The Association between BMI and Osteoarthritis in Adults

Objectives: The prevalence of obesity-related symptomatic OA has been found to increase. We investigated the relationship between BMI and osteoarthritis in 14,058 20-85 year-old participants from the National Health and Nutrition Examination Survey (NHANES). Methods: To estimate the association between BMI and osteoarthritis, multivariate logistic regression analyses were conducted. Fitted smoothing curves. Results: After adjusting for other confounding factors, we found that BMI was positively correlated with osteoarthritis. On subgroup analyses, stratified by sex and race/ethnicity, the positive correlation between BMI and Osteoarthritis in men and women, as well as in whites, blacks, and Mexican Americans, still exists. Conclusions: Our study revealed a positive relationship between BMI and Osteoarthritis in most adults.


Introduction
Osteoarthritis (OA) is the most common type of joint disease and the main cause of pain, restricted mobility, and decreased function, especially in the elderly. It is estimated that approximately 25% of people older than 55 have persistent knee pain, and 10% of them report painful disabling knee OA [1]. The development of OA is related to genetics, age, gender, obesity, previous knee injuries, occupational factors (for example, kneeling and squatting), physical activity, and knee dislocation [2].
Obesity is one of the biggest health risks facing the world today. In recent decades, the worldwide prevalence of obesity has been increasing at an alarming rate, and the tendency to be accompanied by multiple comorbidities is also increasing. In addition, people in developed countries live longer [3]. As obesity gradually increases in the elderly, it is expected that the prevalence of obesity-related symptomatic knee OA will increase, and it may become a major global public health problem.
Worldwide, with the increase in life expectancy, the prevention and treatment of osteoarthritis have become two increasingly important public health issues, which means that there is an urgent need to find more effective methods to reduce the related economic burden [4]. Here, we conducted a cross-sectional study using a large database from the National Health and Nutrition Examination Survey (NHANES) to estimate the association between BMI and osteoarthritis in adults.

Statement of Ethics
The study was approved by the Ethical Review Committee of the National Center for Health Statistics and received written informed consent from each participant, and was per-formed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments and comparable ethical standards.

Study Population
NHANES is a representative survey of the national population of the United States (US), using a complex, multi-stage, probability sampling design to provide a large amount of information about the nutrition and health of the general population of the United States[5].
All data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2006. NHANES was a cross-sectional study of noninstitutionalized US citizens and was conducted by the Centers for Disease Control and Prevention (CDC) and the National Center for Health Statistics (NCHS). NHANES database included personal data including demographic information, past medical history and laboratory data. The participants' information was collected by a household interview and a subsequent physical examination. All of the study protocol, consent documents and relevant information were detailed on the NHANES website. The NHANES study protocol was conducted according to the NCHS Institutional Review Board (IRB). Before data collection and the health examinations, all informed consents had been obtained. All the experimental protocols were approved by NCHS IRB.
Our analysis is based on 1999-2006 data, which represents the three cycles of NHANES. Excluding participants with missing BMI data (n = 6366), osteoarthritis data (n = 19957), cancer participants (n = 1093), a total of 14,058 participants aged 20-85 were included in our analysis.

Variables
The exposure variable of this study is BMI. Weight and height are measured using standardized procedures[6].
The outcome variable is osteoarthritis. As part of the NHANES project, the diagnosis of arthritis is based on a medical condition questionnaire collected through interviews. The following categorical variables are included as covariates in our analysis: gender, race/ethnicity, ethnicity, education level, smoking history, ratio of household income to poverty, vigorous recreational activities, drinking, high blood pressure, diabetes, waist circumference.
Detailed information about BMI, osteoarthritis, and covariates are publicly available at http://www.cdc.gov/nchs/nhanes/. All measurements were standardized according to the guidelines that were recommended by the Centers for Disease Control and Prevention (CDC).

Statistical Analysis
All estimates are calculated based on NHANES sample weights. After adjusting for potential confounding factors, weighted multiple regression analysis was used to estimate the independent relationship between BMI and osteoarthritis.
The weighted generalized additive model and smooth curve fitting were used to solve the nonlinear problems of BMI and osteoarthritis in subgroup analysis.

Research ethics
NHANES study protocols were approved by the research ethics review board of the National Center for Health Statistics. Methods were carried out following the STROBE statement. Written informed consents were obtained from all participants in the study , and was per-formed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments and comparable ethical standards.

Study sample
The characteristics of the samples are shown in were also significantly different between the two groups (P <0.05).

Multiple regression model
The results of the multivariate regression analyses are presented in Table 2.The influence of the correlation between BMI and osteoarthritis is listed in the trend test between them is still significant (P = 0.0061).

Subgroup analyses
In the subgroup analysis stratified by gender and race/ethnicity, as shown in Table 3 We also performed a weighted generalized additive model and smooth curve fitting to evaluate the association between them (Figures 2, 3).

Discussion
In this study, we used these representative samples from NHANES 2001-2006 to assess the association between BMI and osteoarthritis in adults. The results showed that BMI was positively correlated with osteoarthritis.
Obesity is one of the most important modifiable risk factors for the occurrence[7-12] and progression[7, 12-14] of knee OA. Some people believe that being overweight will increase the mechanical load on the joints, leading to increased cartilage degradation and subsequent failure of the entire joint [15]. There is evidence that excessive weight may reduce the biomechanical load placed on weight-bearing joints. Obesity may also cause metabolic dysfunction and joint damage by stimulating the known metabolic homeostasis regulator adipokines, which is reasonable [16,17]. This may partly explain the different association between obesity and the incidence of OA in  Figure 1) In summary, obesity is a common risk factor associated with many diseases, including knee OA. Although effective modification is challenging, it is one of the few risk factors that can be modified. The benefits of preventing obesity in the general population are huge, especially in the Western world where obesity is very common. For example, if this risk factor is eliminated, approximately half of symptomatic knee OA will be prevented in the United States.
On the other hand, osteoarthritis (OA) is a degenerative disease of the joints that occurs when the cartilage or cushion between the joints ruptures causing pain, swelling, and stiffness. OA is the most common chronic joint disease, affecting more than 30 million American adults. Some risk factors include joint damage or overuse, gender, age, obesity, race, and genetics (CDC, 2017). It is very common among the elderly. Symptoms include pain, swelling, and stiffness. This study includes a representative sample of a multi-ethnic population to better generalize the American population, and this large sample size allows us to conduct further subgroup analysis. This is the biggest advantage of this research. There are some restrictions. First, due to the nature of the cross-sectional study, we cannot determine whether BMI affects the changes in osteoarthritis over time, and cannot assess causality.
Secondly, we excluded participants with cancer or malignant tumors, because these special populations have a great influence on BMI and osteoarthritis. Therefore, the conclusions in this study cannot be applied to them.
Third, we did not adjust other variables. Therefore, the bias caused by other potential confounding factors cannot be ruled out. between the variables. The blue bar represents the 95% confidence interval of the fit. The age, gender, race, education level, smoking history, ratio of family income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, and waist circumference were adjusted.

Figure 2
The association between Body mass index and osteoarthritis stratified by sex. Age, race, education level, smoking history, ratio of household income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, waist circumferencewere adjusted.

Figure 3
The association between Body mass index and osteoarthritis stratified by race/ethnicity. Age, gender, education level, smoking history, ratio of household income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, waist circumference were adjusted. Figure 1 The association between BMI and osteoarthritis. The solid arc line represents a smooth curve t between the variables. The blue bar represents the 95% con dence interval of the t. The age, gender, race, education level, smoking history, ratio of family income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, and waist circumference were adjusted.

Figure 2
The association between Body mass index and osteoarthritis strati ed by sex. Age, race, education level, smoking history, ratio of household income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, waist circumferencewere adjusted.

Figure 3
The association between Body mass index and osteoarthritis strati ed by race/ethnicity. Age, gender, education level, smoking history, ratio of household income to poverty, strenuous recreational activities, drinking, high blood pressure, diabetes, waist circumference were adjusted.

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download. Table1.pdf Table2.pdf Table3.pdf