Synovial osteochondromatosis

Osteoarthritis (OA) is a chronic degenerative joint disease that affects more than 16 million Americans,1 most of whom are elderly. By age 65 the majority of the population show radiographic signs of osteoarthritis. 2 OA may affect many joints, and patients usually present to their physicians with complaints of pain in the knee, hip or spine. This pain is often associated with stiffness and decreased range of motion in the affected joint, which ultimately leads to a decrease in daily function.3,4,5 As the population ages, the cost of pain medication, joint replacement, physical, occupational and rehabilitative therapy, and lost wages due to disability, places a burden on our health care system.6 Direct and indirect cost per year for OA range from 15 billion dollars to 20 billion in 2000.2,,6

OA of the knee, a major cause of pain and disability in the elderly, 7, 8, 9 accounts for more functional dependency in terms of walking, stair climbing and other lower extremity tasks than any other disease, particularly in the older population.9

DIAGNOSIS

Initial diagnosis of OA is based on a complete history and physical examination, taking into account the symptoms, the number and the distribution of involved joints as well as X-ray changes. The classic findings of OA on X-Rays are non-uniform loss of joint space and the presence of osteophytes or new bone formation.11, 12, 13 Early in the disease minimal non-uniform joint space may be the only radiographic finding.13 For initial diagnosis of OA, plain films often suffice. The American College of Rheumatology (ACR) diagnostic criteria of knee OA include knee pain and osteophytes, plus one of the following: age over 60, stiffness less than 30 minutes and crepitus.3 However, at times there is a lack of correlation between clinical findings, radiological findings and the pathological changes of hyaline cartilage degeneration.14 When evaluating OA of the knee, initial plain films, done while the patient is standing, allow adequate visualization of the medial and lateral joint spaces. The findings in OA include narrowing in the medial tibiofemoral and patellofemoral joint space. As the disease progresses, subluxation of the tibia may occur along with osteophyte formation. Cartilage is lost and subchondral bone formation occurs.

RISK FACTORS AND PATHOGENESIS

Several factors determine the likelihood of OA developing in a particular joint; i.e., age, sex, weight, genetics, muscle weakness, laxity of ligaments, injury to joint, biomechanical factors, hormonal factors, nutritional factors, andbonedensity. 9, 15, 16, 17, 18, 19, 20,21

Our understanding of the pathogenesis and natural history of OA is incomplete, but it is believed that the cumulative effect of biomechanical stresses on a joint leads to chondrocyte injury and impairs the maintenance of the articular cartilage. As a consequence there is loss or decreased synthesis of proteoglycans, increased collagen turnover, and possibly molecular or spatial changes in collagen. It is believed that chondrocyte integrity depends on the normal loading of the joint and that over or under-loading induces chondrocyte injury. With decades of weight bearing, there is remodeling of the conformation of the articular cartilage with a redistribution of load stresses. With changed weight bearing from the remodeling, the sub-synovial weave of collagen fibers changes, favoring the loss of proteoglycans. Simultaneously, the closely approximated articular surfaces are deprived of the free flow of synovial fluid. Cartilage damage and erosion ensue. The articular cartilage damage initially appears as focal erosions and flaking. Clefts develop at right angles to the surface. These clefts penetrate the subchondral bone are called "cartilage fibrillation." In response to this damage, there is ingrowth of blood vessels into the subchondral bone and into the articular cartilage. Focal, cystic areas appear in the subchondral bone, filled with fibrous tissue, presumably reflecting reactive vascular changes and bone resorption. With further progression, the cartilaginous layer is more deeply eroded and may entirely disappear from focal areas, exposing subchondral bone. The subchondral bone becomes densely sclerotic and micro-fractures may occur as a result of the loss of elasticity of the sclerotic subchondral cushion. This loss of cartilage accounts for the thinning of the joint space seen radio graphically. Concomitant osteophytes (bony outgrowths) develop at the margin of the articular cartilage.22

OA is significantly more common in women over age fifty than men in the same age group.21 However, before the age of fifty men have a higher incidence of OA. Both the incidence and prevalence of OA increase with age until about eighty when both begin to level off or decline.18, 21 The age- associated increase may be due to several factors, such as laxity of the surrounding ligaments making the joint unstable, and decreased responsiveness of chonclrocytes to growth factors that stimulate repair. Additionally, a thinning of the rim of non-calcified cartilage, may increase shear stress at the basal cartilage. There is little evidence to demonstrate an increased incidence in OA based on race.20 Obesity is a risk factor for developing as well as increasing the progression of knee OA, since 3 times the person's weight is transmitted to the knees and hips directly on weight bearing activity. 26 It has been reported that a weight loss of 10-15 pounds decreased the risk of developing OA by half. 27 The association between obesity and hip or hand osteoarthritis is less clear. 28-29(See accompanying article for more details) Other known risk factors associated with knee OA include athletic activities, knee injury and hand OA.

THERAPY

Treatment of early OA often is done through non-pharmacological therapies such as education, exercise, assistive devices and weight management. Additionally, supplements such as glucosamine sulfate and chondroitin sulfate have been used in recent years despite little evidence to support the long- term efficacy of these agents. Initial pharmacological treatment for OA is to use the safest, most benign medication to alleviate pain, typically acetominophen with topical therapy if needed. This is followed by treatment with non-steroidal anti-inflammatory agents such as ibuprofen or naproxen sodium and, finally, intra-articular injections of either steroids or hyaluronuic acid-like products. Severe OA is often treated surgically.

THE OSTEOARTHRITIS INITIATIVE (OAI)

We do not have any treatment regimen that can prevent OA or alter its course or progression. Therefore, research is needed to study the risk factors and biological markers for early onset and progression of knee OA and to better understand its natural history described above. 22,30 Biological markers associated with focal cartilage loss and subchondral bony sclerosis of early osteoarthritis in large observational population studies and the subsequent development of clinical symptoms and radiological changes of OA will help predict the course of the disease. This will greatly enhance future development of new drugs for treatment and or prevention of OA. The best established method for assessing joint damage in OA is joint space width (JSW) measurement using plain X-rays. 4,31,32 However, when radiological diagnosis is established, significant joint damage has already occurred. Moreover, because changes in JSW are small compared to the precision error of X-rays, at least one or two years are usually necessary to accurately assess the progression of joint damage or its reduction by treatment. 33 Therefore, more sensitive markers of OA development and progression should be sought.

In recognition of the urgent need for further studies of knee OA, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is funding four Centers in the US to investigate the risk factors and develop surrogate markers for disease activity. One of these Centers is at Memorial Hospital of RI (Brown Medical School), where we initially will use screening questionnaires, of a multiethnic population, and then follow-up questions regarding diet, physical activity and exercise, intake of medications, vitamins, etc.

We plan to use 3-TESLA magnetic resonance imaging (MRI) to study OA of the knee. MRI is the best technique available for assessment of normal as well as abnormal articular cartilage for it has superior soft tissue contrast and can provide important morphologic information about the area of cartilage damage.41 MRI is more sensitive than plain x-rays and allows detection of changes such as fissuring, cartilage loss and signal changes within residual cartilage and subchondral bone30, meniscal degeneration and tears, osteophyte formation and, sometimes, synovial metaplasia with synovial osteochondromatosis and loose bodies.

Blood samples will be obtained for the future study of genetic and biochemical markers of OA. Potential biomarkers of OA are molecules of connective tissue matrices that are released into biological fluid at the time of tissue turnover. Biomarkers can be divided into skeletal and inflammation markers. They are thought to be more sensitive than x-rays because of their ability to detect more subtle changes in OA progression over relatively short time intervals43.

The risk factors for knee OA and surrogate markers for disease activity include biomechanical, biochemical, hormonal, nutritional and endocrine factors, obesity, quadriceps muscle weakness, a history of trauma or inflammatory arthritis, developmental abnormalities and genetic predisposition. Surrogate markers for disease will eventually be used to characterize the biological markers of OA in large observational population studies to predict the course of the disease. The four Centers OAI will collect information and define standards for 5000 people of diverse ethnic background, over the age of 45, who are at risk of having OA or are at high risk of progressing to severe OA during the course of the 5-year study. The OAI will maintain a natural history database for OA that will include clinical evaluation data and radiological images, both X-Rays and MRI. All images and specimen will be available to researchers worldwide to accelerate scientific studies and biomarker identification. This will enhance future development of new drugs for treatment and for prevention of OA.

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FAIZA FAWAZ-ESTRUP, PHD, MD, FACP, FACR

Faiza Fawaz-Estrup, PhD, MD, FACP, FACR, a rheumatology specialist, is Clinical Professor of Medicine, Brown Medical School.

CORRESPONDENCE:

Faiza Fawaz-Estrup, PhD, MD, FACP, FACR

2221 St. James Drive

Santa Barbara, CA 93105

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