This study investigated the temporal relationships between demographic and OA clinical factors, joint symptoms and depression in patients with symptomatic knee OA. Depression was common in this population with a prevalence of 25.4% and incidence of 11.2% over 24 months. Common OA risk factors such as higher BMI, lower education level and having two or more comorbidities were associated with prevalent depression and being female was associated with incident depression in knee OA patients. Higher levels of knee pain and physical dysfunction and having multi-site pain were associated with increased risks of both prevalent and incident depression. In contrast, baseline depression severity did not predict changes in OA symptoms. These findings provide empirical evidence that management of common OA risk factors, chronic pain and joint dysfunction may be beneficial for preventing and managing depression in knee OA patients.
Numerous studies have explored the demographic factors associated with depression in elderly populations. Female sex, lower education levels and the biological risks including endocrine and inflammatory factors are potential risk factors for depression in the elderly24. However, only a few studies have been conducted in individuals with OA, and most did not assess longitudinal relationships. A cross-sectional study reported that fewer social contacts, increased BMI, perceived pain and limited physical activity were associated with depression severity in 1021 patients with knee OA13. In our current study, we reported similar results and reported that, cross-sectionally, higher BMI, lower education level and having two or more comorbidities were associated with prevalent depression.
Obesity, female sex and a lower education level are known as risk factors for both OA and depression. Therefore, the high prevalence depression in OA individuals may be in part attributed to shared risk factors. Taking higher BMI for example, higher BMI, indicating overweight or obesity, is a well-known risk factor of OA and also can increase vulenrability to depression directly and indirectly through complex mechanisms25 26. Obesity causes a high prevalence of OA, which may be related to combined effects from biomechanical, inflammatory and metabolic factors. In addition, obesity can induce poor self-image, low self-esteem and social isolation, which are well-known contributors to depression. It also can activate inflammatory pathways, involving hypothamlamic-pituitary-adrenal axis dysreuglation, which are associated with increased risk of depression through biological and psychological pathways25. Obesity and lower levels of education are modifiable factors; therefore, management of obesity and improvement of education level may prevent depression and should have beneficial effects in patients with knee OA. Additionally, female sex predicted incident depression over 24 months in knee OA patients. Hence, it is important for clinicians to screen for, and try to prevent and treat depression, especially in female patients with knee OA.
Joint pain and dysfunction, multisite pain and comorbidities are clinical characteristics of OA. Multisite pain, joint pain and joint function limitation are common in musculoskeletal conditions, and have been linked to depression in previous studies27. Individuals who experienced chronic pain and physical activity limitation are at an increased risk of depression28 29. In OA patients, joint pain severity and dsyfunction were associated with depression severity cross-sectionally and longitudinally30–35. Knee OA patients with greater pain associated with higher risk of depression at baseline and slow gait speed may represent an important risk factor for worsening depressive symptoms over time33 35. In our study, although we used a different method to assess depression severity, we found similar results. Individuals who experienced multi-site pain, more severe knee pain and joint dysfunction, and had more than one comorbidity were at a higher risk of prevalent depression cross-sectionally in knee OA patients. Over 24 months, multi-site pain, knee pain and dysfunction were associated with increased incidence of depression over 24 months, suggesting a potentially causal relationship. These supported the notion that management of pain, joint dysfunction and other comorbidities may help to improve depression in knee OA patients15 36.
Depression severity is dynamic, changing over time, and prior depressive illness modifies the experience of currently depressed mood37. The reciprocal relationship between depression severity and pain severity has been well established, but whether current depression severity has causal effects on severity of joint symptoms overtime has been rarely investigated14 16. Kurt et al have reported that change in pain severity over 3 months predicted subsequent depression severity, and vice versa, change in depression severity over 3 months predicted subsequent pain severity over 12 months in patients with persistent back, hip and knee pain14. In knee OA patient, we only found higher levels of knee joint symptoms and having multi-site pain at baseline were associated with increased risks of both prevalent and incident depression, while baseline depression severity did not predict knee joint symptomatic progression over two years. There was one study have explored the causal cumulative effect between depressive symptoms and knee pain among patients with knee radiographic OA. Rathbun reported the causal effect of pain severity significantly increases with the persistence of depressed mood, but depressive symptoms on OA knee pain does not change over time, which was smiliar with this current study16. Our findings suggest the potentially cause-effect relationship is from knee joint pain and physical dysfunction to depression, rather than from depression to knee symptoms, in patients with knee OA.
This study has some potential limitations. It was a post-hoc analysis of a randomized controlled trial which was primarily designed to examine vitamin D supplementation on knee OA outcomes. Nevertheless, the findings from this study were plausible as we found that vitamin D supplementation reduced visual analog scale knee pain, improved physical function and decreased depessive symptoms38 39. The effects on depressive symptoms may be mediated through the effects on knee pain and physical function. In addition, 18% participants did not complete the 24 months follow-up, and loss of follow-up bias may be present; however, the retention rate in this trial was high, and there were no significant differences in the baseline characteristics between those who completed and who did not complete the trial. This suggests a minimal loss of follow-up bias in our study. Furthermore, we defined depression using the patient health questionnaire, which was developed for depression diagnostic, severity measures and assessment of depression outcome changes over time. It may lead to misclassification of depression; however, when we used the self-reported depression as the outcome or exposure and anti-depressant medication as a covariate and the results were largely unchanged.