Data Links High Doses of Bone Drug to Cancer

A Medtronic product, when used in high doses during spinal fusion procedures, might increase patient cancer risks, according to data released Thursday at a national conference of spine surgeons.

The data had been given to the Food and Drug Administration by Medtronic when it sought approval to market a high-strength version of an existing bone growth product called Infuse. Based on those study findings, the F.D.A. rejected that higher-dose formulation, known as Amplify, citing concern about cancer risks.

But in presenting data at the conference on Thursday, Dr. Eugene J. Carragee of Stanford University said that not all the findings of a Medtronic-sponsored clinical trial had been made public before. The trial results showed a significantly higher number of cancers in the study group that received Amplify when compared to a control group that received a bone graft as part of a spinal fusion, he said.

Dr. Carragee added that the Amplify study findings had potential implications for patients who received Infuse, because both products contained the same active ingredient, a bioengineered bone growth protein known as rhBMP-2.

In a telephone interview, Dr. Carragee said that doctors often administered Infuse off-label at levels significantly above the recommended dosages, ones that approach or exceed the amount of rhBMP-2 found in a dose of Amplify.

“This information requires careful consideration because of the large number of patients receiving high doses” of Infuse, he said, adding that he was particularly concerned about its use in certain patients like smokers or those with genetic factors that put them at higher risk for cancer.

Dr. Carragee and researchers detailed the study at a meeting in Chicago of the North American Spine Society, a professional organization. It showed that three years after surgery, there were 20 cancers in the Amplify group versus five cases in the bone graft group. Cancers take many years to develop, so the data might indicate that the bone growth protein plays a role in promoting cancer rather than causing it.

Medtronic’s Infuse had already been at the center of a debate between Dr. Carragee and the drug’s supporters.

In June, a medical publication that Dr. Carragee edits, The Spine Journal, released a special issue containing articles that challenged earlier published research backing the widespread use of Infuse. The researchers involved in the Medtronic-sponsored studies defended their findings.

In response to that publication, Medtronic gave a $2.5 million grant in August to Yale University to conduct an independent review of all study data that examined the safety and effectiveness of Infuse. That report is not expected to be completed until some time next year.

Asked for comment on Dr. Carragee’s presentation Thursday, a Medtronic spokeswoman, Marybeth Thoorsgard, released a statement stating that “the results from the independent reviews being managed by Yale will address the safety and effectiveness” of Infuse.

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By BARRY MEIER