Research should now focus on the role of inflammation in the two conditions, experts say The relationship between obesity and osteoarthritis has thus far been attributed to mechanical loading resulting in "wear and tear" of the joints. Recently, there has been more investigation into obesity as a disease of inflammation, as well as underlying mechanisms contributing to joint destruction. The over-expressed pro-inflammatory cytokines in obesity are considered the link between obesity and inflammation. Excess of macronutrients in adipose stimulates the release of inflammatory mediators, such as tumor necrosis factor α and interleukin 6, reduces production of adiponectin, and overall increases oxidative stress. Many studies have demonstrated that an increase in fat mass is associated with preclinical osteoarthritis, faster loss of knee cartilage, and increased likelihood of joint replacement. This study examined a large cohort (>1,500 patients) and also demonstrated a strong association between knee osteoarthritis and obesity in both men and women. Both disease processes have devastating consequences for mobility and functionality in the aging population, and are worth studying given the growing obesity epidemic. Full Critique A new study provides evidence linking obesity with knee osteoarthritis. With obesity and knee-replacement surgery rates both continuing to rise, experts called for deeper dives into the underlying mechanisms through which obesity affects the joints. The study, which the authors called the first of its kind, found strong associations between knee osteoarthritis and obesity in both men and women. "In this large longitudinal cohort, we found body composition-based obesity and sarcopenic obesity, but not sarcopenia, to be associated with risk of knee osteoarthritis," Devyani Misra, MD, of Beth Israel Deaconess Medical Center in Boston, and colleagues, wrote online in Arthritis & Rheumatology. "Weight loss strategies for knee osteoarthritis should focus on obesity and sarcopenic obesity." The study included 1,653 participants, 61% of whom were women, with a mean age of 62 and a mean body mass index of 30. Among the participants, 315 (19%) developed incident radiographic knee osteoarthritis by the 60-month mark of the study. Misra and colleagues found greater fat mass to be numerically and statistically associated with increased knee osteoarthritis risk at 60 months in the overall population (RR 1.02 [95% CI 1.0-1.04]) and in women (RR 1.03 [95% CI 1.00-1.06]). In men, fat mass was not associated with risk of knee osteoarthritis -- RR 1.00 (95% CI 0.95-1.13). The results were similar between men and women when evaluating body composition based on fat and muscle mass in those categorized as obese, sarcopenic obese, or sarcopenic. Participants who were either obese (RR 2.05 [95% CI 1.56-2.68]) or sarcopenic obese (RR 1.91 [95% CI 1.17-3.10]) had an increased risk of knee osteoarthritis over 60 months. The results in women and men were similar: women who were obese had a more than a two-fold increased risk of radiographic knee osteoarthritis (RR 2.29 [95% CI 1.64-3.20]). A similar finding occurred in women who were sarcopenic obese (RR 2.09 [95% CI 1.17-3.73]). In men, there was a >70% increased risk of radiographic knee osteoarthritis among those who were obese (RR 1.73 [95% CI 1.08-2.78]) and sarcopenic obese (RR 1.74 [95% CI 0.68-4.46]), although in the latter case the results did not reach statistical significance. No significant association between sarcopenia without obesity and risk of radiographic knee osteoarthritis was found in either the overall analysis (RR 0.87 [95% CI 0.06-1.25]) or the sex-stratified analyses (for women, RR 0.96 [95% CI 0.62-1.49]; for men, RR 0.66 [95% CI 0.34-1.30]). Misra and colleagues said the findings should inform how rheumatologists and other care providers approach weight-loss strategies for relevant patients. "Our findings have implications for management of knee osteoarthritis, such that weight loss interventions should target both high fat mass and low muscle mass," the researchers wrote. Asked for his perspective, Steven Heymsfield, MD, of Louisiana State University and current president of The Obesity Society, who was not involved with the study, said the findings were in line with clinical norms. The underpinnings of the connection between the conditions, however, remain less certain. "This shouldn't come as a huge surprise," he said. "Osteoarthritis is much more common in people who are obese. There's not just weight but an inflammatory component here. It reflects the infiltration of adipose tissue by the inflammatory cells." Relatively little is known about the relationship between obesity, inflammation, and osteoarthritis. It is well known that fat cells release adipokines including leptin as an immune protein, and that adipokines can cause lower-level inflammation over time. But the specific interplay is still not widely understood, particularly in comparison with the more obvious problems that occur when joints are supporting abnormally high amounts of weight. The connection between osteoarthritis, obesity, and inflammation could be a key research area moving forward, experts said. "It's not just wear and tear or weight bearing," said Lydia Alexander, MD, an obesity specialist in San Francisco who was not affiliated with the study. "The issue should also be inflammation. We know that obesity has a lot of chemical components within it, and inflammation could be at play." The issue has high importance given the large numbers of Americans receiving knee replacement surgeries -- many of them as a result of obesity, osteoarthritis, or both. According to a 2018 study in the Journal of Bone & Joint Surgery, the number of total knee arthroplasties is expected to rise 85% to 1.26 million procedures by 2030. Better understanding and management of obesity could help avoid surgeries, not to mention the other problems obesity can create, she said. "Osteoarthritis and diabetes are the two biggest problems we have. And obesity, whether upstream or downstream, just makes them worse." Source
