Issue: November 2010
November 01, 2010
2 min read

Atypical femur fracture risk high for bisphosphonate users, study found

Issue: November 2010
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ASBMR Annual Meeting

TORONTO — New data reveal an association between oral bisphosphonate use and atypical subtrochanteric femoral fractures, researchers said at the American Society of Bone and Mineral Research 2010 Annual Meeting.

“There is a very strong association between these medications and these [atypical] fractures,” Christian Girgis, MBBS, clinical associate lecturer and endocrinology trainee at the University of Sydney, Australia, told Endocrine Today. “However, these fractures are very rare — much rarer than the garden-variety, osteoporotic fractures which these drugs are very good at preventing. On balance, [bisphosphonates] prevent more fractures than they are associated with.”

Girgis and colleagues conducted a 5-year, retrospective study that included 152 patients who were admitted to an Australian hospital for a subtrochanteric or mid-shaft femoral fracture between June 2003 and May 2008. The mean age of patients was 78 years, and the majority were women.

The researchers differentiated atypical fractures from osteoporotic fractures, noting that atypical fractures had three distinct features: “The fractures have a transverse or oblique line in an area of cortical thickening with a medial unicortical beak,” Girgis said.

The researchers found that 20 atypical fractures occurred in the shaft region and 132 non-atypical fractures occurred in the subtrochanteric region. Of the 20 patients who experienced atypical fractures, 17 were using bisphosphonates compared with just three of the 132 patients without atypical fractures. Alendronate (Fosamax, Merck) and risedronate (Actonel, Warner Chilcott) were the bisphosphonates used, for less than a mean of 5 years in both groups.

The risk for an atypical vs. typical fracture was calculated as 37.4-fold in bisphosphonate users. In addition, the atypical fracture pattern was 96.7% amongst bisphosphonate users.

The mean annual incidence of atypical femoral fractures was 0.23 per 10,000 people in the general population in Australia and 1.66 per 10,000 people aged 65 years or older. Based on specific bisphosphonate use, the mean annual incidence of atypical fractures was estimated to range from 11 to 33 per 10,000 among alendronate users and from 2.5 to 7.4 per 10,000 risedronate users.

Girgis and colleagues identified a history of low energy fractures, glucocorticoid therapy of six months or more, active rheumatoid arthritis, and low vitamin D levels as risk factors for atypical fractures.

The researchers noted that the frequency of atypical femoral fractures found in the study is “very low and on balance.” Based on these results, the risk-benefit ratio favors the use of bisphosphonates despite evidence of an increased risk for these fractures, they concluded. – by Louise Gagnon


The best of these type of studies are like this one where you are looking at the radiographs and distinguishing between any femoral fracture or subtrochanteric fracture and those (fractures) with those specific atypical features. The limitation with any of these studies, in terms of causality, is that you need to have a randomized, controlled study.

Benjamin Leder, MD

Endocrinologist, Massachusetts General Hospital,
Associate Professor of Medicine, Harvard Medical School

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