Orthopedics

There have been many stories this week on this review in The Spine Journal, which found that a commonly used spinal fusion product is associated with potentially serious complications not previously reported in industry-sponsored studies. Eugene Carragee, MD, the journal’s editor-in-chief and professor of orthopedic surgery at Stanford, said he believes there has been some misleading or inaccurate material carried in these stories about the product, known as rhBMP-2 and marketed as Infuse by its manufacturer, Medtronic, Inc.

For instance, the company’s CEO said in a statement that the review and related articles in the journal “do not raise questions about the data Medtronic submitted to the FDA in the approval process.” However, Carragee notes that while the company did report complications to the FDA, the trial design used by Medtronic for the FDA studies were, based on fundamental design flaws, biased in favor of the company’s products.

“Therefore we strongly disagree with the Medtronic CEO statements that our report finds the data submitted to the FDA to be reliable. We do not. The data in itself, especially in the high-dose Amplify trial, has been pretty soundly discredited by multiple studies,” Carragee said. Several of those studies challenging the FDA study design and biases were published in the same issue of The Spine Journal.

Amplify is the newer version of the product, which has been found to carry a possible increased risk of cancer. It has yet to be approved by the FDA in part because of this concern; however this serious association was not discussed in published studies sponsored by the company.

Carragee also takes issue with a position held by a University of Wisconsin orthopedist who was involved in some of the industry-sponsored studies. The researcher, Thomas Zdeblick, MD, received as much as $23 million from Medtronic, much of it in royalties for the only device tested and approved by the FDA for use with rhBMP-2, Carragee said. Zdeblick has defended himself, telling the New York Times that he did not have a “direct financial interest in the success of Infuse or Medtronic.” However, Carragee calls the conflict-of-interest by Zdeblick and some other physicians involved in the trials “as strong as I have seen in medicine in 30 years.

“Although he holds what can be considered a type of monopoly for on-label use, he repeatedly claims he has absolutely no financial interest in BMP-2,” Carragee said. “This claim is hardly credible, almost ridiculous.”

In a letter to the journal, Zdeblick also claimed that Carragee was absent for 18 months on military duty, during the time of a clinical trial at Stanford that showed the incidence of male sterility associated with the product was about 7 percent, far greater than industry-sponsored studies reported. Carragee said he was at Stanford during the entire trial period of 2002 to 2004 and didn’t return to active duty until 2005, so Zdeblick’s statement is “pure fabrication.” “We are astonished that Dr. Zdeblick would falsely manipulate an Army officer’s wartime service record in this manner,” the journal editors responded.

Previously: Stanford-led study on Medtronic bone product dominates the headlines, Stanford orthopedist reveals problems with Medtronic spinal fusion product, and Stanford study links spine product to male infertility

An extensive review of the data on a commonly used spinal fusion product, which found the Medtronic product causes vastly more complications than reported in previous industry-sponsored studies, has sparked a firestorm of media coverage. The paper (.pdf), written by Stanford orthopedist Eugene Carragee, MD, and colleagues, was published yesterday in The Spine Journal.

A Wall Street Journal article offers a detailed summary of the research, Medtronic’s response and the Senate Finance Committee investigation into whether surgeons’ financial relationships with Medtronic Inc. were a factor in adverse effects going unreported.

A New York Times piece noted that the analysis was a seemingly unprecedented event in medicine:

It is extremely rare for researchers to publicly chastise colleagues, and editors of leading medical journals said they could not recall an instance in which a publication had dedicated an entire issue for such a singular purpose.

…

Both Dr. Howard C. Bauchner, editor in chief of The Journal of the American Medical Association, and Dr. Gregory D. Curfman, executive editor of The New England Journal of Medicine, said they could not think of a time when a journal had devoted an entire issue to questioning an approved product.

And Forbes writer Matthew Herper explains what motivated Carragee to begin looking into claims about published studies on the spinal fusion product and how The Spine Journal intends to make disclosures of financial conflicts more prominent in future publications.

Omar Ishrak, chairman and chief executive officer of Medtronic, Inc, responded to the journal articles in a statement saying, “While the Spine Journal articles raise questions about researchers’ conclusions in their published peer-reviewed literature, the articles do not raise questions about the data Medtronic submitted to the FDA in the approval process or the information available to physicians today through the instructions for use brochure attached to each product sold.”

Previously: Stanford orthopedist reveals problems with spinal fusion product, Stanford study links spine product to male infertility and Spine expert comments on dramatic increase in complex back surgeries

During the course of this past year, Stanford orthopedist Eugene Carragee, MD, and his colleagues have done an extensive review of the data on a commonly used spinal fusion product and have found it causes vastly more complications than reported in early industry-sponsored studies. Their review (.pdf), published in today’s The Spine Journal (which Carragee edits) found the complications, including male sterility, infection, bone and nerve problems and possible increased cancer risk, were at least 10 to 50 times greater than originally reported. The authors of the early studies, who reported virtually no adverse effects, received many millions of dollars from the product manufacturer, Medtronic, Inc., the review found.

“If there weren’t millions of dollars riding on it, this would be a dry discussion on the appropriate use of statistics and methodology,” Carragee, a professor of orthopedic surgery, told me. “The problem is in the last 10 years, between $3 billion and $5 billion has been spent on this product, and it’s not clear what benefit has been achieved, compared with how many patients have been harmed by it. The industry estimate of harm is simply wrong.”

The review of the data, widely reported in the media, already has triggered a Congressional investigation, with the Senate Finance Committee requesting that Medtronic turn over all documents related to complications from the product, including communications with doctors who conducted the early trials. The product, a bioengineered protein known as rhBMP-2, is marketed under the brand names Infuse and Amplify.

Exposing these issues represents a bold move by Carragee, who is taking on an extremely powerful industry. But Carragee, who has served with the U.S. military in Iraq and elsewhere, says he’s just doing his job.

“This should be the bread and butter of what clinical publications do, which is critically evaluate the evidence and create a dialogue about the advantages and disadvantages of treatment,” he said. “It only appears courageous because some others haven’t done it.”

Previously: Stanford study links spine product to male infertility
Photo by Norbert von der Groben

Recent research has shown runners who eschew shoes may be less likely to do serious injury to their feet. However, some doctors have cautioned that the practice can cause injuries rather than prevent them. Interested to know more about the potential benefits and risks of barefoot running, I contacted Michael Fredericson, MD, who has served as the head team physician with the Stanford Sports Medicine Program since 1992. Below, Fredericson discusses shoeless running, things to keep in mind if you’re thinking about doing it, and the importance of foot gear, or lack thereof, in injury prevention.

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For many months, Stanford orthopedic surgeon Eugene Carragee, MD, has been closely examining a growth factor used in spinal fusion procedures that may cause troubling side-effects, including male infertility, that were previously unreported. The first findings in his long inquiry appear today in The Spine Journal, which Carragee edits, and have been widely covered in the media, including the New York Times.

The findings, based on a retrospective study of 240 patients at Stanford, show the product, known commercially as Infuse, carries a higher risk of male infertility than previously thought. Perhaps more troubling: Earlier published reports on the product, which were written by surgeons with ties to the company, cited no adverse events. In an accompanying article in the journal, James Kang, MD, from the University of Pittsburgh, wrote:

There does not seem to be any rational explanation for [these] observational differences other than the fact that Carragee et. al. had no commercial conflicts of interest whereas the original FDA studies were corporate sponsored studies.

The Milwaukee Journal Sentinel, which has run numerous investigative stories on the device, also has an in-depth article on the issue.

Poor Carrie Bradshaw! It turns out everyone’s favorite fictional writer and shoe aficionado could be facing some health issues in the future: According to results of a small study out of Iowa State University, wearing prolonged high-heel wearing may lead to joint and knee problems. From the release:

[Researcher Danielle] Barkema selected three different heel heights – flat, two inches, and 3.5 inches – and had each of the 15 women in her study complete walking trials. She measured the forces acting about the knee joint and the heelstrike-induced shock wave that travels up the body when walking in heels. Using sensors, accelerometers and lab equipment such as a force platform and markers/cameras, she was able to capture motion and force data and translate them into results that could change the way millions of women select their footwear.

While previous studies have examined the effect of high heels on joints, the ISU researchers found that heel height changes walking characteristics such as slower speeds and shorter stride lengths. And as the heels got higher, they also saw an increase in the compression on the inside – or medial side – of the knee.

“This means that prolonged wearing and walking in heels could, over time, contribute to joint degeneration and knee osteoarthritis,” Barkema said.

The findings haven’t been published yet but will be presented at the upcoming annual meeting of the American Society of Biomechanics.

Previously: Ouch! How high heels can shrink leg muscle, cause pain
Photo by the_moog

A new analysis, highlighted today in a WebMD article, shows that professional baseball pitchers suffer higher injury rates than fielders. When looking at data from the 2002-08 seasons, researchers found that pitchers spent 62.4 percent of their days on disability, compared to 37.6 percent for fielders.

Given the physically taxing and repetitive nature of a pitcher’s job, this finding – along with the one that pitchers are more likely to be sidelined by upper extremity injuries than for lower-extremity ones – isn’t terribly surprising. But what I did find surprising, and somewhat perplexing, was that:

It’s especially hazardous for pitchers before the annual mid-season All-Star game. During the period examined, pitchers were 34% more likely than fielders to be injured before the mid-season break. And 77% of all injuries to pitchers happen before the All-Star game.

The researchers also found that 74.4 percent of all player injuries occurred before the All-Star break. (No word, though, on why that’s the case.) They presented their work at the annual meeting of the American Orthopaedic Society for Sports Medicine .

Photo by Keith Allison

I’m proud (though perhaps I should be embarrassed) of the fact that the only flats in my wardrobe are work-out shoes and flip-flops for the beach. I’ve always been a heel kind of girl; even during two pregnancies (and despite my mom’s pleas), I just couldn’t ditch the tall shoes.

I was particularly interested, then, in a new study on what regular heel-wearing does to the legs. As CNN reports today:

[The study] shows that regularly wearing high heels can cause muscle and tendon changes in your legs — to the point where wearing flats or flip-flops can be painful.

Wearing two-inch heels (or higher) five or more days a week shrinks a woman’s calf muscle fibers by 13 percent, on average. It also thickens her Achilles tendon — which attaches the calf muscle to the heel — by 22 percent, according to the study, which was published Thursday in the Journal of Experimental Biology.

These changes alter the resting position of the ankle, causing the foot to point down more than normal. For some habitual high-heel wearers, this can make switching from stilettos to flats a shock…

As pointed out in the article, the findings don’t necessarily apply to everyone: The women in the study who experienced pain wore heels for an average of about 60 hours a week. The study also didn’t focus on whether wearing heels can cause permanent damage to leg muscles. Still, the research may be enough to make me at least consider cutting back on the amount of time I spend in heels.

My mom’s going to be thrilled!

Photo by Shorts and Longs | The Both And

Proteins called Wnts might be the key to speedy bone healing. That’s according to Stanford researchers, who used the protein to re-grow broken bones in animal models three times more quickly than normal. From our release:

They stimulated the rapid bone growth by injecting… Wnt [which is] known to be involved in the growth of many types of tissues in animals like salamanders, zebrafish and mice. The feat marks the first time that researchers have managed to package the Wnt protein in a form that could be used in humans, and opens the door to additional experiments to heal skin, muscle, brain and other tissue injuries.

NatureNews also reported on the study, which appears in the journal Science Translational Medicine, and quoted a Columbia University expert who called the work “a major technological advance.” But developmental biologist Roel Nusse, PhD, stressed there is still a lot of work to do:

Before starting clinical trials, the team will first have to determine whether the Wnt therapy is safe at high doses and over prolonged periods of time. Humans and mice share a similar Wnt pathway, Nusse says. “It’s not unlikely that it would work in humans,” he says. “But I don’t know how dramatic the effect is going to be.”