Aspirin May Fight Osteoporosis

In mice, the drug appears to prevent both improper bone resorption and the death of bone-forming stem cells.
By Beth Dunham
USC researchers Songtao Shi and Takayoshi Yamaza hope that their work will translate into new clinical strategies.

An aspirin regimen appears to help mice recover from osteoporosis in two useful ways, striking a balance between bone formation and resorption, according to associate professor Songtao Shi and research associate Takayoshi Yamaza of the USC School of Dentistry’s Center for Craniofacial Molecular Biology.

Removal of the ovaries and the resulting decrease in estrogen induces osteoporosis in mice, much like the onset of the disease in post-menopausal women, Shi said.

It is commonly thought that T-lymphocytes, a type of immune system cell, play a pivotal part in this process by over-activating osteoclasts, the bone cells that reabsorb bone material from the skeleton. Most current osteoporosis therapies aim to curb overactive osteoclasts.

However, there seems to be another side to the T-lymphocytes’, or T-cells’, role in osteoporosis, Yamaza said. While the immune cells typically attack disease cells and other foreign entities, the T-cells mistakenly can attack healthy stem cells.

“After infusing the mice with T-cells, the T-cells impaired the function of bone marrow mesenchymal stem cells as well as caused osteoclast numbers to increase,” he said.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells, including osteoblasts, the cells responsible for bone formation.

If this process is impaired by T-cells, bone formation cannot keep up with bone resorption caused by osteoclasts and bone mineral density decreases the hallmark of osteoporosis that leads to skeletal structural deterioration and fractures.

An aspirin regimen has been linked in earlier epidemiological studies to better bone mineral density, but the mechanisms of its interactions in regards to bone health had not yet been studied extensively, Shi said.

In their new study published in PLoS ONE, Shi, Yamaza and their colleagues from around the world present evidence that aspirin fights a dual battle.

“We’ve shown how aspirin both inhibits bone resorption and promotes osteoblast formation,” Shi said.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice in order to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he added.

While the species difference is still a factor, the results are promising.

“When we gave a large amount of aspirin to the mouse by injection, it did not work,” Shi said, “but when we (put) a low dose in the mices’ water for a long period of time, similar to a human dosage, the bone mineral density increased.”

Shi and Yamaza hope that their work will translate into new clinical strategies for osteoporosis.

“We have opened a door,” Shi said. “We hope other scientists can confirm what we’ve found and move the treatment forward.”