Central Annals of Orthopedics & Rheumatology

Cite this article: Chaudhary SR, Edwards N, McCarthy CL (2020) Radiological Review of Unusual Femoral Fractures. Ann Orthop Rheumatol 7(1): 1092.

*Corresponding authorCatherine L McCarthy, Department of Radiology Nuffield Orthopaedic Centre, Oxford University Hospitals, Windmill Road, OxfordOX3 7LD, United Kingdom, Tel: +441865738196, Email: catherinemccarthy@doctors.org.uk

Submitted: 26 October 2020

Accepted: 06 November 2020

Published: 09 November 2020

Copyright© 2020 Chaudhary SR, et al.

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Review Article

Radiological Review of Unusual Femoral FracturesSnehansh R Chaudhary, Nathan Edwards and Catherine L McCarthy*Department of Radiology, Nuffield Orthopaedic Centre, Oxford University Hospitals, United Kingdom

Keywords• Unusual femoral fractures• Atypical femoral fracture (AFF)• Stress fracture• Insufficiency fracture• Pathologic femoral fracture

Abstract

Femoral fractures may be caused by direct acute trauma or other causes which are broadly classified into stress fracture, insufficiency fracture, atypical femoral fracture or pathologic fracture and may be grouped together as unusual femoral fractures. Familiarity and recognition of the specific imaging features of unusual femoral fractures is important to ensure early identification, characterisation and appropriate management of these fractures. The aim of this review to is to illustrate the characteristic imaging features of unusual femoral fractures and the role of different radiological modalities including plain radiographs, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), technitium-99m bone scintigraphy and single-photon emission computed tomography (SPECT).

ABBREVIATIONSAFF: Atypical Femoral Fracture; CT: Computed Tomography;

MRI: Magnetic Resonance Imaging; SPECT: Single-Photon Emission Computed Tomography; PET: Positron Emission Tomography; STIR: Short T1 Inversion Recovery; ASBMR: The American Society for Bone and Mineral Research

INTRODUCTIONFemoral fractures may be caused by direct acute trauma or

other causes which are broadly classified into stress fracture, insufficiency fracture, atypical femoral fracture or pathologic fracture.

A stress fracture, also referred to as fatigue fracture, is caused by overuse from chronic repetitive stress on normal bone and is usually seen in weight-bearing bones of athletes.

An insufficiency fracture, also known as fragility fracture, results from normal stresses through bones of reduced strength, which is primarily due to senile or postmenopausal osteoporosis, as well as secondary causes such as renal osteodystrophy and hyperparathyroidism amongst many others [1].

Bisphosphonates have been in wide use to prevent fragility fractures, [2] after multiple clinical trials [3,4] established their long-term efficacy. In 2005, suppressed bone turnover was first suggested as a complication of bisphosphonates [5] and in 2008,the term ‘atypical fracture’ was coined based on characteristic and distinct patterns of femoral fractures caused by bisphosphonate therapy [6].

A pathologic fracture, by definition, is any fracture through an area of underlying bone pathology. This may be either due to an underlying bone tumour (benign or malignant) or non-neoplastic skeletal or metabolic abnormality although a fracture as a result of the latter group of disease processes is commonly classified under insufficiency fracture due to secondary causes [1,7,8] and we have presented it as such in this paper.

Stress, insufficiency, atypical and pathologic femoral fractures form a spectrum of fractures of the femur which are not directly caused by straight forward acute trauma and maybe grouped together as unusual femoral fractures (Table 1). These fractures have unique imaging features and recognising them is important for appropriate and timely treatment of patients. The aim of this review to is to illustrate the key imaging features of unusual femoral fractures on different radiological modalities including plain radiographs, Computed Tomography (CT), Magnetic Resonance Imaging (MRI), technitium-99m bone scintigraphy and single-photon emission computed tomography (SPECT).

STRESS FRACTURESStress fractures are typically caused by chronic repetitive

injury on weight-bearing bones in athletes. Stress fractures in the femur usually occur in the femoral neck and intertrochanteric region [9] and more commonly on the medial aspect [10]. Femoral stress fractures have a higher chance of healing because the compressive load passes through the medial side of the femur [11]. However, proximal femoral fractures, fractures with a fracture line greater than 50% of the femoral neck width and

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fractures with the slightest displacement are still considered to be high-risk for developing into complete fractures [12].

Radiographs are considered to be first line imaging for stress fractures. On plain radiographs, one of the earliest signs of stress response is the “grey cortex sign” which refers to subtle ill-defined lucency of the cortex (Figure 1) and histologically corresponds to microcrack formation [13,14]. As injury persists and healing begins, periosteal reaction, endosteal callus and focal cortical thickening may be seen. In later stages of higher grade injuries, a transverse lucent fracture line indicative of a cortical break may become apparent [15]. In areas with a greater proportion of trabeculae such as the femoral metaphysis, there may be indistinct intramedullary blurring and sclerosis as the earliest signs on x-ray [16], which progresses to an intramedullary sclerotic line (Figure 2) due to microcallus formation along remodelled trabeculae [16,17]. Displacement and comminution are not characteristic features of stress fractures. Despite these radiographic signs, the sensitivity of radiographs are reported to be approximately in the range of 25% for early stage injury and 50% for late stage injury [18].

If radiographs are negative, then MRI should be the next investigation to consider, reporting a specificity and sensitivity approaching 100% [19]. On MRI, a low signal fracture line with

Table 1: Classification of femoral fractures.• Fractures due to direct acute trauma• Unusual femoral fractures

o Stress fracture (overuse due to chronic repetitive stress)o Insufficiency fracture

Primary – senile or postmenopausal osteoporosis Secondary

• Osteogenesis imperfect a, osteopetrosis, polyostotic fibrous dysplasia, Paget’s disease• Exogenous corticosteroids, oestrogen/testosterone deficiency, hyperparathyroidism, osteomalacia,

renal osteodystrophy, scurvy (Vit C deficiency), rheumatoid arthritis, gout, Wilson’s disease, other endocrine/nutritional/haematological/hereditary disorders

• Previous irradiation, stress shielding from total hip replacement, organ transplantation, tabes dorsalis, high-dose fluoride therapy

o Atypical femoral fracture (bisphosphonate related)o Pathologic fracture (fracture through underlying pathology)

Benign – unicameral bone cyst, aneurysmal bone cyst, fibrous dysplasia, enchondroma, giant cell tumour Malignant

• Primary bone sarcoma – osteosarcoma, Paget’s sarcoma, myeloma, lymphoma, chondrosarcoma• Secondary metastasis – breast, lung etc.

Figure 1 Plain radiograph of a stress fracture along the medial femoral neck with subtle ill-defined lucency (grey cortex sign) and irregularity (arrow) of the medial femoral cortex.

A) B)

Figure 2 Plain radiograph and 2b Coronal CT image of a chronic stress fracture along the medial femoral neck demonstrating intramedullary linear sclerosis (arrows) due to microcallus formation along the fracture..

A) B)

Figure 3 Coronal STIR and 3b Coronal T1 MR images of an acute medial femoral stress fracture demonstrating a low signal fracture line (arrow) with surrounding high STIR and low T1 marrow and periosteal oedema (Fredericson Grade 4). The low T1 signal intensity has a heterogeneous appearance with foci of intervening preserved high T1 fatty marrow signal.

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surrounding osseous or soft tissue oedema may be seen (Figure 3) [20]. MRI features of stress fractures can be graded (Table 2) according to Fredericson et al [21] classification system or their slightly modified version by Kijowski et al [22], by using fat saturated T2-weighted (fluid-sensitive) and non-fat saturated T1-weighted sequences.

CT may have a role in demonstrating a fracture line with adjacent sclerosis and reaction depending on the age of the fracture (Figure 2b). CT is also reported to have high specificity for stress fractures approaching nearly 100% [19].

On Technitium-99m bone scintigraphy (planar bone scan), stress fractures are seen as a focal area of increased uptake. Although planar bone scan is considered to be a sensitive investigation for stress fractures, it is less specific than MRI [19]. A comparative study reported a much lower sensitivity of planar bone scan at around 50% when performed alone but approaching 92% when performed with SPECT [23]. Biopsy of stress fractures should always be avoided as histologically it may be confused with aggressive bone turnover [8].

INSUFFICIENCY FRACTURESInsufficiency fractures primarily result from senile or

postmenopausal osteoporosis.

There are many secondary causes [1,7] of insufficiency fractures (Table 1) with some recent case reports demonstrating femoral fractures due to gout [24], Wilson Disease [25], vitamin D deficiency [26] and Paget’s disease [27]. Secondary insufficiency fractures may be thought of in terms of correctable or uncorrectable causes [28]. Correctable causes include conditions such as renal osteodystrophy, osteomalacia and hyperparathyroidism while uncorrectable causes include disease processes such as osteogenesis imperfecta, polyostotic fibrous dysplasia and Paget’s disease amongst many others. It is worth considering that with continuous advancements in medical

sciences, what is deemed correctable or uncorrectable may not only be debatable but can also change over time.

It is reasonable to think of the imaging features of insufficiency fractures as largely similar to stress fractures, although their aetiology and epidemiology are vastly different. Identifying subtle insufficiency fractures in these conditions requires the radiologist to have a broad knowledge of the skeletal manifestations of a wide range of metabolic and systemic disorders to firstly recognise the underlying pathology, and secondly apply the principles of fracture detection on different imaging modalities (Figures 4 and 5).

ATYPICAL FEMORAL FRACTURESAtypical femoral fractures (AFFs) are a relatively uncommon

type of femoral insufficiency fracture linked to the long-term use of medications that suppress osteoclastic-mediated bone turnover, including bisphosphonates and denosumab [8,29,30]. The pathogenesis has been attributed to the suppression of bone marrow turnover and remodelling at the site of repetitive tensile stress along lateral cortex of the subtrochanteric and proximal diaphysis of the femur [29,30]. Biomechanical factors that accentuate this tensile stress, including an increased standing femorotibial angle and femoral bone curvature, are associated with an increased risk of AFFs [31].

AFFs result from minimal or no trauma [32]. Patients usually present with prodromal symptoms, typically dull or aching pain in the groin or thigh [30]. The early radiological findings of AFFs may be subtle and consequently missed, with potential for progression to a complete fracture [9]. The American Society for Bone and Mineral Research (ASBMR) have developed specific clinical and imaging criteria to precisely define AFFs to aid the diagnosis of this entity and differentiate it from other femoral fractures, including exercised-induced stress fractures, low-energy osteoporosis-related fractures, pathologic fractures and high-energy fractures (Table 3) [30,33,34].

Table 2: Grading of MRI features of stress fracture using Fredericson21 and Kijowski22classifications.Grade 1 – periosteal oedemaGrade 2 – periosteal and mild marrow oedema seen on T2w images onlyGrade 3 – periosteal and marrow oedema seen on both T1w and T2w images.Grade 4a – intracortical signal change without a linear shape with periosteal and marrow oedemaGrade 4b – linear intracortical fracture line with periosteal and marrow oedema

Figure 4 Plain pelvic radiograph demonstrating slender bowed osteopaenic femora with marked cortical thinning consistent with osteogenesis imperfecta. There are multiple insufficiency fractures with pseudoarthroses (arrows) and modelling deformity (arrowheads).

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A) B)

Figure 5 Plain radiograph and 5b Coronal CT image of a patient with osteomalacia demonstrating femoral head flattening, shortened femoral necks and femoral bowing. There are insufficiency fractures or looser zones (arrows) of the medial proximal femora which are typically bilateral and symmetrical, orientated perpendicular to the cortex with adjacent sclerosis.

Table 3: Atypical femoral fracture: Major and minor features [30].Major features

• Location anywhere along the femoral diaphysis, from just distal to the lesser trochanter to just proximal to the supracondylar flare• Associated with no or minimal trauma, as in a fall from standing height or less• Transverse or short oblique configuration• Non-comminuted• Incomplete fractures involve only the lateral cortex; Complete fractures extend through both cortices and may demonstrate a medial spike

Minor features• Localised periosteal reaction of the lateral cortex• Generalised increase in cortical thickness of the femoral diaphysis• Prodromal symptoms such as dull or aching pain in the groin or thigh• Bilateral fractures and symptoms• Delayed healing• Comorbid conditions (such as vitamin D deficiency, rheumatoid arthritis, hypophosphatasia)• Use of pharmaceutical agents

An early plain radiographic feature of AFFs issubtle focal periosteal or endosteal thickening of the lateral cortex of the subtrochanteric or proximal femoral diaphysis, referred to as cortical ‘beaking’ or ‘flaring’ (Figure 6) [9,11]. More generalised diffuse lateral femoral cortical thickening may also occur (Figure 7). An incomplete transverse radiolucent line known as the ‘dreaded black line’ can sometimes be noted in the region of cortical thickening (Figure 8). Subsequent progression to the medial femoral cortex results in a complete fracture which is typically transversely orientated and non-comminuted. The fracture may have a short oblique orientation medially leading to a characteristic medial cortical spike (Figure 9) [9,11]. Additional findings include periosteal stress reaction and delayed fracture healing [9]. Initial involvement of the lateral femoral cortex differentiates AFFs from the classical exercised-induced femoral stress fractures and pseudofractures secondary to osteomalacia, which usually occur on the medial cortex due to compressive load through the proximal femur [9]. Atypical femoral fracture margins are well defined with no associated destructive bone lesion, unlike pathologic fractures [9]. Once a unilateral AFF is diagnosed, it is important to image the contralateral femur given the propensity for these fractures to occur bilaterally (Figure 10) [9,32]. Up 62.9% of patients demonstrate a contralateral femoral fracture, most commonly within a year of the index fracture and with similar imaging features, including location along the femur [32].

Other imaging modalities should be considered for patients on long term antiresorptive therapy with classical prodromal symptoms and equivocal or negative radiographic findings [9]. MRI, CT and bone scintigraphy have a higher sensitivity and specificity for detecting early AFFs compared to plain radiographs [9,35]. MRI is the preferred imaging modality, enabling detection of periosteal and endosteal oedema (high T2 and STIR signal), and low signal cortical fracture lines (Figure 10b and 10c) [9,29,36]. CT can detect focal intracortical bone resorption, subtle cortical thickening and periosteal reaction not evident on radiographs (Figure 7b and 7c) [9]. Technitium-99m bone scintigraphy demonstrates focal avid radiotracer uptake at the fracture site centred on the lateral femoral cortex (Figure 10d). It is important to assess for cortical involvement to help differentiate AFFs from other pathologies including bone infarction, osteomyelitis and malignancy, all of which typically demonstrate diffuse radiotracer uptake centred on the medullary cavity [9].

Familiarity with the specific imaging characteristics of atypical femoral fractures is important to ensure an early accurate diagnosis and prompt communication of findings to the referring clinician to enable optimal treatment, prevention of progression to complete femoral fractures and associated complications [8].

PATHOLOGIC FRACTURESPathologic fracture secondary to a tumour can be either due

to a primary bone tumour or secondary metastasis. The femur

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Figure 6 Plain radiograph illustrating focal periosteal and endosteal thickening (arrow) of the lateral cortex of the proximal femoral diaphysis, an early sign of AFF referred to as cortical ‘beaking’ or ‘flaring’.

A) B) C)

Figure 7 Plain radiograph, 7b Coronal CT and 7c Axial CT images demonstrating more generalised diffuse lateral femoral cortical thickening (arrows) indicative of pending AFF.

C)

Figure 8 Plain radiograph of an incomplete transverse radiolucent AFF line referred to as the ‘dreaded black line’ (arrow) traversing the lateral cortical thickening.

is the commonest site of pathologic fracture through a primary bone tumour [37,38], and it is vital to distinguish them into benign or malignant lesions, as their management and prognosis can be substantially different.

The proximal femur is a common location for benign primary bone tumours [39]. Some of the common benign primary bone tumours that can lead to pathologic femoral fracture are giant cell tumour of bone (Figure 11), fibrous dysplasia (Figure 12), unicameral bone cyst, aneurysmal bone cyst and enchondroma [40]. Pathological fractures through benign femoral lesions are usually identified on plain radiographs as a break in the continuity of the cortex and often sclerotic well-defined margin of the lesion. In the case of simple bone cysts, the characteristic ‘fallen fragment sign’ representing a cortical fragment which has

fallen into the cystic matrix of the lesion may be seen [41]. An MRI is customarily performed to characterise the lesion and may identify stress response seen as increased marrow oedema (high T2 and STIR signal) surrounding an otherwise benign appearing lesion, which can be suggestive of an impending fracture. Fractures through benign femoral lesions can achieve complete healing with low risks of non-union or avascular necrosis [40].

Malignant pathologic fractures can be either due to malignant primary bone tumour or secondary metastasis. According to a population-based study, osteosarcoma, Paget’s sarcoma, myeloma and lymphoma were the most common primary malignant bone tumours to present as pathologic femoral fractures [42]. In our experience, pathologic femoral fractures through chondrosarcoma is not uncommon (Figure 13). The femur is the third commonest site of bone metastasis after the spine and pelvis [43], and the commonest cause for femoral metastasis is from breast or lung primary [44,45]. Fractures through malignant bone tumours carry a poorer prognosis with a considerable number of cases requiring amputation [42].

Plain radiographic and CT features of malignant pathological fractures include a fracture traversing a more ill-defined permeative lesion with endosteal scalloping, cortical destruction or aggressive periosteal reaction [46]. A mineralised tumour matrix (Figure 13), associated soft tissue mass and fracture in an unusual location such as avulsion fracture of the lesser trochanter [47,48] in adults should always raise suspicion of underlying malignancy. Multiplicity of lesions is a helpful clue for metastatic disease (Figure 14) or myeloma but is not always definitive.

MRI may be useful to differentiate pathologic fractures from stress or insufficiency fractures, which can be problematic on plain radiographs [8]. MR assessment should be based on the margin and homogeneity of the T1 signal abnormality around

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Figure 9 Plain radiograph illustrating progression to a complete AFF which is typically non-comminuted, transversely orientated laterally with a short oblique orientation medially leading to a characteristic medial cortical spike (arrow).

A) B)

C) D)

Figure 10 a: Plain radiograph, 10b Coronal STIR MR image, 10c Axial T2 fat saturated MR image and 10d Technitium-99m bone scan of bilateral AFF. Lateral symmetrical femoral cortical thickening with subtle incomplete fracture lines (arrows) can be seen on the plain radiograph, low signal lateral cortical thickening (arrows) with high signal intramedullary oedema is present on the MRI and focal radiotracer uptake (arrows) is demonstrated on the bone scan at the fracture site centred on the lateral femoral cortex.

A) B)

Figure 11 a: Plain radiograph and 11b Coronal T1 MR image of a pathological fracture through a tumour extending into the femoral epiphysis with a relatively well-defined margin (arrows) consistent with a giant cell tumour of bone. The T1 signal abnormality has a homogenous mass-like appearance that is clearly delineated from adjacent normal fatty marrow. The fracture line is inconspicuous as tumour infiltrates the fracture space.

A)

Figure 12 Coronal CT image of a transverse pathological mid femoral diaphyseal fracture through a well delineated lesion with a ground glass matrix (arrows) and no aggressive features indicative of fibrous dysplasia.

the fracture [49,50]. In stress or insufficiency fractures, T1 low signal intensity associated with the fracture line correlates to oedema and haemorrhage and demonstrates a poorly defined margin and heterogeneous appearance due to patchy intervening preserved fatty marrow (high T1) signal intensity (Figure 3b). In tumoral pathologies, low T1 signal is at least partly caused by tumour and seen as a more well-defined homogenous mass-like abnormality (Figure 11b) or diffuse replacement of the fatty marrow with tumour [8,49,50]. In such cases, the fracture line

may be inconspicuous as tumour erodes trabecular bone and infiltrates the fracture space (Figure 11b) [8]. Other features such as an associated soft tissue component or muscle oedema may be present on MRI [8].

Positron emission tomography (PET-CT) can also be helpful in differentiating malignant pathologic fractures from stress or insufficiency fracture, with diffuse tracer uptake in the prior and focal or linear tracer uptake in the later [51].

CONCLUSIONFemoral fractures caused by an absence of acute trauma or

by low-energy trauma must be investigated thoroughly with imaging. Awareness of the relevant imaging features of unusual femoral fractures ensures timely identification, characterisation and appropriate management. Plain radiography is recommended

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A) B)

Figure 13 Plain radiograph demonstrating a pathological fracture traversing an ill-defined distal femoral permeative lesion with chondroid matrix mineralisation (arrows) consistent with a chondrosarcoma..

C)

A) B)

Figure 14 Plain radiograph of an angulated subtrochanteric pathological fracture traversing ill-defined sclerotic tumour with multiple deposits throughout the femur and acetabulum consistent with prostatic metastases.

as a first-line imaging tool for screening. However, MRI is the gold-standard imaging modality for making the diagnosis and should be considered as the next choice of investigation after plain radiographs. Conventional CT, bone scan, SPECT and PET-CT have limited roles in certain situations.

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Chaudhary SR, Edwards N, McCarthy CL (2020) Radiological Review of Unusual Femoral Fractures. Ann Orthop Rheumatol 7(1): 1092.

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