The Effect of a Lower Body Positive Pressure Supported Treadmill Exercise Regime on Systemic Biomarkers of Inflammation and Cartilage Degradation in Individuals with Knee Osteoarthritis: A Pilot Study

Stephen Cornish, Jason Peeler


Background: Knee osteoarthritis (OA) has been linked to a chronic low-grade inflammatory response and altered metabolic activity of articular cartilage. Objective: The purpose of this investigation was to evaluate the effectiveness of a 12-week (3 times/week) lower body positive pressure (LBPP) treadmill walking regime on knee pain and systemic biomarkers of inflammation and cartilage degradation. Methods: Sixteen overweight (BMI > 25 kg/m2) knee OA patients were randomized to a LBPP treadmill walking exercise group (N = 7) or non-exercise control group (N = 9). Baseline and 12-week follow-up assessments evaluated the following dependent variables: acute knee pain during full weight bearing treadmill walking; inflammatory biomarkers (C-reactive protein, interleukin-1β, interleukin-6, s100A8/A9, and tumor necrosis factor-α), and catabolic metabolism of articular cartilage (sCOMP). Results: Knee pain at baseline and follow-up remained unchanged for the non-exercise control group (P > 0.05). However, knee pain for the LBPP exercise group was significantly decreased at follow-up (P ≤ 0.05). No differences in the biomarkers of inflammation and cartilage degradation were observed for between and within group comparisons (all P > 0.05). Conclusions: Data suggested that the LBPP supported walking regime could be effectively used to promote regular weight bearing exercise without exacerbation of knee joint pain and did not increase levels of systemic inflammation or catabolic activity of articular cartilage in overweight knee OA patients. This pilot investigation offers important insight regarding the potential role that the LBPP technology could play in facilitating investigations examining the disease modifying effect of exercise on knee OA pathogenesis.


Cytokines, Osteoarthritis, Exercise, Pain, Articular Cartilage, Inflammation

Full Text:



Arokoski, J. P., Jurvelin, J. S., Väätäinen, U., & Helminen, H. J. (2000). Normal and pathological adaptations of articular cartilage to joint loading. Scandinavian Journal of Medicine & Science in Sports, 10(4), 186–198. doi: 10.1034/j.1600-0838.2000.010004186.x

Attur, M., Krasnokutsky, S., Statnikov, A., Samuels, J., Li, Z., Friese, O., Hellio Le Graverand-Gastineau, M.-P., Rybak, L., Kraus, V. B., Jordan, J. M., Aliferis, C. F., & Abramson, S. B. (2015). Low-grade inflammation in symptomatic knee osteoarthritis: Prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers. Arthritis & Rheumatology (Hoboken, N.J.), 67(11), 2905–2915.

Beavers, K. M., Beavers, D. P., Newman, J. J., Anderson, A. M., Loeser, R. F., Nicklas, B. J., Lyles, M. F., Miller, G. D., Mihalko, S. L., & Messier, S. P. (2015). Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis. Osteoarthritis and Cartilage, 23(2), 249–256.

Chilibeck, P. D., Pérez-López, F. R., F Bodary, P., Kang, E. S., & Jeon, J. Y. (2014). Adipocytokines, metabolic syndrome, and exercise. International Journal of Endocrinology, 2014, 597162.

de Boer, T. N., van Spil, W. E., Huisman, A. M., Polak, A. A., Bijlsma, J. W. J., Lafeber, F. P. J. G., & Mastbergen, S. C. (2012). Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis and Cartilage, 20(8), 846–853.

Denning, W. M., Winward, J. G., Pardo, M. B., Hopkins, J. T., & Seeley, M. K. (2015). Body weight independently affects articular cartilage catabolism. Journal of Sports Science & Medicine, 14(2), 290–296. PMCID: PMC4424457

Erhart-Hledik, J. C., Favre, J., Asay, J. L., Smith, R. L., Giori, N. J., Mündermann, A., & Andriacchi, T. P. (2012). A relationship between mechanically-induced changes in serum cartilage oligomeric matrix protein (COMP) and changes in cartilage thickness after 5 years. Osteoarthritis and Cartilage, 20(11), 1309–1315.

Fernandes, L., Hagen, K. B., Bijlsma, J. W. J., Andreassen, O., Christensen, P., Conaghan, P. G., Doherty, M., Geenen, R., Hammond, A., Kjeken, I., Lohmander, L. S., Lund, H., Mallen, C. D., Nava, T., Oliver, S., Pavelka, K., Pitsillidou, I., da Silva, J. A., de la Torre, J., … European League Against Rheumatism (EULAR). (2013). EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis. Annals of the Rheumatic Diseases, 72(7), 1125–1135.

Franz, M. J., VanWormer, J. J., Crain, A. L., Boucher, J. L., Histon, T., Caplan, W., Bowman, J. D., & Pronk, N. P. (2007). Weight-loss outcomes: A systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. Journal of the American Dietetic Association, 107(10), 1755–1767.

Gleeson, M., Bishop, N. C., Stensel, D. J., Lindley, M. R., Mastana, S. S., & Nimmo, M. A. (2011). The anti-inflammatory effects of exercise: Mechanisms and implications for the prevention and treatment of disease. Nature Reviews. Immunology, 11(9), 607–615.

Herger, S., Vach, W., Liphardt, A.-M., Egloff, C., Nüesch, C., & Mündermann, A. (2019). Dose-response relationship between ambulatory load magnitude and load-induced changes in COMP in young healthy adults. Osteoarthritis and Cartilage, 27(1), 106–113.

Hoch, J. M., Mattacola, C. G., Medina McKeon, J. M., Howard, J. S., & Lattermann, C. (2011). Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: A systematic review and meta-analysis. Osteoarthritis and Cartilage, 19(12), 1396–1404.

Hyldahl, R. D., Evans, A., Kwon, S., Ridge, S. T., Robinson, E., Hopkins, J. T., & Seeley, M. K. (2016). Running decreases knee intra-articular cytokine and cartilage oligomeric matrix concentrations: A pilot study. European Journal of Applied Physiology, 116(11–12), 2305–2314.

Jinks, C., Jordan, K., & Croft, P. (2007). Osteoarthritis as a public health problem: The impact of developing knee pain on physical function in adults living in the community: (KNEST 3). Rheumatology (Oxford, England), 46(5), 877–881.

Jordan, K. M., Arden, N. K., Doherty, M., Bannwarth, B., Bijlsma, J. W. J., Dieppe, P., Gunther, K., Hauselmann, H., Herrero-Beaumont, G., Kaklamanis, P., Lohmander, S., Leeb, B., Lequesne, M., Mazieres, B., Martin-Mola, E., Pavelka, K., Pendleton, A., Punzi, L., Serni, U., … Standing Committee for International Clinical Studies Including Therapeutic Trials ESCISIT. (2003). EULAR Recommendations 2003: An evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Annals of the Rheumatic Diseases, 62(12), 1145–1155. doi: 10.1136/ard.2003.011742.

Kohn, M. D., Sassoon, A. A., & Fernando, N. D. (2016). Classifications in Brief: Kellgren-Lawrence Classification of Osteoarthritis. Clinical Orthopaedics and Related Research, 474(8), 1886–1893.

Lawrence, R. C., Felson, D. T., Helmick, C. G., Arnold, L. M., Choi, H., Deyo, R. A., Gabriel, S., Hirsch, R., Hochberg, M. C., Hunder, G. G., Jordan, J. M., Katz, J. N., Kremers, H. M., Wolfe, F., & National Arthritis Data Workgroup. (2008). Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis and Rheumatism, 58(1), 26–35.

Leiter, J. R. S., MacDonald, L., McRae, S., Davidson, M., & MacDonald, P. B. (2012). Intrinsic stresses on bone and cartilage in the normal and anterior cruciate ligament-reconstructed knee before and after a half marathon: A magnetic resonance imaging analysis. Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine, 22(5), 439–442.

Lohmander, L. S., Saxne, T., & Heinegård, D. K. (1994). Release of cartilage oligomeric matrix protein (COMP) into joint fluid after knee injury and in osteoarthritis. Annals of the Rheumatic Diseases, 53(1), 8–13.

Lotz, M., Martel-Pelletier, J., Christiansen, C., Brandi, M.-L., Bruyère, O., Chapurlat, R., Collette, J., Cooper, C., Giacovelli, G., Kanis, J. A., Karsdal, M. A., Kraus, V., Lems, W. F., Meulenbelt, I., Pelletier, J.-P., Raynauld, J.-P., Reiter-Niesert, S., Rizzoli, R., Sandell, L. J., … Reginster, J.-Y. (2013). Value of biomarkers in osteoarthritis: Current status and perspectives. Annals of the Rheumatic Diseases, 72(11), 1756–1763.

Messier, S. P., Mihalko, S. L., Legault, C., Miller, G. D., Nicklas, B. J., DeVita, P., Beavers, D. P., Hunter, D. J., Lyles, M. F., Eckstein, F., Williamson, J. D., Carr, J. J., Guermazi, A., & Loeser, R. F. (2013). Effects of intensive diet and exercise on knee joint loads, inflammation, and clinical outcomes among overweight and obese adults with knee osteoarthritis: The IDEA randomized clinical trial. JAMA, 310(12), 1263–1273.

Michael, J. W.-P., Schlüter-Brust, K. U., & Eysel, P. (2010). The Epidemiology, Etiology, Diagnosis, and Treatment of Osteoarthritis of the Knee. Deutsches Aerzteblatt Online.

Miller, G. D., Nicklas, B. J., & Loeser, R. F. (2008). Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy. Journal of the American Geriatrics Society, 56(4), 644–651.

Mündermann, A., King, K. B., Smith, R. L., & Andriacchi, T. P. (2009). Change in serum COMP concentration due to ambulatory load is not related to knee OA status. Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society, 27(11), 1408–1413.

Nicklas, B. J., Ambrosius, W., Messier, S. P., Miller, G. D., Penninx, B. W. J. H., Loeser, R. F., Palla, S., Bleecker, E., & Pahor, M. (2004). Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: A randomized controlled clinical trial. The American Journal of Clinical Nutrition, 79(4), 544–551.

Oliveria, S. A., Felson, D. T., Reed, J. I., Cirillo, P. A., & Walker, A. M. (1995). Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis and Rheumatism, 38(8), 1134–1141. DOI: 10.1002/art.1780380817

Paradowski, P. T., Englund, M., Lohmander, L. S., & Roos, E. M. (2005). The effect of patient characteristics on variability in pain and function over two years in early knee osteoarthritis. Health Qual.Life Outcomes., 3(1477-7525 (Electronic)), 59.

Peeler, J., Christian, M., Cooper, J., Leiter, J., & MacDonald, P. (2015). Managing Knee Osteoarthritis: The Effects of Body Weight Supported Physical Activity on Joint Pain, Function, and Thigh Muscle Strength. Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine, 25(6), 518–523.

Peeler, J., Leiter, J., & MacDonald, P. (2018). Effect of Body Weight-Supported Exercise on Symptoms of Knee Osteoarthritis: A Follow-up Investigation. Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine.

Peeler, J., & Ripat, J. (2018). The effect of low-load exercise on joint pain, function, and activities of daily living in patients with knee osteoarthritis. The Knee, 25(1), 135–145.

Roberts, H. M., Law, R.-J., & Thom, J. M. (2019). The time course and mechanisms of change in biomarkers of joint metabolism in response to acute exercise and chronic training in physiologic and pathological conditions. European Journal of Applied Physiology, 119(11–12), 2401–2420.

Roberts, H. M., Moore, J. P., & Thom, J. M. (2018). The effect of aerobic walking and lower body resistance exercise on serum COMP and hyaluronan, in both males and females. European Journal of Applied Physiology, 118(6), 1095–1105.

Roos, E. M., & Lohmander, L. S. (2003). The Knee injury and Osteoarthritis Outcome Score (KOOS): From joint injury to osteoarthritis. Health Qual.Life Outcomes., 1(1477-7525 (Electronic)), 64.

Samut, G., Dinçer, F., & Özdemir, O. (2015). The effect of isokinetic and aerobic exercises on serum interleukin-6 and tumor necrosis factor alpha levels, pain, and functional activity in patients with knee osteoarthritis. Modern Rheumatology, 25(6), 919–924.

Stannus, O., Jones, G., Cicuttini, F., Parameswaran, V., Quinn, S., Burgess, J., & Ding, C. (2010). Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults. Osteoarthritis and Cartilage, 18(11), 1441–1447.

Takacs, J., Anderson, J. E., Leiter, J. R. S., MacDonald, P. B., & Peeler, J. D. (2013). Lower body positive pressure: An emerging technology in the battle against knee osteoarthritis? Clinical Interventions in Aging, 8, 983–991.

Takacs, J., Leiter, J. R. S., & Peeler, J. D. (2011). Novel application of lower body positive-pressure in the rehabilitation of an individual with multiple lower extremity fractures. Journal of Rehabilitation Medicine, 43(7), 653–656.

Thorogood, A., Mottillo, S., Shimony, A., Filion, K. B., Joseph, L., Genest, J., Pilote, L., Poirier, P., Schiffrin, E. L., & Eisenberg, M. J. (2011). Isolated aerobic exercise and weight loss: A systematic review and meta-analysis of randomized controlled trials. The American Journal of Medicine, 124(8), 747–755.

Vina, E. R., & Kwoh, C. K. (2018). Epidemiology of osteoarthritis: Literature update. Current Opinion in Rheumatology, 30(2), 160–167.

Walsh, N. P., Gleeson, M., Shephard, R. J., Gleeson, M., Woods, J. A., Bishop, N. C., Fleshner, M., Green, C., Pedersen, B. K., Hoffman-Goetz, L., Rogers, C. J., Northoff, H., Abbasi, A., & Simon, P. (2011). Position statement. Part one: Immune function and exercise. Exercise Immunology Review, 17, 6–63. PMID: 21446352

Witvrouw, E., Lysens, R., Bellemans, J., Cambier, D., & Vanderstraeten, G. (2000). Intrinsic risk factors for the development of anterior knee pain in an athletic population. A two-year prospective study. Am.J.Sports Med., 28(0363–5465), 480–489.

Woods, J. A., Wilund, K. R., Martin, S. A., & Kistler, B. M. (2012). Exercise, inflammation and aging. Aging and Disease, 3(1), 130–140. PMCID: PMC3320801

Zanchi, N. E., Almeida, F. N., Lira, F. S., Rosa Neto, J. C., Nicastro, H., da Luz, C. R., de Siqueira Filho, M. A., Felitti, V., Vainzof, M., Seelaender, M., Poortmans, J. R., & Lancha, A. H. (2012). Renewed avenues through exercise muscle contractility and inflammatory status. TheScientificWorldJournal, 2012, 584205.

Zhang, W., Moskowitz, R. W., Nuki, G., Abramson, S., Altman, R. D., Arden, N., Bierma-Zeinstra, S., Brandt, K. D., Croft, P., Doherty, M., Dougados, M., Hochberg, M., Hunter, D. J., Kwoh, K., Lohmander, L. S., & Tugwell, P. (2008). OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis and Cartilage, 16(2), 137–162.



  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

2013-2022 (CC-BY) Australian International Academic Centre PTY.LTD.

International Journal of Kinesiology and Sports Science

You may require to add the '' domain to your e-mail 'safe list’ If you do not receive e-mail in your 'inbox'. Otherwise, you may check your 'Spam mail' or 'junk mail' folders.