UC Davis repairs dog bones with protein from human medicine

May 30, 2019
Don Vaughan

Don Vaughan is a freelance writer based in Raleigh, North Carolina. His work has appeared in Military Officer, Boys Life, Writers Digest, Mad and other publications.

Recombinant human bone morphogenetic protein (BMP)helpful with jaw repair and long bone defects in dogsworks wonders, is expensive ($1,000 per milligram) and requires care: If you were to get a little BMP on your instruments or glove, and you touch, say, a muscle, there would be bone growth in that muscle, says one veterinary surgeon.

Ethel, a patient treated with bone morphogenetic protein at UC Davis. (Background illustration by Vecteezy.com)

To see Ethel frolic on four good limbs, one would never know that the 2-year-old Yorkshire terrier came perilously close to losing her right front leg following two unsuccessful surgeries to repair a broken ulna and radius. Instrumental in her remarkable recovery was the use of recombinant human bone morphogenetic protein (BMP), which grows new bone over a special scaffold.

When Ethel was referred to the UC Davis School of Veterinary Medicine, her prognosis was not good. Amy Kapatkin, DVM, MS, DACVS, professor of small animal orthopedic surgery, approved the use of BMP in a last-ditch effort to save Ethel's damaged limb, but gave the procedure just a 1% chance of success. Though hopeful, Ethel's owner, Mary Ann Lawson, gave Dr. Kapatkin permission to amputate the damaged limb if the procedure failed.

The extent of the injury and Ethel's diminutive size proved problematic. The use of BMP requires that the affected bone be stabilized with plates to facilitate proper bone growth. However, 50% of Ethel's distal radius was gone, and her remaining bone was smaller than most commercially available plates.

Ethel's healed leg before plate removal. (All photos courtesy of UC Davis)

Ethel's leg healed after plate removal.

But Dr. Kapatkin still felt BMP was worth a try and suggested that Ethel be kept at the hospital while she healed to prevent her from accidentally reinjuring herself. At one point, due to the limited soft tissue and thin skin in her tiny distal limb, the plate started to protrude from her leg and had to be removed. However, Ethel was well on her way to healing fully by that point, so the plate was no longer necessary. Ethel healed so well that by her three-month recheck, she was able to run on her new leg.

Ethel is one of more than 60 dogs treated using BMP at UC Davis since 2012. The school receives the compound for compassionate use from a manufacturer at no cost, which allows doctors to provide the bone growth protein to approved patients free of charge.

 

Radiograph of Ethel's leg preop.

How BMP is used by veterinarians and physicians

BMP was discovered in 1965 by Marshall Urist, MD, considered the grandfather of modern tissue engineering, according to Boaz Arzi, DVM, DAVDC, DEVDC, associate professor of dentistry and oral surgery at UC Davis. In human medicine, BMP is most commonly used during spinal fusion and to repair nonunion tibia fractures.

In veterinary medicine, anecdotal use of BMP has been reported by researchers at Tufts University, the University of Pennsylvania and other institutions. At UC Davis, BMP is employed to repair damaged long bones that don't heal through fixation and for jaw regeneration, primarily the mandible. According to Frank Verstraete, BVSc, DrMedVet, MedVet, professor of dentistry and oral surgery at the university, there are three common indications:

1. Fractures resulting in a defect so large that the body cannot bridge it, even if plates are used

2. Defects resulting from surgery for oral tumors and other conditions

3. Gunshot wounds. “Thankfully, these are very uncommon,” Dr. Verstraete says.

BMP has not been used in cats so far, primarily because feline tumors are usually too advanced by the time they're referred to the UC Davis School of Veterinary Medicine, Dr. Verstraete reports.

“The case selection is more toward dogs because dogs are larger, and tumors tend to be relatively smaller when they're noticed by their owner,” he says. “We've been waiting for a suitable cat candidate but haven't had one yet.”

Extremely effective … sometimes too effective

BMP is extremely effective at growing bone-sometimes too effective. Great care must be taken when applying BMP to the scaffold because it will grow bone on any tissue with which it comes in contact.

“If you were to get a little BMP on your instruments or glove, and you touch, say, a muscle, there would be bone growth in that muscle,” Dr. Verstraete notes. Because of this risk, UC Davis veterinary orthopedic specialists invited A. Hari Reddi, MS, PhD, director of the school's Center for Tissue Regeneration and Repair, to mentor them on how to use BMP responsibly.

Dosing also must be exact: Use too little, and you'll get only cartilage; use too much, and you run the risk of exuberant bone reaction. “Dosing is species specific,” Dr. Arzi says.

When used with a scaffold, known as a compression-resistant matrix, BMP can help bridge some fairly large bone gaps. Dr. Kapatkin reports using it successfully to repair gaps that were half of the bone length.

There are restrictions, however. Some researchers discourage the use of BMP to repair bone gaps following cancer surgery because of concerns that the protein could spark renewed cancer growth, Dr. Kapatkin says.

Looking to the future

Research into the veterinary use of BMP is ongoing, but two factors play an important role in its continued use: accessibility and cost.

“We only have access to it through compassionate use,” Dr. Kapatkin says. “Veterinarians in the United States cannot buy it, and that is a big issue. The restrictions in Europe are fewer. And the cost is high, about $1,000 per milligram. When we use it in dogs, a full dose is about 2.25 mg, which would cost approximately $2,500 if we were paying for it.”

Despite such issues, the use of BMP likely will increase in coming years as orthopedic researchers fine-tune current applications and identify new ones. Right now, however, as Ethel's story demonstrates, it offers a unique option to pet owners desperate to keep their pets whole.

“Dogs can live on three legs, but owners want their dogs to have their limbs, and we have the ability to make that happen,” Dr. Kapatkin says. “Owners are free to choose what course they want for their pets.”

Radiograph of Ethel's leg after plate removal.

 

Don Vaughan is a freelance writer based in Raleigh, North Carolina. His work has appeared in Military Officer, Boys' Life, Writer's Digest, Mad and other publications.