Osteoporosis International

, Volume 21, Issue 4, pp 701–703 | Cite as

Alendronate-related femoral diaphysis fracture—what should be done to predict and prevent subsequent fracture of the contralateral side?

Case Report



Atypical fractures of the femoral diaphysis have recently been associated with alendronate therapy (Neviaser et al. J Orthop Trauma 22(5):346–350, 2008; Kwek et al. Injury 39:224–231, 2008; Lenart et al. N Engl J Med 358:1304–1306, 2008).


In many cases, fractures have occurred bilaterally prompting debate regarding appropriate screening of the unaffected side (Kwek et al. N Engl J Med 359(3):316–317, 2008).

Case report

We report a case of sequential, bilateral, femoral diaphysis fractures associated with prolonged alendronate therapy and the failure to predict the subsequent fracture of the contralateral side despite radiological imaging.


We review the current literature and discuss potential management strategies.


Alendronate Bisphosphonate Dual energy X-ray absorptiometry Femoral diaphysis fracture Osteoporosis Radiological imaging 

Case report

We report a 60-year-old woman with a combination of chronic obstructive airways disease and asthma which was steroid dependent and necessitated doses of prednisolone between 10 and 30 mg/day for the preceding 20 years. When she developed multilevel vertebral collapse, a presumptive diagnosis of corticosteroid-induced osteoporosis was made without DXA scanning. She was commenced on alendronate, and after 6 years of treatment, she sustained an atraumatic spontaneous fracture of the right femoral diaphysis (Fig. 1a) that was preceded by mild right thigh pain. The fracture was treated with an intramedullary nail, and the patient was able to return to weight-bearing activity. Due to the nature of the fracture, a skeletal survey including an X-ray of the left femur and an isotope bone scan were performed. Appearances of the left femur on plain radiograph and isotope bone scan were reported as normal. A DXA scan showed relatively well-preserved bone density with a spine T-score of 0.1, femoral neck T-score of −1.1 and total hip T-score of 0.5. Due to the continued need for long-term oral corticosteroid, the patient was allowed to continue taking alendronate.
Fig. 1

a Right femoral diaphysis fracture; b left femoral diaphysis fracture; c area of lateral cortical thickening in left femur prior to fracture

Two years after the first fracture, the patient sustained a spontaneous fracture of her contralateral left femoral diaphysis (Fig. 1b). On this occasion, there was no preceding pain. A retrospective review of the plain radiograph taken after her initial fracture identified an area of minor thickening seen on the lateral cortical margin of the left femur (white arrow—Fig. 1c), possibly indicating an area of cortical stress. This area was not apparent on the isotope bone scan and corresponds to the site of the subsequent fracture.


There are a number of case series documenting atypical low-trauma fractures of the femoral shaft in association with long-term alendronate therapy. Radiologically, these fractures demonstrate a simple transverse pattern with hypertrophy of the fractured diaphyseal cortex [1, 2, 3]. Moreover, thickening of the lateral cortical margin of the unfractured contralateral femur has also been described [2]. Our patient, with a 6-year history of alendronate therapy and identical radiological findings, appears to fit well within this cohort.

However, a definite causal link with alendronate therapy has yet to be proven, and recent reports have disputed the association. Potential confounding factors need to be considered, and in this case, it is quite possible that previous exposure to long-term glucocorticoids may have contributed to the fractures that occurred. Authors presenting data from a large Danish registry suggest that atypical fractures may simply reflect the fact that patients on alendronate are already at a higher risk for all types of fracture [4].

Stress fractures in patients on bisphosphonates might be related to suppression of normal bone turnover. One study has found reduced bone turnover and delayed or absent fracture healing in a small group of patients who sustained low-trauma fractures whilst taking long-term alendronate [5]. There is evidence that bisphosphonate therapy may lead to the accumulation of micro-damage or micro-fractures [6] which could cause an increased propensity to fracture.

Bilateral atypical fractures, as in our patient, are not unusual with 64% of cases demonstrating some involvement of the contralateral femur [7], suggesting potential benefit in assessing the fracture risk to the contralateral femur. Proposed screening modalities include plain X-ray, computed tomography, magnetic resonance imaging (MRI), and isotope bone scanning [7, 8]. Taking into account the suggested mechanisms of bisphosphonate associated fracture, one might also theorise a role for micro-computed tomography [9, 10], positron emission tomography [11] or possibly bone turnover markers.

Our case highlights the inadequacy of plain radiography and isotope bone scans in predicting subsequent fracture and how subtle changes can be easily missed. In addition, we need to consider whether there is a role for routine repetition of these investigations. In our patient, 18 months had elapsed between completion of screening and subsequent fracture. In the absence of symptoms to guide further investigation, we suggest that it may be prudent to undergo serial imaging.

Management of patients, once an initial femoral fracture has occurred, is another area of debate. Given the apparent frequency of bilateral involvement [7], once an incomplete contralateral stress fracture has been identified, it may be prudent to consider prophylactic fixation. Whether bisphosphonate therapy should be stopped is also unclear. Some authors feel that bisphosphonates should be continued [12], whilst others feel that treatments such as a parathyroid hormone (PTH) analogue provide a more rational alternative [8].

More research is required to inform the management of patients following an alendronate-associated femoral diaphysis fracture. Our experience, and review of the current literature, leads us to suggest that plain radiography, isotope bone scan and MRI should ideally be included in the initial assessment; close attention should be paid to minor abnormalities, and serial imaging should be considered. Alendronate might perhaps be best stopped and replaced with a PTH analogue, and there should be a low threshold for considering prophylactic fixation of the contralateral femur to prevent a further disabling fracture.


Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • M. H. Edwards
    • 1
  • F. C. McCrae
    • 1
  • S. A. Young-Min
    • 1
  1. 1.Rheumatology DepartmentQueen Alexandra HospitalPortsmouthUK

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