Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review

Abstract

Importance: Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA.

Observations: Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adjusted mortality. Several physical examination findings are useful diagnostically, including bony enlargement in knee OA and pain elicited with internal hip rotation in hip OA. Radiographic indicators include marginal osteophytes and joint space narrowing. The cornerstones of OA management include exercises, weight loss if appropriate, and education-complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) in those without contraindications. Intra-articular steroid injections provide short-term pain relief and duloxetine has demonstrated efficacy. Opiates should be avoided. Clinical trials have shown promising results for compounds that arrest structural progression (eg, cathepsin K inhibitors, Wnt inhibitors, anabolic growth factors) or reduce OA pain (eg, nerve growth factor inhibitors). Persons with advanced symptoms and structural damage are candidates for total joint replacement. Racial and ethnic disparities persist in the use and outcomes of joint replacement.

Conclusions and relevance: Hip and knee OA are highly prevalent and disabling. Education, exercise and weight loss are cornerstones of management, complemented by NSAIDs (for patients who are candidates), corticosteroid injections, and several adjunctive medications. For persons with advanced symptoms and structural damage, total joint replacement effectively relieves pain.

Figure 1A:

Bilateral varus deformity with medial joint space narrowing (nearly bone on bone) and osteophyte formation. Thin arrows show joint space narrowing and thick arrows medial marginal osteophytes.

Figure 1B:

MRI (proton density, fat saturated) of right knee of 63 year old female. Coronal view on left and saggital view on right. Bone marrow lesions are identified with thin, solid white arrows on the coronal view; meniscal damage and cartilage damage are identified with dashed arrow on saggital view and retropatellar effusion as solid arrow on saggital view.

Figure 2.

Molecular Mediators of Osteoarthritis. A number of pro-inflammatory factors and anabolic factors are present in joint tissues and in the synovial fluid. Pro-inflammatory mediators contribute to joint tissue destruction in large part by stimulating production of matrix degrading enzymes, including the matrix metalloproteinases, but also through inhibition of matrix synthesis. The anabolic factors stimulate matrix production and, in some cases, also inhibit the catabolic signaling stimulated by pro-inflammatory mediators. Some factors including TGFβ and bFGF are capable of initiating either catabolic or anabolic activity depending on cell type and specific receptors expressed. TGFβ and BMP-2 can also stimulate osteophyte formation. The overall activity in the OA joint is tipped in favor of the pro-inflammatory side. (IL, interleukin; LIF, leukemia inhibitory factor; MCP, monocyte chemoattractant protein, MIF, macrophage migration inhibitory factor; MIG, monokine Induced By Interferon-Gamma; bFGF, basic fibroblast growth factor; TGF, transforming growth factor; IGF, insulin-like growth factor, BMP, bone morphogenetic protein; CDMP; cartilage-derived morphogenetic protein.)

Figure 3.

Joint Tissue Involvement in Osteoarthritis. OA can involve all joint structures at some point in the disease process. Although articular cartilage degradation and loss is a central feature, changes in the neighboring bone accompany the cartilage damage. These include subchondral bone remodeling resulting in increased thickness, osteophytes, bone marrow lesions and vascular invasion into the overlying cartilage. Inflammatory cells, primarily macrophages, are present in the synovium and can also be noted in peri-articular fat. Meniscal and ligament damage is often found as well. All of these tissues are capable of producing a host of pro-inflammatory factors and matrix degrading enzymes and thus contribute to the progressive remodeling and destruction of the joint.