Effects of prebiotics and exercise on the progression of osteoarthritis in a rat-model of metabolic disturbance

Abstract

Purpose: While there is evidence that early exercise and prebiotic fibre supplementation can prevent the development of osteoarthritis (OA) in a rat-model of diet-induced metabolic disturbance, it remains unknown if these interventions remain successful in preventing or slowing the progression of OA when started at time points after the introduction of the high-fat/high-sucrose (HFS) diet, and once knee OA-like damage has been established to a certain degree. Therefore, the purpose of this study was to determine the effects of prebiotic fibre supplementation, aerobic exercise, and the combination of prebiotic fibre and aerobic exercise on the progression of knee OA-like damage in a HFS diet-induced rat-model of metabolic disturbance. Methods: Twelve-week-old male CD-Sprague-Dawley rats were either fed a standard chow diet, or a HFS diet. After 12 weeks on diets, rats consuming the HFS diet were randomized into four sub-groups: a sedentary, an aerobic exercise, a prebiotic fibre supplementation, and an aerobic exercise combined with prebiotic fibre supplementation group. The aerobic exercise intervention consisted of a progressive treadmill-training program for 12 weeks, while the prebiotic fibre was used to supplement the HFS diet at a dose of 10% in weight for 12 weeks. The primary outcome measures included knee joint damage, that was evaluated at the end of the experimental protocol using a combination of a modified Makin and OARSI score, that we called the Total Modified Mankin Score; while the secondary outcome measures included markers of metabolic syndrome, such as insulin sensitivity, and serum lipid profiles, that were measured at baseline, week 12 and week 24 of the experiment protocol. Non-parametric Kruskal-Wallis testing with pairwise comparisons was used to determine differences between the five animal groups for all variables. We further investigated differences between time-points within groups using Friedman’s test with pairwise comparisons for insulin sensitivity and serum lipid profiles. Results: There were no differences between groups for the Total Modified Mankin Score (Figure 1). Overall, rats in the exercise, and combined prebiotic fibre/exercise groups had a better metabolic profile at week 24 than the HFS group rats. However, metabolic markers did not return to their baseline values in the intervention groups, suggesting that these rats still had some degree of metabolic disturbance. Interestingly, 36-week-old rats fed a chow diet displayed signs of metabolic disturbance, exhibiting decreased insulin sensitivity and increased non-HDL cholesterol levels compared to when they were 24 weeks old. Triglyceride levels in 36-week-old chow fed rats are similar to those of 24-week-old HFS fed rats. Additionally, the age-matched (36 weeks) chow fed rats had similar joint damage scores as the HFS fed rats. Conclusions: Prebiotic fibre supplementation, aerobic exercise, or the combination of the two interventions, did neither slow nor accelerate the progression of pre-existing knee osteoarthritis-like damage, but improved selected markers of metabolic disturbance, suggesting that these interventions may be safe strategies for populations with metabolic knee osteoarthritis who want to use exercise or prebiotics to alleviate other health related problems, such as diabetes or cardiovascular problems. However, caution should be exercised when interpreting results from this study, due to the joint damage and metabolic disturbance observed in the chow-fed rats.