Obesity's Challenges to Bone Health: Pathogenesis and Comprehensive Intervention of Osteoarthritis

I. Overview Osteoarthritis (OA) is a chronic, progressive musculoskeletal disease that seriously endangers human health. The pathogenesis of OA is not fully understood, but it may be related to many factors such as aging, obesity, overuse injuries, trauma, congenital joint abnormalities, and joint deformities. The prevalence of OA in the general population is 2%–6%, while a large-scale epidemiological survey in China showed that the overall prevalence of primary osteoarthritis in people over 40 years of age was 46.3%, showing a trend of increasing with age, and a higher prevalence in women than in men. The main characteristics of OA are degenerative damage to articular cartilage and reactive hyperplasia of the joint margins and subchondral bone. The main clinical manifestations are joint pain, deformity, functional impairment, and decreased quality of life, which can bring a huge social and economic burden. Obesity, as an important factor influencing OA, has been actively studied. However, early research mainly focused on the effects of obesity on weight-bearing joints such as the knee and hip joints, believing that obesity mainly promotes the onset and progression of OA in weight-bearing joints by increasing the load on the joint surfaces, affecting joint alignment, and altering the patient's gait. An epidemiological study on the relationship between obesity and knee osteoarthritis (OA) suggests that in individuals with a BMI > 27 kg/m², the incidence of knee OA increases by 15% for every 1 kg/m² increase in BMI. Karlson et al. suggest that a high BMI at age 18 increases the risk of total hip replacement surgery later in life. A Swedish study involving 259 patients who underwent hip replacement surgery for primary OA showed a positive correlation between high BMI and OA incidence. Recent studies have also confirmed a close relationship between obesity and the progression of non-weight-bearing joint problems. Multiple international studies have shown that the incidence of hand OA is significantly higher in overweight and obese patients than in those of normal weight. A recent meta-analysis also indicates that increased BMI is associated with increased susceptibility to radiographic and/or clinical hand OA. This phenomenon suggests that obesity not only induces OA by affecting mechanical weight-bearing but may also promote OA formation and progression by altering the systemic and local metabolic environment of the joints. II. Pathophysiological Changes Under prolonged overload, normal joints can experience abnormalities in chondrocytes and osteoblasts, as well as changes in the extracellular matrix. When the cartilage load exceeds a critical value, swelling of the articular cartilage begins, with a significant increase in proteoglycan loss. Subsequently, chondrocyte necrosis and cartilage thinning gradually occur, thus initiating the pathological process of osteoarthritis (OA). Chondrocytes and osteoblasts also possess mechanoreceptors on their surfaces. When these receptors are activated, they can induce the secretion of inflammatory factors such as interleukin (IL)-1β, cyclooxygenase-2, prostaglandin E2, matrix metalloproteinases (MMP)-2, MMP-3, IL-6, MMP-9, MMP-13, fibroblast growth factor-2, and IL-8, leading to OA. Adipose tissue not only stores and provides energy but also secretes various adipokines, including leptin, adiponectin, endothelin, and resistin. Leptin, as the main adipokine, has been the most extensively studied biologically and was the first adipokine detected in synovial fluid. In osteoarthritis (OA) patients, leptin expression and concentration are positively correlated with OA prevalence. Subsequent animal experiments showed that leptin can induce growth factor expression, stimulate proteoglycan and collagen synthesis, and regulate bone tissue. Leptin can reduce the degradation of glycosaminoglycans and decrease the concentration of fatty acids in the joint cavity. High concentrations of fatty acids accelerate the catabolism of articular cartilage, and leptin may inhibit articular cartilage catabolism by reducing intracellular fatty acid concentration. In addition to the above-mentioned protective effects on bone and joints, leptin can also affect osteoblast function, leading to abnormal bone metabolism and inducing the expression of matrix metalloproteinases (MMPs), thereby promoting the progression of osteoarthritis. Furthermore, numerous studies have found adiponectin, resistin, visceral adipokines, and other adipokines in synovial fluid, and the levels of adipokines in the synovial fluid of OA patients are higher than those in healthy individuals. These findings suggest that adipokines are involved in the pathological process of OA; however, the exact mechanism is not fully understood and requires further investigation. Obesity is closely related to many metabolic diseases, and a high-glycemic environment inhibits collagen synthesis and mediates articular cartilage destruction. Hypertension, diabetes, and atherosclerosis can cause vascular lesions in articular cartilage, leading to cartilage ischemia and irreversible cartilage damage. III. Clinical Manifestations Early clinical manifestations of osteoarthritis (OA) are mainly localized joint pain, often presenting as resting pain or clicking sounds as the initial symptom, which can be effectively relieved by rest. Late-stage manifestations include increased pain, joint swelling, joint effusion, flexion deformity, and significantly limited mobility. Diagnosis of OA should be based on a comprehensive assessment of medical history, physical examination, and imaging studies. IV. Treatment and Prognosis Weight loss and exercise are the best methods for treating osteoarthritis in obese patients. The most effective and safe way to lose weight is through a combination of dietary changes and exercise. For obese patients with OA, weight loss through exercise is more difficult than for the general obese population. However, in addition to aiding weight loss, exercise has been shown to strengthen the muscles supporting the joints, reduce pain, and improve physical function in OA patients. For those whose lifestyle changes are difficult, medication and surgical weight loss are also feasible. Furthermore, weight management after successful weight loss and after joint surgery is also very important. Osteoarthritis (OA) can be treated with oral medications to relieve symptoms, such as acetaminophen, selective and non-selective cyclooxygenase-2 inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs). Topical NSAIDs, intra-articular injections of corticosteroids and hyaluronic acid, glucosamine and chondroitin sulfate, glucosamine sulfate, chondroitin sulfate, and diacerein are also options. For patients with hip or knee OA whose symptoms are difficult to relieve and whose function has not recovered after the above conservative treatments, joint replacement surgery should be considered. Surgical treatment is more beneficial and less costly for patients with severe clinical symptoms, severely impaired function, and reduced quality of life.