Even the most effective current treatments for osteoarthrosis do not restore the joint2,4. Non-operative treatments, including modifications of lifestyle, exercise programs, medications, and physical therapy, can decrease symptoms and improve mobility, but they do not detectably alter the course of the disease for most patients4. Arthrodesis of degenerated joints relieves pain but sacrifices mobility. Osteotomies of the hip and knee can decrease pain and, in some patients, can lead to formation of a new articular surface2,10, but the results vary considerably among patients. Resection of degenerated joints and replacement of these joints with implants fabricated from polyethylene, metal, or another synthetic material predictably relieves pain and improves function. However, these procedures have important limitations, especially for young, active patients, primarily because they do not restore an articular surface with the mechanical properties and durability of articular cartilage. Moreover, synthetic materials must be fixed to the bone of the patient. Thus, the wear of the implant surfaces limits the life span of the implant. Within this life span, the bond between the implant and the bone may fail. For all of these reasons, treatments that restore the structure and function of osteoarthrotic joints would be appropriately heralded as breakthroughs and could benefit many patients.
Osteoarthrosis consists of the progressive loss of articular cartilage that begins with fraying or fibrillation of the articular surface and progresses to exposure of subchondral bone. Attempted repair of the cartilage, remodeling of subchondral bone, and, in many instances, formation of osteophytes accompany the degeneration of the articular cartilage8,9. Once degeneration of the joint begins, it usually progresses inexorably, causing increasing pain and loss of mobility despite attempted repair of the articular surface. The limited capacity of articular cartilage for repair or regeneration3,8 has led to the widely accepted view that an osteoarthrotic joint cannot be restored to normal structure and function. However, recent reports of methods that promote the formation of new articular surfaces in localized cartilage defects1,5,7,12 have created a great interest among scientists and physicians in the possibilities for restoration of osteoarthrotic joints. The reports have also led patients who have osteoarthrosis to seek treatments that would repair or regenerate the articular cartilage rather than replace the joints.
Promising experimental methods for facilitating the repair of cartilage include the use of drugs that may alter the course of osteoarthrosis, the removal of molecules that interfere with repair of cartilage, and the use of cytokines, artificial matrices, and cell transplants to stimulate replacement of damaged cartilage. Drugs that have the potential to preserve articular cartilage or to stimulate repair include some non-steroidal anti-inflammatory medications, agents with heparinoid-like properties, bone antiresorptive agents, and tetracyclines6. Selective enzymatic removal of dermatan sulfate proteoglycans and possibly other molecules at the site of the cartilage damage may make it possible for cells and newly synthesized matrices to bind to the remaining cartilage surface and thus to form new tissue11. Certain cytokines stimulate host or transplanted cells to form cartilage, transplanted chondrocytes or mesenchymal cells can survive in cartilage defects and produce new tissue, and artificial matrices provide a vehicle for the implantation of cytokines or cells as well as a framework for the formation of new tissue in regions of cartilage loss1,2,5,7,12.
Reports of these experimental methods for facilitating the repair of cartilage have encouraged patients to expect that current treatments for osteoarthrosis soon will be replaced. However, much work needs to be done before these approaches to the repair or regeneration of articular cartilage can be accepted as effective treatments for osteoarthrotic joints. None of these methods, when applied to the osteoarthrotic joint, has thus far been shown to stimulate the formation of tissue that duplicates the structure, composition, mechanical properties, and durability of articular cartilage. Moreover, none of them has been shown to improve function and relieve symptoms predictably. In order to realize the potential of these new methods for maintaining or restoring articular cartilage in the treatment of osteoarthrosis, it will be necessary to invest in additional basic-science studies as well as prospective clinical trials. The trials must include random assignment of patients to treatment and control groups as well as objective evaluation of the results, including measurements of the function of the joint and of the patient and studies of the articular surfaces and subchondral bone.
Osteoarthrotic joints present far more complex problems than localized defects of cartilage in otherwise normal joints, and the available studies do not show a clear association between the development of a new articular surface and the relief of pain in osteoarthrotic joints2. Therefore, it seems unlikely that stimulating the formation of new articular surfaces alone will predictably restore the function of degenerated joints and relieve symptoms. Instead, the available clinical and experimental evidence indicates that, in the future, the successful restoration of osteoarthrotic joints will require a detailed analysis of the structural and functional abnormalities of the involved joint followed by application of a treatment plan. This plan may include use of medications that help to maintain or restore articular cartilage; correction of any mechanical or structural abnormalities (including malalignment, instability, and intra-articular causes of mechanical dysfunction); treatment of degenerated articular surfaces to remove or block the effects of molecules that inhibit repair; and use of articular implants, which may consist of a synthetic matrix that incorporates cells or cytokines. Understandably, patients and physicians want to apply treatments that offer the promise of immediate restoration of a degenerated joint. However, only careful, controlled studies will make it possible to evaluate and develop the full potential of the promising new approaches to the treatment of osteoarthrosis.
Henry J. Mankin, M.D.
Joseph A. Buckwalter, M.D., M.S.