Spine Surgeons React to BMP-2 Cancer Data

By John Fauber, Reporter, Milwaukee Journal Sentinel/MedPage Today

CHICAGO -- Spine surgery patients who got a bone growth stimulating agent as part of a clinical trial were three to five times more likely to develop cancer two to three years after being implanted with the product, according to a new analysis reported here.

The report is the latest cautionary note involving Medtronic's bone morphogenetic protein-2, or BMP-2, a popular genetically engineered product used in spinal fusion surgery as an alternative to using a small amount of a patient's own bone.

The analysis led by Eugene Carragee, MD, a Stanford University orthopedic surgeon, who presented the findings at the North American Spine Society's annual meeting, echoes findings in a Journal Sentinel/MedPage Today investigative report earlier this month. That story showed an elevated cancer risk in the clinical trial of an investigative Medtronic product containing BMP-2.

If approved it would be marketed under the brand name Amplify. Medtronic currently manufactures another BMP-2 product under the brand name InFuse. That product is FDA approved.

"This is a provocative study that should make surgeons most concerned," said Dan Spengler, MD, a professor of orthopedic surgery at Vanderbilt University Medical School. "I can't see a justification for its use except in extreme cases."

Carragee's analysis drilled down into data from a pivotal trial in which 239 patients were treated with the Amplify product and 224 controls, who had spinal fusion using autologous hip bone grafts.

Among those who underwent follow-up about three years after the surgery, 5% of those who got Amplify, or 12 patients, were diagnosed with a new cancer, compared with 1.3%, or three patients, who got a graft of their own hip bone. The difference was statistically significant P=0.02.

After two to three years of follow up, Amplify patients were four to five times more likely to develop at least one new malignancy, the analysis found. Viewed another way, one extra patient would be expected to develop cancer out of every 20 to 25 treated with Amplify.

Cancer cases that were diagnosed after spinanl fusion surgery among 239 patients who were implanted with BMP-2 as part of the Amplify clinical trial.


The cancer findings were not discussed when the findings were initially published.

"Who do we believe?" asked John Jacquemin, MD, an orthopedic surgeon from Cincinnati in response to Carragee's presentation. "When the literature comes out, what's real and what is not?"

Jacquemin said he was especially troubled by allegations of bias in papers written by doctors with financial conflicts.

"That scares me and troubles me," he said.

Jerry Knirk, MD, an orthopedic surgeon from New Hampshire, said he was concerned that most funding for medical devices comes from corporations.

"Money corrupts," he said.

The authors of the 2009 paper mentioned the cancer link only in a table accompanying the paper. The text itself never addressed the concern of whether BMP-2 might fuel cancer.

It was written by six physician authors. The first three authors of the paper - or entities they are associated with - received about $10 million from Medtronic, mostly in royalties, in 2010 alone. The royalties were for other products, not for BMP-2.

While the authors failed to warn of the cancer concern, the Journal Sentinel/MedPage Today found a full airing of the cancer question in more than 1,000 pages of U.S. Food and Drug Administration records. That information included FDA reports and information filed with the agency by Medtronic as part of its application to win approval for Amplify.

At a 2010 Amplify hearing, for example, an FDA staffer said "the primary statistical concern is an apparent association with malignancy."

Since coming on the market in 2002, BMP-2 has become popular in spinal surgery. By stimulating bone growth, it can eliminate the need to harvest a small amount of a patient's own bone for use in a spinal fusion surgery.

The product was approved for a narrow use after an earlier clinical trial showed it worked about as well as a standard hip bone graft in a specific kind of spinal fusion surgery. But doctors quickly began using BMP-2 in other, unapproved ways, known as "off-label" use. That helped fuel annual sales of $700 million.

Carragee said only a small portion of BMP-2 use follows the protocols of how the product originally was approved by the FDA. Most of its use is in so-called off-label applications.

He noted the doses of BMP-2 as well as the carrier used in the Amplify clinical trial are commercially available and as such are used off-label by surgeons.

Carragee said he thinks BMP-2 may fuel existing cancers.

He said in theory as people get older they have more cancer cells in their body, which the immune system tries to keep in check.

The addition of BMP-2, especially in higher doses, may disturb that balance and allow a cancer to grow, he said.

"At higher doses in people who are older and who have less resiliency to cancer, it's more worrisome," he said. "I would say, why risk it?"

Chiropractic Care Contributes to Optimal Performance of Baseball World Series Champions 2011 St. Louis Cardinals and 2010 San Francisco Giants

Cardinal pitcher Jason Motte advocates chiropractic care
CARMICHAEL, Calif. – Nov.  3, 2011 – As the St. Louis Cardinals celebrate their 11th World Series title and the San Francisco Giants relive their 2010 championship, the Foundation for Chiropractic Progress points to the role of chiropractic care in promoting faster recoveries, reduced risk of injury and enhanced on-field performance.  Chiropractic team doctors Ralph Filson, D.C. of the Cardinals, and Michael Gazdar, D.C. of the San Francisco Giants, explain that regular chiropractic care provides baseball players with proper spinal function and balance to reduce the risk of spine-related injuries, enhance recovery time and improve overall performance.
Dr. Filson, who began providing care to the players in 1990 through its then manager, Joe Torre, Major League Baseball (MLB) legend, says, “Chiropractic care is always available for players of the Cardinals and the visiting team, it is utilized by many.  With chiropractic care, players report that they feel better and have better endurance.  Body mechanics are significantly improved, enabling better pitching, hitting and throwing.”
Jason Motte, relief pitcher for the St. Louis Cardinals, shares, "I had issues with my shoulder and arm for a long time.  I started seeing Dr. Filson this year. Since then, I have not had any arm problems. The whole team appreciates him and the work he did throughout the season. I know while being under Dr. Filson's care, I was able to feel 100 percent while on the mound.”
In 2006, Dr. Filson was awarded a World Series ring for his role with the Cardinals, and was proud to play a similar role in the 2011 championship.  He also treated David Eckstein, Most Valuable Player on the Cardinals 2006 World Series Team, citing the importance of chiropractic care in helping players to achieve optimal performance:  “I am proud to have provided chiropractic care to the Cardinals for so many years, and gratified that chiropractic has contributed to the players’ optimal performance during every game.  We are all excited about bringing home the 2011 World Series title.”
According to Dr. Gazdar, who began working with the San Francisco Giants in 2008, and was seen by millions celebrating at the pitcher’s mound with the players following the game-ending play that resulted in the Giants World Series title, “Chiropractic care was a significant factor in the San Francisco Giants 2010 victory.  One of the Giants’ pitchers relied upon chiropractic adjustments for all of his pitching starts, and virtually every player benefitted from chiropractic services.” 
Both doctors express their enthusiasm for the inclusion of chiropractic care for virtually every team participating in professional sports, including golf, football, hockey, basketball and baseball. 



This press release was sent yesterday by the Foundation for Chiropractic Progress to 10,000 newspapers/wire services. Accompanying the article was a picture of Dr. Filson between GM Joe Torre and coach Tony LaRussa.