Off-label Use of Bone Graft Substitutes

Medical products which are manufactured and sold for one application can be used by physicians for other purposes. This “off-label” use is perfectly legal. It relies on the medical judgment of the responsible physician for safety. But there’s a possible danger as well – because the product hasn’t been tested for that specific use, a physician may not be aware of the dangers. This is why the FDA issues warnings to the medical community when it finds out about misuse.

The current Food and Drug Administration warning concerns an off-label use for bone graft substitutes.

We usually think of bone as a desiccated, rock-like material, more like porcelain than a living tissue. But in the body, bone has a blood supply and is capable of growth and healing, like other tissues, only slower. The slow growth is a problem when doctors need to make a major repair. Since bone provides structure to the body (like the wood framing in a house), the wait while bone heals means a limb has to be immobilized for an extended period. You can’t stress the bone you are trying to heal and expect it to repair itself properly. But the lack of movement also affects the attached muscles and tendons, possibly causing other problems.

In x-rays, you sometimes see metal screws and plates. The hardware helps stabilize damaged bone by taking the stress off, allowing both good alignment and healing. Another solution is grafting bone tissue from a donor (either the patient herself, or, as is common, a cadaver). With a graft, the missing bone doesn’t have to be entirely regrown by the patient – the graph can act as a “patch” and a filler. This is a huge advantage, since it reduces healing time.

How Bone Graft Substitutes Work

Bone grafts, or transplants are the second most common type of transplant procedure. Only blood transfusions happen more often. And just as there are blood banks, there are bone banks with supplies of material for grafts.

Finally, we have bone graft substitutes, the subject of the FDA warning. These are artificial substances, or natural substances (like cow bone cartilage) which are inactive. Some are putties or gels which can be injected where needed, and some are bone-like in appearance. But all are non-living and meant to provide a structure for new bone from the patient to grow one.

Because about half of bone grafts are used in spinal fusions, this, along with dental procedures, make up the bulk of the use for both natural and substitute bone. The demand is huge. However, to get the patient’s own bone to grow on the “patch” – the artificial scaffolding – chemical messengers are included in the products. These molecules trigger the patient’s healthy bone (where the patch is applied) to start making new cells, and these new cells will eventually form the final repair. These messenger molecules are called recombinant proteins or synthetic peptides. They are mixed in (or coated on) the bone graft substitute .

The Problem and the Warning

In an adult (someone over 18) none of the above causes problems. And bone graft substitutes are already approved for adults. Although there is some expected swelling from the disturbance, it eventually settles down and healing occurs as expected. But what about someone under 18, whose bones are still growing as they continue to mature?

The essence of the FDA warning is that off-label use of bone graft substitutes in patients less than 18 years of age comes with an added risk: the patient’s own growing bone, even at another nearby location, can mean the “patch” doesn’t stay where it is intended. There’s a serious risk of the repair pushing into an area where it not only isn’t wanted, but may cause harm. In a spinal graft, damage can happen if the patch “overgrows” and pushes against the spinal cord. But this overgrowth into an unwanted area can happen elsewhere too. And, the younger the patient, the greater the risk, since everything is closer and packed tighter in the more compact body of a younger person.

For an older adult, normal bone growth is at a minimum. They are as big as they will ever be. The orthopedic surgeon can estimate the swelling and new growth which will occur after the graft and take it into account. But with a younger patient, this isn’t as easy. Even years later, normal growth may push a repair into an area where it isn’t wanted, and possibly cause injury.

The Bottom Line

The FDA still allows bone graft substitutes to be used, off-label, in patients under 18. However, they strongly recommend a physician look to other options instead. It’s still up to the doctor (and the patient’s parents, who must approve the procedure) to decide if the risk is worth it.

By publishing the warning, the FDA is attempting to inform both doctors (and dentists, who use the same products for jaw repairs), of the known risks. Doctors should at least pass the information on to their patients under informed consent rules, and doctors may be taking on greater liability as well, since they cannot say they weren’t warned. But it is still legal to use substitute grafts in those under 18, and manufacturers are scrambling to get a product approved which will overcome the dangers.

The FDA’s specific recommendations for parents are:

• Ask your healthcare provider about the benefits and risks of treatments for bone defects and discuss his/her experience with performing these procedures.
• Ask your healthcare provider if the treatment option recommended is FDA-approved or cleared and appropriate for the procedure you or your child is undergoing.
• If you or your underage child was treated with these products, discuss with your healthcare provider how often bone healing should be monitored.
• Contact your healthcare provider if you or your underage child was treated with these products and is experiencing adverse events, such as fever, swelling, rash, pain, or physical changes near the implantation site.