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Epidemiology and definition of atypical femoral fracture (AFF)
Bisphosphonate (BP) is a potent anti-resorptive agent and was proven to be effective in prevention and treatment of osteoporosis through many randomized prospective studies. BP decreases the risk of osteoporotic vertebral and hip fractures by around 50%. However, excessive suppression of normal and pathologic bone remodeling has been a concern. Odvina et al.[1] reported nonunion after low-energy injury among patients who took BP for several years for treatment of osteoporosis. Bone biopsy revealed lack of viable osteoblasts, osteocytes, and osteoclasts in the specimen. The authors thought that prolonged suppression of bone remodeling by BP caused frozen bone. Goh et al.[2] reported atypical subtrochanteric fractures in their patients who took alendronate for several years. Fractures were caused by minor injuries and were associated with periosteal callus at the lateral femoral cortex. As the number of reports of this type of fracture increased,[3456789] the American Society of Bone and Mineral Research (ASBMR) organized a task force team and reported the results on two occasions (Fig. 1).
AFF occurs even in those patients who are not exposed to BP therapy. However, in most of the cases, AFF occurs in the patients who are taking or who took BP for several years for treatment of osteoporosis or other metabolic bone diseases. Both oral and iv BP agents have been reported to cause AFF. It is difficult to estimate the incidence of AFF due to its low occurrence in BP users. The estimated incidence of AFF is 5 to 100 per hundred thousand patient-years. AFF occurs 4 to 5 times more frequently in Asian descendants compared to Caucasians. The longer the patient takes BP, the higher the risk of AFF. Also, the higher the adherence, the higher the risk of AFF. It is time to declare that BP is the causative agent of AFF although BP decreases the incidence of hip and vertebral fractures significantly.
Diagnosis
The incidence of AFF increases significantly when the patient takes BP for 4 years or more than 4 years.[4] Prodromal symptoms such as dull pain and tenderness over the lateral aspect of the thigh are noted in 40% to 70% of the patients. It is recommended to check for prodromal symptoms if the patients are taking BP for more than 4 to 5 years. It is necessary to take a simple radiogram of the femur if AFF is suspected.
Simple radiogram often reveals a beak or flare like periosteal and/or endosteal callus in the lateral femoral cortex. Sometimes, the so-called 'dreaded black line' can also be detected in the lateral cortex. If the simple radiogram appears looks normal even though the patient complains of prodromal symptoms, then bone scan or magnetic resonance imaging (MRI) examination can identify tiny lesions in the lateral aspect of the femur. In Korea, dual energy X-ray absorptiometry (DXA) examination of axial bone is performed every year to obtain reimbursement from national insurance. We may occasionally detect a tiny periosteal callus in the lateral aspect of the femoral cortex (Fig. 2, 3).[11]
Medical treatment
BP should be stopped immediately after AFF is diagnosed and calcium and vitamin D (1,000 to 2,000 IU) should be administered. The patient should be advised not to put full weight on the injured limb. Daily subcutaneous injection of recombinant human parathyroid hormone (PTH; 1-34) is recommended if the patient can afford it. Prophylactic femoral nailing is indicated when the dreaded black line is visible in the lateral femoral cortex, especially in the subtrochanteric area.[12]
Surgical treatment
Intramedullary nailing is the treatment of choice for AFF. However, excessive femoral bowing, which is often associated with AFF, is an obstacle during femoral nailing. It causes an iatrogenic fracture and straightening of the femur.(Fig. 4) Delayed healing is reported in 28% of the cases, but the real incidence seems to be higher. In order to prevent delayed union or nonunion, restoration of correct anatomical alignment is recommended after intramedullary nailing. Minor malreduction, which is acceptable in cases of ordinary fracture, occasionally causes nonunion and metal failure in AFF. Daily subcutaneous injection of recombinant human PTH (1-34) is also recommended after surgical fixation. Careful examination of the contralateral femur is recommended because of the high incidence of bilateral lesions.[12]
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