Monash researchers in osteoporosis find

An international collaboration including Melbourne researchers has uncovered two reasons for calcium deposits in bones and joints, setting the foundation for new osteoporosis therapies.

The scientists have found that the enzymes PC1 and alkaline phosphatase, found in bone and cartilage, are implicated in the control of bone density.

The collaboration comprised researchers from Monash University's Department of Pathology and Immunology, and the University of California and Burnham Institute in San Diego.

Now, in conjunction with pharmaceutical giant Pfizer, the scientists are testing thousands of compounds to find possible drugs to interfere with the mechanism on the enzymes.

"Our research has improved the basic understanding of bone calcification," said Prof James Goding of Monash. "In the long term, this understanding of the PC1 and alkaline phosphatase enzymes may lead to improved treatments for diseases like osteoporosis and some forms of arthritis."

Studies into the enzymes began through a joint effort between Goding, Monash colleague Adnan Sali and Prof Robert Terkeltaub at the University of San Diego. Their work showed that high levels of the PC1 enzyme caused abnormal calcification of cartilage and led to a condition similar to osteoarthritis.

The Melbourne researchers subsequently studied knockout mice in which the gene for the PC1 enzyme was removed and noticed that the rodents could not curl their fingers or toes because of a kind of arthritis.

"When we x-rayed the mice, we found abnormal calcium deposits in and around the joints, and their vertebrae were osteoporotic," Goding explained.

In a separate study, Prof Jose Luis Millan of the Burnham Institute investigated mutations in the alkaline phosphatase gene, which can cause the condition known as brittle bone disease, or hypophosphatasia, where the bones are soft and can fracture spontaneously. He found the mice that were missing the gene lived just a week after birth and suffered severe abnormalities in their bones.

To test their discoveries, the three groups then teamed up to study double knockout mice that had neither the PC1 gene or the alkaline phosphatase gene.

Their findings, published in the July Proceedings of the National Academy of Sciences, showed that animals missing both genes had less severe problem and lived longer than if just the alkaline phosphatase gene was knocked out, indicating that one gene counterbalanced the other.

Goding said the research showed that normal bone development required a balance between the actions of the two enzymes. He said as well as leading to potential new treatments for osteoporosis and some forms of arthritis, the discovery brought new hope for children suffering hypophosphatasia.

"The fact that PC1 partially corrects hypophosphatasia in mice means drugs that inhibit PC1 might help children with this disorder," he said.

The National Health and Medical Research Council and Pfizer funded the work.