Bisphosphonates are widely prescribed medications used to strengthen bone and prevent fractures in conditions such as osteoporosis. They have been shown to significantly reduce the risk of hip, vertebral, and other fragility fractures. However, with long-term use, a small number of patients may develop an atypical femoral fracture, a rare type of break that occurs with minimal or no trauma. Understanding how and why these fractures arise is essential for prevention and early detection. What is the relationship between bisphosphonates and fractures? 

What Are Bisphosphonates?

Bisphosphonates, such as alendronate, risedronate, and zoledronic acid, work by reducing bone resorption. They inhibit osteoclasts, the cells that break down bone, thereby increasing bone density over time. While this helps prevent osteoporotic fractures, long-term suppression of bone turnover can also make the bone more brittle and less able to repair stress damage.

What Is an Atypical Femoral Fracture?

An atypical femoral fracture is a rare type of break that usually occurs in the shaft or just below the lesser trochanter of the femur. These fractures differ from typical osteoporotic fractures, which typically involve the femoral neck or spine. They are called “atypical” because of their unusual location, characteristic appearance of a transverse fracture, and the fact that they often occur with little or no trauma. They tend to happen in people who have been on bisphosphonates for many years, typically more than five.

Generally, these fractures start in the outer (lateral) part of the femur bone. 

Incidence and Risk Factors

The risk of atypical femoral fracture increases with the duration of bisphosphonate use. Estimates suggest an incidence of 3 to 50 cases per 100,000 patient-years — very low compared with the number of fractures prevented by these medications.

Risk factors for atypical femoral fractures include:

  • Prolonged bisphosphonate therapy – usually beyond 5 years

  • Other prescription drug use, such as proton pump inhibitor (omeprazole), corticosteroid and denosumab (another drug for osteoporosis)

  • Vitamin D deficiency

  • Certain genetic factors affecting collagen or bone metabolism

  • Asian population 

Despite these associations, the benefits of bisphosphonates in fracture prevention outweigh the risks.

Clinical Presentation of Atypical Femoral Fracture 

Patients with atypical femoral fractures often report dull, aching pain in the thigh or groin that develops gradually over weeks or months. The pain is often on one side but may affect both sides. In some cases, the fracture occurs spontaneously during normal walking or minor activities.

Studies suggest that 30-70% of patients experience early warning pain — before a complete break occurs. These symptoms occur from 2 weeks to 2 years before a complete fracture occurs. Because these symptoms can be subtle, they are often overlooked until the fracture has fully developed. Sometimes, there are no warning signs before the break occurs. 

There are other reports of atypical fractures in different areas, such as the tibia and wrist. But the incidence is much lower than that of the femur. 

Investigations

Diagnosis starts with a high index of suspicion in patients on long-term bisphosphonate therapy who report thigh or groin pain.

  • X-rays typically show a transverse fracture pattern on the lateral femoral cortex, often with a beak-like thickening (periosteal reaction). The medial cortex may remain intact in early stages.

  • MRI can detect stress reactions or incomplete fractures before they progress. MRI is particularly sensitive for early bone oedema and cortical thickening. Bilateral imaging is essential, as up to 25% of patients may have changes or fractures in both femurs.

Blood tests may include calcium, phosphate, vitamin D, and bone turnover markers to assess metabolic bone status.

Management of Atypical Femoral Fracture 

Treatment depends on whether the atypical femoral fracture is complete or incomplete.

Incomplete fractures (where the bone has not completely broken):

Treatment depends on the presence of hip or thigh pain. 

In cases of no pain, most doctors recommend medical management, including optimising Vitamin D and calcium levels and stopping high-impact activities such as running and jumping. If pain occurs, protected weight-bearing should begin. 

In cases of pain, treatment is controversial. Generally, surgery with a femoral nail to prevent a fracture is advised, as outcomes are better. A recent review found that patients treated with surgery were more likely to be pain-free at follow-up than those treated with medical management (84 vs 64%). 

Complete fractures,

Surgical fixation using an intramedullary nail is the standard of care. These fractures can be slow to heal, and close follow-up is essential. Care should be taken when inserting a femoral rod, as atypical fractures lead to bone bowing, making it difficult to insert the nail. Complications include malunion, leg length discrepancy and gapping of the fracture site on the inside. 

Alternative bone therapies may be introduced after stopping bisphosphonates, such as anabolic agents (e.g., teriparatide), which stimulate bone formation and promote healing. Recent studies suggest that teriparatide has positive effects on femoral fracture healing. 

Follow-Up and Prevention

Patients who have been on bisphosphonates for more than five years should have their therapy reviewed. In low-risk patients, a “drug holiday” of 2-3 years may be appropriate, allowing bone turnover to recover while maintaining some residual benefit.

Regular monitoring for thigh or groin pain and early imaging when symptoms develop are critical in preventing progression to a complete fracture.

Final Word from Sportdoctorlondon about Atypical Femoral Fracture 

Atypical femoral fracture is a rare but recognised complication of long-term bisphosphonate use. While the overall benefits of these drugs in preventing osteoporotic fractures remain clear, awareness of this condition allows for early detection and timely management. Patients on long-term bisphosphonates who develop unexplained thigh or groin pain should seek assessment — early imaging can identify incomplete fractures before they become serious. In most cases, stopping the drug, correcting nutrition, and using alternative therapies can help restore bone health and reduce risk.

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