Endgames Case Report

Sequential bilateral femoral fractures

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e7361 (Published 14 November 2012) Cite this as: BMJ 2012;345:e7361

This article has a correction. Please see:

  1. Seyed Ali Moeinoddini, foundation year 2 trainee, orthopaedic surgery 1,
  2. Rajkumar James Parikh, consultant geriatrician1,
  3. Sarah Ruth Moore, specialist registrar, rheumatology and general (internal) medicine 2,
  4. David James Moore, consultant radiologist 3
  1. 1Pennine Acute Hospitals NHS Trust, Royal Oldham Hospital, Oldham OL1 2JH, UK
  2. 2Sheffield Teaching Hospitals NHS Trust, Northern General Hospital, Sheffield, UK
  3. 3East Cheshire NHS Trust, Macclesfield District General Hospital, Macclesfield, UK
  1. Correspondence to: R J Parikh raj.parikh{at}pat.nhs.uk

A 78 year old woman presented to the emergency department with an off-ended, shortened, anteriorly deviated, long oblique fracture of the right femoral diaphysis. She had been experiencing thigh pain for several weeks before this acute presentation and analgesia had been prescribed.

She described feeling the bone “crack” as she turned around. There was no history of trauma. The fracture was surgically treated with an intramedullary nail.

Six months earlier she had sustained a similar fracture of the midshaft of her left femur. Again, there was no trauma and she described feeling the bone “crack” as she twisted slightly to go through her front door. She was unable to reach a telephone to call for help and spent some time on the ground before a passer by called an ambulance. After initial treatment with a Thomas splint, she was treated surgically with an intramedullary nail. After two weeks of rehabilitation she returned home to live independently and was able to go out with one stick to do her shopping.

Her medical history included osteoporosis and hypovitaminosis D. The diagnosis of osteoporosis was made after she sustained a vertebral crush fracture. She had been receiving bisphosphonates to prevent further fractures for nearly five years.


  • 1 Why are such fractures described as “atypical”?

  • 2 What underlying mechanism might explain such fractures?

  • 3 What are the main clinical and radiological features of atypical femoral fractures?

  • 4 How would you investigate her thigh pain?


1 Why are such fractures described as “atypical”?

Short answer

Atypical fractures involve little or no trauma.1

Long answer

“Typical” subtrochanteric or femoral shaft (ST/FS) fractures are comminuted (sometimes obliquely, rarely transversely) and result from trauma. In atypical fractures, structural failure occurs in the absence of trauma.1 Thus, they are by definition pathological. The differential diagnoses of atypical fractures include well described causes such as a bony metastasis from a disseminated cancer, haematological cancers, and primary bone sarcoma. Prolonged treatment with bisphosphonates is increasingly thought to predispose to atypical fractures,2 and we thought this might be the cause in our case.

Initial case reports linking bisphosphonates to ST/FS atypical fractures were controversial.3 In addition, secondary analysis of large bisphosphonate studies (Fracture Intervention Trial (FIT), FIT Long-Term Extension (FLEX) Trial, and Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture trial (PFT)) failed to show a significant increase in such fractures. However, the studies were underpowered.4

Park-Wyllie and colleagues therefore used a population based case-control study to investigate the use of oral bisphosphonates and fractures in women aged 68 years or more from Ontario, Canada.5 They found that five years or more of bisphosphonate treatment increased ST/FS fractures (adjusted odds ratio 2.74, 95% confidence interval 1.25 to 6.02) and reduced femoral neck or intertrochanteric (FN/IT) fractures (0.76, 0.63 to 0.93). In addition, of the 52 595 women who were treated for more than five years, ST/FS fractures occurred in 0.13% of women during the first year after the first five years of treatment and in 0.22% within two years. However, on the basis of the literature from 1994 to 2010 Rizzoli and colleagues estimated that the risk of ST/FS fracture was 0.1% each year,6 and this estimate agrees with the analysis of the large bisphosphonate studies.4

Park-Wyllie and colleagues assert that 64% of ST/FS fractures can be explained by long term bisphosphonate treatment, and that 11% are avoidable if treatment is limited to five years. However, a recent data commentary highlights the difficulties in ascribing absolute risk values with the evidence available.7

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) concluded (after reviewing European data) that atypical fractures were a bisphosphonate class effect.8 However, balance of risk favours treatment:

  • Data from FIT and HORIZON-PFT show that 90 women with osteoporosis need to be treated to prevent one hip fracture, 35 to prevent one non-vertebral fracture, and 14 to prevent one vertebral fracture

  • Overall, 100 fractures are prevented per 1000 women treated for three years,3 with the risk of one potential ST/FS fracture after five years of treatment.6

More common adverse effects of oral bisphosphonates include oesophagitis, gastritis, abdominal pain, and diarrhoea. Headache, rash, and musculoskeletal pain occur in one in 10 to one in 100 patients.

A causal association between osteonecrosis of the jaw and bisphosphonates used to treat osteoporosis has not been proved. Concerns have been raised about an increased risk of oesophageal cancer and atrial fibrillation, but a recent review concluded that current evidence is inconclusive.9

2 What underlying mechanism might explain such fractures?

Short answer

Suppression of remodelling by bisphosphonate treatment might prevent microscopic damage being repaired.1

Long answer

About 8% of bone surfaces are actively being remodelled at any time. Osteoclasts resorb bone and form pits that osteoblasts fill. Over time, new bony material is mineralised. Bisphosphonates potently inhibit osteoclast function while after initiation osteoblasts fill existing pits. Thus, bone volume and density rise. After the pits have been filled, rates of turnover are low. During the first three years of treatment bone density rises before starting to plateau. Microscopically, bony deterioration is “arrested” for five years.3

However, remodelling is necessary for microscopic cracks to be repaired. Over longer time periods bisphosphonates prevent repair and reduce toughness (the ability to sustain deformation without breaking).10 They also increase mineralisation, reduce elasticity, and predispose bone to fail under tension.3 10

Microdamage is prominent in highly mineralised areas of cortical bone, such as ST/FS regions. Structural failure occurs initially on the lateral aspect of the femur before propagating medially as higher tensile forces are applied to lateral surfaces.1

Before complete failure occurs, focal lateral cortical thickening (representing the cortical changes described above) may be seen radiographically. Atypical fractures may be mirrored on the contralateral side and patients may have prodromal symptoms, such as pain in the thigh or groin.1 11 12 Figures 1 and 2 show radiographs from the patient’s previous and current admissions.


Fig 1 Radiograph taken at the time of the patient’s previous presentation. The radiograph shows a left off ended, shortened, anteriorly deviated, long oblique fracture of the femoral diaphysis


Fig 2 Radiograph taken at the time of the patient’s current presentation. The radiograph shows a right off ended, shortened, anteriorly deviated, long oblique fracture of the femoral diaphysis and essentially mirrors the left sided fracture

3 What are the main clinical and radiological features of atypical femoral fractures?

Short answer

Distal to lesser trochanter or proximal to supracondylar flare; minimal trauma; transverse or short oblique configuration; non-comminuted; incomplete fracture involving the lateral cortex.11

Long answer

The American Society for Bone and Mineral Research defined major and minor features for atypical femoral fractures (box).11

Major and minor features of atypical femoral fractures

Major features (all required)
  • Located anywhere along the femur 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

  • Complete fractures extend through both cortices and may be associated with a medial spike; incomplete fractures affect only the lateral cortex

Minor features (not essential but help make the diagnosis)
  • Localised periosteal reaction of the lateral cortex

  • Generalised increase in cortical thickness of the 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 drugs (such as bisphosphonates, glucocorticoids, proton pump inhibitors)

4 How would you investigate her thigh pain?

Short answer

By organising imaging of the femur.3

Long answer

Thigh pain in a patient using bisphosphonates should prompt femoral imaging.

The pain results from the generation of a fracture line in the lateral cortex that spreads medially. Microscopic damage to bony architecture cannot be repaired if bone turnover is effectively “switched off,” and this predisposes to fracture. The tensile forces experienced on the lateral side of the femur during weight bearing “open up” the fracture line and cause pain. Thigh pain therefore alerts clinicians to the possibility of impending complete structural failure.

After atypical fracture, imaging of the contralateral side should be routinely ordered to look for focal lateral cortical thickening (or a fracture line, or both).1 2 3 Because plain radiographic features “may be subtle or lag behind clinical symptoms,”1 further imaging should be considered, including magnetic resonance imaging and computed tomography.

Treatment for incomplete ST/FS fractures is controversial.1 2 The American Society for Bone and Mineral Research recommends:11

  • Prophylactic reconstruction nail fixation for incomplete fractures that are accompanied by pain

  • Limited weight bearing for incomplete fractures not associated with pain

  • Medical management:

    • Discontinue bisphosphonates

    • Assess (and, if required, supplement) calcium and vitamin D

    • Consider teriparatide to improve fracture healing.

Patient outcome

After surgical fixation, the patient underwent a two week period of rehabilitation in hospital. She made a good functional recovery and was able to return to independent living. She achieved her baseline level of function—being able to go out with one stick to visit the local shops by herself.

Bisphosphonate treatment was discontinued after the left FS fracture. A dual energy x ray absorptiometry scan a few weeks later showed a T score of −2.2 at the right hip. A decision was taken to monitor her bone mineral density and consider drugs from alternative classes (such as teriparatide, strontium, or denosumab) if her T score deteriorated.

Follow-up radiographs were ordered when she attended the fracture clinic two months after the second surgical procedure. The orthopaedic team was satisfied with the fixation. Figure 3 shows the right and left proximal femoral images, which are essentially mirror images. This figure again illustrates the need to image the contralateral femur after an atypical fracture because the contralateral femur often fails at the same level.


Fig 3 Follow-up radiographs of the right (left hand panel) and left (right hand panel) proximal femur. The fractures have been reduced and internally fixed using hip screws and locked intramedullary nails. The fractures have united


Cite this as: BMJ 2012;345:e7361


  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Patient consent obtained.