Surgeons who repair bones are closely watching clinical experiments on a "bone glue" discovered at UCLA. If it works as expected, orthopedic, plastic and dental surgeons will apply it to human tissues to promote fresh, new bone development, strengthen the bond between living bone and artificial joints or prostheses, and speed healing.
The glue is a protein found in powders made from the bones of humans, cows and pigs. Surgeons will mix the protein with collagen chips--particles made from crushed animal bones--and use it like putty to shape and repair bones damaged by accidents, disease or aging. (Bone gets its hardness from collagen, also a protein, that serves as bone's major structural material.)
Because it promotes new bone growth around surgical screws, nuts and bolts, the protein preparation is expected to help attach artificial joints to adjacent bones in the shoulder, hip or knee and help dental surgeons anchor loose teeth and dental implants to the jawbone.
Glues for repairing and implanting joints have been around for a decade but they are more like cements. Dr. Marshall Urist's discovery is more like a "living glue," a bio-active material that causes regeneration of bone instead of scar tissue.
For 20 years, Urist, professor of surgery (orthopedics) and director of UCLA's Bone Research Center, had been experimenting with demineralized human bones. Demineralized bone is made from chunks of bones that are washed with acids or other chemicals to leach out calcium and phosphorous, the main mineral components.
Urist says it will take about two years of clinical testing for the Food and Drug Administration to approve the bone-building substance for commercialization and widespread use by surgeons.
Thus, Urist's high hopes await scientific validation by medical research teams across the country. The researchers must prove to the FDA that the bone protein not only works, but does so without harmful side effects.
Approval Years Away
According to Dr. Hari Reddi, chief of bone cell biology at the National Institute of Dental Research in Bethesda, Md., the FDA approval process may take five to seven years.
"That's a cautious, conservative estimate," Reddi said. "We shouldn't unnecessarily raise the hopes of the public. At the same time, I am very optimistic about the clinical usefulness of the bone factor. I see its most important use in craniofacial surgery and orthopedic surgery."
Urist named the substance "bone morphogenetic protein" or BMP, meaning that it can induce bone to form or take shape.
"The availability of the protein," he said, "will make it possible to repair large bone defects caused by old infection, injuries, removal of tumors, and congenital deformities in children and adults."
His finding has set off a race among pharmaceutical and biotechnology companies. Annual retail sales of the pure protein could total hundreds of millions of dollars.
Collagen Corp. in Palo Alto is one of several companies interested in the commercial possibilities of bone glue. Bruce Pharriss, Ph.D. and vice president for research and development for Collagen Corp., said Urist's discovery "has great potential" for orthopedics.
Every year in the United States, surgeons replace 150,000 hip joints, 75,000 knees and 10,000 to 20,000 shoulders. Within five years, 5% to 10% fail. More than 5 million traumatic bone fractures occur each year in the United States. Five percent of them fail to heal properly when placed in a cast, with crippling outcomes, sometimes requiring amputation.
Those are frustrating statistics for orthopedic surgeons. Their best efforts often are not enough to fully restore bones ravaged by breaks, aging and diseases like arthritis.
Bones and Aging
Because bones weaken with age, surgeons are familiar with elderly patients whose legs, hips, ribs or shoulders crack, unable to take the stress of walking, lifting or exercise. To replace the joint, surgeons implant a prosthesis made of stainless steel, titanium or ceramics. But, sometimes the old, eroding bones just don't hold the surgical nuts, bolts and glues needed to install the new joint.
Ounce for ounce, healthy bone is stronger than steel and reinforced concrete. One cubic inch can bear a load of 19,000 pounds, roughly the weight of five standard pick-up trucks.
But unlike a steel shaft or a slab of concrete, bone is a living tissue that continually renews itself, destroying worn cells and replacing them with new bone cells instead of scar tissue.
Why does bone mend itself with bone instead of scar tissue? Researchers puzzled over that question, and wondered if they could find the biochemical that sparks healing.
Urist appears to have made the breakthrough, finding in the bone powders he prepared something that promotes the growth of fresh bone. Urist's discovery was made after 20 years of basic research funded by the National Institutes of Health and the Max Factor Family Foundation.
In early studies conducted at UCLA and Harvard from 1979 through 1981, the powder, which was then a crude mixture of proteins from demineralized bone, healed defects in the long bones of the arm and leg and repaired facial bones in children with birth defects.
Front-runners in the race to produce the bone glue believe they have almost purified the protein. According to Pharriss, Collagen Corp. will be conducting human clinical trials this year using a mixture of proteins called "osteogenic factor extract." International Genetic Engineering in Santa Monica expects to begin human studies on the bone protein in 1988, said Arup Sen, Ph.D., the company's vice president for corporate development. And a Boston-area company, Genetics Institute, is also close to testing a protein preparation.