Subtrochanteric fractures

(Fosamax Femur Fractures) Features Background incidence Database studies Incidence X-ray gallery Theories about etiology Management My invited paper that was rejected References

This page is a work in progress. Currently this is a controversial topic, and studies are on-going. The information is likely to change as we gain more experience.

Features

I have reviewed the medical literature and found 121 cases reported, including 72 individual cases. This table shows the main features. You can download an Excel file showing my notes on these cases (Reported cases) and on the studies (Studies about these fractures).

Subtrochanteric or shaft (diaphyseal) part of the femur
Minimal or no trauma (all)
Frequently preceded by weeks to months of thigh pain
Bilateral in 47% of cases
Patients younger than typical femur fractures (mean age 64)
Bisphosphonate use longer than 5 years in 75% of cases
Frequently another cause of osteoblast suppression
Bone density not severely decreased
X-rays show thick cortices, especially on lateral side (all)
Often a "beaking" that resembles a stress fracture
Fractures may not heal very well
Femur more likely to crack during surgery

Background incidence

There have always been fractures of the femur, even before bisphosphonates. Here is a graph of data in women from Rochester, Minnesota, between 1965 and 1984 (Arneson)

In Finland, from 1985 to 1994, low-trauma fractures of the femoral shaft were seen in 7.8 per 100,000 people older than 60. The majority were the spiral type (Salminen).

In the elderly, these femur fractures are about 1/10 as common as hip fractures.

Database studies

A study by Abrahamsen B, however, casts some doubt about how often subtrochanteric fractures are related to bisphosphonates. The Danish hospital registry identified all patients older than 51 who had any fracture except hip. 5187 who were then started on alendronate and remained on treatment for at least 6 months were compared to 11160 controls, matching for age, sex, and location of the fracture. Then they were followed to see how many hip and subtrochanteric fractures occured. The rate per year of subtrochanteric fractures was 0.19% in alendronate group and 0.10% in control; the rate of hip fractures was 1.7% in alendronate group and 1.1% in controls. Thus, the relationship between alendronate and hip fractures was similar to subtrochanteric fractures. It is interesting that the alendronate-treated patients actually had higher fracture rates even though they were matched. There could have been some other factors that caused physicians to give the bisphosphonates to the patients in the first place. The registry-based analysis does not allow for any details about the patients or their clinical symptoms.

A similar study was recently presented at the ASBMR using the Veteran's Administration database (Saord). There are several other studies that have not shown an increase in the rate of subtrochanteric fractures which might be expected if these were increasing due to bisphoshonates (Nieves, Adachi, Curtis)

X-ray gallery

Here is a LINK to some thumbnails of all the published x-rays from these patients. I am in the process of getting permission to show the images and only a few are available. Click on the stars to see the images and on the names to find the abstracts in PubMed. I will update these as I get permission.

Incidence

At this time the incidence is not known. One paper estimated it was 1/1000 in long-term users (Schilcher J).

Theories about etiology

Bone biopsies often show very low bone formation, but some have not seen this. Biopsies at the site of the fracture are usually done to rule out cancer or other pathology, and there have been mixed reports about whether osteoclasts are increased.

Perhaps the suppressed bone turnover allows accumulation of micro-cracks, which then can result in a stress fracture.

Many features of these fractures resemble the "march fractures" seen in military recruits. Perhaps these younger women with less severe osteoporosis are more active and thus are accumulating damage at a higher rate than the more usual elderly woman with severe osteoporosis.

There are also some abnormalities in the chemical crystal structure of the bone mineral that might make the bone more brittle (ASBMR09 Boskey).

Management

At this time there is no consensus about management. There is some rationale for treating with teriparatide. If there is a fracture line seen on an x-ray, the risk of a complete fracture is not really known, but some experienced orthopedic surgeons suggest this is an indication for rodding the femur.

My invited paper that was rejected

The editor of the Journal of Clinical Metabolism and Endocrinology asked me to write a paper about the way to approach a patient who had been taking long-term bisphosphonates. However, the reviewers thought it was too biased, and the paper was rejected. Here is a .pdf file of my rejected paper.

The reviewers of the paper said: "This is an opinion paper, based upon a very sparse literature that calls attention to an exceedingly rare event recently associated with long-term bisphosphonate therapy. There are many issues that although mentioned are not dealt with in depth or in a scholarly manner. The literature cited is selective and the interpretation is even more so."

" The abstract suggests a very negative view about continuing bisphosphonate therapy beyond 5 years. This unqualified view, repeatedly emphasized in a discussion that is rather loose, rambling and not consistent, runs counter to many experts and also much literature arguing the other view."

"This paper allows the author to express her practice pattern to stop BP treatment in all patients after 5 years. She readily admits that this action is not based on any solid evidence, but rather her concerns about potential harm. The paper summarizes the current literature on subtrochanteric fractures among patients receiving BPs. The paper would be better if it focused on patients who have done well on treatment."

"The issue of subtrochanteric hip fractures is evolving. I think it is premature to go into detail here. There is evidence that these fractures are not related to bisphosphonate treatment but rather an uncommon fracture due to osteoporosis."

The following is from my previous page on this topic and will soon be edited:

This shows a lateral stress fracture on plain film and on a bone scan in a patient who had been taking alendronate for many years. She fractured her femur about a month later.

Another patient who had been on alendronate about ten years. Both these patients had tetracycline-labelled bone biopsies with no tetracycline in the cancellous bone.

A report by Odvina described 9 patients who had been using alendronate for 3 to 8 years, who had very low bone formation rates and unusual fractures, many of which did not heal properly. There have been several other anecdotal reports about unusual fractures in patients on long-term or high-dose bisphosphonates (Schneider JP, Whyte MP, Imai K, Sayed-Noor AS, and Visekruna M). These cases do not prove that alendronate caused the fractures, but they might be clues to potential long term harmful effects of these drugs (Ott SM)

(Armamento-Villareal R) from St. Louis reviewed all bone biopsies from patients who were seen between 2004 and 2007 who had an unusual cortical fracture while taking a bisphosphonate. Very low bone formation rates were seen in 11 of the 16 patients

Goh SK then reviewed all cases of subtrochanteric fractures from a hospital in Singapore. They had 13 fracture cases in a year, and 9 of them had been taking alendronate. The radiographs of the ones on alendronate were significantly younger and showed less osteoporosis than the ones without alendronate.

The second series was all subtrochanteric fractures seen over 5 years from a large New York hospital. There were 69 patients, and 36% of them had been taking alendronate. Of those, 76% had an unusual radiographic appearance of thick cortices, which was seen in only 1 patient with a subtrochanteric fracture who was not taking alendronate (Lenart BA, Neviaser AS)