Imagine schussing down that ski hill when a tree rudely makes its way into your path, leaving you with a broken leg and three months of down time.
Wouldn’t it be nice to know that your fractured tibia could heal in a month and a half rather than the usual three? Or that if your Auntie Ida falls and breaks her hip, the surgery she will need will work the first time?
The solutions to these problems may lie in a simple gel or a sponge in a cylinder.
Within the next few years, compounds to grow bone and possibly cut healing time as much as 50 percent will be available for orthopedic surgery patients and those with broken bones.
There are about 7.5 million bone fractures in the United States each year, and 750,000 are malunions or non-unions, meaning bones that don’t heal right or heal slowly.
“In any 100 spinal surgeries on healthy young people, even when everything is done technically correctly, there will be 10 non-unions,” explained Dr. Avi Bernstein, chief of orthopedic surgery at Lutheran General Hospital in Park Ridge.
Already in use
To combat such problems, Bernstein said, he uses the surgical devices known as BMP and BMP7 to facilitate and accelerate complete bone healing and ensure that repeat surgeries are unnecessary.
BMP devices are sponges saturated with bone protein and placed into a small, dissolvable cylinder in the spine.
“Within the next three to five years, BMP will become the standard of care in this country,” Bernstein said.
Bone-morphogenetic proteins (BMPs) were recognized as bone-healing proteins as early as the l950s. In the mid-1960s, Marshall Uris, a world-renowned orthopedic surgeon at UCLA, wanted to identify what was different about bone cells from other cells in the body so they could be reproduced. He managed to isolate the protein in bone cells at that time, but doing so required massive amounts of bone to synthesize and was not practical.
Genetic engineering
In recent years two pharmaceutical companies, Stryker Pharmaceutical and Medtronic, have isolated BMP and through genetic engineering have been able to mass-produce it (this sentence as published has been corrected in this text). It is these two products Bernstein is using in spinal operations. They have completed clinical trials and have been approved by the Food and Drug Administration.
“It’s an amazing protein. And if something works in the spine, it will work just about anywhere,” said an enthusiastic Bernstein. He added that it has been so successful, it is being used off-label for some patients, meaning it is being applied to bone regrowth beyond the spine.
“Up until now we have used conductive substances to grow bone rather than inductive–in essence, live cells–to make bone,” explained Dr. John Lubicky, chief of staff and orthopedic surgeon at Shriners Hospital for Children in Chicago.
“BMP is the latest thing and is tremendously effective, especially for people who smoke or who have osteoporosis, which makes it harder for bones to heal,” Lubicky said. “If you use it [BMP] alone or with bone grafts, it tends to have things heal faster and allows people to return to their normal activities sooner.”
Fast healing time
In addition to BMP, a revolutionary new product known only by its code name, CP-536, is being tested not only for healing non-unions and malunions but also for reducing healing time of broken bones by at least 25 percent; there is hopeful speculation about a 50 percent reduction.
“If someone breaks a major bone that takes three months to heal, reducing that time to a month and a half could be very significant,” said David Thompson, project director of the Pfizer Inc. Osteoporosis and Frailty Group, the team of researchers that discovered CP-536.
This “bone-formation stimulator” applied in tiny amounts that could fit in an eyedropper has been shown to decrease bone-growth time in laboratory animals and is now being tested at three sites, one of them in the Chicago area.
The gel was discovered in the Pfizer laboratory of molecular biology and toxicology while scientists were researching new therapies for osteoporosis.
“We are interested in all conditions of bone fragility or bone disease. There are more than 300,000 hip fractures due to osteoporosis each year in the U.S. My [research] team at Pfizer is interested not only in new theory to prevent osteoporosis but also in restoring bones,” Thompson said, adding that “the gel was one of the byproducts of our pursuit.”
How bones heal
He explained that bone healing goes through several stages. First there is a blood clot that occurs at the site of any fracture. This is an important stage because it sets the parameters for the bone regrowth. The next stage of healing is inflammation, which brings cells to the site to which they are going to form new bone growth, or “the matrix.” The gel can be introduced at any step in the healing process.
Thompson explained than the FDA is extremely cautious in testing new drugs. Once discoveries are made in the laboratory, drugs are put through three phases of human trials that must take place before approval is given for public use. CP-536 is in Phase 1, a double-blind study to determine if the gel is safe. Results from the test, involving about 30 people, are expected early this year.
In a double-blind study, neither the doctor nor the patient knows if the patient is getting a placebo or the real gel. The final results are determined by X-rays and how the patient feels.
Phase 2 trials involve a few hundred people in which the efficacy of the drug is tested.
And Phase 3 is a repeat of the test on several hundred people throughout the country.
Only after all three phases have been completed successfully can the drug companies apply to the FDA for licensing.
Approval of this bone-growth gel could take five years.
2 approaches
What are the differences in BMP and CP-536?
Essentially the expectations for both drugs are the same, but CP-536 shows more promise for speeding healing time. Furthermore, the delivery systems are different.
Unlike BMP, which is time-released, the gel is applied directly onto the bone or injected into it. Thompson said that because the compound is “transient” (one that dissipates in the body), there is little risk of cancer or other such side effects.
Can this gel be used safely on children whose bones are still growing?
Yes. “If a bone is fractured and this gel is applied locally to the site of the injury, this will not cause injury to the ends of the bone that are involved in the growth process,” Thompson said.
“From my perspective this mechanism is very exciting as an induction of bone formation. It’s one of the more interesting mechanisms of inducing bone formation that I have seen.”
