Osteoarthritis (OA) is the most common form of arthritis and affects more than 20 million Americans.
OA is a disease of hyaline cartilage, the tough "gristle" that caps the ends of long bones. Hyaline cartilage consists of a matrix of proteoglycans which are complex arrangements of proteins and sugar molecules. In addition, there is a framework of tough collagen fibers.
Inside this proteoglycan/collagen matrix are cells called chondrocytes. The maintenance of cartilage is dependent on normal metabolic function of these chondrocytes.
Cartilage, when loaded or exposed to shearing forces, acts as a shock absorber. It will partially deform but springs back to its normal shape. It also provides a gliding surface which is facilitated by a small amount of synovial fluid, produced by the joint lining, that acts as a lubricant.
OA is a wear and tear disease of articular cartilage and results from the lack of ability of cartilage to keep up with excessive breakdown.
A disturbance in the matrix causes loss of cartilage resiliency. Inflammatory proteins, called cytokines, and destructive enzymes, called proteases degrade cartilage.
While there are no therapies that can halt the gradual destruction and wearing away of cartilage, there are some treatments that provide palliative relief.
These include analgesic medicines (pain relievers), non-steroidal anti-inflammatory drugs (NSAIDS), physical therapy, exercise, and injections of glucocorticoids and viscosupplements.
A new treatment, called nerve growth blocking factor, was initially tested in clinical trials a few years ago. These drugs block nerve growth factor, a protein causing certain nerve cells to grow. This drug proved to be profoundly effective for relieving the pain of OA of the knee.
Unfortunately, a significant number of volunteers in the studies experienced complications, termed "joint failure."
"These included 83 cases of rapidly progressing osteoarthritis where bone and cartilage deteriorated and 30 cases of osteonecrosis, which is bone death caused by poor blood supply," according to Nona Colburn, a clinical reviewer with the FDA's Center for Devices and Radiological Health.
The makers of these drugs feel these complications were due to patients using anti-nerve growth factor drugs along with NSAIDS and have recommended that if the drugs are marketed patients not use them alongside NSAIDS.
The manufacturers also have said that if studies are resumed, they will use lower doses of the anti-nerve growth factor drugs, limit the amount of NSAID a patient can take during the trials, and also screen volunteers for conditions that might predispose them to joint failure complications.