| |
Mixed Analysis Findings Adds to Evidence of Unusual Bone Fractures and Bisphosphonates
|
| |
| |
By Michael Smith, North American Correspondent, MedPage Today
Published: October 20, 2010
"A large study presented here has added more evidence linking the use of bisphosphonate drugs used to treat osteoporosis to an elevated risk of what are being called "atypical" femur fractures......A second study presented at the meeting, from Olmstead County in Minnesota, found evidence for an increase in atypical femur fractures after bisphosphonate drugs entered wide use in 1996 -- but no link to the drugs themselves."
Action Points
* Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
* Explain that the FDA has ordered labelling changes for bisphosphonate drugs to warn about the risk of atypical femur fractures -- and that these studies attempted to look at the incidence and prevalence of such fractures with bisphosphonate use.
TORONTO -- A large study presented here has added more evidence linking the use of bisphosphonate drugs used to treat osteoporosis to an elevated risk of what are being called "atypical" femur fractures.
In an analysis of data collected by the large California health maintenance organization Kaiser Permanente, the vast majority of people with such atypical fractures were taking a bisphosphonate drug, according to Susan Ott, MD, of the University of Washington.
In fact, over a three-year period, the HMO's doctors recorded 135 atypical fractures -- out of nearly 16,000 broken femurs -- and all but 3.7% of the patients involved were taking a bisphosphonate, Ott reported at the annual meeting of the American Society for Bone and Mineral Research.
In addition, she noted that the rate of atypical fractures appeared to rise with longer duration of bisphosphonate use.
But, Ott said, those 135 fractures occurred among a much larger population of people using the drugs -- some 365,000 patients cared for by Kaiser Permanente doctors filled at least one prescription for the antiresorptive drugs during the study period.
The atypical fractures are characterized by a transverse break in the diaphyseal region of the femur, with lateral cortical thickening and flaring of the lateral cortex, associated with low or no trauma. There is often prodromal pain in the thigh or groin and the fracture can be bilateral.
The FDA ordered labeling changes for bisphosphonate drugs to warn about the risk of atypical fractures after an ASBMR task force found 310 cases -- in which 94% of patients were taking bisphosphonates.
For the current analysis, Ott and colleagues had access to medical reports -- including x-rays -- of the 15,819 femur fractures that Kaiser covered in 2007, 2008, and 2009.
Among the 135 fractures they found:
* 98% of patients were women, with an average age of 71 and an average body mass index of 26.6.
* 53% had previous fragility fractures, but only 2% died in the year following the atypical fracture.
* On average, the patients had been talking bisphosphonates for 6.3 years.
* 67% had prodromal pain and 25.9% had bilateral fractures.
* 60% of the breaks were on the shaft and 40% were subtrochanteric.
The proportion of patients with such fractures rose steadily with the duration of use, Ott said, rising from about two per 100,000 if bisphosphonates were used for less than a year to almost 250 per 100,000 after 12 years of use.
The estimates suggest that the atypical fractures are rare in the general population but may be higher among those taking bisphosphonates, Ott concluded, adding that the risk of such a fracture is much less than the risk of hip fracture in people with osteoporosis.
But the picture may not be without some complexity. A second study presented at the meeting, from Olmstead County in Minnesota, found evidence for an increase in atypical femur fractures after bisphosphonate drugs entered wide use in 1996 -- but no link to the drugs themselves.
According to Alvin Ng, MBBS, of the Mayo Clinic in Rochester, Minn., more people -- mostly women -- had such fractures after 1996 than in previous years, but the increase was seen even after the small number of bisphosphonate users was excluded from the analysis.
Ng and colleagues looked at medical records for the county from 1984 to 2007 and found 730 non-hip femoral fractures in 691 residents, including those associated with major trauma, minimal or moderate trauma, or pathological causes.
Non-hip femoral fractures rose from 21.9 per 100,000 person-years in the years 1984 through 1995 to 30.4 per 100,000 person-years in the rest of the study period, a difference that was significant at P=0.001. Ng reported.
Most of the rise was attributable to breaks caused by minimal or moderate trauma, which jumped from 7.4 to 12 per 100,000 person years between the two periods, which was significant at P=0.003, he said.
In the bisphosphonate era, Ng reported, there were 164 fractures due to minimal or no trauma, including 21 in 20 residents who were taking one of the drugs at the time.
When those patients were excluded, he said, the increase in such fractures, compared with the previous period, was still evident.
The apparent contradiction might be a result of limited and retrospective data, according to Eugene McCloskey, MD, of the University of Sheffield in Sheffield, England, who was not part of either study but who moderated the session during which they were presented.
"One of the problems here is that we've got an association that may or may not be real," he told MedPage Today. But in order to tease out information, researchers are forced to use medical records that may be full of "noise generated by the data capture," he said.
As well, he noted, the Olmstead study was small and regionally limited, so it's possible the findings are the result of chance.
The California study was supported by Kaiser Permanente. Ott said she had no disclosures.
The Olmstead County study was supported by the NIH. Ng said he had no disclosures.
McCloskey said he had no disclosures.
Primary source: American Society for Bone and Mineral Research
Source reference:
Dell R, et al "A Retrospective analysis of all atypical femur fractures seen in a large California HMO from the years 2007 to 2009" ASBMR 2010; Abstract 1201.
Additional source: American Society for Bone and Mineral Research
Source reference:
Ng A, et al "Non-Hip femoral fractures in patients on bisphosphonate therapy: A population-based study from Olmsted County, Minnesota" ASBMR 2010; Abstract 1200.
| |
| |
| |
|
|
|
