Imaging Findings and Atypical Fractures
In the absence of reliable evidence, it is the opinion of the workgroup that imaging findings of lateral cortical thickening may be associated with increased atypical femur fracture risk.

Rationale

Atypical femur fracture is a well-recognized complication of long-term administration of bone targeted agents. These fractures have consistent radiographic features, typically starting as thickening of the lateral cortex ("beaking") in the subtrochanteric or diaphyseal femur. A transverse radiolucency that develops through the lateral thickening is concerning for impending fracture and is sometimes referred to as the "dreaded black line" (Kim, 2014). If these signs are undetected, the patient may progress onto a transverse or oblique fracture (Shane, 2014). In 70% of patients, fracture is preceded by prodromal thigh pain (Dell, 2018).

Atypical femur fractures are believed to be stress or insufficiency reactions, possibly exacerbated by reduced remodeling at the fracture site due to the action of bisphosphonates (Shane, 2014). Multiple epidemiological studies have documented increased incidence of subtrochanteric fractures 
as bisphosphonates became more widely prescribed, while the incidence of femoral neck and intertrochanteric fractures decreased (Shane, 2014).

The incidence of atypical femur fractures in one large population study was 55 per 100,000 person-years, compared with 1 per 100,000 person-years in bisphosphonate-naive patients (Van De Laarschot, 2017). However, it is important to remember that an estimated 162 osteoporosis- related fractures are prevented for every 1 AFF that may be associated with treatment with an antiresorptive medication (Van De Laarschot, 2017). Asians may be up to 8 times more at risk for AFF than whites (Dell, 2018). Concurrent use of glucocorticoids is associated with increased risk of AFF (Shane, 2014), which may be relevant to patients being treated for multiple myeloma.

Dual-Energy X-ray Absorptiometry Images (DEXA) scanning, used routinely in surveillance for osteoporosis, has been shown to be effective in screening for lateral cortical thickening (Kim, 2014). DEXA scanning also requires significantly less radiation exposure than routine radiographs (Van De Laarschot, 2017). One retrospective review noted a 40% of AFFs occur in the diaphysis (Unnanuntana, 2012), therefore it is important that screening DEXA scans are extended to include the diaphysis (Unnanuntana, 2012).

If a patient suffers an atypical femur fracture, stopping bisphosphonates exposure can reduce contralateral fracture, which is otherwise ~25%. There is some evidence that treatment benefit from bisphosphonates reduces after 5 years, while risk of AFF increases from 1.78/100k/year to 113/100k/year with exposure >8 years (Dell, 2018).

Patients with symptomatic lateral cortex thickening, medial callus formation or transverse lucency should undergo prophylactic intramedullary nailing (Shane, 2014). In the case of completed fractures, external rotation of the intramedullary nail during insertion can reduce the risk of malreduction of the bowed femur and accelerate fracture union (Park, 2017).

Future Research

While many of the risk factors for atypical femur fractures have been described, a validated risk calculator and/or clinical pathway to guide physicians would be helpful. As of yet, there is no evidence on which to base guidance for how long patients with AFFs or radiographic signs concerning for AFF should go on a drug "holiday". The sharply increased risk of AFF in Asians and case reports of symptomatic and/or radiographic improvement following treatment with teriparatide may merit further investigation.

 


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