Traditional Treatment of Cleft Lip and Palate

In 1974, Dr. Phillip Boyne, an oral and maxillofacial surgeon (specializing in handling facial bone disorders), suggested utilization of a child’s hip bone to repair the gap in the upper jaw that results from a cleft. This technique became standard care and has remained unchanged for the last 40 years. Some surgeons tried to obtain bone from alternative sources including: another human (cadaver), an animal (cow), or synthetic bone substitute. Other surgeons tried amassing bone from different locations on the child, such as the skull, leg, and jaw. Hip harvesting remained the most common practice for decades. Although the results are generally good there are significant drawbacks to the approach. Harvesting bone from a child’s hip is associated with a number of potential problems, some of which include:

1. Significant pain at the hip bone harvesting site
2. Occasional long term difficulty walking
3. Prolonged hospital stay
4. A permanent scar over the harvest site

In addition to the inherent problems incurred when a child is subjected to hip surgery, there is often a limit to the amount of bone that can be harvested, especially in young and small patients. The size of the hip may not offer the ideal amount of bone to perform a repair at the child’s age.

Morphogenesis with BMP

Use of bone morphogenetic protein (BMP) for repair of cleft palates and other craniofacial disorders is one of the early benefits of the biotechnology revolution in surgical practice. These naturally occurring agents (BMP) have the ability to grow living bone in patients with missing bone segments, such as in cleft palates. Unlike previous treatments, this process requires no initial bone and therefore spares children the hazards and trauma of harvesting bone from their own skeletons. Beyond Faces’ surgeons have pioneered the use of BMP and techniques such as distraction osteogenesis for the correction of cleft palates and other facial bone deficiencies.

What is BMP?

Bone morphogenetic proteins (BMPs) are a group of molecules that occur naturally in all human beings. During the development of the embryo, BMPs are important in the formation of the fetal skeleton. In an adult skeleton, there are still small quantities of this protein housed inside the bones to help maintain the bone and repair fractures. Dr. Marshall Urist, an orthopedic surgeon, was able to isolate BMPs and now it is manufactured by pharmaceutical companies Wyeth and Stryker. The particular molecule used by Beyond Faces, BMP-2, is the same for all humans.

Urist was the first person to conceptually understand the role of bone morphogenetic protein (BMP-2). His research showed that BMPs could stimulate the formation of bone without the presence of bone cells to begin with. The process involved use of BMPs to recruit adult stem cells to a site and then to direct the cells to become bone forming cells called osteoblasts.

Later, Dr. John Wozney used modern biotechnology methods to sequence human BMP-2 and clone it. The recombinant (rh) technology used by Wozney and the pharmaceutical industry allows for the production of large and pure quantities of rhBMP-2.

What does BMP do?

When placed into the cleft region, bone morphogenetic protein (BMP-2) does two things. First, it chemically signals a person’s own stem cells to migrate into the cleft site. Second, it attaches itself to the stems cells and instructs them to become bone cells. The resultant newly formed bone cells then grow new bone, filling in the missing part that nature forgot.

Is BMP bone as good as a child’s own bone?

The bone grown in response to bone morphogenetic protein (BMP-2) is the patient’s own bone. BMP simply stimulates the body to grow its own bone. After observing the performance of the newly constructed bone segments in both children and adults, it’s clear that the bone responds normally to tooth development, growth, and subsequent surgery.

Is BMP reconstruction better than hip grafting?

The most obvious and compelling advantages of using bone morphogenetic protein (BMP-2) is that it spares the child the trauma and hazards of undergoing hip surgery. Benefits, however, go beyond avoiding hip surgery. Benefits of utilizing BMP to repair clefts include:

1. The entire upper jaw cleft can be repaired instead of just the front segment, which is the practice when performing hip graft surgery
2. Decreased pain/hospitalization time and increased recovery rate
3. No scarring
4. Shorter anesthesia exposure
5. A 98 percent success rate

There’s no need to wait until a child’s hip grows big enough to allow for an adequate harvest (bone with sufficient volume) because BMP is manufactured. With this added treatment flexibility, timing of the repair can be done at an ideal stage of maturity to optimize development of facial bones and teeth. In the past, only a limited portion of the cleft was repaired due to the limitation of available bone. With BMP, the whole cleft can be repaired and the natural volume of the upper jaw restored.

What is BMP's failure rate?

Repair of skeletal clefts is a multifaceted problem and no technique is 100 percent successful. A success rate of 91 percent is expected when using conventional cleft repair methods (obtaining bone from the child’s hip). Clefts were successfully closed 98 percent of the time using bone morphogenetic protein (BMP-2). Roughly five patients in 100 underwent a second placement of BMP to either establish bone fusion of the cleft or increase the volume of bone grown in a prior BMP surgery. Of the patients that failed hip grafting and elected BMP for the second repair, all of the patients to date were successfully treated. In some cases, a combination of distraction osteogenesis (DO) and BMP were required to attain a successful outcome.

Is the use of BMP experimental?

The use of bone morphogenetic protein (BMP-2) for the repair of craniofacial (skull and facial) disorders including cleft repair is not experimental. Use of BMP is effective in humans and approved by the Food and Drug Administration (FDA). The FDA issues approval for a device or medication for a specific use. BMP is currently approved for:

1. Spine fusion surgery
2. Treatment of orthopedic fracture non-unions
3. Maxillary bone construction for dental implants

These specific approvals were issued by the FDA after scientific studies were completed on humans undergoing these specific procedures. It’s not possible to perform formal clinical trials on every possible application. It’s common and appropriate practice for doctors to use devices and medications in similar but not identical manners specifically approved by the FDA. This practice is called off-label use. Using BMP to repair cleft palates is considered off-label. It should be understood that there has not been a formal controlled study supervised by the FDA on the use of BMP in cleft surgery. Practicing doctors use the experience described in published journal articles and their own experience and judgment when making a decision to offer treatments that are off-label. Many medications and devices prescribed by doctors every day are for off-label applications. It’s extremely difficult to do controlled studies on devices and medications on children because it may require that a randomly selected group of patients must consent to having an inactive or less potent form of treatment just to provide data to compare the real medication. Therefore, most medications and devices used for pediatric treatment are or were once used in an off-label capacity.