Bisphosphonates are widely prescribed to strengthen bone and prevent fractures in conditions such as osteoporosis, and they substantially reduce the risk of hip, spine, and other fragility fractures. But with long-term use, a small number of people may develop an atypical femoral fracture — a rare break that occurs with minimal or no trauma. Understanding why these fractures arise is key to preventing and catching them early. So what’s the relationship between bisphosphonates and fractures?

Important: This is a rare complication, and for most people, the benefits of bisphosphonates far outweigh the risks. Never stop a bisphosphonate on your own — it’s a decision to make with your doctor.

What are bisphosphonates?

Bisphosphonates — such as alendronate, risedronate, and zoledronic acid — reduce bone resorption. They block osteoclasts, the cells that break down bone, increasing bone density over time. This prevents osteoporotic fractures, but very long-term suppression of bone turnover can also make bone more brittle and less able to repair stress damage.

What is an atypical femoral fracture?

An atypical femoral fracture is a rare break, usually in the shaft of the femur or just below the lesser trochanter. It differs from typical osteoporotic fractures, which usually involve the femoral neck or spine. It’s called “atypical” because of its unusual location, its characteristic transverse (straight across) appearance, and the fact that it often happens with little or no trauma. These fractures tend to occur in people who’ve taken bisphosphonates for many years — typically more than five — and usually start in the outer (lateral) part of the femur.

How common is it, and who’s at risk?

The risk rises with the duration of bisphosphonate use, but it remains very low — an estimated 3 to 50 cases per 100,000 patient-years, tiny compared with the number of fractures these drugs prevent.

Risk factors include prolonged bisphosphonate therapy (usually beyond five years), other medications (proton pump inhibitors such as omeprazole, corticosteroids, and denosumab), vitamin D deficiency, certain genetic factors affecting collagen or bone, and Asian ancestry. Even so, for most people, the fracture-prevention benefits of bisphosphonates outweigh these risks.

Warning signs of an atypical femoral fracture

People often report a dull, aching pain in the thigh or groin that gradually builds over weeks or months, usually on one side but sometimes on both. Occasionally, the fracture happens spontaneously during normal walking.

Crucially, 30–70% of people get warning thigh pain before the bone completely breaks, from as early as two weeks to as long as two years beforehand. Because this pain can be subtle, it’s often overlooked until the fracture is complete. This is the single most important message of the page: new thigh or groin pain in someone on long-term bisphosphonates should be checked promptly. (Atypical fractures occasionally occur elsewhere, such as the tibia or wrist, but far less often than the femur.)

Investigations

Diagnosis starts with suspicion in anyone on long-term bisphosphonates who reports thigh or groin pain.

  • X-rays typically show a transverse fracture on the outer femoral cortex, often with a beak-like thickening (periosteal reaction); the inner cortex may be intact early on.
  • MRI can detect a stress reaction or an incomplete fracture before it progresses, and is especially sensitive to early bone oedema and cortical thickening. Imaging both legs is essential, as up to 25% of people have changes in both femurs.
  • Blood tests (calcium, phosphate, vitamin D, and bone turnover markers) assess the metabolic status of the bone.

Management of an atypical femoral fracture

Treatment depends on whether the fracture is complete or incomplete.

Incomplete fractures (bone not fully broken)

If there’s no pain, most doctors recommend medical management — optimising vitamin D and calcium and stopping high-impact activities such as running and jumping — with protected weight-bearing if pain develops. If there is pain, treatment is more debated. Still, surgery with a femoral nail to prevent a complete fracture is generally advised, as outcomes are better — one review found that surgically treated patients were more likely to be pain-free at follow-up than those managed medically (84% vs 64%).

Complete fractures

Surgical fixation with an intramedullary nail is the standard of care. These fractures can be slow to heal, so close follow-up is essential. Surgery can be technically harder because atypical fractures often occur in bowed bone, and complications include malunion, leg-length difference, and gapping at the fracture site.

After stopping the bisphosphonate, anabolic (bone-building) agents such as teriparatide may be introduced to stimulate bone formation and aid healing, which recent studies suggest helps femoral fracture healing.

Follow-up and prevention

Anyone on bisphosphonates for more than five years should have their therapy reviewed. In low-risk people, a “drug holiday” of 2–3 years may be appropriate — allowing bone turnover to recover while keeping some residual benefit. But this is always a decision for your doctor, balancing fracture-prevention benefits against the small risk of atypical fractures. Reporting thigh or groin pain promptly and seeking early imaging when it occurs are key to preventing progression to a complete fracture.

Frequently asked questions about atypical femoral fractures

Should I stop my bisphosphonate because of this risk?

Not on your own. Atypical femoral fractures are rare, and bisphosphonates prevent far more fractures than they cause. Whether to continue, pause (“drug holiday”), or switch is a decision for your doctor, based on how long you’ve taken the drug and your fracture risk.

What’s the warning sign of an atypical femoral fracture?

New, dull thigh or groin pain in someone on long-term bisphosphonates — often one-sided, building over weeks to months. Because warning pain precedes 30–70% of these fractures, this symptom should always be assessed, ideally with imaging.

How long do you have to take bisphosphonates before the risk of adverse effects increases?

The risk increases mainly after about five years of use, which is why long-term therapy is reviewed at that point. The risk falls again after stopping the drug.

How is an atypical femoral fracture different from a normal hip fracture?

A typical osteoporotic fracture is usually at the femoral neck after a fall. An atypical fracture is lower, in the femoral shaft, runs straight across, and often occurs with little or no trauma — a different pattern that points to the bisphosphonate link.

Can the bone heal, and can I take other osteoporosis treatments?

Yes. After stopping the bisphosphonate, correcting vitamin D and calcium and using a bone-building drug such as teriparatide can aid healing. Your doctor will plan ongoing osteoporosis treatment to keep protecting your bones.

Final word from Sport Doctor London about atypical femoral fractures

An atypical femoral fracture is a rare but recognised complication of long-term bisphosphonate use. The overall benefits of these drugs in preventing osteoporotic fractures remain clear, but awareness allows early detection. Anyone on long-term bisphosphonates who develops unexplained thigh or groin pain should seek assessment, as early imaging can find an incomplete fracture before it becomes serious. In most cases, reviewing the drug regimen, correcting nutrition, and using alternative therapies help restore bone health and reduce risk.

If you’re on long-term bisphosphonates and have unexplained thigh or groin pain, Dr Masci can assess you in London and arrange the right imaging. Contact the team here or call +44 (0) 203 488 0350.

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