Does long-term bisphosphonate use in an older postmenopausal woman with osteopenia increase her risk for atypical femoral fractures and minor tears, and how are they treated?

Does Long-Term Bisphosphonate Use Increase Risk for Atypical Femoral Fractures?

Yes, long-term bisphosphonate use significantly increases the risk of atypical femoral fractures (AFFs), with risk escalating sharply after 5 years of continuous therapy and becoming substantially elevated beyond 8 years of treatment. 1

Understanding the Risk Timeline

The risk profile for AFFs follows a clear temporal pattern:

• Risk begins increasing significantly after 5 years of bisphosphonate treatment 1
• Risk escalates sharply beyond 8 years, with AFF incidence rising from 1.78 per 100,000 person-years to 113 per 100,000 person-years with exposure greater than 8 years 1
• At 5 years, the AFF risk is 120 per 100,000 if treatment continues ≥3 years versus 27 per 100,000 if treatment is discontinued before 3 years 2
• By 10 years, the risk jumps to 363 per 100,000 for those treated ≥3 years compared to only 27 per 100,000 for shorter treatment 2

The overall incidence ranges from 3.0 to 9.8 cases per 100,000 patient-years, but this increases substantially with longer duration 3, 1

High-Risk Features to Monitor

Certain patient characteristics dramatically amplify AFF risk:

• Asian ethnicity carries up to 8 times higher risk than White patients (595 versus 109 per 100,000 person-years) 1
• Concurrent glucocorticoid use increases susceptibility 4, 5
• Longer treatment duration is the most consistent risk factor for both AFFs and osteonecrosis of the jaw 3, 1

Clinical Recognition of Impending AFFs

Prodromal symptoms occur in most patients before complete fracture and represent a critical window for intervention:

• Thigh or groin pain preceding fracture (present in 7 of 8 patients in one case series) 4
• Radiographic warning signs include cortical thickening, "beaking" of the cortical margin, and transverse lucency in the subtrochanteric or diaphyseal region 4, 6
• Bilateral involvement occurs in approximately 25-37% of cases, so contralateral femur imaging is mandatory when AFF is suspected 1, 4

Risk-Benefit Context

Despite the increased AFF risk, the absolute numbers remain relatively small:

• An estimated 162 osteoporosis-related fractures are prevented for every one AFF that may occur with antiresorptive treatment 1
• However, this favorable ratio deteriorates with longer treatment duration as fracture prevention benefits plateau while AFF risk continues climbing 3, 1

Treatment of Minor Tears (Incomplete Atypical Femoral Fractures)

Incomplete AFFs require immediate bisphosphonate discontinuation, protected weight-bearing, and prophylactic surgical fixation in most cases to prevent progression to complete fracture.

Immediate Management Steps

When an incomplete AFF is identified:

1. Stop bisphosphonate therapy immediately 1, 4
2. Obtain bilateral femur radiographs to assess for contralateral involvement, as 25% will have bilateral disease 1, 4
3. Implement protected weight-bearing with crutches or walker to reduce mechanical stress 4
4. Ensure adequate calcium (1000-1200 mg/day) and vitamin D (800-1000 IU/day) supplementation 3, 7

Surgical vs. Conservative Management

Prophylactic intramedullary nailing is strongly recommended for most incomplete AFFs because:

• The natural history shows high progression rates to complete fracture with conservative management 4, 8
• Complete AFFs have worse outcomes and more difficult surgical repair 8
• Bisphosphonate-altered bone has reduced fracture toughness and impaired healing capacity 8

Conservative management may be considered only if:

• The cortical lucency is very small (<50% cortical width)
• The patient can reliably maintain strict non-weight-bearing status
• Close radiographic follow-up every 4-6 weeks is feasible 4

Adjunctive Therapies

After bisphosphonate discontinuation for AFF:

• Teriparatide (anabolic therapy) may accelerate healing in incomplete AFFs, though evidence is limited to case reports 4, 6
• Do NOT use denosumab as it is also an antiresorptive agent that may perpetuate the same pathophysiology 3, 1
• Vitamin D deficiency must be corrected as it impairs fracture healing 1

Prevention Strategy for High-Risk Patients

The American College of Physicians strongly recommends stopping bisphosphonates after 5 years unless strong indications for continuation exist 3, 1:

• Patients eligible for drug holiday: no previous hip/vertebral fractures during treatment and hip BMD T-score > -2.5 1
• Patients requiring continuation beyond 5 years: previous hip/vertebral fractures, multiple non-spine fractures, or T-score ≤ -2.5 despite treatment 1
• High-risk patients on long-term therapy need periodic skeletal surveys to detect early cortical changes 4

Critical Pitfall to Avoid

If a patient suffers an AFF on one side, stopping bisphosphonates can reduce the 25% risk of contralateral fracture 1. Never continue bisphosphonate therapy after an AFF diagnosis, as this perpetuates the underlying pathophysiology of oversuppressed bone turnover 8.