Atypical femoral fractures are being identified as a specific type of femoral fracture with regards to the anatomical location extending from subtrochanteric to supracondylar region of femur, fracture pattern showing transverse or short oblique configuration with medial spike, low energy trauma, female preponderance and possible association with long-term usage of bisphosphonates [1] [2][3][4] . Bisphosphonates form a very important class of drugs used in day to day practice for multiple indications. It becomes essential to continue therapy in certain conditions but there have been incidences where the patient continues therapy beyond the necessary duration of therapy [1]. Though there is no conclusive evidence to suggest a causal association of bisphosphonates with this type of femur fracture, the recent increase in reporting of such fractures in patients under long-term usage of bisphosphonates justifies the need for research into the association between the two [1]. The clinical challenge posed by this type of fracture is identifying and treating it accordingly as this has a major bearing in post-injury functionality status and on quality of life [4].

We intend to report two such cases that presented to our institution. Informed consent was obtained from the patients to use their clinical data for academic purposes alone. Patient demographics are summarized in Table 1. Both patients presented with the characteristics of atypical femoral fractures which included low energy trauma, characteristic anatomical location, transverse or short oblique configuration with a medial spike, no comminution and lateral cortical thickening.

Case 1
A 62-year-old male pensioner without any pre-existing co-morbid conditions reported to our institution during September 2013 with alleged history of fall from standing position and sustained Sub-trochanteric fracture of left femur. The patient underwent fixation with Angled blade plate and was under follow-up. The fracture showed delayed union, therefore the patient was kept under toe touch weight bearing but unfortunately patient suffered a second trivial fall one year after the first fracture and developed sub-trochanteric fracture on the opposite side. This made us ponder about the unusual presentation and made us to do a detailed retrospective analysis of the patient characteristics. On probing, the patient revealed history of taking bisphosphonates for three years on prescription by a primary care physician for Osteopenia, which was not elucidated on first presentation. The patient also admitted to have had thigh pain since two weeks prior to the second fracture. Relook at the first radiograph (Figure 1) showed stress reaction on the lateral cortex of contralateral femur. This made us do a detailed literature search regarding this type of fracture and confirm that this specific pattern matches the typical description of atypical femoral fractures reported in literature [1] [2] [3]. We stopped bisphosphonate medication and fixed both femurs with proximal femoral nail (Figure 2). Both fracture healed at about six months. At one year follow-up patient is doing full weight bearing without any difficulty (Figure 3).

Case 2
A 73-year-old female, a known case of hypertension and dyslipidemia, presented with proximal third femur fracture left side with lateral tibial plateau fracture right knee with alleged history of fall from standing position. The radiograph (Figure 4) showed features matching the description of atypical femoral fractures and on detailed elucidation of history the patient revealed that she was on bisphosphonate medication for last five years on prescription by her gynecologist. The patient too had been having vague thigh pain since two weeks prior to the injury. This patient had lateral cortical stress reaction on contralateral femur but did not have thigh pain on that side. We advised stopping the medication and patient underwent fixation with ante-grade femoral nail for femur fracture and percutaneous screw fixation for lateral tibial plateau fracture. We had advised prophylactic fixation for the contralateral femur but since the patient was not willing for it, she has been given a word of caution and advised to report immediately if she developed thigh pain on right side. Patient is presently under follow-up and radiograph (Figure 5) taken 12 weeks following surgery showing evidence of fracture union on operated side.

Bisphosphonates being a very important class of drugs in management of osteoporosis have been prescribed very commonly by primary care physicians and surgeons. There have been many publications reporting fractures in patients on long-term bisphosphonate medications [2][3][4]. Majority of these fractures have been reported in female patients [2]. The percentage of population who took bisphosphonate medication and developing fracture while on treatment is low [3]. There have been postulates indicating genetic polymorphism among general population that may contribute to increased risk of development of these fractures in certain individuals in comparison to general population [1]. The American Society of Bone and mineral research has devised a diagnostic criteria with major and minor features to classify a fracture as atypical femoral fracture [1]. The important features being low energy trauma, location of fracture which should be distal to lesser trochanter and proximal to supracondylar region, transverse or short oblique configuration with a medial spike without comminution, presence of prodromal thigh pain.

The fracture may present bilateral in some cases or may show features of lateral cortical stress reaction [1] [5]. All the above features have been noted in our cases. It should be noted that stress fractures which occur in young and fit athletes usually starts from the medial cortex in contrast to atypical femoral fractures where the fracture line starts from the lateral cortex and progresses medially [1]. The possible mechanisms by which bisphosphonates could contribute to development of fractures include altering collagen integrity, homogeneity of bone mineral density distribution, decreased bone remodeling which is manifested as micro-architectural deterioration, crack initiation, crack progression, delayed healing of cracks [1][2]. Though bisphosphonates do not interfere with callus formation they have been postulated to interfere with fracture healing during the phase of remodeling from immature callus to mature bone [1]. This causes retention of callus which is seen as lateral cortical thickening in radiograph. They have also postulated that bisphosphonates could cause indirect inhibition of angiogenesis which is usually coupled with osteoclastic remodeling [1]. But majority of the above postulates are based on animal studies and there is no conclusive evidence yet to establish a causal association between bisphosphonates and atypical femoral fractures. In vitro studies to demonstrate that bisphosphonates do inhibit osteogenesis have also been published [6].

There have been reports of fractures occurring in other bones in patients on long-term bisphosphonate medications but majority seem to be case reports [7] [8]. There have been debates about the ideal duration of therapy for bisphosphonates but evidence from literature supports that there is no proven efficacy beyond five years of continuous therapy [1]. Literature review shows the duration of treatment in cases reported with atypical femoral fractures ranged from 2–8 years [2]. With regards to diagnosis, majority of the fractures are identified based on the typical radiograph findings. In case of patients who present with incomplete fractures or doubtful findings on routine radiographs, it is suggested to do CT scan or MRI scan to confirm the lateral cortical stress reactions [1] [2]. Some publications also include bone scan studies to detect stress reactions [1] [2]. Histomorphometric analysis with biopsy samples obtained from iliac crest or fracture site have been considered to be added valuable evidence for research purposes [1].

Recommendations regarding management of these fractures depend on the patient presentation, with all manifested fracture to be ideally fixed with intramedullary devices, since they did not interfere with fracture hematoma and are biomechanically in advantage when compared to extramedullary devices [1] [9]. Both of our cases were fixed with intramedullary device with first case requiring revision from angled blade plate. For patients who present with thigh pain and lateral cortical stress reaction, current literature suggest prophylactic fixation which significantly reduces morbidity to the patient [10]. For patients not willing for surgery, after explaining the risk of fracture the physician may advise partial weight bearing until radiological appearance of union [1], which was done in our second case. Literature evidence also supports use of teriparatide to hasten healing in this type of fracture [1], but we have not used it in both of our cases. Supplementation of vitamin D and calcium is justified for patients in whom investigations confirm deficiency [1].

Identifying this specific fracture and treating it with caution is necessary as they tend to take more time to heal in comparison with high energy trauma femoral fracture. Educating physicians and surgeons regarding this type of fracture is of prime importance both in prevention and treatment of this type of fracture, which contributes to significant reduction of morbidity and mortality to the patient. More research is needed to arrive at a risk benefit ratio which might justify administration of bisphosphonates in a patient and to decide on the appropriate duration of individualized therapy.

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