Recent case series and individual reports from several orthopedic surgical centres have described atypical (diaphyseal) and subtrochanteric fractures after low-impact trauma in patients on long-term bisphosphonates (see perspective article at http://www.ejbjs.org/Comments/2009/cp_nov09_lane.dtl). As stated by these authors, the underlying causes of these fractures are undoubtedly multifactorial (age, comorbidities, corticosteroid, smoking, vitamin D status, etc.). Subsequently, two population studies, in Australia and Denmark, were reported to ascertain more accurately the true population incidence of such fractures, and neither demonstrated a relationship specifically with bisphosphonate use.^1,2

Clues to the clinical presentation of these atypical fractures are worth noting: significant osteoporosis, previous fracture events, corticosteroid use (a major determinant in the Danish cohort), smoking history and age. The acute event may be preceded by more chronic upper thigh discomfort. Thus, early on, x-rays may demonstrate subtle changes of bony insufficiency. A bone scan might also be useful as a helpful and simple means of documenting early bone damage if there is a high index of suspicion. Bone turnover markers (Beta crosslaps test, if available) may be markedly suppressed, and vitamin D status should be ascertained.

To summarize these studies’ findings, the relationship of bisphosphonate use to atypical fractures is marginal if any, and the risk-benefit ratio for these agents in fracture prevention still strongly supports their use as first-line agents. The rare events that do occur highlight a subgroup of patients who by virtue of multiple factors are at increased susceptibility to fragility fracture as a result of impaired bone remodelling, that might be further altered by antiresorptive therapy. This shows the importance of recognizing the prodromal features of these rare cases, but also to the continuing investigation of the optimal approaches to drug therapy for osteoporosis and fracture.

References

1. CMAJ Mar 2010;182:384-5.
2. Journal of Bone and Mineral Research 2009; 24:1095-102

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