Association between metabolic syndrome and knee osteoarthritis: a cross-sectional study

This observational study was conducted in the Department of Health Examination Center Xiangya Hospital, Central South University in Changsha, Hunan Province, China. It was approved by the ethics committee at Xiangya Hospital, Central South University. Also, written informed consent was obtained from the participants in our study. The study design has been published in peer-reviewed journals [20‐22]. Besides, some part of the detailed methodology, including study population, assessment of radiographic knee OA, blood biochemical analyses and assessment of other exposures, in the present study were also described in our previously published work [23‐25]. In order to collect information on demographic characteristics and health-related habits, a standardized questionnaire was used by registered nurses to interview all participants during the examination. As previously described [24], participants were selected according to the following inclusion criteria: 1) ≥ 40 years old; 2) undergone weight-bearing bilateral anteroposterior radiography of the knee; 3) availability of all basic characteristics, including age, gender, body mass index (BMI), blood pressure etc.; 4) availability of biochemical test results; 5) availability of information related to the living habits, including education background, activity level, smoking, drinking and medication status. At the beginning, 13,631 subjects were undergone routine checkups including knee radiography at the Department of Health Examination Center Xiangya Hospital, Central South University in Changsha, Hunan Province, China, from October 2013 to November 2014. Finally, 5764 participants were included in the present study (132 diagnosed with other joint diseases based on radiographic evidence, such as osteochondroma or other bone tumors; 191 participants were not available of biochemical test results; 440 participants were not available of basic characteristics; 1207 participants were younger than 40 years old; 5897 did not offer the information of living habits).

As described in our previous work [21], all subjects included in the present cross-sectional study had undergone weight-bearing bilateral anteroposterior radiography of the knee. Two orthopedists, blinded to subjects’ basic information, assessed the radiographs independently by using the Kellgren-Lawrence (K-L) radiographic atlas. Inconsistent opinions were resolved through discussions. The weighted kappa coefficient for knee x-Ray scoring was 0.85 for inter-reader reliability and 0.86 for intra-reader reliability. The severity of OA was classified into five grades according to the K-L atlas: 0 = absence of OA; 1 = suspected OA; 2 = minimal OA; 3 = moderate OA; 4 = severe OA [26]. A participant would be considered as radiographic knee OA if at least one of his/her knee joint was graded K-L 2 or above, however, pain was not taken into account and symptomatic knee OA was not diagnosed in the present study. In addition, JSN and OSP were assessed individually based on a scale of 0–3 (0 = normal; 3 = most severe) according to the Osteoarthritis Research Society International (OARSI) atlas [27].

MetS was diagnosed according to the Chinese Diabetes Society (CDS) criteria [28‐30]. CDS criteria for MetS requires 3 items or all of the four items: (1) BMI ≥ 25 kg/m²; (2) Fasting plasma glucose (FPG) ≥ 6.1 mmol/L, or treatment of diagnosed diabetes; (3) Systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg, or treatment of previously diagnosed hypertension; (4) Triglycerides ≥1.7 mmol/L and/or HDL-cholesterol <0.9 mmol/L in male or <1.0 mmol/L in female, or treatment for this lipid abnormality. Besides, the NCEP-ATPIII (Asian revised version) criteria [31, 32] was also used to assess MetS and it was based on presence of at least three of following risk factors: waist circumference ≥ 90 cm in men and ≥80 cm in women; triglycerides ≥150 mg/dL (1.7 mmol/L); HDL cholesterol <40 mg/dL (1.03 mmol/L) in men and <50 mg/dL (1.29 mmol/L) in women; systolic BP ≥ 130 mmHg, diastolic BP ≥ 85 mmHg, or currently using antihypertensive medication; and FPG ≥ 100 mg/dL (5.6 mmol/L) or currently undergone drug treatment for blood glucose control.

All blood samples were drawn after a 12-h overnight fast and were kept at 4 °C until analysis. The fasting blood glucose concentration and blood lipid assessment were performed using a Beckman Coulter AU 5800 (Beckman Coulter Inc., Brea, CA, USA). The high sensitivity C reactive protein (hsCRP) was measured by Latex turbidity method. The inter- and intra-assay coefficients of variation were tested by low concentrations (2.5 mmol/L for glucose) and high concentrations (6.7 mmol/L for glucose) of standard human samples. The intra-assay coefficients of variation were 0.98% (2.5 mmol/L) and 1.72% (6.7 mmol/L) for glucose. The inter-assay coefficients of variation were 2.45% (2.5 mmol/L) and 1.46% (6.7 mmol/L) for glucose.

Assessment of other exposures was also described in our previous work [21]. Specifically, blood pressure of each participant was measured using an electronic sphygmomanometer. The weight and height of each participant was measured respectively to calculate the BMI. Participants were also asked about their average frequency of physical activity (never, one to two times per week, three to four times per week, five times and above per week) and average duration of physical activity (within half an hour, half an hour to one hour, one to two hours, more than two hours) through a standard questionaire. The smoking and alcohol drinking status were asked face to face.

The continuous data are expressed as mean ± standard deviation, and the category data are expressed in percentage. Differences in continuous data were evaluated by Mann-Whitney U test, while differences in category data were assessed by the χ² test.

Associations between knee OA with MetS and MetS components in the present cross-sectional study were evaluated by conducting age-sex adjusted and multivariable adjusted logistic regression. The following confounding factors were considered to be included in the multivariable model: age, sex, activity level, smoking status, alcohol drinking status and educational background [33‐35]. Sensitivity analysis was conducted through adding hsCRP into the multivariable model. Associations between MetS with JSN and OSP were also assessed by multivariable adjusted logistic regression. We also assessed the association between OA and the number of MetS components through multivariable adjusted logistic regression. Moreover, the association between MetS diagnosed according to the NCEP-ATPIII (Asian revised version) criteria was examined. Crude OR, age-sex-BMI adjusted OR and multivariable (BMI, age, sex, activity level, smoking status, alcohol drinking status and educational background) adjusted OR and their related 95%CI were calculated for evaluating the associations. Besides, the association between MetS and radiographic severity of knee OA was also examined.