Zeitschrift für Rheumatologie

, Volume 76, Supplement 1, pp 1–4 | Cite as

OVERLOAD of joints and its role in osteoarthritis

Towards understanding and preventing progression of primary osteoarthritis. English version
  • B.M. Willie
  • T. Pap
  • C. Perka
  • C.O. Schmidt
  • F. Eckstein
  • A. Arampatzis
  • H.-C. Hege
  • H. Madry
  • A. Vortkamp
  • G.N. Duda
Neues aus der Forschung

Intact joints are necessary for skeletal function and mobility in daily life. A healthy musculoskeletal system is the basis for a functional cardiovascular system as well as an intact immune system. Locomotion, physiotherapy, and various forms of patient activity are essential clinical therapies used in the treatment of neurodegeneration, stroke, diabetes, and cancer. Mobility is substantially impaired with degeneration of joints and, in advanced stages, nighttime pain and sleep disturbance are particularly cumbersome.

Osteoarthritis (OA) is also known as degenerative joint disease. OA involves structural and compositional changes in the articular cartilage, as well as in the calcified cartilage, subchondral cortical bone, subchondral cancellous bone, meniscus, joint capsular tissue, and synovium; which eventually lead to degeneration of these tissues comprising synovial joints.

Epidemiology and treatment of osteoarthritis

OA is the most prevalent joint disease, affecting over...


Articular Cartilage Calcify Cartilage Mechanical Overload Axial Malalignment Intact Joint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Adam Trepczynski and Heide Boeth for designing figures and providing insights related to our research approach. This work was supported by a grant from the Bundesministerium für Bildung und Forschung (OVERLOAD–PrevOP consortium). The Berlin-Brandenburg School for Regenerative Therapies is funded by the Deutsche Forschungsgemeinschaft, GSC 203.

Compliance with ethical guidelines

Conflict of interest. B.M. Willie, T. Pap, C. Perka, C.O. Schmidt, F. Eckstein, A. Arampatzis, H.-C. Hege, H. Madry, A. Vortkamp, and G.N. Duda state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.


  1. 1.
    Robert-Koch-Institut (2007) Gesundheit in Deutschland. InGoogle Scholar
  2. 2.
    Robert-Koch-Institut (2012) Beiträge zur Gesundheitsberichterstattung des Bundes. InGoogle Scholar
  3. 3.
    Felson DT, Naimark A, Anderson J et al (1987) The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 30:914–918CrossRefPubMedGoogle Scholar
  4. 4.
    Beaupre GS, Stevens SS, Carter DR (2000) Mechanobiology in the development, maintenance, and degeneration of articular cartilage. J Rehabil Res Dev 37:145–151PubMedGoogle Scholar
  5. 5.
    Grodzinsky AJ, Levenston ME, Jin M, Frank EH (2000) Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng 2:691–713CrossRefPubMedGoogle Scholar
  6. 6.
    Mow VC, Ratcliffe A, Poole AR (1992) Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13:67–97CrossRefPubMedGoogle Scholar
  7. 7.
    Maniwa S, Nishikori T, Furukawa S et al (2001) Alteration of collagen network and negative charge of articular cartilage surface in the early stage of experimental osteoarthritis. Arch Orthop Trauma Surg 121:181–185CrossRefPubMedGoogle Scholar
  8. 8.
    Otterness IG, Weiner E, Swindell AC et al (2001) An analysis of 14 molecular markers for monitoring osteoarthritis. Relationship of the markers to clinical end-points. Osteoarthritis Cartilage 9:224–231CrossRefPubMedGoogle Scholar
  9. 9.
    Felson DT, Lawrence RC, Dieppe PA et al (2000) Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med 133:635–646CrossRefPubMedGoogle Scholar
  10. 10.
    Van de Velde SK, Bingham JT, Hosseini A et al (2009) Increased tibiofemoral cartilage contact deformation in patients with anterior cruciate ligament deficiency. Arthritis Rheum 60:3693–3702CrossRefGoogle Scholar
  11. 11.
    Lotz MK, Kraus VB (2010) New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther 12:211CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Goldring MB, Otero M (2011) Inflammation in osteoarthritis. Curr Opin Rheumatol 23:471–478CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Litwic A, Edwards MH, Dennison EM, Cooper C (2013) Epidemiology and burden of osteoarthritis. Br Med Bull (Epub ahead of print)Google Scholar
  14. 14.
    Ratzlaff CR, Koehoorn M, Cibere J, Kopec JA (2012) Is lifelong knee joint force from work, home, and sport related to knee osteoarthritis? Int J Rheumatol 2012:584193CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Radin EL, Paul IL, Rose RM (1972) Role of mechanical factors in pathogenesis of primary osteoarthritis. Lancet 1:519–522CrossRefPubMedGoogle Scholar
  16. 16.
    Radin ER, Paul IL, Rose RM (1972) Pathogenesis of primary osteoarthritis. Lancet 1:1395–1396CrossRefPubMedGoogle Scholar
  17. 17.
    Felson DT (1993) The course of osteoarthritis and factors that affect it. Rheum Dis Clin North Am 19:607–615PubMedGoogle Scholar
  18. 18.
    Bellido M, Lugo L, Roman-Blas JA et al (2010) Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther 12:R152CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Intema F, Sniekers YH, Weinans H et al (2010) Similarities and discrepancies in subchondral bone structure in two differently induced canine models of osteoarthritis. J Bone Miner Res 25:1650–1657CrossRefPubMedGoogle Scholar
  20. 20.
    Karsdal MA, Leeming DJ, Dam EB et al (2008) Should subchondral bone turnover be targeted when treating osteoarthritis? Osteoarthritis Cartilage 16:638–646CrossRefPubMedGoogle Scholar
  21. 21.
    Grynpas MD, Alpert B, Katz I et al (1991) Subchondral bone in osteoarthritis. Calcif Tissue Int 49:20–26CrossRefPubMedGoogle Scholar
  22. 22.
    Burr DB (2005) Increased biological activity of subchondral mineralized tissues underlies the progressive deterioration of articular cartilage in osteoarthritis. J Rheumatol 32:1156–1158 (discussion 1158–1159)PubMedGoogle Scholar
  23. 23.
    Burr DB, Gallant MA (2012) Bone remodelling in osteoarthritis. Nat Rev Rheumatol 8:665–673CrossRefPubMedGoogle Scholar
  24. 24.
    Brown TD, Radin EL, Martin RB, Burr DB (1984) Finite element studies of some juxtarticular stress changes due to localized subchondral stiffening. J Biomech 17:11–24CrossRefPubMedGoogle Scholar
  25. 25.
    Orth P, Cucchiarini M, Wagenpfeil S et al. (2014) PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis. Osteoarthritis Cartilage 22:813–21CrossRefPubMedGoogle Scholar
  26. 26.
    Vincent TL (2013) Targeting mechanotransduction pathways in osteoarthritis: a focus on the pericellular matrix. Curr Opin Pharmacol 13:449–454CrossRefPubMedGoogle Scholar
  27. 27.
    Guilak F, Alexopoulos LG, Upton ML et al (2006) The pericellular matrix as a transducer of biomechanical and biochemical signals in articular cartilage. Ann N Y Acad Sci 1068:498–512CrossRefPubMedGoogle Scholar
  28. 28.
    Goldring SR, Goldring MB (2004) The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 427 Suppl:27–36CrossRefGoogle Scholar
  29. 29.
    O’Conor CJ, Leddy HA, Benefield HC et al (2014) TRPV4-mediated mechanotransduction regulates the metabolic response of chondrocytes to dynamic loading. Proc Natl Acad Sci U S A 111:1316–1321CrossRefGoogle Scholar
  30. 30.
    Beller G, Belavy DL, Sun L et al (2011) WISE-2005: bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity. Bone 49:858–866CrossRefPubMedGoogle Scholar
  31. 31.
    Lang T, LeBlanc A, Evans H et al (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19:1006–1012CrossRefPubMedGoogle Scholar
  32. 32.
    Setton LA, Mow VC, Muller FJ et al (1997) Mechanical behavior and biochemical composition of canine knee cartilage following periods of joint disuse and disuse with remobilization. Osteoarthritis Cartilage 5:1–16CrossRefPubMedGoogle Scholar
  33. 33.
    Palmoski M, Perricone E, Brandt KD (1979) Development and reversal of a proteoglycan aggregation defect in normal canine knee cartilage after immobilization. Arthritis Rheum 22:508–517CrossRefPubMedGoogle Scholar
  34. 34.
    Hunziker EB (2004) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432–463CrossRefGoogle Scholar
  35. 35.
    Glyn-Jones S, Palmer AJ, Agricola R et al (2015) Osteoarthritis. Lancet (Epub ahead of print)Google Scholar
  36. 36.
    Hennig A, Abate J (2007) Osteochondral allografts in the treatment of articular cartilage injuries of the knee. Sports Med Arthrosc 15:126–132CrossRefPubMedGoogle Scholar
  37. 37.
    Heijink A, Gomoll A, Madry H et al (2012) Biomechanical considerations in the pathogenesis of osteoarthritis of the knee. Knee Surg Sports Traumatol Arthrosc 20:423–435CrossRefPubMedGoogle Scholar
  38. 38.
    Miyazaki T, Wada M, Kawahara H et al (2002) Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis. Ann Rheum Dis 61:617–622CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Sharma L, Song J, Dunlop D et al (2010) Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann Rheum Dis 69:1940–1945CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • B.M. Willie
    • 1
  • T. Pap
    • 2
  • C. Perka
    • 3
    • 4
  • C.O. Schmidt
    • 5
  • F. Eckstein
    • 6
  • A. Arampatzis
    • 7
  • H.-C. Hege
    • 8
  • H. Madry
    • 9
  • A. Vortkamp
    • 10
  • G.N. Duda
    • 1
    • 3
    • 11
  1. 1.Julius Wolff InstituteCharité – Universitätsmedizin BerlinBerlinGermany
  2. 2.Institute of Experimental Musculoskeletal MedicineWestfalian Wilhelms-University MünsterMünsterGermany
  3. 3.Berlin-Brandenburg Center for Regenerative TherapiesBerlinGermany
  4. 4.Orthopädische KlinikCentrum für Musculoskeletale ChirurgieBerlinGermany
  5. 5.Institute for Community MedicineUniversity Medicine GreifswaldGreifswaldGermany
  6. 6.Institute of AnatomyParacelsus Medical University Salzburg & NurembergSalzburgAustria
  7. 7.Department of Training and Movement SciencesHumboldt-Universität zu BerlinBerlinGermany
  8. 8.Zuse Institute Berlin (ZIB)BerlinGermany
  9. 9.Center of Experimental OrthopaedicsSaarland UniversityHomburgGermany
  10. 10.Department of Developmental Biology and Centre for Medical BiotechnologyUniversity Duisburg-EssenEssenGermany
  11. 11.Berlin-Brandenburg School for Regenerative TherapiesBerlinGermany

Personalised recommendations