Atypical Femoral Fractures: Findings and Task Force Recommendations Based on the Symposium

1. Atypical Femoral Fractures: • Findings and • Task Force Recommendations • Based on the Symposium • “Task Force Report on Atypical Femoral Fractures” • Chairs: Elizabeth Shane, David Burr • Speakers: Elizabeth Shane, Thomas Einhorn, Bo Abrahamsen, Peter Ebeling, David Burr • Saturday, October 16, 2010 • ASBMR 2010 • Toronto, Ontario • And the publication • Atypical subtrochanteric and diaphyseal femoral fractures: • Report of a Task Force of the American Society for Bone and Mineral Research. • Shane et al. JBMR 2010;Epub ahead of print.

2. Rationale for the Task Force • • Reports linking long-term use of the bisphosphonates (BPs) • with atypical femoral fractures (AFFs) • • AFFs are rare in both the general population and BP-treated patients,accounting for <1% of all hip/thigh fractures but have been reported most prominently in individuals who have been treated with BPs • • The Task Force reviewed 310 cases of atypical subtrochanteric and diaphyseal femoral fractures. Ninety-four per cent of patients had taken BPs, most for more than 5 years

3. Bisphosphonate Facts • In patients at high risk of osteoporotic fracture, the benefits of BP use far outweigh the risk of AFF • FIT (Fracture Intervention Trial): • • In women without baseline vertebral fractures, BP use prevented 700 non-vertebral and 1000 clinical vertebral fractures per 100,000 person-years • • In women with prior vertebral fractures, BPs would prevent 1000 non-vertebral and 2300 clinical vertebral fractures per 100,000 person-years

4. What are AFFs? • • Most commonly observed in the proximal one-third of the femoral shaft • • Typically occur as a result of no or minimal • trauma (fall from a standing height or less) • • May be incomplete, manifested by a transverse radiolucent line in the lateral cortex • • Complete AFFs are generally transverse • • Complete and incomplete fractures are • commonly associated with a periosteal stress • reaction and thickening of the lateral cortex • at the fracture site • • Healing may be delayed • On X-ray, presentation of an AFF appears similar to a stress fracture or a pseudofracture

5. Signs and Symptoms of AFF • • Approximately 70% of patients with confirmed stress fracture report prodromal pain in the thigh or the groin several weeks prior to the diagnosis • – Pain can be anywhere from aching to sharp, generally in the thigh bone but occasionally in the groin • • Approximately 25% of patients with AFF have simultaneous or sequential bilateral fractures • • AFFs often occur in the setting of comorbid conditions with known adverse events on bone quality including glucocorticoid therapy or vitamin D deficiency • • Pain is exacerbated on weight bearing

6. AFF Incidence Rate • • The overall incidence of hip fracture is 103 per 10,000 person-years • • In the SOF (Study of Osteoporotic Fractures), the incidence of subtrochanteric fractures was very low at 3 per 10,000 person-years • • The highest incidence rate comes from preliminary estimates from a large US HMO survey indicating the incidence of AFF increases progressively from 2 per 100,000 cases per year with 2 years of BP use to 78 per 100,000 cases per year with 8 years of BP use • • In the SOF, predictors of subtrochanteric hip fracture are: • – Older age • – Lower total hip BMD • – A history of falls • • AFF can occur in the absence of BP exposure • Note: While fractures are certainly associated with BP use, BP use may or may not be causal.

7. Prevalence of AFF • A population-based study in Olmsted County, Minnesota, compared incidence rates of minimally traumatic non-hip femoral fractures (NHFF) before and after 1996, when alendronate was approved for OP. Rates were compared to historical incidence rates from 1965 to 1984 • • The total cumulative age and sex-adjusted incidence of NHFF from 1984 to 2007 was 26.8 per 100,000 person-years • • Incidence rates for first-ever NHFF for women increased between 1984 and 1995 as well as between 1996 and 2007 (P=0.001) but did not change for men (P=0.125) • • Between 1984 and 1995 (prior to alendronate), the cumulative incidence was 21.9 per 100,000 person-years while between 1996 and 2007 (after alendronate), the cumulative incidence was 30.4 per 100,000 person-years • Ng et al. ASBMR 2010, Abstract 1200.

8. Key Task Force Recommendations • • Physicians and patients should be made aware of the possibility of AFF through a change in labelling of BP • • New diagnostic and procedure codes should be developed for AFF to improve quality of case reporting and better review of medical records • • An international registry should be established to better identify and track patients experiencing AFF • • More research is needed to determine whether and how BPs cause these uncommon fractures • • Patients at high risk of osteoporotic fracture should not stop taking BPs out of fear of developing AFF as BPs prevent far more hip fractures than the AFFs possibly may cause