Research Offers Hope of New Therapies to Prevent Bone Loss and Destruction

A study recently published in Annals of the Rheumatic Diseases shows promise for potential new therapies to prevent bone loss and bone destruction in patients with rheumatoid arthritis (RA).¹

The investigators conducting the study have identified several genes linked to osteoclast-mediated bone resorption. By preventing these cells from maturing and being activated, researchers believe they can more effectively stop both bone loss and bone destruction in patients with RA and related forms of joint inflammation.

Steven R. Goldring, MD, chief scientific officer at the Hospital for Special Surgery in New York, is the principal investigator on the project, which was funded through an ACR Research and Education Foundation Within Our Reach: Finding a Cure for Rheumatoid Arthritis research grant. Dr. Goldring believes current treatments targeting osteoclasts work reasonably well at preventing systemic bone loss but have been inadequate at preventing bone destruction in inflamed joints. “There is an unmet need for more effective agents to block the activity of the osteoclast at sites of joint inflammation,” he says.

An osteoclast undergoes specific and unique specializations that allow it to form the acidic environment needed for the removal of the mineral and protein content of bone. “In thinking about therapies, we looked at the pathways and genes that control the differentiation and adaptation that allow the osteoclast to become this super resorbing cell,” he explains. “If we could identify these molecules, it would provide an opportunity to develop more specific and uniquely targeted therapies to block the osteoclast, and these therapies would be expected to have less toxicity.”

In their research, Dr. Goldring and his colleagues were able to identify several candidate genes related to the final specialization of the osteoclast. The researchers are now working to develop pharmacologic agents to block these pathways.

“The clinical application of these agents would be relevant not just for rheumatoid arthritis and other inflammatory diseases, but also potentially for systemic osteoporosis and for other skeletal complications as well,” Dr. Goldring says.

To learn more about this and other research funded through Within Our Reach, please visit www.WithinOurReach.info or www.rheumatology.org/REF.

Reference

1. McHugh KP, Shen Z, Crotti TN, et al. The role of cell–substrate interaction in regulating osteoclast activation: Potential implications in targeting bone loss in rheumatoid arthritis. Ann Rheum Diseases. 2010;69(Suppl 1):i83-i85.