In the present study, we developed and internally validated a model for predicting the 4-year risk of systematic KOA among the Chinese population, based on data from the CHARLS cohort. We also developed an easy-to-use clinical score model to identify individuals at the greatest risk of developing KOA. The final prediction model included ten convenient and accessible variables: age, sex, waist circumference, residential area, ADL/IADL difficulty, history of hip fracture, depressive symptoms, number of chronic comorbidities, self-reported health status, and level of MPA. Among these variables, age, sex, and waist circumference are the factors most commonly included in previous models for predicting KOA risk, while the others have been controversial or have not been considered in relation to KOA risk. To our knowledge, ours is the first model for predicting KOA risk in China, and our results suggest that this model can be used to aid in the prevention of KOA, thereby helping to reduce disease burden.
While older age was identified as a risk factor for KOA in our study, the most significant increase in risk was observed in the 60–69 years group. As estimated, the cumulative incidence of systematic KOA gradually increased beginning at 45 years of age, increasing rapidly after 55 years of age. The peak rate of increase was observed at approximately 65 years of age. However, after 70 years of age, increases in the cumulative incidence of KOA were no longer significant [34]. When taken with the results of previous studies, our findings highlight the need to prevent the incident of KOA in individuals from 45 to 70 years of age. Consistent with the results of previous studies[18, 19], female sex was also identified as a significant risk factor for the incident of KOA: after adjustment for other factors, the risk of developing KOA was 33% higher in women than in men.
Overweight/obesity increases the risk of KOA, in part because obesity creates an abnormal loading environment for weight-bearing joints. Obesity may also contribute to the pathogenesis of KOA by promoting chronic low-grade systemic inflammation or inducing mechanical damage to joint tissues, which in turn may lead to local inflammation. Together, these factors may weaken and degrade joint tissues [35]. Alternatively, the increased risk of KOA may be caused by the positive energy balance and metaflammation associated with obesity [36]. Metabolic syndrome has also been associated with the incident and progression of KOA [36]. Although BMI has been illustrated as an important predictor of KOA [37], Wallace et al. [35] reported that increased abdomen size is associated with a greater risk of radiographic KOA than high BMI. Further studies are required to determine whether BMI or waist circumference comprehensively influences KOA risk due to mechaflammation and metaflammation. In the present study, we separately analyzed the effect of BMI, waist circumference, and metabolic syndrome on KOA incident in the Chinese population using univariate logistic regression analyses. However, none of these three factors was identified as a significant predictor of KOA incident. While similar insignificance also been reported for other ethnic groups [38], additional studies are required to verify this lack of significance in the Chinese population.
Our findings also indicated that depressive symptoms are a significant predictor of KOA risk. Patients with mild or moderate-to-severe depression were two or three times more likely to develop KOA than those without depression, respectively. Previous studies [39, 40] have revealed that KOA and other chronic diseases increase the odds of depression due to long-term treatment, chronic pain, or high treatment costs. Indeed, the pooled prevalence of depressive symptoms in patients with osteoarthritis has been reported as 19.9% [39]. Xu et al. demonstrated that depression, hypertension, diabetes, arthritis, asthma, and osteoarthritis are prone to be comorbid with other conditions [41]. In patients without any comorbidities at baseline, the risk of KOA remained higher in patients with depressive symptoms than in those without depressive symptoms. Adjusted ORs were 1.84 (95% CI: 1.39–2.43) and 3.29 (95% CI: 1.50–7.18) in patients with mild or moderate-to-severe depressive symptoms, respectively. Seavey et al. indicated that depressive symptoms represented a risk factor for arthritis incident based on data obtained from a 20-year longitudinal cohort study (OR: 1.72, 95% CI: 1.27–2.35) [28]. Jinks et al. also reported that depression was a significant predictor of knee pain (OR: 1.4, 95% CI: 1.1–1.8) while pain is the dominant physical symptom among patients with systematic KOA [42]. Although a bidirectional causal association has rarely been illustrated either between arthritis and depression or any other chronic disease and depression, depressive symptoms may be a significant risk factor for KOA. Targeted strategies for addressing depressive symptoms may therefore aid in reducing the s incidence of KOA.
As patients with chronic diseases often exhibit comorbidities that interact with the disease in complex ways [41], we assessed relationships for 12 main types of comorbidities. The risk of developing KOA was 24% higher in patients with one or two comorbidities than in those without comorbidities. However, the risk of KOA increased by 54% in patients with three or more comorbidities. KOA and some comorbidities may accelerate the progression of one another [18], and comorbidities have been shown to predict worse pain and deteriorating physical function in patients with KOA [43]. The present study considered the effect of comorbidities when developing a prediction model for KOA in the Chinese population. Further studies including patients of different ethnic groups are required to determine whether this model can be applied more broadly.
Although physical activity is a modifiable risk factor for KOA, the reported associations between physical activity and outcomes have been inconsistent. In the present study, we observed no significant association between VPA/LPA and the incident of KOA; however, MPA positively predicted the incident of KOA. After adjustment for other factors, the risk of developing KOA was 30% greater in individuals engaging in all levels of MPA (low, middle, high) than in those engaging in no MPA. Notably, a previous study also reported that walking and other recreational activities did not increase the risk of OA in older adults [22]. Results from the Chingford cohort demonstrated that physical activity related to work (OR: 1.48, 95% CI: 0.34–5.64) and sports (OR: 1.23, 95% CI: 0.54–2.81) increases the risk of osteophytes, while physical activities such as walking decrease the risk of osteophytes (OR: 0.60, 95% CI: 0.22–1.71) in middle-aged women [44]. However, additional studies are required to verify these effects given that the differences were not statistically significant. Findings from the Framingham Heart Study [45] indicate that long hours of heavy habitual physical activity per day are associated with an increased risk of KOA (OR: 1.3 per hour), with stronger effects occurring when strenuous physical activity is performed for more than 3 h per day (OR: 2.9, 95% CI: 1.2–6.9 for radiographic KOA and OR: 5.3, 95% CI: 1.2–24 for systematic KOA). In their study, the effects of MPA and LPA were insignificant. This discrepancy between our findings and previous results may be due in part to differences in the method of assessing physical activity levels or differences in the characteristics of the population. Given these differences, additional studies should aim to verify the influence of different types of physical activity on the risk of KOA. Such studies should seek to determine the most appropriate type, duration, frequency, and intensity of physical activity for preventing KOA in different populations.
Assessments of difficulty in performing ADLs or IADLs may aid in the prediction of KOA incident. In the present study, the risk of developing KOA was 49.0% greater in individuals with ADL/IADL difficulty than in those without difficulty. Impairments in ADLs prior to KOA onset may represent a predictive signal for KOA. Hence, preventive interventions may be useful in reducing the incident of KOA in those who have difficulty with ADL/IADL.
Our prediction model for KOA included one patient-reported outcome (PRO): self-rated health status. Numerous previous studies have focused on PROs, which may capture important disease-related information prior to the onset of clinical signs or pathophysiological changes [46]. Although Silverwood et al. noted that poor self-rated health status was a potential risk factor for KOA, no significant associations were observed [18]. In the present study, the odds of developing KOA increased as health status worsened. Compared to participants who rated their health status as “very good”, those who rated their health status as “fair” exhibited a 21% increase in the risk of KOA, while those who rated their health status as “poor” or “very poor” exhibited a 199% and 267% increase in the risk of KOA, respectively. Self-ratings of health status comprehensively reflect one’s physical and psychological function, as well as one’s knowledge and ability to cope with diseases and self-efficiency. Although previous researchers have identified several potential risk factors, most of these factors were pooled from epidemiological analyses or clinical experience. Our findings highlight the need to consider the patient’s perspective, as this may aid in furthering our understanding of KOA while reducing the incidence of the disease.
Given that the knee and hip joints are the two most important weight-bearing joints, we sought to determine whether a history of hip fracture increases the risk of developing KOA. Our findings indicated that a history of hip fracture was associated with a 53% increase in the risk of KOA. Related studies [47, 48] have demonstrated that rheumatoid arthritis increases the risk of hip fracture due to bone loss induced by chronic inflammation, use of glucocorticoids, and physical inactivity. However, studies reporting an association between hip fracture and KOA incidence are rare. Further studies are therefore required to determine whether hip fracture can be used to predict KOA risk, and to identify the potential mechanisms underlying this association.
In our study, the 4-year cumulative incidence of KOA in rural and urban areas was 10.9% and 8.1%, respectively. Residents of rural areas exhibited a 24% increase in the risk of developing KOA when compared with residents of urban areas, after controlling for other factors. Several previous studies have noted that symptomatic KOA is more common in rural residents of China than in urban residents [30, 49]. Limited access to knowledge regarding the prevention of KOA and other chronic diseases, a lack of economic resources for timely treatment of chronic diseases, poor ability to manage one’s health, and earlier impairments in physical function due to strenuous farm work may explain the increased risk of KOA in rural residents. These results suggest that policies and resources should be directed toward preventing KOA among residents of rural areas in China.
The present study possesses several limitations of note. First, although we used the imputation method to handle missing data and a bootstrap strategy to limit the influence of bias, incomplete data may still have biased our findings. Second, to efficiently predict the risk of KOA, we considered some new variables as predictors in our model. Though they were significantly associated with the incident of KOA, further studies are required to elucidate the mechanisms underlying these associations. Lastly, although we used a nationally representative cohort to develop the prediction model, the model was internally validated. Therefore, external validation in other Chinese populations and different ethnic groups remains necessary.