Off-Label Bone Growth Protein in Children Raises Concerns: Study

Nearly 10% of all spinal fusion surgeries for children involve the use bone morphogenic proteins (BMP), such as Medtronic’s Infuse, despite potential safety concerns about the long-term complication rates and the fact that the products have not been approved for use with minors. 

According to a letter to the editor published in the Journal of the American Medical Association on October 10, researchers indicate that the off-label use of the bone-growth proteins on children raises questions about complications that have been linked to their use in adults, including excessive or ectopic bone growth, cancer, respiratory problems and death.

Bone Growth Proteins (BMP) are used as an alternative to traditional spine fusions, where bone is harvested from another part of the body or a cadaver. The bio-engineered protein is used to stimulate bone growth, and promote the fusion of vertebrae in the spine.

The letter was submitted by Emily Dodwell, MD, of the Hospital for Special Surgery in New York and her colleagues. They analyzed data from 4,121 hospitals in the United States and found 8,289 spinal fusion procedures. When they looked at those that involved the use of BMPs and those that did not, they found no statistical difference among the rate of complications.

Bone Growth Protein (BMP) Problems Often Appear After Patients Are Sent Home

Despite the findings, the researchers warned that many complications linked to Medtronic Infuse and other BMPs do not appear until after the patient has been released from the hospital. They concluded that off-label use of BMPs among children, although legal, should be halted until the side effects of bone growth proteins are better understood.

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

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.

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.

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.

Authors of the letter expressed concerns about the use of bone growth protein in children, citing added expenses and questions about the potential long-term complications. However, they did not indicate that the products should never be used among minors.