In breakthrough, Vignery grows bones

For anybody who has ever known the pain of a broken bone, the work of Dr. Agnès Vignery may come as a relief.

Dr. Vignery, an associate professor of orthopaedics at the Yale School of Medicine, has spent the last seven years working alongside a team of researchers, from both Yale and elsewhere, to perfect a potentially revolutionary bone growth procedure. The procedure, which combines bone-marrow removal with daily injections of PTH, or parathyroid hormone, can lead to new bone formation within a week of treatment, Vignery said.

“It has been known for a long time that if you remove the marrow from the bone, it leads to very transient bone formation, so we used that template as inspiration for this procedure,” Vignery said.

Currently available treatment requires surgery and artificial materials, Vignery said. With her new, minimally invasive procedure, she said new bone can be created much more quickly and in specifically targeted locations.

Thus far, the procedure has only been tested in small rodents, but plans are in place to test next on rabbits, before finally moving on to human clinical trials. Vignery said her colleagues at Johns Hopkins University in Baltimore have already begun the process of setting up human trials.

Vignery said she has high hopes for future trials, given the procedure’s success in previous experiments.

“So far we have been pretty successful,” Vignery said. “We have been very lucky … We are not using just one treatment, but the combination of two.”

But some scientists said they are less enthusiastic about the new procedure.

PTH has only been approved by the FDA for a usage time of two years or less because of serious side effects that can result from long-term use — high persistent levels of PTH can cause osteoporosis, and early animal studies have reported brain tumors in mice that were exposed to high levels of the hormone for long periods of time. No humans have reported these side effects from the hormone.

Seth Dodds, an assistant professor of orthopaedics at the Yale School of Medicine, said he is hesitant about the new treatment. He said the current prevailing method of administering bone-morphogenic proteins, or BMPs, is still the best treatment available for bone development.

“Removing bone marrow can be somewhat painful, but that is not to say that it wouldn’t be helpful in some situations,” Dodds said. “[BMPs] have only been available in hospitals over the past one to five years, so we’re still learning how effective they are.”

Still, he said the relatively new BMPs have been shown to advance bone healing in animals without any negative side effects.

But Vignery said her PTH procedure provides advantages that are lacking with the use of BMPs — she claims her treatment is much simpler and more cost-effective.

Gary Friedlaender, chairman of the Orthopaedics and Rehabilitation Department at Yale, said he is intrigued by the implicit questions that Vignery’s work raises, especially why there is room for the marrow in the first place — if marrow removal allows for bone growth, then why does bone not grow there?

He said he thinks the answer lies in some inhibitory products or mechanisms inherent to the marrow and hopes Vignery’s research will allow for further exploration of the question.

“Science is really a step-wise of building one observation upon another, to effect a change in the way we think,” Friedlaender said. “I think this is a very important step in learning how to help the skeleton cure itself.”

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