Bone health specialists typically spend their time trying to figure how to slow or stop the bone loss that leads to osteoporosis. What if they could find a new way to stimulate the growth of new bone tissue instead?
With support from the Department of Medicine’s Pathways Consult Service and two students from Harvard Medical School, Massachusetts General Hospital endocrinologist Marc Wein, MD, PhD, is now exploring this intriguing new avenue of research.
An Unexpected Finding
The catalyst for this project was a patient who first sought treatment for skin nodules on her eyelids and an unexpectedly high level of an antibody in her blood from Mass General hematologist Elizabeth O’Donnell, MD.
While screening the patient for a condition called Erdheim-Chester Disease (which was eventually ruled out), Mass General rheumatologists Zach Wallace, MD, and John Stone, MD, MPH, discovered that she also had unusually high levels of bone mass.
Wallace and Stone then referred her to Wein, who specializes in osteoporosis and other disorders of bone metabolism.
“There are a series of diseases that we think about when it comes to high bone mass, but we checked her for those and it didn’t seem like she had any of the usual suspects, nor any negative side effects that are common with high bone mass, such as difficulty seeing or hearing due to the thickening of the skull bones, or being more prone to fractures,” Wein says.
A Spark of Curiosity
This unusual set of symptoms piqued Wein’s interest.
“I am a physician-scientist, I see patients for half a day during the week, but most of the time I am running a lab, thinking about bone biology and trying to understand how bone works. So I took off my doctor hat and put on my scientist hat and started to think about how to tie everything together.”
Wein didn’t come up with any obvious answers but thought it was likely that the abnormal antibody levels in her blood could be stimulating the additional bone growth.
He also knew that unraveling this connection could have treatment implications for osteoporosis, a condition that affects an estimated 75 million people in the United States, Europe and Japan.
Healthy bones typically maintain a balance between creating new bone tissue and destroying old tissue, which allows the bones to completely regenerate over time.
In osteoporosis, more bone tissue is destroyed than is being made, which hollows out the bones and makes them weaker and more subject to fractures.
If Wein could figure how the antibody was promoting the growth of new bone tissue, it could point to new treatment strategies that could strengthen bones. But without dedicated funding to support this research, there was only so much he could do on his own.
“We tried a couple of experiments, and they looked kind of promising, but it was difficult to get this project off the ground. We have many other things going on in the lab, and I would describe this as a high-risk, high-reward type of experiment.”
Wein was excited when the Pathways Consult Service accepted his patient into the program and even happier when two Harvard Medical School students, Brandon Law and Joyce Hwang, were assigned to work on the project.
The Pathways Service was established by the Department of Medicine in 2017 to provide medical residents and students with the opportunity to take a closer look at patients who present to the hospital with unusual or extreme disease symptoms.
With the support of the Pathways Service, Law and Hung were able to spend four weeks digging into the case and identifying a broad spectrum of possible reasons for the excessive bone growth.
“They came up with a bunch of ideas that I never thought of and really had a broad perspective, which I think all trainees should have,” Wein says.
In the end, the team decided that Wein’s initial hunch—that the antibody, or something else in her blood, was somehow triggering the bone growth—was the most promising avenue to pursue.
They completed an initial round of studies that produced some encouraging results, which now need to be repeated and confirmed.
The case also caught the attention of Rafael Szalat, MD, from the Dana Farber Cancer Institute, who is an expert on the specific type of skin nodules that the patient developed. Dr. Szalat is looking through his database to see if he can identify other patients who may have this unique combination of nodules, abnormal antibody levels and excessive bone growth.
“That’s the wonderful thing about this program,” Wein says. “We’re identifying various experts and bringing them together and having this academic exercise that may end up helping patients, which is really amazing.”
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