The role of nutrition for early knee osteoarthritis : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Human Nutrition, Massey University, Albany, New Zealand
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2023
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Massey University
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Abstract
Background:
Osteoarthritis (OA) is a complex disease of the joints resulting in inflammation and degradation of all joint tissues. OA is a major cause of disability worldwide and its prevalence globally is rising. There is no cure for OA and at present no wholly effective treatments. Nutritional interventions have been shown to have efficacy in helping relieve signs and symptoms of the disease. Previous research suggests GreenShell™ mussels (GSM) may have cartilage sparing and anti-inflammatory properties and therefore warrants further investigation of its ability as an OA therapeutic.
Aims and Objectives:
The primary aim of this research was to investigate the effects of GSM consumption on signs and symptoms of knee OA through a randomised placebo-controlled trial. Secondary to this, the research examined associations between inflammatory marker concentrations and subjective measures of OA and how these relate to inflammatory status of the diet. Further, the research looked at the associations between subjective and objective measures of OA and whether a cut-off score for OA on the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire could be established.
Methods/Design:
Data was collected from the REACH (Researching Eating, Activity, and Cognitive Health), and the ROAM (Researching Osteoarthritis and GreenShell Mussels) studies. REACH was a cross-sectional study primarily investigating associations between dietary patterns and cognitive health. The ROAM study was a 6-month randomised double-blind, placebo-controlled trial investigating the effects of GSM on signs and symptoms of OA.
REACH study participants comprised community-dwelling adults living in the greater Auckland area of New Zealand aged 65-74 years (n=365, mean age 69.7±2.57 years, 64% female). Data collection included fasted blood samples analysed for the cartilage degradation biomarkers C-terminal telopeptide of collagen type II (CTX-II) and Cartilage Oligomeric Matrix Protein (COMP), knee ultrasound scans measured and graded for cartilage thickness, and scores on the Knee Injury and Osteoarthritis Outcome Score questionnaire subscales (Pain, P; Symptoms, S; Activities of Daily Living, ADL, Sport & Recreation, SP; and Quality of Life, QoL), measuring pain and functionality.
ROAM study participants comprised adults living in the North Island of New Zealand aged 55-80 years (n=120, mean age 65.9±6.43 years, 63% female) and screened for signs and symptoms of OA using a KOOS cut-off score of <86 in any of the KOOS subscales. Participants consumed either 3g of powdered whole GSM or placebo (pea protein) for six months. Baseline and end data collection included blood and urine samples analysed for CTX-II, COMP and inflammatory markers, performance measures: 30 second chair stand, stair test and 40m fast-paced walk, and subjective measures: KOOS, Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) and Visual Analogue Scales (VAS) of pain and symptoms. Dietary intake was also taken using a food frequency questionnaire and analysed to gain a Dietary Inflammatory Index (DII) score.
Results:
The REACH data showed weak negative correlations of right knee ultrasound medial (r = -0.11 to -0.14, p = <0.05) and thinnest part (r = -0.07 to -0.14, p = <0.05) of the femoral condyles with all Knee Injury and Osteoarthritis Outcome Score subscales, except Activities of Daily Living for thinnest part and Quality of Life for medial. Cartilage Oligomeric Matrix Protein was also negatively correlated with the ADL subscale (r = -0.11, p = <0.05). Further, for right knee ultrasound grading and COMP there was a significant difference between those who score <86 and ≥86 in all KOOS subscales and QoL subscale respectively.
Results for the ROAM study inflammatory marker data found interleukin-23 (IL-23) was negatively associated with all KOOS subscales; Pain: β coefficient -0.18, (95%CI -0.31, -0.04) P=0.01, Symptoms: -0.31 (-0.48, -0.14) P=0.001, Activities of Daily Living: -0.20 (-0.34, -0.05) P=0.01, Sport & Recreation: -0.43 (-0.72, -0.15) P=0.003 and Quality of Life: -0.28 (-0.48, -0.08) P=0.008 and positively associated Visual Analogue Scale Pain: 0.36 (0.17, 0.55) P=<0.001 and VAS symptoms: 0.25 (0.002, 0.50) P=0.048. Monocyte chemoattractant protein-1 (MCP-1) was negatively associated, and interleukin-12 (IL-12) was positively associated with KOOS P: -0.14, (-0.28, -0.01) P=0.04 and 0.23 (0.07, 0.40) P=0.01 respectively. Interleukin-17 (IL-17) was positively associated with KOOS SP: 0.45, (0.14, 0.77) P=0.006 and interferon-alpha (IFN-α) was positively associated with VAS pain: 0.24 (0.003, 0.48) P=0.047. The inflammatory markers were not associated with the Measure of Intermittent and Constant Osteoarthritis Pain scores and neither inflammatory markers nor subjective measures were associated with Dietary Inflammatory Index scores.
The results of the ROAM intervention trial showed a significantly greater reduction in percentage change for Visual Analogue Scale Symptoms for GSM than placebo [-28.1 (-59.2, 43.2) vs. 0.00 (-28.6, 100), P=0.03]. Further, a larger (although non-significant) percentage change improvement was observed for the GSM group versus placebo, in 40m fast paced walk [2.51 (-3.55, 8.12) vs. 0.20 (-6.58, 4.92), P=0.09], KOOS SP [11.4 (-4.48, 27.0) vs. 0.00 (-11.1, 17.7), P=0.09], and ICOAP intermittent pain scale [-27.7 (-77.3, 0.00) vs. -14.6 (-50.0, 36.4), P=0.08]. When stratified by body mass index (BMI), those taking GSM with BMI<25kg/m2 displayed a greater improvement in both the KOOS S and ADL compared to placebo, [6.35 (3.49, 12.7) vs. 0.00 (-4.65, 4.49), p=0.03] and [3.29 (1.01, 8.79) vs. 1.01 (-5.75, 4.30), p=0.07] respectively. Whereas those taking GSM with a BMI≥25kg/m2 displayed a greater improvement in KOOS SP compared to placebo, [13.6 (-4.76, 33.3) vs. 0.00 (-12.5, 20.0), p=0.07]. An interaction effect of treatment x time on COMP (P=0.02) was observed. COMP increased in the placebo group, showing a %change of 16.1±35.4%, whereas it decreased in the GSM group, a %change of -2.88±25.7%. There was no treatment effect seen for CTX-II or any of the inflammatory markers.
Conclusions:
This research indicates that subjective perceptions and objective measures of knee joint issues are related, indicating subjective measures are a useful tool in the assessment of OA. Further, a cut-off score of <86 in any KOOS subscale could be a cost-effective and easy way to assess for early signs and symptoms of OA. The results also suggest the inflammatory markers IL-23, MCP-1 IFN-α, IL-12 and IL-17 are involved in OA pathogenesis and therefore may potentially be useful as diagnostic and intervention assessment markers for OA. However, further research is needed to understand their exact roles and the mechanisms by which they work. Lastly, this research indicates GSM consumption may be cartilage protective and has the potential to alleviate symptoms and improve functionality. GSM consumption could be beneficial to those with early knee OA.
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osteoarthritis, greenshell mussels