ASPIRIN MAY FIGHT OSTEOPOROSIS ON TWO FRONTS
In mice, the drug appears to prevent bone resorption and the death of bone-forming stem cells.
8/01/08
By Beth Dunham

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 (CCMB).

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 says. 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 says. While the immune cells typically attack disease cells and other foreign entities, the T-cells can mistakenly 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 says.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells including osteoblasts, the cells responsible for bone formation. If this processed 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 “Pharmacologic Stem Cell Based Intervention as a New Approach to Osteoporosis Treatment in Rodents,” their new study to be published in PLoS ONE on July 9, 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 says.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he adds. 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 says, “but when we gave a low dose in the mice’s 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 says. “We hope other scientists can confirm what we’ve found and move the treatment forward.”

The international team of researchers also includes Drs. WanJun Chen, Yanming Bi, Yongzhong Liu, Voymesh Patel, Silvio Gutkind and Marian Young from the National Institute of Dental and Craniofacial Research, National Institutes of Health; Dr. Yasuo Miura from Kyoto University, Japan; Dr. Stan Gronthos from the Institute of Medical and Veterinary Science, Australia; Dr. Cun-Yu Wang from UCLA; and Drs. Kentaro Akiyama, An Le and Wataru Sonoyama from CCMB.