Side Effects of Bone Graft Substitutes Linked to Child Health Risks, FDA Warns

Federal drug regulators are warning against the use of bone graft substitutes, such Medtronic Infuse, among children, indicating that the bone growth proteins have been linked to reports of serious injury. 

The FDA issued a safety communication on January 21, warning doctors against routine use of bone graft substitutes containing recombinant proteins or synthetic peptides in minors. The agency warns that the use of Medtronic Infuse and other similar products may cause bone growth problems for children.

Medtronic Infuse bone graft is one of the most widely used bone morphogenic protein (BMP) products, which is applied to an absorbable collagen sponge that is then placed within a cage implanted to encourage bone growth and fuse the gabs between vertebrae.

Although the FDA only approved the Medtronic Infuse for limited spinal procedures in adults, involving a single-level anterior lumbar interbody fusion (ALIF), where the spine is approached from the front, the Medtronic Infuse has been widely used “off-label” for other types of spine fusion surgery, which have been linked to an increased risk of severe and painful complications caused by excessive or ectopic bone growth.

“Reports of serious injuries, such as excess bone growth, fluid accumulation, inhibited bone healing, and swelling, have increased the FDA’s concern,” the communication warns. “While these types of events are similar to those seen in patients over age 18, they are of more concern in patients under 18 because of their overall smaller size and because their bones are still growing.”

Concerns over the use of bone graft substitutes among children stretch back to at least 2012, when researchers published a letter in the Journal of the American Medical Association (JAMA), warning that nearly 10% of all spinal fusion surgeries for children involved the use of BMPs, despite the long-term risks.

The FDA warning appears to verify that the risks are magnified in children.

“In a body that is still growing, vital organs and tissues are closer together than in a body that is done growing. This could potentially allow small changes from one organ/tissue to have serious effects on another,” the FDA warns. “For example, there is less space between the spinal cord and the bones surrounding it. If one of these products is used in the spine of a patient under age 18, who then experiences the same amount of excess bone growth or fluid accumulation as a patient over age 18, it may more easily lead to spinal nerve injury, pan, or weakness.”

The FDA recommends that doctors consider other options for minors who have significant bone defects or rare bone disorders, such as autograft bone, taken from another part of the body, and allograft bone transplanted from another person. The FDA also recommended that doctors look at bone graft substitutes that do not contain recombinant proteins or synthetic peptides.

Medtronic Infuse Bone Growth Concerns

Since introducing the product in 2002, Medtronic has aggressively promoted Infuse bone graft surgery as an alternative to traditional spine fusions, where bone is harvested from another part of the body or from cadavers.

In 2008, the FDA issued an alert about the risks associated with such unapproved uses of Medtronic Infuse, after receiving a number of reports involving serious complications and deaths, often involving use in the cervical spine where the bone growth problems may impact the airway.

Medtronic has been accused of illegally promoting off-label use of Infuse by providing false and misleading statements and paying “opinion leaders” to encourage uses beyond what was approved by the FDA.  As a result, some estimates suggest that as much as 85% of all sales for Medtronic Infuse were for such off-label uses.

Medtronic has agreed to pay about $22 million to settle about 950 Infuse BMP lawsuits filed on behalf of individuals nationwide who have experienced problems after receiving the bone graft product.  

Estimates suggest that litigation costs, including all Medtronic Infuse settlements, will ultimately cost the company between $120 and $140 million.