Volume 194 - Issue 2
Atypical femoral fractures: a complication of prolonged bisphosphonate therapy?
Authors: Christian M Girgis and Markus J Seibel
Med J Aust 2011; 194 (2): 102-103. || doi: 10.5694/j.1326-5377.2011.tb04182.x
Published online: 17 January 2011
Published online: 17 January 2011
In reply: We thank Falkenberg for his comments in reference to our article in the Journal.1 Two recent large-scale population-based studies have suggested that subtrochanteric femur fractures are rare both in the general population and among bisphosphonate users.2,3 While personal experience may often suggest otherwise, a cluster of atypical fractures cannot be used as an indicator of true incidence in the absence of data on the frequency of bisphosphonate use in a particular population.
It is certainly safe to say that atypical fractures occur much less frequently than osteoporotic hip fractures. In a 5-year retrospective analysis of femur fractures at our centre, osteoporotic hip fractures outnumbered atypical fractures by a factor of greater than 60.4 Given the body of high-quality evidence on the antifracture efficacy of bisphosphonates, we agree that discarding an effective class of drugs because of a presumed association with an uncommon fracture pattern would be like throwing out the baby with the bathwater.
Should we routinely advise patients to take a drug holiday after, say, 5 years of bisphosphonate therapy? There is no good evidence for that either. Although bisphosphonates bind to bone for extended periods, severely suppressed bone turnover or signs of mechanical failure (microcracks) are rarely, if at all, seen in patients chronically treated with bisphosphonates. Similarly, the few bone biopsy studies in patients with atypical fractures do not uniformly support the hypothesis of severely suppressed bone turnover as a cause of these fractures.5,6 Instead of being based on the theoretical assumption of an uncertain risk, the decision for a drug holiday should be made on a case-by-case basis, guided by factors such as the patient’s on-drug fracture history, the presence of other relevant risk factors for osteoporosis, and changes in bone density and bone turnover.
Many questions remain unanswered regarding atypical femoral fractures and their biomechanical evolution. Until further research is conducted, the fear of the unknown, namely the impact of bisphosphonates on bone remodelling and microfracture accumulation, should not replace strong evidence in support of their antifracture efficacy.
Competing interests
Markus Seibel is a member of advisory boards for Merck Sharp and Dohme, Novartis, Amgen and Sanofi-Aventis. He has also received funding from these companies for institutional research.
References
- Girgis CM, Seibel MJ. Atypical femur fractures: a complication of prolonged bisphosphonate therapy [editorial]? Med J Aust 2010; 193: 196-198. BGBDGJFB
- Nieves JW, Bilezikian JP, Lane JM, et al. Fragility fractures of the hip and femur: incidence and patient characteristics. Osteoporos Int 2010; 21: 399-408. BGBBEFCE
- Abrahamsen B, Eiken P, Eastell R. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. J Bone Miner Res 2009; 24: 1095-1102. BABBFECB
- Girgis CM, Sher D, Seibel MJ. Atypical femoral fractures and bisphosphonate use. N Engl J Med 2010; 362: 1848-1849. BGBIDEIC
- Somford MP, Draijer F, Thomassen BJ, et al. Bilateral fractures of the femoral diaphysis in a patient with rheumatoid arthritis on long term treatment with alendronate. J Bone Miner Res 2009; 24: 1736-1740. BGBFGDCC
- Visekruna M, Wilson D, McKiernan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab 2008; 93: 2948-2952. BABEFCCD