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Spotlight on Research 2012
Bone Drug Holds Promise as Therapy for People with OA
Researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have shown that a medication that triggers new bone formation in people with osteoporosis can restore cartilage in a mouse model of injury-induced osteoarthritis of the knee. Their findings were reported in Science Translational Medicine.
Osteoarthritis (OA) is a painful and often debilitating disease that occurs when cartilage, which normally cushions the bones, breaks down. Currently, there are no medications that treat the cartilage loss in OA. The disease has many causes and, while it can occur in any joint, the knee is commonly affected. Knee OA is often the result of an injury that causes damage to the menisci (cartilage that cushions the knee joint) or ligaments (bands of tissue that support the knee).
Teriparatide, a form of human parathyroid hormone approved to treat osteoporosis, works to restore bone strength by targeting bone-building cells. However, based on the discovery that cartilage in arthritic joints — but in not healthy joints — expresses receptors for parathyroid hormone, combined with the hormoneís known effects on cartilage cells called chondrocytes in the growth plate areas of bone, Michael Zuscik, Ph.D., Randy Rosier, M.D., Ph.D., and their colleagues at the University of Rochester Medical Center, wondered whether teriparatide might also target chondrocytes in arthritic joints. Reports that people with OA who were taking teriparatide for their osteoporosis had less arthritis pain further supported this approach.
In the study, the team used an OA mouse model in which injury to the menisci and ligaments of the knee results in a breakdown of cartilage. In a series of experiments, they demonstrated that mice that received teriparatide daily for one month had nearly a third more cartilage than mice that did not receive the drug.
The researchers made additional observations in the treated mice. Normally, in addition to being present in joint cartilage, chondrocytes are also present in bone. The cells in bone act differently than they do in cartilageómaturing more fully and helping to mineralize (harden) bone tissue. But in OA, chondrocytes in the joint behave as they would in bone, maturing excessively and mineralizing the cartilage, resulting in a gradual destruction of the joint. In the study, the scientists identified a decrease in the proteins linked to excessive chondrocyte maturation in the mice treated with teriparatide. The scientists also found that, in the treated mice, there was an increase in regenerative chondrocyte activity in cartilage, and a reduction in cartilage breakdown.
Given that teriparatide is already clinically available, the researchers believe that these findings make a case for further investigation of the medication in people with OA. If future studies show that teriparatide has a favorable risk-benefit profile in people with OA, it would be the first disease-modifying drug for this debilitating disease that affects millions of Americans.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at http://www.niams.nih.gov.
Sampson ER, Hilton MJ, Tian Y, Chen D, Schwarz EM, Mooney RA, Bukata SV, O'Keefe RJ, Awad H, Puzas JE, Rosier RN, Zuscik MJ. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med. 2011 Sep 21;3(101):101ra93.