April 08, 2020

Bangor doctor’s bone-disorder projects have global reach

BANGOR – A person can learn a lot in a half-hour with Dr. Clifford Rosen. The charismatic physician and researcher maintains a busy schedule of patient appointments here in Bangor while tending to research projects around the globe, in studies from Bar Harbor and South Portland to Anhui province in China.

As a member of an international group of specialists, Rosen is working to raise public awareness of bone and joint disorders. He points out that the years from 2000 to 2010 have been declared the Bone and Joint Decade by the federal government. And this week is National Action Week, but only four states – Connecticut, Indiana, Maine and Michigan – have issued proclamations to that effect.

On Thursday morning Rosen was at his office on outer Broadway, seeing patients and preparing for a trip to Maryland, where he was to start his latest adventure as a member of an influential advisory panel for the federal Food and Drug Administration.

The panel reviews studies of drugs designed to treat metabolic and endocrine disorders and makes recommendations to the FDA regarding which should be approved for use, which might be safe to sell without a prescription, which need special labeling, which should be studied further, and so on.

“We meet four times a year. The meetings are televised and open to the public. It’s very political. The audience is packed with hundreds of drug company people, investment advisers, consumer advocates, politicians, you name it,” Rosen said, admitting to some trepidation at being in the public spotlight.

Later this month, just in time for Halloween, Rosen will co-host the 12th annual meeting of the New England Bone Club in southern Maine. About 150 physicians and researchers from throughout the region will gather to talk shop and learn what’s new in the complex and evolving field of bone-related science and medicine. Rosen is a founding member of the group, which now is supported by St. Joseph Healthcare of Bangor. Rosen is director of the Maine Center for Osteoporosis Research and Education at St. Joseph Hospital.

“Just a bunch of boneheads getting together,” he said with evident relish. The two-day conference includes presentations on bony matters ranging from the effect of eating disorders and methadone maintenance therapy on bone health to studies of bone disorders such as osteoporosis and Paget’s disease. Case studies are on the agenda, too, with such alluring and alarming titles as “A 94 Year Old Man with Spine Fractures: a Surgeon’s Delight” and “A Mysterious Case of a Man with an Episode of Hypercalcemia and Persistent Elevated Bone Turnover.”

Rosen said there’s a lot to be excited about in bone research. New studies and technologies are advancing knowledge, such as understanding the relationship between bone density and obesity. For example, a recently concluded study of more than 13,000 men and women in China determined that high percentages of body fat are linked to increased rates of osteoporosis and other bone-weakening conditions. That study, published in the April edition of the American Journal of Clinical Nutrition, supports theories about the higher risk of bone disease in overweight or obese people, but also provides a foundation for more advanced work, Rosen said.

Using a powerful new computerized tomography imaging device Rosen calls “Extreme CT,” scientists in Massachusetts have found that the process of bone thinning and weakening begins in many women as young as age 18. And they’ve been surprised to learn that when the structural framework inside the bone itself deteriorates and disappears, the space doesn’t just sit there empty, it fills up with fat cells, leaving the bone weak, brittle and prone to fracture. The phenomenon is more pronounced in individuals with a high percentage of body fat.

Researchers at The Jackson Laboratory in Bar Harbor, where Rosen is a senior scientist, have found that mouse bones change in essentially the same way. Scientists also have learned that fat cells and bone cells evolve from the same kind of “blank” stem cell, Rosen said, and are in the process of determining how the cell “decides” which form to take. It appears that if a certain element in the cell, called PPAR-gamma, gets stimulated, the cell is more likely to turn into a fat cell.

“This could sound like stupid stuff,” if there’s no clinical application, Rosen acknowledged. He said studies at the Maine Medical Center Research Institute in South Portland have determined that certain medications, including a powerful new diabetes drug called Avandia or rosiglitazone, appears to accelerate PPAR-gamma production as a side effect. So while diabetics may find the insulin-stimulating drug extremely effective at controlling blood sugar, it may put them at higher risk for bone loss.

Rosen said physicians have asked the drug manufacturer to study the phenomenon, but have been met with predictable resistance. “Why would the company want to do a study that shows a negative result?” he asked rhetorically. So instead, Rosen is asking the National Institutes of Health to fund an impartial study. His proposal to the NIH calls for 150 nondiabetic but insulin-resistant women in Bangor and San Francisco to take either the medication or a placebo for two years. As well as monitoring the drug’s effect on the women’s insulin levels and blood sugar, researchers will measure their bone density and the percentage of fat cells inside their bones. The results not only will demonstrate the comparative risk and safety of rosiglitazone therapy, they also may yield greater understanding of how bone loss can be prevented or reversed.

More information on bone health, bone disease, research and related activities is available online at www.boneandjointdecade.org

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