Cartilage in Osteoarthritis by Corticosteroid Injections"> The Deterioration of Articular Cartilage in Osteoarthritis by Corticosteroid Injections

Cartilage in Osteoarthritis by Corticosteroid Injections"> Author: Ross A. Hauser, MD

Osteoarthritis (OA) is a major cause of pain and disability, as well as cost, to both the individual and society. The average direct out-of-pocket expenditure of OA is approximately $2600 per person per year, but the total annual cost per person (including lost productivity) is between $5700 and $9600.^1,2 OA and related conditions cost the U.S. economy nearly $128 billion per year in medical care and indirect expenses, including lost wages and productivity.³ A major component of the economic burden associated with the treatment of arthritis relates to surgical joint replacements of the hips and knees. In 2004, the national bill of hospital charges for hip/knee replacements was $26 billion, and the hospital cost was $9.1 billion.⁴ Musculoskeletal procedures, including hip and knee replacements, account for ten percent of all hospital care in the United States. From 1997 to 2005, the number of knee replacements climbed by 69 percent, from 328,000 to 555,800. The number of hip replacements rose from 290,700 to 383,500 procedures.⁵ The number of these procedures is increasing at an alarming rate. Nearly 600,000 hip replacements and 1.4 million knee replacements will be performed in the year 2015.⁶ By 2030, it is estimated that the number of hip and knee replacements annually will increase to 1.85 and 3.48 million, respectively.⁷ (See Figure 1.) The question to ask is why has there been such an alarming rate of articular cartilage deterioration necessitating all of these joint replacements? What is causing it?

OA currently affects more than 27 million Americans, up from 21 million in 1990. By the year 2030, it is expected that more than 67 million Americans will have arthritis.⁸ (See Figure 2.) While much is known about what happens at the level of the joint after the start of OA, there is no consensus as to why the condition starts in the first place. Factors influencing the incidence of OA have been identified through epidemiological and small group studies. These factors include sex (women, especially after entering menopause), low hormone levels, nutritional factors, obesity, inheritance, knee injury, quadriceps strength, ligament laxity, and joint injury due to misalignment, overload or trauma.^9-11 While many of these have been well studied, it is doubtful that they alone could account for the dramatic rise in OA over the last forty years, and the predictions of OA in epidemic proportions for the near future.


The hallmark feature of OA is a breakdown in the articular cartilage of joints such as the knee and hip. The articular cartilage covers the connecting surfaces of two bones where they join, allowing them to glide effortlessly, one bone over the other. The first feature of OA is a fraying and fibrillation of the articular cartilage surface. (See Figure 3.) This coincides with a loss of proteoglycans from the matrix of articular cartilage.¹² Articular cartilage contains chondrocytes embedded in an extracellular matrix composed primarily of type II collagen and proteoglycans. Articular cartilage bulk chemical analysis reveals that it is composed of 10 to 15 percent collagen, 10 to 15 percent protein polysaccharide (proteoglycan), and 70 to 80 percent water.¹³ Chondrocytes make up one to five percent of the volume in adult cartilage tissue. Chondrocytes are the cells responsible for the formation, maintenance, and repair, of articular cartilage.¹⁴ Despite a poor oxygen tension, limited nutrient supply, and anaerobic metabolism, chondrocytes can still produce large amounts of collagen and proteoglycans.¹⁵ The collagen provides strength to the cartilage, the proteoglycans provide elasticity and stiffness on compression. The proteoglycans are very hydrophilic, meaning they are attracted to water. The proteoglycans form aggregates, which give articular cartilage its unique abilities to act as a shock absorber for joints such as the knee and hip.¹⁶ (See Figure 4.)

OA begins immediately once chondrocyte function is altered. This leads to a decrease in the ground substance, or proteoglycans. This weakens the cartilage structure. The cartilage breaks down further causing fissures in it. Eventually there is enough breakdown of the cartilage that it can be seen on X-ray as joint space narrowing. This causes a transmission of pressures that are too high for the bones to handle. Eventually the space between the bones becomes completely obliterated. This is when the orthopedic surgeon tells the patient he/she has bone on bone and needs a joint replacement. (See Figure 5.)


Early in the course of OA, the tissue mounts an attempt at repair. Chondrocytes proliferate with a resulting increase in matrix synthesis. However, in the face of chronic mechanical degenerative forces, degradative enzymes overwhelm the synthetic capability. The net result is too much degradation of cartilage and not enough repair. Traditional pharmacological treatments, including nonsteroidal anti-inflammatory drugs and corticosteroids shots, are typically used to not only decrease symptoms, but also to hopefully improve the physiology of the disease process. Unfortunately the preponderance of evidence shows that these treatments actually accelerate the osteoarthritic process.^17,18 The rest of this paper will focus on the evidence that corticosteroids deteriorate normal and degenerated articular cartilage.

Intraarticular injections of corticosteroids have been used for the treatment of OA of the knee and other joints for more than 50 years, but there is little controlled evidence to support their use.^19-22 Since 1951, when Thorn first injected hydrocortisone into the knee joint of a patient with rheumatoid arthritis, the anti-inflammatory effects of intraarticular corticosteroid compounds have been established.²³ Cortisol, and the synthetic analogs of cortisol, have the capacity to prevent or suppress the development of the local heat, redness, swelling, and tenderness, by which inflammation is recognized. At the microscopic level, they inhibit not only the early phenomena of the inflammatory process, edema, fibrin deposition, capillary dilatation, migration of leukocytes into the inflamed area, and phagocytic activity, but also the later manifestations of capillary proliferation, fibroblastic proliferation, deposition of collagen, and still later, cicatrization.²⁴

The first evidences that steroids injected locally produced adverse effects came a few years after doctors started using corticosteroids. Several case studies reported rapidly progressive degenerative arthritis following intraarticular hydrocortisone injections.^25-27 Researchers then started looking at intraarticular corticosteroid injected joints in animals, comparing them to similar joints injected with saline (control). The feeling was that these studies should provide a useful indication of the clinical effects of these drugs on normal or diseased joints in man.