3.18 Atypical fractures
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1 Introduction
Bisphosphonate (BP) therapy has been widely used for management of osteoporosis and has been shown to reduce the risk of vertebral and femoral neck fractures in postmenopausal osteoporotic patients. The use of BPs is also extended to metabolic bone diseases including Paget′s disease, hypercalcemia due to a variety of causes, and skeletal metastases from cancer.
Long-term suppression of bone remodeling may impair microdamage repair and alter the biomechanical properties of bone. Overmineralization may have deleterious effects on bone quality, elasticity, and resistance in the long term. Long-term oversuppression of bone turnover with BPs has generated many reports of spontaneous peripheral fractures [1–4]. These so-called atypical femoral fractures occur after minimal trauma and have a distinct pattern and radiographic appearance when compared with typical osteoporotic fractures ( Case 1: Fig 3.18-1 ). Although the subtrochanteric femoral location is the usual site of these atypical fractures, other weight-bearing sites have also been affected, including tibia, ulna, and other bones [5, 6].
In this chapter, we mainly describe atypical fractures of the femur that have been widely reported and are clinically important.
2 Epidemiology and etiology
All current evidence indicates that the atypical femoral fracture (AFF) represents a rare subset of subtrochanteric and femoral shaft fractures. The atypical femoral fracture has been associated with various factors, including Asian ethnicity, the use of BPs, glucocorticoids, and proton pump inhibitors, as well as medical conditions including rheumatoid arthritis, diabetes mellitus, or vitamin D deficiency.
Long-term use of BPs represents a relevant risk factor:
The American Society for Bone and Mineral Research (ASBMR) task force reported an incidence of 2 per 100,000 cases per year after 2 years of BP use, increasing to 78 per 100,000 cases per year after 8 years of use [4].
Almost 40% of patients who sustained a subtrochanteric or femoral shaft fracture had used BPs for a significantly longer period than subjects who sustained an intertrochanteric or femoral neck fracture.
However, there has been no statistically significant increase in the risk of subtrochanteric femoral fracture in patients treated with BPs for as long as 10 years.
Therefore, there is a lack of specificity for associating BP use only with AFFs.
There have been several studies speculating about the etiology. It is likely multifactorial, although no specific underlying mechanism has been demonstrated.
Bisphosphonates inhibit osteoclast function and induce osteoclast apoptosis, and thus, they increase bone mineral density and suppress bone turnover. It has been suggested that this change in bone metabolism produces hypermineralized bone that is more brittle and therefore more susceptible to low-energy or stress fractures.
CASE 1
Patient
A 61-year-old woman suffered a subtrochanteric fracture of the right femur after slipping and falling in her kitchen. Bisphosphonates had been used in this patient for more than 5 years to treat osteoporosis.
Comorbidities
Osteoporosis
Treatment and outcome
After the patient had suffered a subtrochanteric fracture of the right femur, a periosteal reaction was seen on the lateral cortex of the left femur, at the same level of the fracture as on the right femur ( Fig 3.18-1a ). Intramedullary nailing was performed in both femurs ( Fig 3.18-1b–c ). Fracture healing was achieved on the right femur, and the previous stress reaction disappeared on the left femur ( Fig 3.18-1d–e ).
Recently, it has been suggested that there may be an association between proximal or diaphyseal femoral geometry and the presence of AFFs. Hagen et al [7] reported that an association between varus proximal femoral geometry and a propensity to sustain AFFs in patients taking long-term BP therapy existed. Sasaski et al [8] also found that a significant increase in the lateral and anterior bow of the femur was associated with low-energy femoral shaft fractures. These patients were taking medications for osteoporosis but not exclusively BPs. The alteration of femoral geometry may result in an imbalance in strains and develop an AFF partly for biomechanical reasons.
3 Localization
Atypical fractures usually affect the femur as described. However, these fractures may also occur in other long bones including the tibia, ulna, clavicle, and pedicles of vertebrae [9–11]. Particularly in a patient taking long-term BPs, long bones with weight-bearing function may be susceptible to fractures,. In that situation, prompt investigation should be performed with x-rays and other modalities.
Recently, BP-induced periprosthetic fractures of the femur have been reported. As a high proportion of older osteoporotic patients are undergoing hip replacement, arthroplasty surgeons should consider the possibility of AFFs in patients receiving long-term BPs who present with thigh pain despite a well-fixed femoral component.
4 Diagnostics
It is inappropriate to screen all patients with prolonged BP treatment for AFFs, as the incidence is low and the actual incidence of abnormal radiographic features in the entire patient population taking BPs is unknown. The ASBMR defined AFF as atraumatic or low-trauma fractures located in the subtrochanteric region or femoral shaft [4]. The diagnosis of AFF specifically excludes high-trauma fractures, fractures of the femoral neck, intertrochanteric fractures with spiral subtrochanteric extension, pathological fractures associated with primary or metastatic bone tumors, and periprosthetic fractures.
4.1 Clinical symptoms
It seems to be important to raise awareness of prodromal symptoms of atypical fractures to facilitate the early diagnosis of an incomplete lesion. The development of groin or thigh pain in a patient on long-term BP treatment should raise the index of suspicion of an AFF. If the patient is at high risk, the same applies but for other reasons such as rheumatoid arthritis, diabetes, or the use of glucocorticoid therapy. As AFFs may represent stress fractures that progress over time, the pain in the thigh may be the only clinical symptom in incomplete fractures. It often comes with severe and constant pain in the lateral area of the affected hip and/or radiating to the knee area. Usually with this prodromal pain, the complete fracture develops with low-energy trauma, such as an injury caused by the equivalent to a fall from a standing height or less.
4.2 Imaging
4.2.1 Plain x-rays
Characteristic radiographic features of AFFs are as follows:
There is no comminution.
There is a transverse fracture line at the point of origination in the lateral cortex.
As the fracture propagates across the diaphysis to the medial cortex, the orientation may become more oblique and when it becomes complete, a prominent medial “spike” may be present.
Focal or diffuse periosteal reaction of the lateral cortex surrounding the region where the fracture initiated. This reaction may appear as cortical “beaking” or “flaring” adjacent to a discrete transverse lucent fracture line, or as focal thickening of the lateral cortex.
Focal and diffuse endosteal reactions near the fracture site. This focal cortical thickening represents cortical hypertrophy and may be unilateral or bilateral.
Generalized cortical thickening.
Incomplete lesions can often convert to complete or displaced fractures by low-energy mechanisms, when a preceding history of thigh pain has been present in the ipsilateral extremity. Therefore, it is important to find the precursor lesion, which may need preventive treatment. Koh et al [12] described the presence of the ‘‘dreaded black line’’ (ie, a form of transverse radiolucency) indicative of increased risk of developing a complete insufficiency fracture. This line was interpreted as accumulated, partially healed microdamage.
4.2.2 Magnetic resonance imaging
As radiographic findings alone may not be sufficient to support preventive measures, magnetic resonance imaging (MRI) or technetium (Tc) bone scintigraphy should be considered if a stress fracture is suspected. Magnetic resonance imaging findings of an incomplete AFF are often visible before they become evident on plain x-rays and they include:
An incomplete cortical stress reaction that has been detected [13].
A prominent or complete line from the outer to the inner border of the lateral cortex, which seems to be the precursor of the lesion on plain x-rays.
Serial axial and coronal MRIs may reveal intracortical damage or the presence of bone marrow edema in contrast with only focal cortical protrusion or a faint transverse line on plain x-rays.
If these findings are associated with thigh pain, it can have the potential to develop into a complete fracture.
4.2.3 Bone scintigraphy
Three-phase skeletal scintigraphy with Tc-99m methylene diphosphonate can identify incomplete AFFs. Focal tracer uptake may be shown at the lesion ( Case 2: Fig 3.18-2 ). It is particularly useful to find the lesion of the contralateral side when a complete fracture has developed. In incomplete lesion, focal tracer uptake may be shown at the lesion. Also, mild uptake in multifocal endosteal thickening of the lateral femoral diaphysis can be noted, which is diagnostic of a BP-associated AFF in the femoral shaft.
CASE 2
Patient
A 53-year-old woman had thigh pain for 3 months, which progressively increased over the course of time. She had a medical history of rheumatoid arthritis and use of corticosteroids ( Fig 3.18-1a–b ).
Comorbidities
Rheumatoid arthritis
Treatment and outcome
The patient′s thigh pain progressively increased. There was visible thickening of the lateral cortex of the femur as well as a localized lesion in the subtrochanteric area ( Fig 3.18-2a–b ). A so-called “dreaded black line” was detected at the lateral cortex of the subtrochanteric area, which was shown on magnetic resonance imaging to be a stress reaction. Therefore, a prophylactic fixation was recommended to this patient ( Fig 3.18-2c–d ). On the day of admission for planned surgery, the patient had a fracture after falling and suffered a subtrochanteric fracture at the same height as the previously diagnosed area ( Fig 3.18-2e ). Intramedullary nailing was performed ( Fig 3.18-2f–g ) resulting in healing 6 months postoperative ( Fig 3.18-2h–i ).
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