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

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).

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

AFF: 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

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.

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 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 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 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].

Table 1: Classification of femoral fractures.

Insufficiency 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 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, lowenergy osteoporosis-related fractures, pathologic fractures and high-energy fractures (Table 3) [30,33,34].

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].

Table 2: Grading of MRI features of stress fracture using Fredericson21 and Kijowski22classifications.

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

Pathologic fracture secondary to a tumour can be either due to a primary bone tumour or secondary metastasis. The femur 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 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 masslike 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].

Femoral 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 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 PETCT have limited roles in certain situations.

1. Krestan C, Hojreh A. Imaging of insufficiency fractures. Eur J Radiol. 2009; 71: 398-405.

2. Bottai V, Giannotti S, Dell’osso G, De Paola G, Menconi A, Falossi F, et al. Atypical femoral fractures: Retrospective radiological study of 319 femoral fractures and presentation of clinical cases. Osteoporos. Int. 2014; 25: 993-997.

3. Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A, et al. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocrine Reviews. 2002; 23: 517- 523.

4. Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, et al. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocrine Reviews. 2002; 23: 508-516.

5. Odvina CV, Zerwekh JE, Sudhaker Rao D, Maalouf N, Gottschalk FA, Pak CYC, et al. Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005; 90: 1294-1301.

6. Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. New England Journal of Medicine. 2008; 358: 1304-1306.

7. Soubrier M, Dubost JJ, Boisgard S, Sauvezie B, Gaillard P, Michel JL, et al. Insufficiency fracture. A survey of 60 cases and review of the literature. Joint Bone Spine. 2003; 70: 209-218.

8. Marshall RA, Mandell JC, Weaver MJ, Ferrone M, Sodickson A, Khurana B, et al. Imaging features and management of stress, atypical, and pathologic fractures. Radiographics. 2018; 38: 2173-2192.

9. Patel RN, Ashraf A, Sundaram M. Atypical Fractures Following Bisphosphonate Therapy. Semin. Musculoskelet. Radiol. 2016; 20: 376-381.

10. DeFranco MJ, Recht M, Schils J, Parker RD. Stress fractures of the femur in athletes. Clinics in Sports Medicine. 2006; 25: 89-103.

11. Akgun U, Canbek U, Aydogan NH. Reliability and diagnostic utility of radiographs in patients with incomplete atypical femoral fractures. Skeletal Radiol. 2019; 48: 1427-1434.

12. Shin AY, Morin WD, Gorman JD, Jones SB, Lapinsky AS. The superiority of magnetic resonance imaging in differentiating the cause of hip pain in endurance athletes. Am J Sports Med. 1996; 24:168-176.

13. Mulligan ME. The ‘gray cortex’: an early sign of stress fracture. Skeletal Radiol. 1995; 24: 201-203.

14. Rheinboldt M, Harper D, Stone M. Atypical femoral fractures in association with bisphosphonate therapy: A case series. Emerg Radiol. 2014; 21: 557-562.

15. Daffner RH, Pavlov H. Stress fractures: Current concepts. AJR Am J Roentgenol. 1992; 159: 245-252.

16. Anderson MW, Greenspan A. Stress fractures. Radiology. 1996; 199: 1-12.

17. Fazzalari NL. Trabecular microfracture. Calcif Tissue Int. 1993; 53: S143-S147.

18. Lassus J, Tulikoura I, Konttinen YT, Salo J, Santavirta S. Bone stress injuries of the lower extremity: A review. Acta Orthopaedica Scandinavica. 2002; 73: 359-368.

19. Wright AA, Hegedus EJ, Lenchik L, Kuhn KJ, Santiago L, Smoliga JM, et al. Diagnostic Accuracy of Various Imaging Modalities for Suspected Lower Extremity Stress Fractures. American Journal of Sports Medicine. 2016; 44: 255-263.

20. Hodnett PA, Shelly MJ, MacMahon PJ, Kavanagh EC, Eustace SJ. MR Imaging of Overuse Injuries of the Hip Magnetic Resonance Imaging Clinics of North America. 2009; 17: 667-679.

21. Fredericson M, Bergman AG, Hoffman KL, Dillingham MS. Tibial Stress Reaction in Runners: Correlation of Clinical Symptoms and Scintigraphy with a New Magnetic Resonance Imaging Grading System. Am J Sports Med. 1995; 23: 472-481.

22. Kijowski R, Choi J, Shinki K, Del Rio AM, Smet AD. Validation of MRI classification system for tibial stress injuries. AJR Am J Roentgenol. 2012; 198: 878-884.

23. Bryant LR, Song WS, Banks KP, Bui-Mansfield LT, Bradley YC. Comparison of planar scintigraphy alone and with SPECT for the initial evaluation of femoral neck stress fracture. AJR Am J Roentgenol. 2008; 191: 1010-1015. 

24. Jeon YS, Hwang DS, Hwang JM, Lee JK, Park YC. Pathological Fracture of the Femoral Neck due to Tophaceous Gout: An Unusual Case of Gout Hip Pelvis. 2019; 31: 238-241.

25. hatnagar N, Lingaiah P, Lodhi JS, Karkhur Y. Pathological Fracture of Femoral Neck Leading to a Diagnosis of Wilson’s Disease: A Case Report and Review of Literature J Bone Metab. 2017; 24: 135-139.

26. Ying LJ. A case of pathological fracture caused by vitamin D insufficiency in a young athlete and a review of the literature. J Clin Orthop Trauma. 2019; 10: 1111-1115.

27. Petrescu PH, Izvernariu DA, Iancu C, Dinu GO, V?duva MMB, Cri?an D, et al Pathological fracture of the femur in a patient with Paget’s disease of bone: A case report Rom J Morphol Embryol. 2016; 57: 595-600.

28. Brown CM, Heckman JD, McQueen MM, Ricci WM, Tornetta III. Rockwood and Green’s Fractures in Adults. Wolters Kluwer Health, 2015; 667.

29. Png MA, Mohan PC, Koh JSB, Howe CY, Howe TS. Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy-a long-term radiological follow-up Osteoporos Int. 2019; 30: 2417-2428.

30. Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, et al. Atypical subtrochanteric and diaphyseal femoral fractures: Second report of a task force of the American society for bone and mineral research. J Bone Miner Res. 2014; 29: 1-23.

31. Saita Y. The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment Bone. 2014; 66: 105- 110.

32. Probyn L, Cheung AM, Lang C, Lenchik L, Adachi JD, Khan A, et al. Bilateral atypical femoral fractures: how much symmetry is there on imaging? Skeletal Radiol. 2015; 44: 1579-1584.

33. Adams AL, Xue F, Chantra JQ, Dell RM, Ott SM, Silverman S, et al Sensitivity and specificity of radiographic characteristics in atypical femoral fractures Osteoporos Int. 2017; 28: 413-417.

34. Szolomayer LK, Ibe IK, Lindskog DM. Bilateral atypical femur fractures without bisphosphonate exposure. Skeletal Radiol. 2017; 46: 241-247.

35. Seong YJ, Shin JK, Park WR. Early detected femoral neck insufficiency fracture in a patient treated with long-term bisphosphonate therapy for osteoporosis: A need for MRI. Int J Surg Case Rep. 2020; 70: 213- 215.

36. Larsen MS, Schmal H. The enigma of atypical femoral fractures: A summary of current knowledge EFORT Open Reviews. 2018; 3: 494- 500.

37. Fuchs B, Valenzuela RG, Sim FH. Pathologic Fracture as a Complication in the Treatment of Ewing’s Sarcoma. Clin Orthop Relat Res. 2003; 25- 30.

38. Abudu A, Sferopoulos NK, Tillman RM, Carter SR, Grimer RJ. The surgical treatment and outcome of pathological fractures in localised osteosarcoma. J Bone Joint Surg Br. 1996; 78: 694-698.

39. Enneking W. Modification of the system for functional evaluation of surgical management of musculosketal tumors in Limb Salvage in Musculoskeletal Oncology 626-639 New York, Churchill-Livingstone. 1987.

40. Wai EK, Davis AM, Griffin A, Bell RS, Wunder JS. Pathologic fractures of the proximal femur secondary to benign bone tumors. Clin Orthop Relat Res. 2001; 393: 279-286.

41. Struhl S, Edelson C, Pritzker H, Seimon LP, Dorfman HD. Solitary unicameral bone cyst - The fallen fragment sign revisited. Skeletal Radiol. 1989; 18: 261-265.

42. Godley K, Watts AC, Robb JE. Pathological femoral fracture caused by primary bone tumour: A population-based study Scott Med J. 2011; 56: 5-9.

43. Anderson PR, Coia LR. Fractionation and outcomes with palliative radiation therapy. Semin Radiat Oncol. 2000; 10: 191-199. 44.Angelini A, Trovarelli G, Berizzi A, Pala E, Breda A, Maraldi M, et al. Treatment of pathologic fractures of the proximal femur. Injury. 2018; 49: S77-S83.

45. Choy WS, Kim KJ, Lee SK, Yang DS, Jeung SW, Choi HG, et al. Surgical treatment of pathological fractures occurring at the proximal femur. Yonsei Med J. 2015; 56: 460-465.

46. Helms CA. Malignant Tumors in Fundamentals of Skeletal Radiology. Elsevier Saunders. 2014; 32-36.

47. James SLJ, Davies AM. Atraumatic avulsion of the lesser trochanter as an indicator of tumour infiltration Eur Radiol. 2006; 16: 512-514.

48. Bertin KC, Horstman J, Coleman SS. Isolated fracture of the lesser trochanter in adults: An initial manifestation of metastatic malignant disease. J Bone Joint Surg Am. 1984; 66: 770-773.

49. Pauleit D. MRT-diagnostik bei longitudinalen stressfrakturen: Differentialdiagnose zum Ewing-sarkom RoFo Fortschritte auf dem Gebiete der Rontgenstrahlen und der Neuen Bildgeb Verfahren. 1999; 170: 28-34.

50. Fayad LM, Kawamoto S, Kamel IR, Bluemke DA, Eng J, Frassica FJ, et al. Distinction of long bone stress fractures from pathologic fractures on cross-sectional imaging: How successful are we? American Journal of Roentgenology. 2005; 185: 915-924.

51. Fayad LM, Kamel IR, Kawamoto S, Bluemke DA, Frassica FJ, Fishman EK, et al Distinguishing stress fractures from pathologic fractures: A multimodality approach Skeletal Radiol. 2005; 34: 245-259.