Rare Side Effects — ONJ and Atypical Femur Fractures

• What ONJ and atypical femur fractures actually are
• How rare they truly are — with real numbers
• Who is at higher risk and what increases that risk
• Practical prevention steps you can take
• Warning signs to watch for
• Why the benefits of treatment almost always outweigh these risks

Before we explain these conditions, let us put the numbers in context:

The risk of a life-threatening fracture from untreated osteoporosis is hundreds of times higher than the risk of these rare side effects. That said, you deserve to understand them so you can take steps to minimize your risk even further.

These side effects are real, but they are rare. Knowing about them empowers you to protect yourself — not to fear your medication.

What is ONJ?

Osteonecrosis of the jaw (ONJ) is a condition in which a small area of jawbone becomes exposed and does not heal properly. It can cause pain, swelling, infection, or — in mild cases — no symptoms at all.

The name sounds alarming, but most cases are mild to moderate and respond well to treatment (usually conservative management with antibiotics and mouth rinses, without major surgery).

How rare is it?

For patients taking oral bisphosphonates (like alendronate or risedronate) for osteoporosis:

• The estimated incidence is approximately 1 in 10,000 to 1 in 100,000 per year
• This is the same range as many everyday risks we accept without thinking twice

For patients taking denosumab for osteoporosis:

• The risk is similarly low — estimated at about 1 to 2 per 10,000 patient-years

For comparison, the risk is significantly higher in patients receiving high-dose IV bisphosphonates for cancer treatment (a different use, with much higher doses). Most of the alarming stories you may have heard relate to cancer doses, not osteoporosis doses.

What increases the risk?

The most significant risk factor is dental surgery (especially tooth extraction) while on bone-protecting medication. Other risk factors include:

• Poor oral hygiene or existing dental disease
• Long duration of treatment (many years on bisphosphonates)
• Smoking
• Diabetes
• Use of corticosteroids (such as prednisone)
• Cancer treatment (much higher doses of bone medications)

How to protect yourself

Prevention is straightforward and highly effective:

1. Have a dental checkup before starting any bone medication. If you need dental work (extractions, implants, or gum surgery), ideally complete it before beginning treatment.
2. Maintain good oral hygiene — brush twice daily, floss, and see your dentist regularly.
3. Always tell your dentist that you take bone medication — every single visit. Dentists who know about your medication can plan procedures safely.
4. If dental surgery is needed while you are on treatment, your dentist and doctor can work together to manage the timing and minimize risk.
5. Report any unusual jaw symptoms — persistent pain, swelling, numbness, or exposed bone — to your doctor promptly.

The single most important thing you can do to prevent ONJ is to tell your dentist about your bone medication and maintain good oral hygiene. This simple step dramatically reduces your already-small risk.

What are atypical femur fractures?

Atypical femur fractures are unusual breaks in the thigh bone (femur) that occur in a specific location — the shaft of the femur, below the hip joint. They are called "atypical" because they happen in a different location and pattern than the typical hip fractures caused by osteoporosis.

These fractures are thought to be related to the way bisphosphonates (and, very rarely, denosumab) suppress bone remodeling. Over many years, this suppression may make bone slightly more brittle in certain areas, leading to small stress fractures that can eventually become complete breaks.

How rare are they?

• The estimated incidence is approximately 3 to 50 per 100,000 person-years of bisphosphonate use
• The risk increases with longer duration of treatment (5 or more years of continuous use)
• The risk decreases rapidly after stopping bisphosphonates

To put this in perspective: for every atypical femur fracture caused by bisphosphonate treatment, the same treatment prevents an estimated 100 to 200 osteoporotic fractures (including hip fractures, which carry a 20% mortality rate).

Warning signs

The most important warning sign is:

• New or unusual pain in the thigh or groin — especially if it develops gradually, is present when bearing weight, and is not related to an injury

This pain may indicate a stress reaction in the femur before a complete fracture occurs. Early detection is key — if caught early, treatment can prevent the bone from breaking completely.

What increases the risk?

• Long-term bisphosphonate use (more than 5 years of continuous treatment)
• Long-term glucocorticoid use (prednisone or similar medications)
• Asian ethnicity (some studies suggest slightly higher risk)
• Bowing of the thigh bones

How to protect yourself

1. Report any new thigh or groin pain to your doctor promptly — do not dismiss it as "just getting older"
2. Discuss drug holidays with your doctor after 3 to 5 years of bisphosphonate treatment — this is one of the main reasons doctors recommend periodic breaks
3. Keep your follow-up appointments — regular monitoring helps catch problems early
4. If you experience bilateral thigh pain (both sides), tell your doctor right away

It is human nature to focus on risks. But consider this:

For a 70-year-old woman with osteoporosis who takes a bisphosphonate for 3 years:

• The medication prevents an estimated 50 to 70 fractures per 10,000 women treated (including potentially life-threatening hip fractures)
• The risk of ONJ is approximately 1 per 10,000 to 100,000
• The risk of AFF is approximately 3 to 50 per 100,000

The mathematics are overwhelming: treatment prevents many more serious problems than it causes.

International expert bodies — including the American Society for Bone and Mineral Research (ASBMR), the American Association of Oral and Maxillofacial Surgeons (AAOMS), the International Osteoporosis Foundation (IOF), and the National Osteoporosis Foundation (NOF) — all affirm that for patients with osteoporosis, the benefits of treatment far outweigh the risks of these rare complications.

Do not let fear of a rare side effect stop you from protecting yourself against common, life-changing fractures. Talk to your doctor about any concerns — but please do not stop your medication on your own.

Contact your doctor if you experience:

• Jaw symptoms: Persistent jaw pain, swelling, numbness, a feeling of heaviness in the jaw, loose teeth, or exposed bone in the mouth
• Thigh or groin pain: New, unexplained pain in the thigh or groin that is not related to an injury, especially if it worsens with weight-bearing activity
• Any concern about side effects: Your doctor would rather hear from you and reassure you than have you stop treatment on your own

• See your dentist for a checkup and cleaning — mention every bone medication you take
• Practice good oral hygiene — brush, floss, and keep regular dental appointments
• Pay attention to your body — report any new thigh or groin pain to your doctor
• Do not stop your medication because of fear — talk to your doctor about your concerns
• Remember the numbers — these side effects are rare, and your medication is protecting you from far more common and serious fractures

Q: Should I stop my bisphosphonate before having a tooth pulled? A: Not necessarily — and definitely not without talking to your doctor first. For patients on oral bisphosphonates for osteoporosis, the risk of ONJ from dental procedures is very low. Your dentist and doctor can discuss the best approach for your specific situation. In many cases, dental procedures can proceed safely without stopping medication.

Q: I have been on a bisphosphonate for 7 years. Am I at higher risk for these side effects? A: Long-term use does slightly increase the risk. This is why your doctor may recommend a "drug holiday" after 3 to 5 years (or after 6 years for zoledronic acid). Talk to your doctor about whether a treatment break is appropriate for you.

Q: If I get ONJ, is it permanent? A: No. Most cases of ONJ related to osteoporosis-dose medications are mild and respond well to conservative treatment — antibiotics, antimicrobial mouth rinses, and careful monitoring. Severe cases requiring surgery are rare.

Q: Can I get dental implants while on bone medication? A: This is a conversation to have with both your dentist and your doctor. In many cases, dental implants can proceed safely, but the timing may need to be coordinated with your treatment. Your healthcare team can develop a plan that works for you.

Q: Does denosumab carry the same risks as bisphosphonates? A: The risks of ONJ and AFF exist with denosumab as well, though they remain rare. The risk profile is slightly different because denosumab does not accumulate in bone the way bisphosphonates do — its effect wears off within months of stopping. However, denosumab has its own unique concern: rebound bone loss if stopped without transitioning to another medication.

• Khan AA, et al. Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus. J Bone Miner Res. 2015;30(1):3-23.
• Shane E, et al. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the ASBMR. J Bone Miner Res. 2014;29(1):1-23.
• American Association of Oral and Maxillofacial Surgeons (AAOMS). Position Paper on Medication-Related Osteonecrosis of the Jaw. 2022 Update.
• Black DM, et al. Bisphosphonates and Fractures of the Subtrochanteric or Diaphyseal Femur. N Engl J Med. 2010;362(19):1761-1771.
• International Osteoporosis Foundation (IOF). Patient Information: Medication Safety. 2023.

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