Osteoarthritis: New Insights. Part 1: The Disease and Its Risk Factors

Osteoarthritis: The Disease and Its Prevalence and Impact Dr. David T. Felson (Boston University School of Medicine, Boston, Massachusetts), Ms. Reva C. Lawrence (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [NIH], Bethesda, Maryland), Dr. Paul A. Dieppe (University of Bristol, Bristol, United Kingdom), Dr. Rosemarie Hirsch (National Center for Health Statistics, Centers for Disease Control and Prevention [CDC], Hyattsville, Maryland), and Dr. Charles G. Helmick (National Center for Chronic Disease Prevention and Health Promotion, CDC, Atlanta, Georgia): For many years, osteoarthritis has been seen as a dull, commonplace disorder with few treatment options. That view is rapidly changing. Recent epidemiologic, clinical, and treatment studies have combined to produce a picture of a surprisingly complex disease whose pathophysiology bridges biomechanics and biochemistry and whose treatments range from surgery to nutriceuticals to patient education interventions. These understandings have already led to a shift in the approach to treatment. This article is part 1 of a two-part summary of an NIH conference, Stepping Away from OA: Prevention of Onset, Progression, and Disability of Osteoarthritis. The conference brought together experts in osteoarthritis from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. For research questions and opportunities identified at the conference, see www.nih.gov/niams/reports/oa/oareport.htm(accessed on 25 May 2000). Osteoarthritis is the most common form of arthritis. Among U.S. adults 30 years of age or older, symptomatic disease in the knee occurs in approximately 6% and symptomatic hip osteoarthritis in roughly 3% (1). Since osteoarthritis is a disease whose prevalence increases with age, it will become even more prevalent in the future as the bulging cohort of baby boomers grows older. Because of its prevalence and the frequent disability that accompanies disease in the knee and hip, osteoarthritis accounts for more trouble with climbing stairs and walking than any other disease (2). Osteoarthritis is the most common reason for total hip and total knee replacement. Because of the longevity of working careers and the substantial prevalence of osteoarthritis in middle-aged persons, osteoarthritis causes a considerable burden in lost time at work and early retirement (3). Recent estimates suggest that total costs for arthritis, including osteoarthritis, may exceed 2% of the gross domestic product (3). Clear prevalence patterns emerge from most epidemiologic studies of osteoarthritis. Osteoarthritis increases with age, and sex-specific differences are evident (4-7). Before 50 years of age, the prevalence of osteoarthritis in most joints is higher in men than in women. After about age 50 years, women are more often affected with hand, foot, and knee osteoarthritis than men. In most studies, hip osteoarthritis is more frequent in men (4, 8). In a community-based survey, the incidence and prevalence of disease increased 2- to 10-fold from 30 to 65 years of age and increased further thereafter (9) (Figure 1). Figure 1. Incidence of osteoarthritis of the hand, hip, and knee in members of the Fallon Community Health Plan, 1991 1992, by age and sex. Osteoarthritis can be defined by symptoms or pathology. The pathology of osteoarthritis involves the whole joint in a disease process that includes focal and progressive hyaline articular cartilage loss with concomitant changes in the bone underneath the cartilage, including development of marginal outgrowths, osteophytes, and increased thickness of the bony envelope (bony sclerosis). Soft-tissue structures in and around the joint are also affected. These structures include synovium, which may show modest inflammatory infiltrates; ligaments, which are often lax; and bridging muscle, which becomes weak. Many people with pathologic and radiographic evidence of osteoarthritis have no symptoms (10). From a clinical perspective, the most compelling definition of disease is one that combines the pathology of disease with pain that occurs with joint use. Unfortunately, the cause of pain in osteoarthritis is unknown (11). It is unclear whether osteoarthritis is a single disease or many disorders with a similar final common pathway. The following points argue in favor of the idea that osteoarthritis is several distinct entities: 1. Osteoarthritis of the knee and hip may be associated with different risk factors, suggesting that we should regard them as unique diseases (12). It remains unclear whether osteoarthritis of other joints (such as interphalangeal joints or the spine) should also be regarded as separate entities. 2. Generalized osteoarthritis may be a distinct disease (13, 14) in which systemic (genetic) predisposition is more important than local (mechanical) factors (15). 3. One classification divides people with osteoarthritis into those in whom the cause is known (secondary) or those in whom the cause is unknown (primary) (16). 4. Osteoarthritis of the hip has been divided into hypertrophic and atrophic forms (17) on the basis of a person's tendency to develop large osteophytes; other joints may respond similarly to the presence of disease. Hypertrophic osteoarthritis may be associated with pyrophosphate crystal deposition and diffuse idiopathic skeletal hyperostosis, a disease of bony proliferation at ligament and tendon insertion sites; atrophic forms may be associated with the presence of basic calcium phosphate crystals and osteoporosis (18-20). Severe joint injury may be sufficient to cause osteoarthritis; however, the disease is often the product of an interplay between systemic and local factors (21) (Figure 2). For example, a person may have an inherited predisposition to develop the disease but will develop it only where a biomechanical insult (such as a knee injury) has occurred. Figure 2. Pathogenesis of osteoarthritis with putative risk factors. We focus on osteoarthritis in the knees, hips, and, to a lesser extent, hands, since disease in these weight-bearing joints has great clinical impact. Although many of the same pathologic changes of disease occur in the back and neck, it is not clear whether clinical syndromes of back and neck pain are necessarily related to osteoarthritis. Systemic Risk Factors for Osteoarthritis Ethnicity Dr. Joanne M. Jordan (University of North Carolina, Chapel Hill, North Carolina), Dr. Raynard S. Kington (National Center for Health Statistics, CDC, Hyattsville, Maryland), Dr. Nancy E. Lane (University of California at San Francisco, San Francisco, California), Dr. Michael C. Nevitt (University of California, San Francisco), Dr. Yuqing Zhang (Boston University School of Medicine), Dr. MaryFran Sowers (University of Michigan, Ann Arbor, Michigan), Dr. Timothy McAlindon (Boston University School of Medicine), Dr. Tim D. Spector (St. Thomas' Hospital, London, United Kingdom), and Dr. A. Robin Poole (McGill University, Montreal, Quebec, Canada): Ethnic differences in knee and hip osteoarthritis have been best studied in African-Americans and white persons, and evidence is conflicting. Results from one large national study, the National Health and Nutrition Examination Survey I, suggested higher rates of knee osteoarthritis in African-American women but not men. Another study from the rural South, the Johnston County Osteoarthritis Project, suggested no differences in disease prevalence (22, 23). The National Health and Nutrition Examination Survey I did not reveal ethnic differences in the prevalence of osteoarthritis of the hip (24), whereas in the Johnston County Osteoarthritis Project (25), African-American men were 35% more likely than white men to have hip osteoarthritis. African-Americans with knee or hip osteoarthritis have more severe radiographic features of disease and more frequent bilateral involvement and mobility impairment than do white persons (23, 26). The relative contributions of biological, lifestyle, and socioeconomic factors to ethnic differences in osteoarthritis and disability are unclear. Although ethnic differences in such factors as body mass index might partially explain ethnic variation in radiographic osteoarthritis, ethnic differences in biomarkers of osteoarthritis suggest that biological and genetic factors may also play a role (27). Hormonal Status and Bone Density The high incidence of osteoarthritis in women just after menopause has suggested that estrogen deficiency plays a role in causing disease. Cohort studies have reported that women taking estrogen have a decreased prevalence (28) and incidence (29) of radiographic osteoarthritis. However, casecontrol studies evaluating current or past estrogen use in women with and those without symptomatic osteoarthritis (30, 31) have been inconsistent in their findings; as a result, the current evidence is at best suggestive of a protective effect of estrogen on osteoarthritis. Furthermore, any protective effect might be confounded by healthy habits of estrogen users, which might protect them from disease. Evidence suggests an inverse relationship between osteoarthritis and osteoporosis. The preponderance of cross-sectional studies demonstrate that high bone mineral density is associated with an increased prevalence of hip, hand, and knee osteoarthritis. For example, in the Study of Osteoporotic Fractures (32), women with radiographic hip osteoarthritis with osteophyte formation had an 8% to 12% increase in bone density compared with women without osteoarthritis (P <0.001). Women with knee osteoarthritis also appear to have relatively high bone density (33). The effect of bone density on the course of osteoarthritis and the impact of osteoarthritis on bone loss have only recently been probed. A longitudinal study of premenopausal and perimenopausal women