Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, BSN, RN, Nurse PlannerTake Posttest meta-analysis of randomized trials found no association. But a registry-based study suggested that the risk of atypical fracture was more than doubled when bisphosphonates were taken for longer than 5 years (JAMA 2011; 305: 783-789).
In 2010, the FDA confirmed that bisphosphonate drugs for osteoporosis carried a small but meaningful risk of femoral fractures and ordered an update to product labels.
To add to the data on the subject, Meier’s group identified patients admitted to their level I trauma center with a fracture of the subtrochanteric femoral shaft area between 1999 and 2010 and divided them into two groups.
One arm consisted of patients with atypical fractures, defined as “a transverse or short oblique fracture line originating at the lateral femoral cortex between the lesser trochanter and the distal metaphysis.”
Another arm was made up of patients with common or classic fractures that were in the same location as atypical fractures, but with spiral, wedge, segmental, or complex irregular appearance.
They also established a control group of people who did not have a history of femoral fracture.
In addition to more atypical fractures among the group taking bisphosphonates, 28.2% of the atypical group had a contralateral fracture compared with 0.9% in the classic-fracture group.
In the atypical group, all of the complete and incomplete fractures were in patients taking bisphosphonates.
Recurrent fracture was also more common in the atypical-fracture group compared with the classic-fracture group (OR 42.6, 95% CI 12.8-142.2).
After adjustment for potential risk factors, including vitamin D status, corticosteroids, proton pump inhibitor use, sex, and age, the authors found that any bisphosphonate use was associated with an OR of 69.1 (95% CI 22.8-200.5) for an atypical fracture versus a classic fracture.
When categorized by duration of treatment compared with no treatment, the OR for an atypical fracture compared with a classic fracture was:
- OR 35.1 for less than 2 years of treatment
- OR 46.9 for 2 to 5 years
- OR 117.1 for 5 to 9 years
- OR 175.7 for more than 9 years
When comparing the atypical-fracture group with the control group, the authors reported that bisphosphonate treatment was associated with an OR of 35.2 (95% CI 15.9-155.9, P0.001).
Despite these results, the authors pointed out that “averaged over the 12 years of observation … the incidence rate [for atypical fracture] is very low; there were 11 times more classic fractures during the same period,” adding that bisphosphonate therapy still comes out ahead for reducing vertebral fractures by as much as 70% and wrist fractures by 50%.
And they cautioned that their retrospective design does not allow for definitive conclusions on causality.
But the study “adds further data suggesting that the association between bisphosphonate use and atypical fractures is causal,” said Douglas Bauer, MD, of the University of California San Francisco, in an accompanying commentary.
“These and other high-quality studies lead to the following conclusions: bisphosphonate therapy can prevent spine and nonspine fractures among appropriately selected high-risk individuals … and atypical subtrochanteric and femoral shaft fractures may be more frequent after bisphosphonate therapy but are rare compared with typical osteoporotic fractures,” wrote Bauer.
The current data also draw attention to the idea that the antifracture efficacy of bisphosphonates may not last beyond a certain number of years. Bauer suggested that some older women could consider stopping therapy after 3 to 5 years, which may mean less atypical fractures but at the cost of additional vertebral fractures.
Meier’s group, which acknowledged that they lacked sufficient information on confounding factors such as bone density, use of other medications, body mass index, smoking history, and exercise history, called for more research to determine why so few patients taking bisphosphonates have atypical fractures, and why these fractures also occur in people without any history of bisphosphonate use.
One study co-author attended paid advisory boards and has received consultancy and lecturing fees from Servier, Novartis, Eli Lilly, Amgen, Roche, Nycomed, Merck Sharp and Dohme, Alken, and Danone.
Bauer disclosed relationships with Amgen and Novartis.
Primary source: Archives of Internal Medicine
Meier R, et al “Increasing occurrence of atypical femoral fractures associated with bisphosphonate use” Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.1796.
Additional source: Archives of Internal Medicine
Bauer D “Atypical femoral fracture risk in patients treated with bisphosphonates” Arch Intern Med 2012; DOI: 10.1001/archinternmed.2012.1827.
- No Link to Femur Fractures Found with Bisphosphonates
- FDA Confirms Small Fracture Risk With Bisphosphonates
Article source: http://www.medpagetoday.com/Endocrinology/Osteoporosis/32806