Existing Osteoporosis Drug may Prevent Development of Long-Term Osteoarthritis

An existing osteoporosis drug can prevent cartilage loss from osteoarthritis following injury to a joint, and also regenerate some cartilage that has been lost, according to initial findings of a new study.

Presented at the annual meeting of the American Society for Bone and Mineral Research in Denver, the findings were made via experiments on mice.

The experts that presented the findings said that mice were chosen for the study because they closely mimic human osteoarthritis that develops following knee injuries.

Many kinds of injury and mechanical stresses that come with age can damage cartilage. Over time, damaged cartilage deteriorates to cause osteoarthritis (OA), with its attendant joint inflammation and pain.

Drugs like steroids or non-steroidal anti-inflammatory agents reduce pain, but they do not address the loss of cartilage behind the osteoarthritis.

The cell type at the heart of osteoarthritis is the chondrocyte, the cartilage-producing cell responsible for maintaining the integrity of joint cartilage.

Past studies have shown that parathyroid hormone (PTH), known as teriparatide in drug form, prevents harmful chondrocyte maturation-a normal process that helps to form bone as part of fracture healing and bone growth in children-in the joint cartilage.

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The current study has shown that chondrocytes within injured and degenerating cartilage have more PTH type 1 receptors on their surfaces, which makes them especially sensitive to the PTH signal.

Thus, say the authors, PTH therapy should increase the cartilage supply exactly where cartilage loss is causing disease.

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"Right now physicians have no way to bring back cartilage in patients who have lost it to osteoarthritis," said Dr. Randy Rosier, professor within the Department of Orthopaedics and Rehabilitation at the University of Rochester Medical Center.

"Our current results, at least in mice, show that we can inhibit cartilage degeneration and improve the volume of cartilage in diseased joints. It's remarkable enough that this compound delays the loss of cartilage, but these results show it also may be able to restore, at least to some extent, cartilage in already degraded joint surfaces," the researcher added.

During the study, one group of mice with cartilage and ligament injuries was randomized to receive either saline as a control or a generic version of teriparatide on daily basis for 12 weeks.

A second group of mice with joint injuries did not receive treatment until 8 weeks after injury. The delay was an attempt to determine the effect of treatment once the osteoarthritic process was already underway and some cartilage lost, a scenario that more closely mimics clinical reality.

After 12 weeks, the researchers observed that there was approximately 27 percent more joint cartilage in the mice that received the generic PTH treatment as compared to the saline-treated ones.

Delayed teriparatide treatment was found to be even more effective in improving the amount of cartilage, with up to 35 percent more cartilage in the PTH-treated groups than in the saline group, suggesting an ability to regenerate at least some of the lost cartilage.

With a new use patent application in place, the team will next seek to confirm the durability of the effect in further animal studies.

The researchers also hope to begin pilot clinical studies of PTH treatment of osteoarthritis in humans in the later half of 2010.

"These pre-clinical findings provide strong proof-of-concept support for the potential use of teriparatide to slow joint cartilage degeneration in OA patients, and perhaps even reverse it. In the near future, we hope this serves as the foundation of new treatments that restore function to long injured joints, perhaps staving off joint replacement surgeries for some years," Rosier said.

Source-ANI
RAS