be weighed against your personal danger of leaving osteoporosis untreated. Fragility fractures of the hip and spine can lead to chronic pain, permanent loss of independence, and an increased risk of mortality.

• Untreated Fracture Risk: For patients with established osteoporosis, the danger of doing nothing can be substantial. For example, one cohort study of older women (aged 65 and over) with osteoporosis found a 5.5% risk (550 per 10,000 women) of suffering a hip fracture in a single year ^[13]. Another study found that women aged 80 and older with osteoporosis had a 13% probability of a hip fracture over 5 years ^[14].
• Medication Benefits: Osteoporosis medications are highly effective at preventing these exact events. Clinical evidence shows that they offer relative risk reductions of roughly 40% to 70% for spinal fractures and 40% to 53% for hip fractures ^[15][16].

The decision to treat should be individualized. However, for a patient with a high risk of breaking a bone, the absolute number of typical fractures prevented by treatment is much larger than the rare side effects it might cause. Talk to your doctor about your personal baseline fracture risk to understand exactly how much benefit you stand to gain.