Comparative Effect of Weight-Bearing and Non-Weight-Bearing Exercises on Psychological Well-Being, Neurobiological, and Cellular Oxygenation Outcomes: A Pathway to Recovery

Background: Knee osteoarthritis (OA) is a degenerative and complex disease influenced by mechanical, neurological, and psychological factors. Due to its increasing prevalence associated with aging and obesity, it is essential to understand how different types of exercise affect psychological well-being, neurobiological indicators, and cellular oxygenation is essential for optimizing recovery. Objective: To compare the effectiveness of weight-bearing and non-weight-bearing exercises on psychological well-being, neurobiological markers, and cellular oxygenation.

Methods: Eighty volunteers with persistent knee pain (≥3 months) were enrolled in a single-blind randomized controlled trial conducted at the Riphah Rehabilitation Center in Lahore, Pakistan. Participants aged 40 years and older were randomly allocated to two intervention groups. Both groups received baseline treatment, Group A additionally performed non-weight-bearing exercises, whereas Group B performed weight-bearing exercises, including quadriceps strengthening, for a duration of six weeks. Outcomes were assessed using the Depression Anxiety and Stress Scale (DASS 2.1), ELISA, and arterial blood gas analysis to evaluate oxygenation. Data were analyzed using SPSS version 25, with a p < 0.05 considered statistically significant.

Results: Following the intervention, significant improvements were observed in stress, anxiety, depression, BDNF level, and oxygenation in both the weight-bearing and non-weight-bearing exercise groups (p < 0.05). Comparative analysis revealed no significant difference in anxiety between the groups; however, the weight-bearing group demonstrated significantly greater improvements in stress, depression, BDNF levels, and oxygenation (p < 0.05).

Conclusion: Both interventions resulted in improvements in psychological and physiological outcomes among patients with knee osteoarthritis. However, weight-bearing exercises demonstrated greater benefits in terms of neurobiological markers and psychological well-being.

1. Lespasio MJ, Piuzzi NS, Husni ME, Muschler GF, Guarino A, Mont MA. Knee Osteoarthritis: A Primer. Perm J. 2017;21:16-183. PMID: 29035179. PMCID: PMC5638628. https://doi.org/10.7812/tpp/16-183

2. Allen KD, Thoma LM, Golightly YM. Epidemiology of osteoarthritis. Osteoarthritis Cartilage. 2022;30(2):184-195. PMID: 34534661. PMCID: PMC10735233. https://doi.org/10.1016/j.joca.2021.04.020

3. Swain S, Sarmanova A, Mallen C, et al. Trends in incidence and prevalence of osteoarthritis in the United Kingdom: findings from the Clinical Practice Research Datalink (CPRD). Osteoarthritis Cartilage. 2020;28(6):792-801. PMID: 32184134. https://doi.org/10.1016/j.joca.2020.03.004

4. Giorgino R, Albano D, Fusco S, Peretti GM, Mangiavini L, Messina C. Knee Osteoarthritis: Epidemiology, Pathogenesis, and Mesenchymal Stem Cells: What Else Is New? An Update. Int J Mol Sci. 2023;24(7):6405. PMID: 37047377. PMCID: PMC10094836. https://doi.org/10.3390/ijms24076405

5. Binvignat M, Sokol H, Mariotti-Ferrandiz E, Berenbaum F, Sellam J. Osteoarthritis and gut microbiome. Joint Bone Spine. 2021;88(5):105203. PMID: 33962035. https://doi.org/10.1016/j.jbspin.2021.105203

6. Dainese P, Wyngaert KV, De Mits S, Wittoek R, Van Ginckel A, Calders P. Association between knee inflammation and knee pain in patients with knee osteoarthritis: a systematic review. Osteoarthritis Cartilage. 2022;30(4):516-534. PMID: 34968719. https://doi.org/10.1016/j.joca.2021.12.003

7. Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD. The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA. 2001;286(2):188-195. PMID: 11448282. https://doi.org/10.1001/jama.286.2.188

8. Driban JB, Harkey MS, Barbe MF, et al. Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review. BMC Musculoskelet Disord. 2020;21(1):332. PMID: 32471412. PMCID: PMC7260785. https://doi.org/10.1186/s12891-020-03367-2

9. Oo W.M., Hunter J., Intra-articular therapies for knee osteoarthritis: current update. Curr Treat Options in Rheum. 2023;9(3):99-119. https://doi.org/10.1007/s40674-023-00207-x

10. López-Bravo MD, Zamarrón-Cassinello MD, Touche R, Muñoz-Plata R, Cuenca-Martínez F, Ramos-Toro M. Psychological Factors Associated with Functional Disability in Patients with Hip and Knee Osteoarthritis. Behav Med. 2021;47(4):285-295. PMID: 32910744. https://doi.org/10.1080/08964289.2020.1813682

11. Nah S, Park SS, Choi S, Jang HD, Moon JE, Han S. Association between Chronic Knee Pain and Psychological Stress in Those over 50 Years of Age: A Nationwide Cross-Sectional Study Based on the Sixth Korea National Health and Nutrition Examination Survey (KNHANES 2013-2015). Int J Environ Res Public Health. 2021;18(18):9771. PMID: 34574694. PMCID: PMC8467605. https://doi.org/10.3390/ijerph18189771

12. Silva MJ. Treating Anxiety-Based Cognitive Distortions Pertaining to Somatic Perception for Better Chronic Pain Outcomes: A Recommendation for Better Practice in the Present Day and the Cyber Age of Medicine. J Clin Med. 2024;13(19):5923. PMID: 39407983. PMCID: PMC11478175. https://doi.org/10.3390/jcm13195923

13. Li B, Yang Z, Li Y, Zhang J, Li C, Lv N. Exploration beyond osteoarthritis: the association and mechanism of its related comorbidities. Front Endocrinol (Lausanne). 2024;15:1352671. PMID: 38779455. PMCID: PMC11110169. https://doi.org/10.3389/fendo.2024.1352671

14. Wojcieszek A, Kurowska A, Majda A, Liszka H, Gądek A. The Impact of Chronic Pain, Stiffness and Difficulties in Performing Daily Activities on the Quality of Life of Older Patients with Knee Osteoarthritis. Int J Environ Res Public Health. 2022;19(24):16815. PMID: 36554695. PMCID: PMC9779661. https://doi.org/10.3390/ijerph192416815

15. Merry Del Val B, Shukla SR, Oduoye MO, Nsengiyumva M, Tesfaye T, Glinkowski WM. Prevalence of mental health disorders in knee osteoarthritis patients: a systematic review and meta-analysis. Ann Med Surg (Lond). 2024;86(8):4705-4713. PMID: 39118762. PMCID: PMC11305717. https://doi.org/10.1097/ms9.0000000000002258

16. Sorkpor SK, Galle K, Teixeira AL, et al. The Relationship Between Plasma BDNF and Pain in Older Adults With Knee Osteoarthritis. Biol Res Nurs. 2021;23(4):629-636. PMID: 33910384. PMCID: PMC8726424. https://doi.org/10.1177/10998004211012479

17. Xiong HY, Hendrix J, Schabrun S, et al. The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation. Biomolecules. 2024;14(1):71. PMID: 38254671. PMCID: PMC10813479. https://doi.org/10.3390/biom14010071

18. Gowler PRW, Li L, Woodhams SG, et al. Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain. Pain. 2020;161(1):61-73. PMID: 31479064. https://doi.org/10.1097/j.pain.0000000000001694

19. Cappoli N, Tabolacci E, Aceto P, Dello Russo C. The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception. J Neuroimmunol. 2020;349:577406. PMID: 33002723. https://doi.org/10.1016/j.jneuroim.2020.577406

20. Manukyan G, Gallo J, Mikulkova Z, et al. Phenotypic and functional characterisation of synovial fluid-derived neutrophils in knee osteoarthritis and knee infection. Osteoarthritis Cartilage. 2023;31(1):72-82. PMID: 36216277. https://doi.org/10.1016/j.joca.2022.09.011

21. Puts S, Njemini R, Bilterys T, et al. Linking Intra-Articular Inflammatory Biomarkers with Peripheral and Central Sensitization in Late-Stage Knee Osteoarthritis Pain: A Pilot Study. J Clin Med. 2024;13(17):5212. PMID: 39274424. PMCID: PMC11395782. https://doi.org/10.3390/jcm13175212

22. Semenistaja S, Skuja S, Kadisa A, Groma V. Healthy and Osteoarthritis-Affected Joints Facing the Cellular Cross-talk. Int J Mol Sci. 2023;24(4):4120. PMID: 36835530. PMCID: PMC9964755. https://doi.org/10.3390/ijms24044120

23. Fu L, Zhang L, Zhang X, Chen L, Cai Q, Yang X. Roles of oxygen level and hypoxia-inducible factor signaling pathway in cartilage, bone and osteochondral tissue engineering. Biomed Mater. 2021;16(2):022006. PMID: 33440367. https://doi.org/10.1088/1748-605x/abdb73

24. Zhang, Z., Cheng D., Pan J., et al. Lubricating MXenzyme-based hybrid hydrogel reverses oxidative damage to alleviate osteoarthritis. Chem Eng J. 2024;482:148815. https://doi.org/10.1016/j.cej.2024.148815

25. Munteanu C., et al., Cellular and Molecular Homeostatic Micro-environmental im-balances in Osteo-arthritis and Rheumatoid Arthritis. Balneo and PRM Res J. 2023;14(2):564.

26. Khan S., Islam S., Khan R et al. Evaluating the Impact of Weight Bearing and Non-Weight Bearing Exercises on Pain and Physical Function in Obese Knee Osteoarthritic Patients: A Randomized Controlled Trial. Allied Medical Research Journal. 2023;1(2):27-37.

27. Jeevitha D., Kotteeswaran K. Compare the Effectiveness of Weight Bearing Exercises and Plyometric Training Improve Joint Position Sense in Osteoarthritis Knee Subjects. Indian Journal of Physiotherapy & Occupational Therapy. 2024:18.

28. Bennell KL, Nelligan RK, Kimp AJ, et al. Comparison of weight bearing functional exercise and non-weight bearing quadriceps strengthening exercise on pain and function for people with knee osteoarthritis and obesity: protocol for the TARGET randomised controlled trial. BMC Musculoskelet Disord. 2019;20(1):291. PMID: 31208435. PMCID: PMC6580522. https://doi.org/10.1186/s12891-019-2662-5

29. Norato O, Velez S, Lleshi A, et al. Elderly Hip Osteoarthritis: A Review of Short-Term Pain Relief Through Non-Weight-Bearing Therapies. J Funct Morphol Kinesiol. 2025;10(2):124. PMID: 40566421. PMCID: PMC12015921. https://doi.org/10.3390/jfmk10020124

30. Lawford BJ, Bennell KL, Allison K, Schwartz S, Hinman RS. Challenges With Strengthening Exercises for Individuals With Knee Osteoarthritis and Comorbid Obesity: A Qualitative Study With Patients and Physical Therapists. Arthritis Care Res (Hoboken). 2022;74(1):113-125. PMID: 32886868. https://doi.org/10.1002/acr.24439

31. Hall M, Dobson F, Van Ginckel A, et al. Comparative effectiveness of exercise programs for psychological well-being in knee osteoarthritis: A systematic review and network meta-analysis. Semin Arthritis Rheum. 2021;51(5):1023-1032. PMID: 34416624. https://doi.org/10.1016/j.semarthrit.2021.07.007

32. Ma X, Zhang H, Li G, et al. A clinical study based on bidirectional Mendelian randomization: Correlation between generalized anxiety disorder and weight-bearing joints osteoarthritis. Heliyon. 2024;10(12):e32988. PMID: 39021945. PMCID: PMC11252706. https://doi.org/10.1016/j.heliyon.2024.e32988

33. Puts S, Liberman K, Leysen L, et al. Exercise-induced effects on inflammatory markers and brain-derived neurotrophic factor in patients with knee osteoarthritis. A systematic review with meta-analysis. Exerc Immunol Rev. 2023;29:22-53. PMID: 37358362

34. Tudorachi NB, Totu EE, Fifere A, et al. The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis. Antioxidants (Basel). 2021;10(6):985. PMID: 34205576. PMCID: PMC8233827. https://doi.org/10.3390/antiox10060985