Current Understanding of Epidemiology, Pathophysiology, and Management of Atypical Femur Fractures

Abstract

Purpose of ReviewTo summarize reports published since the 2013 American Society of Bone and Mineral Research Task Force Report on atypical femoral fractures (AFF).Recent FindingsThe absolute incidence of AFFs remains low. AFFs are primarily associated with prolonged bisphosphonate (BP) exposure, but have also been reported in unexposed patients and those receiving denosumab for osteoporosis and metastatic bone disease. Asians may be more susceptible to AFFs. Lateral femoral bowing and varus hip geometry, which increase loading forces on the lateral femoral cortex, may increase AFF risk. Altered bone material properties associated with BP therapy may predispose to AFFs by permitting initiation and increasing propagation of micro-cracks. Relevant genetic mutations have been reported in patients with AFFs. Single X-ray absorptiometry femur scans permit early detection of incomplete and/or asymptomatic AFFs. Orthopedists recommend intramedullary rods for complete AFFs and for incomplete, radiologically advanced AFFs associated with pain and/or marrow edema on MRI. Teriparatide may advance AFF healing but few data support its efficacy.SummaryGreater understanding of biological and genetic predisposition to AFF may allow characterization of individual risk prior to initiating osteoporosis therapy and help allay fear in those at low risk for this complication, which remains rare in comparison to the osteoporotic fractures prevented by antiresorptive therapy.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition

“…(114,115) AFFs can occur in the general population but are most common in patients who are taking bisphosphonates. (117)(118)(119)(120)(121) It is difficult to be sure of the background incidence of an event as rare as AFF. (117)(118)(119)(120)(121) It is difficult to be sure of the background incidence of an event as rare as AFF.…”

“…(124,125) Patients who are Asian, (114,117) relatively younger (<65 to 70 years old), (124,126) with higher bone mineral density, (127) or have used glucocorticoids for 1 year or more (128) may also have an increased AFF risk. Metabolic factors, such as impaired response of parathyroid hormone to hypocalcemia, and bone mechanical/geometric factors (eg, neck-shaft angle) have been suggested as contributing to the risk of AFF.…”

“…(116) There have also been reports of AFF occurring in patients on denosumab and other medications, although many (but not all) of the reported patients also had extensive prior exposure to bisphosphonates. (117)(118)(119)(120)(121) It is difficult to be sure of the background incidence of an event as rare as AFF. Moreover, epidemiologic studies describing the incidence of AFF in the general population and in bisphosphonate users vary in the use of radiographic adjudication in their case definitions, as well as study design, treatment and comparator groups, and populations, which adds to the uncertainty.…”

“…Metabolic factors, such as impaired response of parathyroid hormone to hypocalcemia, and bone mechanical/geometric factors (eg, neck-shaft angle) have been suggested as contributing to the risk of AFF. (124,125) Patients who are Asian, (114,117) relatively younger (<65 to 70 years old), (124,126) with higher bone mineral density, (127) or have used glucocorticoids for 1 year or more (128) may also have an increased AFF risk. Genetic risk factors may exist as well, although evidence is still developing.…”

Atypical femoral fractures related to bisphosphonate use: a comprehensive review of 19 patients

“…[2][3][4] However, studies have shown that long-term use of BPs may result in atypical femur fractures (AFF). [5][6][7] The definition of an AFF suggested by the American Society for Bone and Mineral Research (ASBMR) task force in 2010 was revised in 2013. According to this, AFFs were defined as fractures located in femoral diaphysis between the distal part of the lesser trochanter and the proximal part of the supracondylar region and that meet at least four of the five major criteria ( Table 1).…”