Bisphosphonates have been in use since the 1960s for the treatment of osteoporosis. They reduce bone resorption by inhibiting the action of osteoclast cells and also by inducing osteoclast apoptosis.1, 2 Since 2005, multiple studies have shown an increased prevalence of minimal-trauma subtrochanteric and diaphyseal femoral fractures in patients taking long-term bisphosphonate therapy.2, 3, 4, 5, 6, 7, 8, 9, 10 It is presumed that bisphosphonates disrupt the balance in bone turnover and remodeling, thereby leading to microdamage over time.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 This predisposes the individual to increased skeletal fragility and can lead to atypical fractures in the subtrochanteric or femoral shaft regions.2, 3, 4, 5, 6, 7, 8, 9, 10 This increased fracture risk has been reported in individuals who have been on bisphosphonate therapy for more than 3-9 years.5, 6, 7, 8, 9, 10, 11 In 70% of patients there is a prodrome of weeks or months of thigh or groin discomfort with weight bearing before the fracture occurs.6 In 2013 a task force proposed a case definition of atypical femoral fractures: location along the femoral diaphysis from distal to the lesser trochanter to proximal to the supracondylar flare and at least 4 of 5 major features: minimal or no trauma; fracture line originates at the lateral cortex and is substantially transverse in orientation (although it may become oblique as it progresses medially across the femur); complete fractures extending through both cortices and may be associated with a medial spike and incomplete fractures involving only the lateral cortex; localized periosteal or endosteal thickening of the lateral cortex present at fracture site (beaking or flaring); and lack of (or minimal) comminution. Minor criteria include increased cortical thickness of the femoral diaphysis, bilateral incomplete or complete femoral diaphysis fractures, prodrome of thigh or groin pain, and delayed fracture healing.10 Imaging results in these individuals show a distinct beak-appearing pattern of thickening of the lateral femoral cortex, a transverse orientation of the fracture, and lack of comminution.4, 6, 9, 10,11, 12 Several studies have also reported the presence of a stress reaction or fracture line of the contralateral femur.4, 5, 6 The delay in diagnosis and treatment of atypical fractures may result from a lack of knowledge of this condition.6, 13
We present the case of a 62-year-old woman who was admitted to a hospital-based hip fracture program with an atypical low-energy right subtrochanteric femur fracture. She presented with severe right hip pain after pivoting her right hip and lowering herself gently to the floor. Before this, she reported having bilateral hip pain for the past 2 months, right worse than the left. She was previously diagnosed with osteoporosis (bone density test with a lumbar spine T-score of −2.6) and had taken alendronate 70 mg weekly for 6 years. She was treated with omeprazole 20 mg daily since age 40 years for severe reflux disease. She reported a history of early menopause, with cessation of menstrual cycles after the age of 42 years, and had been taking estrogen 0.625/medroxyprogesterone 2.5 mg daily for 10 years until age 52 years. Since the age of 50 years she had been taking calcium and vitamin D supplementation once daily. Her alcohol intake included 2 to 3 beverages daily since her 20s, and she had a remote smoking history. Nine months before presentation she sustained a right fifth metatarsal Jones fracture after merely stepping on uneven ground. This required an uneventful open reduction and internal fixation, and fracture healing was achieved.
Assessment
The initial right hip radiographs were concerning for an atypical right subtrochanteric hip fracture with cortical thickening and a transverse fracture pattern (Figure 1). Further imaging with magnetic resonance imaging of the hip showed a distinct pattern of a stress reaction, with lateral cortical thickening surrounding the area of the fracture (Figure 2). Because of the suspicious injury mechanism and fracture pattern atypia, a metastatic workup consisting of computed tomography scans of the chest/abdomen/pelvis were done and showed no evidence of malignancy. Laboratory studies revealed normal values for calcium, total vitamin 25-hydroxy-D, intact parathyroid hormone, albumin, and alkaline phosphatase. The patient underwent right hip repair of her fracture with cephalomedullary fixation. Magnetic resonance imaging of her contralateral hip was performed to evaluate her chronic left thigh pain, because of suspicion of an occult fracture. This also showed evidence of a significant stress reaction and cortical thickening, but without evidence of an obvious fracture at the subtrochanteric region (Figure 3). However, the orthopedic surgeon believed that the patient was at high risk for developing a fracture and recommended prophylactic surgery to stabilize her left hip. Intraoperatively she was found to actually have a transverse hairline fracture in the left subtrochanteric region and therefore underwent prophylactic cephalomedullary fixation of the left hip 3 days after her initial right hip surgery (Figure 4). Deep bone biopsies of both hips were negative for malignancy and notable only for reactive bone, cartilage, and fibroconnective tissue.
To read this article in its entirety please visit our website.
-Lisa N. Miura, MD, Sandhya V. Srikantom, MD, Joseph Schenck, MD
This article originally appeared in the January 2017 issue of The American Journal of Medicine.
