Using Cumulative Load to Explain How Body Mass Index and Daily Walking Relate to Worsening Knee Cartilage Damage Over Two Years: The <scp>MOST</scp> Study

Voinier, Dana; Neogi, Tuhina; Stefanik, J.J.; Guermazi, Ali; Roemer, Frank W.; Thoma, Louise M.; Master, Hiral; Nevitt, Michael C.; Lewis, Cora E.; Torner, James C.; White, Daniel K.

doi:10.1002/art.41181

Cited by 39 publications

(28 citation statements)

References 50 publications

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“… 25 Previous research has reported a U-shaped relationship between PA and OA progression where both underloading and overloading are detrimental to the OA joint. 49 , 50 Finding the optimal dose of PA for each individual may be a challenge for the clinician. In the SOASP in Sweden, the acceptable pain model is used to guide the clinician and patient in deciding the optimal dose of exercise.…”

Section: Discussionmentioning

confidence: 99%

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Östlind

Eek

Stigmar

et al. 2022

Clin Med�Insights�Arthritis�Musculoskelet Disord

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Objective: Previous research has suggested an association between physical activity (PA), joint function, and molecular biomarkers, but more studies are needed. The aim of this study was to explore the associations between PA or self-reported joint function and molecular biomarkers of cartilage and inflammation in individuals with hip and/or knee osteoarthritis (OA). Specific objectives were to explore the correlations between (1) the change over 3 months in self-reported PA/joint function and the change in molecular biomarkers (2) objectively measured PA and molecular biomarkers measured at 3-month follow-up. Design: Working age participants (n = 91) were recruited from a cluster randomized controlled trial. Self-reported PA, joint function, and serum samples were collected at baseline and after 3 months. Serum concentrations of the inflammatory marker C-reactive protein (CRP) and the cartilage markers Alanine-Arginine-Glycine-Serine (ARGS)-aggrecan, cartilage oligomeric matrix protein (COMP), and type II collagen C2C were analyzed by immunoassays. Objectively measured PA (steps/day) was collected during 12 weeks from activity trackers used by 53 participants. Associations were analyzed with Spearman’s rank correlation. Results: There was a weak negative correlation between the change in self-reported PA and the change in COMP ( rs = −0.256, P = .040) but not for the other molecular biomarkers. There were no correlations between the change in self-reported joint function and the change in molecular biomarkers or between the average steps/day and the molecular biomarkers at follow-up ( rs ⩽ −0.206, P ⩾ .06). Conclusion: In general, no or only weak associations were found between PA/joint function and molecular biomarkers. Future research recommends including participants with lower PA, extend the follow-up, and use a design that allows comparisons.

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Section: Discussionmentioning

confidence: 99%

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Östlind

Eek

Stigmar

et al. 2022

Clin Med�Insights�Arthritis�Musculoskelet Disord

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“…Though chondrocytes laying in different layers of cartilage respond differently to the compressive loading, it is believed that loading strain below 5% represents the physiological situation as walking while strain above 20% exceeds the normal range (Madden et al, 2013). As for the frequency choice, data from the Multicenter Osteoarthritis Study (MOST) showed that the range of moderate daily walking steps is 6,000 to 7,900 (Voinier et al, 2020), indicating that the cartilage in each knee joint bears 3,000 to 4,000 compressions per day. Thus, we selected a condition that resulted in 3,600 times of loading per day in this study.…”

Section: Discussionmentioning

confidence: 99%

Urolithin A Protects Chondrocytes From Mechanical Overloading-Induced Injuries

Yocum

Alexander

et al. 2021

Front. Pharmacol.

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Physiological mechanical stimulation has been shown to promote chondrogenesis, but excessive mechanical loading results in cartilage degradation. Currently, the underlying mechanotransduction pathways in the context of physiological and injurious loading are not fully understood. In this study, we aim to identify the critical factors that dictate chondrocyte response to mechanical overloading, as well as to develop therapeutics that protect chondrocytes from mechanical injuries. Specifically, human chondrocytes were loaded in hyaluronic hydrogel and then subjected to dynamic compressive loading under 5% (DL-5% group) or 25% strain (DL-25% group). Compared to static culture and DL-5%, DL-25% reduced cartilage matrix formation from chondrocytes, which was accompanied by the increased senescence level, as revealed by higher expression of p21, p53, and senescence-associated beta-galactosidase (SA-β-Gal). Interestingly, mitophagy was suppressed by DL-25%, suggesting a possible role for the restoration mitophagy in reducing cartilage degeneration with mechanical overloading. Next, we treated the mechanically overloaded samples (DL-25%) with Urolithin A (UA), a natural metabolite previously shown to enhance mitophagy in other cell types. qRT-PCR, histology, and immunostaining results confirmed that UA treatment significantly increased the quantity and quality of cartilage matrix deposition. Interestingly, UA also suppressed the senescence level induced by mechanical overloading, demonstrating its senomorphic potential. Mechanistic analysis confirmed that UA functioned partially by enhancing mitophagy. In summary, our results show that mechanical overloading results in cartilage degradation partially through the impairment of mitophagy. This study also identifies UA’s novel use as a compound that can protect chondrocytes from mechanical injuries, supporting high-quality cartilage formation/maintenance.

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“…Both intervention groups receive consistent, standardised general OA/activity education, graded walking and strengthening components, but have a contrasting OA pain education component. The EPIPHA-KNEE group receives contemporary PSE underpinned by principles of self-regulated learning and conceptual change theory [ 29 , 51 – 53 ] and modified to integrate contemporary biological science of OA [ 14 , 16 , 17 , 43 , 44 ]. The Best Practice Control group receives best practice OA education, consistent with OA management clinical practice guidelines [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

“…We undertook a feasibility pilot study of a PSE-driven individualised education and walking program for people with knee OA [ 42 ]. The OA PSE intervention drew from established ‘Explain Pain’ programs (originally developed for back pain; see Moseley & Butler for an overview [ 29 ]), that were then modified to include contemporary understanding of the science of OA [ 16 , 17 , 43 ], including the impact of movement and loading of the knee joints [ 15 , 18 , 44 ]. The PSE intervention had high levels of participant-rated credibility and acceptability, with promising effects on pain knowledge and clinical outcomes of pain, function, and physical activity levels [ 42 ].…”

Section: Introductionmentioning

confidence: 99%

The EPIPHA-KNEE trial: Explaining Pain to target unhelpful pain beliefs to Increase PHysical Activity in KNEE osteoarthritis – a protocol for a multicentre, randomised controlled trial with clinical- and cost-effectiveness analysis

Stanton

Braithwaite

Butler

et al. 2021

BMC Musculoskelet Disord

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Background Despite well-established benefits of physical activity for knee osteoarthritis (OA), nine of ten people with knee OA are inactive. People with knee OA who are inactive often believe that physical activity is dangerous, fearing that it will further damage their joint(s). Such unhelpful beliefs can negatively influence physical activity levels. We aim to evaluate the clinical- and cost-effectiveness of integrating physiotherapist-delivered pain science education (PSE), an evidence-based conceptual change intervention targeting unhelpful pain beliefs by increasing pain knowledge, with an individualised walking, strengthening, and general education program. Methods Two-arm, parallel-design, multicentre randomised controlled trial involving 198 people aged ≥50 years with painful knee OA who do not meet physical activity guideline recommendations or walk regularly for exercise. Both groups receive an individualised physiotherapist-led walking, strengthening, and OA/activity education program via 4x weekly in-person treatment sessions, followed by 4 weeks of at-home activities (weekly check-in via telehealth), with follow-up sessions at 3 months (telehealth) and 5 and 9 months (in-person). The EPIPHA-KNEE group also receives contemporary PSE about OA/pain and activity, embedded into all aspects of the intervention. Outcomes are assessed at baseline, 12 weeks, 6 and 12 months. Primary outcomes are physical activity level (step count; wrist-based accelerometry) and self-reported knee symptoms (WOMAC Total score) at 12 months. Secondary outcomes are quality of life, pain intensity, global rating of change, self-efficacy, pain catastrophising, depression, anxiety, stress, fear of movement, knee awareness, OA/activity conceptualisation, and self-regulated learning ability. Additional measures include adherence, adverse events, blinding success, COVID-19 impact on activity, intention to exercise, treatment expectancy/perceived credibility, implicit movement/environmental bias, implicit motor imagery, two-point discrimination, and pain sensitivity to activity. Cost-utility analysis of the EPIPHA-KNEE intervention will be undertaken, in addition to evaluation of cost-effectiveness in the context of primary trial outcomes. Discussion We will determine whether the integration of PSE into an individualised OA education, walking, and strengthening program is more effective than receiving the individualised program alone. Findings will inform the development and implementation of future delivery of PSE as part of best practice for people with knee OA. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12620001041943 (13/10/2020).

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Using Cumulative Load to Explain How Body Mass Index and Daily Walking Relate to Worsening Knee Cartilage Damage Over Two Years: The MOST Study

Cited by 39 publications

References 50 publications

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Associations Between Physical Activity, Self-reported Joint Function, and Molecular Biomarkers in Working Age Individuals With Hip and/or Knee Osteoarthritis

Urolithin A Protects Chondrocytes From Mechanical Overloading-Induced Injuries

The EPIPHA-KNEE trial: Explaining Pain to target unhelpful pain beliefs to Increase PHysical Activity in KNEE osteoarthritis – a protocol for a multicentre, randomised controlled trial with clinical- and cost-effectiveness analysis

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