69-year-old woman referred by her general practitioner to orthopaedic outpatients with a 6 week history of right thigh pain. The patient had a past medical history of osteoporosis and vertebral wedge fractures treated with risedronate for 3 years.
X-ray of the right femur revealed focal lateral cortical thickening of the distal femur (Fig. 1). Diagnosis was uncertain and myeloma screen was performed, which was negative. Bone scintigraphy was requested and demonstrated symmetrical, localised increased uptake in the lateral aspect of both distal femurs. (Fig.2)
Subsequent X-ray of the left femur revealed similar lateral cortical thickening to the right, with a lateral cortical beak characteristic of bisphosphonate associated stress fracture (Fig.3). Bilateral atypical femoral stress fractures were now suspected. Subsequent MRI scan demonstrated bone oedema in the symptomatic femur with symmetrical lateral cortical thickening and incomplete transverse fracture lines within both the asymptomatic and symptomatic femur (Fig.4 and 5). Appearances were typical of bilateral bisphosphonate associated femoral shaft stress fractures. Bisphosphonate therapy was stopped and the patient was treated conservatively by rheumatologists.
Atypical femoral fractures from long term bisphosphonate therapy are uncommon with an incidence of 1 per 1, 000 per year [1]. Since 2007 there have been a few case reports of atypical femoral shaft insufficiency fractures associated with prolonged use, typically 5 years. With growing evidence, in 2011 the European Medicine Agency issued guidance that a warning of this rare complication should be added to prescribing information for all bisphosphonate containing medicines.
The theories proposed for the pathophysiology is that there is suppression of bone turnover and increased mineralisation of bone. Alterations in the composition of its mineral/matrix composite lead to more brittle bones susceptible to micro fractures and delay in bone healing.
The typical history for an atypical femoral fracture is a femoral fracture in a patient known to have osteoporosis with minimal trauma. There is a history of prodomal thigh pain and prolonged bisphosphonate therapy.
Other fractures can occur with minimal history of trauma such as stress, pathological or insufficiency fracture. Typical stress fractures begin at the medial cortex of the femur and progress laterally. This contrasts with atypical stress fracture associated with bisphophonate therapy which start laterally and progress medially.
The patient usually presents with a complete fracture which can occur at any level of the femoral diaphysis [2]. The challenge is to identify the precomplete atypical femoral fracture. Findings at the early stage are very subtle but characteristic. The fracture starts as a focal cortical thickening and beaked margin of the lateral cortex with or without a lucent line [3]. These features are unique and diagnostic on plain radiograph with the appropriate history.
Bisphosphonate associated femoral fractures are reported as being bilateral in 30-60%. Once a diagnosis of an atypical femoral fracture has been made in one femur the contra-lateral femur should also be imaged.
As a consequence of the infrequent nature of this complication there is no consensus on definitive management. Most centres advocate immediate cessation of bisphosphonate on diagnosis. The management of a precomplete fracture is controversial and can be managed conservatively or surgically. MRI is useful as a tool to predict incomplete fractures at higher risk to progress to complete fracture [4]
A characteristic description of atypical femoral fractures in patients on prolonged bisphosphonate therapy has emerged. A transverse fracture in the femur associated with lateral cortical thickening is diagnostic. Once the suspicion is raised imaging of the contralateral femur should be performed.
Bisphosphonate associated femoral shaft stress fracture
Based on the provided X-ray, bone scan, and MRI images, there is a notable thickening of the lateral cortex in the near-mid portion of the right femoral shaft, with local sclerosis or a “beak-like” change, and a suspected fracture line extending from the lateral to the medial side. In the mid-portion of the left femur, a similar but milder change is observed. There is no clear indication of extensive soft tissue swelling or bony destruction in the surrounding area. The bone scan reveals symmetric increased tracer uptake in the mid femoral shafts, and MRI demonstrates bone marrow edema and cortical discontinuity in the corresponding regions. Considering the patient’s complaint of localized thigh pain and clinical history, these findings suggest an early or incomplete atypical femoral fracture.
Combining the patient’s:
• Older age and known osteoporosis
• Long-term bisphosphonate use (3 years)
• Persistent femoral pain with minimal or no trauma
• Imaging showing bilateral lateral femoral cortex thickening with local sclerosis or occult damage
All these factors collectively indicate the most likely diagnosis is: Bisphosphonate-Related Atypical Femoral Fracture (Early to Incomplete Fracture Stage).
Rehabilitation should be tailored according to the stability of the fracture and whether surgery was performed, and carried out progressively.
Brief Application of the FITT-VP Principle:
• Frequency: 3–5 times/week, focusing on low to moderate intensity exercises.
• Intensity: Choose low-impact or moderate-intensity activities based on pain level, stage of fracture healing, and bone density.
• Time: 15–30 minutes per session, possibly split into segments; begin with shorter sessions initially and lengthen as rehabilitation progresses.
• Type: Protective weight-bearing exercises, range-of-motion training, and light to moderate resistance exercise, avoiding jumping or other high-impact maneuvers.
• Progression: As the fracture heals and pain lessens, gradually increase the intensity and frequency while closely monitoring symptoms. If severe discomfort or pain intensifies, seek medical attention or adjust the plan promptly.
Because of osteoporosis and the risk of fractures, unprotected vigorous exercise should be avoided, and progression should be supervised by professionals. Any significant pain or discomfort should prompt immediate medical evaluation.
This report is based on the analysis of existing imaging and clinical data and is provided for reference only. It cannot substitute a face-to-face clinical diagnosis or specialized medical advice. For specific diagnosis and treatment, please combine individual patient circumstances and consult a qualified healthcare professional.
Bisphosphonate associated femoral shaft stress fracture
