Serum Leptin and Resistin Levels in Knee Osteoarthritis—Clinical and Radiologic Links: Towards Precise Definition of Metabolic Type Knee Osteoarthritis

Abstract

Obesity is considered a major risk factor for the development and progression of knee osteoarthritis (OA). Apart from the mechanical effect of obesity via increase in mechanical overload of weight-bearing joints, an association with hand OA has been observed. There has been increasing interest in the role of adipokines in the pathogenesis of OA in the recent years. It has been suggested that their systemic effects link obesity and OA. In this regard, the aim of the current study was measurement and analysis of serum levels of leptin and resistin in patients with knee OA with different body mass index (BMI). Seventy-three patients with primary symptomatic knee OA at the age between 35 and 87 years (mean age 66 years) were included in the study (67 women and 6 men). The patients were from 2nd to 4th radiographic stage according to Kellgren–Lawrence scale. 43 patients were with concomitant obesity (BMI ≥ 30 kg/m2, mean values 38.34 ± 8.20) and 30 patients with BMI < 30 kg/m2 (mean values 25.07 ± 2.95). Eleven individuals with different BMIs, including cases with obesity but without radiographic knee OA, were examined as a control group. Serum levels of leptin and resistin were measured via ELISA method. In patients with knee OA and BMI ≥ 30 kg/m2, serum levels of leptin (39.546 ± 12.918 ng/mL) were significantly higher as compared with healthy individuals (15.832 ± 16.531 ng/mL, p < 0.05) and the patients with low BMI (p < 0.05). In patients with BMI < 30 kg/m2 the levels of leptin (13.010 ± 10.94 ng/mL) did not differ significantly from the respective values in the control group (p = 0.48). Serum levels of resistin were also higher in knee OA patients in comparison with healthy controls, but the difference was statistically significant only for patients with high BMI (2.452 ± 1.002 ng/mL in the group with BMI ≥ 30 kg/m2; 2.401 ± 1.441 ng/mL in patients with BMI < 30 kg/m2; 1.610 ± 1.001 ng/mL in the control group, p < 0.05). A correlation was found between the serum levels of leptin and radiographic stage of OA, i.e., higher leptin levels were present in the more advanced 3rd and 4th radiographic stage, while for resistin a correlation was observed in the patient subgroup with BMI < 30 kg/m2. Serum leptin and resistin levels and clinical characteristics were analyzed in patients with different clinical forms of OA. Novel clinical correlations have been found in the current study in patients with isolated knee OA vs. cases with presence of other disease localizations. It has been observed that patients with isolated knee OA were significantly younger and had higher BMI as compared with cases in whom OA is combined with other localizations i.e., spondyloarthritis ± presence of hip OA and with generalized OA. This supports the hypothesis that presence of obesity promotes earlier development of knee OA as an isolated localization of the disease in younger patients before appearance of osteoarthritic changes at other sites. The levels of leptin and resistin in isolated knee OA were also higher. Serum levels of leptin and resistin in combination with patients’ clinical characteristics suggest existence of different clinical and laboratory profile through which more precise definition of metabolic phenotype of knee OA would be possible. Considering the fact that obesity is a modifiable risk factor that has an impact on progression of knee OA, different approaches to influence obesity may offer potential for future disease-modifying therapeutic interventions.

Effect of short-term high fat diet on resistin levels and expression of autophagy-related genes in the cartilage of male rats

“…Regardless of the fact that there is a well-established link between obesity and OA, the underlying mechanisms are still poorly understood. In recent years, the involvement of adipokines in the development of OA pathogenesis has gained increasing attention, and it is suggested to be crucial mediators linking obesity to chronic, low-grade inflammation and joint damage 33 .…”

Knee Osteoarthritis—How Close Are We to Disease-Modifying Treatment: Emphasis on Metabolic Type Knee Osteoarthritis

“…Interestingly, serum leptin levels were correlated with the radiological stage of the disease, i.e., higher levels were present in cases with more advanced structural changes (radiological stages of III and IV). Novel clinical correlations were observed in patients with isolated knee OA who were significantly younger and had higher BMI compared to the patients who had also OA with other localization (spondylarthritis, hip OA, and generalized OA) [ 13 ]. Although the age above 50 years is an established classification criterion for knee OA, recent studies report an increase in the incidence of the disease in patients below 40 years [ 14 ].…”

“…Consequently, metabolic knee OA is emerging as a distinct clinical phenotype that may be considered as an additional musculoskeletal component of metabolic syndrome. It is thought to occur earlier in younger patients with obesity and is associated with increased adipokine levels [ 13 ].…”

Leptin in Osteoarthritis and Rheumatoid Arthritis: Player or Bystander?

“…Moreover, leptin levels correlated with WOMAC-pain score and radiographic stage of knee OA where high levels were observed in more advanced stages of the disease. This indicates that leptin promotes OA progression [ 50 ].…”

“…Accordingly, leptin amounts were significantly higher only in knee OA obese patients (with BMI > 30) as compared with the control group. Obesity, in association with high levels of adipokines (leptin and resistin), was reported to promote earlier development of knee OA in younger patients [ 50 ].…”