US Pharm. 2019:44(9):2.
Scientists at Duke University have identified a pharmaceutical target that can reverse bone degradation caused by osteoporosis in mouse models.
“The most widely used drugs currently approved by the FDA to treat osteoporosis can prevent further bone loss, but they don’t help rebuild the bone,” said Shyni Varghese, professor of biomedical engineering, mechanical engineering and materials science, and orthopedics at Duke.
“We’ve discovered a biochemical receptor that, when activated, can do both,” added Yu-Ru “Vernon” Shih, the study’s first author. The findings appeared online August 21 in the journal Science Advances.
Bone, in spite of its rigidity, is living tissue that constantly breaks down and is replaced by the body. When old tissue is lost faster than new tissue can be made, causing the bone to become weak and brittle, osteoporosis results. The disease afflicts more than 40 million men and women in the United States alone and is most prevalent in older women after menopause.
Five years ago, Varghese was studying the role of popular biomedical devices made of calcium phosphate in promoting bone repair and regeneration, and she found that the biochemical adenosine acting on the A2B receptor plays a large role in promoting bone growth. It was plausible, she reasoned, that a lack of the chemical might play a role in osteoporosis.
In the investigation, Varghese and her colleagues studied mice that had had their ovaries removed to mimic postmenopausal osteoporosis. They examined the expression levels of two enzymes that help produce adenosine in addition to the levels of adenosine traveling between cells. As expected, the scientists discovered that the mice’s lack of estrogen was causing all three to fall.
The researchers then tested whether increasing adenosine levels in the mice would help reverse the damaging effects of the disease. But rather than pumping in adenosine itself, they injected a nonhormonal small molecule produced by Bayer that activates the A2B receptor.
“The mice that received the drug were completely cured,” said Varghese.
While the discovery of a pharmaceutical target capable of reversing osteoporosis is exciting, creating a small molecule drug that can activate it without side effects is a challenge. Researchers cannot simply add it to the bloodstream to stop bone degradation without side effects.
With the A2B receptor identified, Varghese and others can explore ways to deliver activators to bones without flooding other areas of the body. One of Varghese’s students is beginning to study methods of tethering adenosine-like molecules to carriers that target bone tissue.
For a look at current conventional treatment regimens, see “Updates in the Treatment of Postmenopausal Osteoporosis,” by Mackenzie Moritz, PharmD Candidate, May 2020; Emily Knezevich, PharmD, BCPS, CDE, FCCP; and Mikayla Spangler, PharmD, BCPS (this issue, page 32).
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