Against the dense black background of the X-ray film are several white streaks--new bone cells generated by bone morphogenetic protein, or BMP. Several months before the X-ray was made, Boden, an associate professor of ortho-paedics at Emory and director of the Emory Spine Center, had surgically placed BMP near the monkey's spine when the animal was anesthetized.
"The new bone cells appear almost identical to the old bone," said Boden. If the findings from Boden's Yerkes studies continue to be positive, BMP will be considered for use in surgery on human patients to fuse spinal bones dislodged by accidents, tumors or diseases such as rheumatoid arthritis.
Each year in the United States, surgeons perform almost 200,000 spinal fusions. Most of these operations are lumbar spinal fusions--the focus of Boden's research--which attempt to reunite spinal bones in the lower back. Some spinal fusions are conducted near the neck. While at the University of Virginia Medical Center after the horse riding accident that left him paralyzed, actor Christopher Reeve underwent such a surgery to stabilize damaged vertebrae near his neck.
As many as 35 percent of these fusions fail for reasons unknown to Boden and other orthopaedic surgeons. Because an unstable lower spine can cause chronic back pain, many people with this condition readily undergo the surgery, and some patients will attempt a second operation if the first one fails, despite its high cost, relatively high failure rate, and the long post-surgical recovery time during which physical activities must be limited.
When Boden and other spine surgeons now perform a lumbar spinal fusion on a human patient, they use a surgical procedure that is regarded as the "gold standard" for this operation. Clinical studies have indicated that this procedure, called an autogenous iliac crest bone graft, results in more fused spines than any other fusion technique thus far evaluated in human patients.
In an autogenous iliac crest bone graft, bone from the patient's own pelvis is used to "seed" the bone cells that are needed to create the bridge to fuse dislodged bones in the patient's spinal column. However, this procedure can cause blood loss as well as chronic hip pain.
These serious potential side effects and the relatively high failure rate of this procedure have "promoted the search for bone graft substitutes to achieve spinal fusion," said Jeffrey Schimandle, one of Boden's research colleagues.
BMP is one potential substitute.
Soon after arriving at Emory in 1992, Boden began dividing his time between patient care at the Emory Spine Center and the research lab where he soon focused on possible materials such as BMP that would serve as a seed to grow bone cells that would reunite dislodged spinal bones.
Boden soon turned to rhesus monkeys. "The primate model is a critical step to clinical trials with human patients," he said.
The tissue healing, immune system and bone composition of these animals and humans are similar. "In lower animals such as rodents, bone forms very easily," added Boden, an affiliate scientist in molecular medicine at Yerkes. "That is not the case in primates or humans." Indeed, in several studies conducted with lower animals, bones fuse equally well in "control" and "experimental" animals, Schimandle and Boden noted in a report that was published in the journal Spine.
Unlike some human patients after spinal trauma, the rhesus monkeys selected for Boden's study do not have unstable spines, and this condition is not induced. "Our basic goals with the primate model have been to demonstrate whether BMP can make bone, make it near the spine, and make the spinal bones fuse," said Boden. These goals can be accomplished in animals with normal spines.
Thus far, Boden is enthusiastic about the results of his research with BMP in rhesus monkeys. The quality and quantity of the new bone are excellent. "Another good thing is that the rhesus monkey is not making new bone all over the place," he added. "It's occurring where we want it to--near the monkey's spine."
Like most scientists whose research findings suggest a benefit for human patients, Boden is reluctant to estimate when clinical studies of BMP in human patients may begin. If the clinical studies show that BMP safely and effectively promotes lumbar spinal fusion in human patients, Boden and his colleagues will consider using the agent in other spinal fusion operations, as well as in treatments to repair fractures and large bone defects.
--Cathy Yarbrough