Osteoarthritis and therapy

Abstract

Introduction Osteoarthritis (OA) is the leading cause of disability in older persons, affecting 10% of the population 60 years of age. In the United States alone, there are currently at least 20 million persons afflicted with OA, which costs the economy approximately $60 billion annually. Eighty percent of individuals with OA have limited mobility and 25% cannot perform major daily activities (1). Because the population is aging rapidly, it is anticipated that OA will affect almost 60 million individuals in the United States by 2020, with consequent increased spending on diagnosis, therapy, side-effect prevention, and loss of productivity. Most cases of OA develop without a known cause of joint degeneration in what is referred to as primary or idiopathic OA. Less frequently, OA develops as a result of joint degeneration caused by traumatic injury or a variety of hereditary; inflammatory; or developmental, metabolic, and neurologic disorders, a group of conditions referred to as secondary OA. Genetic predisposition, age, obesity, female sex, greater bone density, joint laxity, and excessive mechanical loading have been identified as risk factors for primary OA (1). OA diseases are a result of both mechanical and biologic events that destabilize the normal coupling of degradation and synthesis of articular cartilage chondrocytes, extracellular matrix, and subchondral bone. Ultimately, OA diseases are manifested by morphologic, biochemical, molecular, and biomechanical changes to both cells and extracellular matrix, which lead to softening, fibrillation, ulceration, loss of articular cartilage, sclerosis, and eburnation of subchondral bone, osteophytes, and subchondral cysts. When clinically evident, OA diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects (2). Although intensive research has been carried out on the effects of different cytokines, growth factors, and mechanical loading on the regeneration of cartilage and subchondral bone, there is still no comprehensive understanding of mechanism of OA. Although synovitis is not directly related to the severity of OA (3), it is proposed to be involved with the progression of OA and can be predictive of future chondropathy (4). Therefore, it is imperative to develop a better understanding of how synovitis affects the progression of OA. Recently, the potential role of subchondral bone in the mechanism of OA has attracted more attention. Several theories relate subchondral bone to OA. First, a stiffer subchondral bone, either caused by healing of trabecular microfacture (5) or abnormal metabolism of osteoblasts (6), is no longer an effective shock absorber and causes damage to cartilage. Second, abnormal function of OA osteoblasts in subchondral bone may lead to an increase in bone volume without a concomitant increase in mineralization due to an inappropriate isoform and structure of collagen, which reduces bone strength (6). Third, bone-derived products (7) and cytokines from subchondral bone (8) may pass through channels and fissures between cartilage and bone to initiate OA (9). Much clinical therapy of OA is focused on improving conditions of OA in subchondral bone.