|DAI, ZHAOLI - Boston University|
|JAFARZADEH, S. REZA - Boston University|
|NIU, JINGBO - Boston University|
|FELSON, DAVID - Boston University|
|JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|LI, SHANSHAN - Boston University|
|ZHANG, YUQING - Boston University|
Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/21/2018
Publication Date: 12/10/2018
Citation: Dai, Z., Jafarzadeh, S., Niu, J., Felson, D.T., Jacques, P.F., Li, S., Zhang, Y. 2018. Body mass index mediates the association between dietary fiber and symptomatic knee osteoarthritis in the Osteoarthritis Initiative and the Framingham Osteoarthritis Study. Journal of Nutrition. 148:1961-1967. https://doi.org/10.1093/jn/nxy231.
Interpretive Summary: Obesity is a major cause of osteoarthritis in the knee, with overweight and obesity increasing the risk of knee osteoarthritis (OA) by 2 to 4 fold. Obesity increases the loading across the knee as well as systemic inflammation as measured by C-reactive protein (CRP), which may also accelerate knee OA development and increase the risk of joint pain. There are currently very few safe and effective treatments available for knee OA, but dietary modification may offer a safe and effective prevention strategy. We recently reported that high intake of dietary fiber was associated with a lower risk of incident symptomatic knee OA. Because dietary fiber has previously been shown to help reduce body weight and lessen systemic inflammation reflected by CRP levels, we speculated that the protective association between fiber and knee OA was mediated, at least in part, through fiber's effect on BMI and inflammation. In this study, we conducted mediation analyses to quantify the extent to which the reduction in symptomatic knee OA from dietary fiber could be explained by the association of fiber with BMI and CRP. Identifying the causal pathway for the association of fiber intake with knee OA may inform a prevention strategy for this common disabling disease. We used longitudinal data from the Osteoarthritis Initiative (OAI) and the Framingham Offspring Osteoarthritis Study (FOS). In the OAI study, men and women (mean age 61 y) with or at risk of knee OA at baseline were followed for 48 months. Adults (mean age 53 y) were followed for 9.5 years in FOS. Dietary fiber intake was estimated using a validated food frequency questionnaire. Serum high sensitive CRP was measured in FOS only. Incident symptomatic knee OA was defined as new onset of a combination of knee pain and radiographic OA. We applied marginal structural statistical models to quantify the mediating effect of through BMI in OAI and the sequential mediating effects through BMI and CRP in FOS. New knee OA occurred in 1004 knees among 3847 persons in the two cohorts. We observed evidence of a modest indirect mediation effect by BMI, but not CRP, for new knee OA with consumption of at least 21 g/d compared with intakes below 21 g/d. Our findings suggest that the inverse association of fiber intake and the risk of incident symptomatic knee OA is partially due to the effect of higher dietary fiber consumption on lower BMI levels.
Technical Abstract: Background: Dietary fiber reduces body weight and inflammation in clinical trials. It is unclear whether body mass index (BMI) and inflammation might explain the observed association between higher fiber intake and the lower risk of symptomatic knee osteoarthritis (SXKOA). Objectives: We quantified the extent to which BMI and inflammation influenced the relation between dietary fiber and SXKOA. Methods: We used longitudinal data from the Osteoarthritis Initiative (OAI) and the Framingham Offspring Osteoarthritis Study. At baseline of each study, men and women (mean age: 61 y) with or at risk of knee osteoarthritis were followed for 48 mo in the OAI. Adults (mean age: 53 y) were followed for 9.5 y in the Framingham study. Dietary fiber intake was estimated using a validated food-frequency questionnaire. Measured weight and height were used to calculate BMI. Serum high-sensitivity C-reactive protein (CRP) was measured in the Framingham study only. Incident SXKOA was defined as new onset of a combination of knee pain and radiographic osteoarthritis. We applied marginal structural models to quantify the mediation through BMI in the OAI and the sequential mediation through BMI and CRP in the Framingham study. Results: Incident SXKOA occurred in 861 knees among 2876 persons in the OAI and in 143 knees among 971 persons in the Framingham study. In persons whose fiber intake was >/= 21 g/d compared with those with intakes <21 g/d, the OR (95% CI) was 0.70 (0.53, 0.91) for the overall association with SXKOA and was 0.93 (0.92, 0.95) for the mediation via BMI (per kg/m^2) in the OAI. In the Framingham study, the overall association was 0.57 (0.30, 1.09), the mediation through BMI (via BMI and the influence of BMI on CRP) was 0.94 (0.85, 1.02), and the mediation through CRP (per milligram per liter) was 0.99 (0.84, 1.19). Conclusion: Our findings suggest that the inverse association of fiber intake and the risk of incident symptomatic knee osteoarthritis is partially mediated by BMI.