Skip to main content

Advertisement

SpringerLink
Log in

Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis

  • Osteoarthritis (M Goldring, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review describes the contributions of abnormal bone circulation to the pathophysiology of osteoarthritis. Combining dynamic imaging with MRI and PET with previous observations reveals that venous stasis and a venous outlet syndrome is most likely the key circulatory pathology associated with the initiation or progression of osteoarthritis.

Recent Findings

MRI and PET have revealed that venous outflow obstruction results in physicochemical changes in subchondral bone to which osteoblasts are responsive. The osteoblasts express an altered pattern of cytokines, many of which can serve as structural or signaling molecules contributing to both bone remodeling and cartilage degeneration.

Summary

The patterns of circulatory changes are associated with alterations in the physicochemical environment of subchondral bone, including hypoxia. Osteoblast cytokines can transit the subchondral bone plate and calcified cartilage and communicate with chondrocytes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Fell HB, Jubb RW. The effect of synovial tissue on the breakdown of articular cartilage in organ culture. Arthritis Rheum. 1977;20(7):1359–71.

    Article  CAS  PubMed  Google Scholar 

  2. Boniface RJ, Cain PR, Evans CH. Articular responses to purified cartilage proteoglycans. Arthritis Rheum. 1988;31(2):258–66.

    Article  CAS  PubMed  Google Scholar 

  3. Aaron RK, Sledge CB, Shortkroff S. Experimental arthritis induced by polysaccharide macromolecules. Arthritis Rheum. 1987;30(6):679–88.

    Article  CAS  PubMed  Google Scholar 

  4. Brooks M, Revell W. Blood supply of bone: scientific aspects. London: Springer; 1998.

    Book  Google Scholar 

  5. Welch RD, Johnston 2nd CE, Waldron MJ, et al. Bone changes associated with intraosseous hypertension in the caprine tibia. J Bone Joint Surg Am. 1993;75(1):53–60.

    Article  CAS  PubMed  Google Scholar 

  6. Arnoldi CC. Vascular aspects of degenerative joint disorders. A synthesis. Acta Orthop Scand Suppl. 1994;261:1–82.

    CAS  PubMed  Google Scholar 

  7. Arnoldi CC, Djurhuus JC, Heerfordt J, et al. Intraosseous phlebography, intraosseous pressure measurements and 99mTC-polyphosphate scintigraphy in patients with various painful conditions in the hip and knee. Acta Orthop Scand. 1980;51(1):19–28.

    Article  CAS  PubMed  Google Scholar 

  8. Arnoldi CC, Lemperg K, Linderholm H. Intraosseous hypertension and pain in the knee. J Bone Joint Surg Br. 1975;57(3):360–3.

    CAS  PubMed  Google Scholar 

  9. Arnoldi CC, Linderholm H, Mussbichler H. Venous engorgement and intraosseous hypertension in osteoarthritis of the hip. J Bone Joint Surg Br. 1972;54(3):409–21.

    CAS  PubMed  Google Scholar 

  10. Lemperg RK, Arnoldi CC. The significance of intraosseous pressure in normal and diseased states with special reference to the intraosseous engorgement-pain syndrome. Clin Orthop Relat Res. 1978;136:143–56.

    Google Scholar 

  11. • Aaron RK. Circulatory pathology in osteoarthritis. In: Aaron RK, editor. Skeletal circulation in clinical practice. Singapore: World Scientific; 2016. p. 233–51. Overview of the vascular pathophysiology in OA.

    Chapter  Google Scholar 

  12. Ma HT, Griffith JF, Yeung DK, et al. Modified brix model analysis of bone perfusion in subjects of varying bone mineral density. J Magn Reson Imaging. 2010;31(5):1169–75.

    Article  PubMed  Google Scholar 

  13. Dyke JP, Aaron RK. Noninvasive methods of measuring bone blood perfusion. Ann N Y Acad Sci. 2010;1192:95–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Piert M, Zittel TT, Becker GA, et al. Assessment of porcine bone metabolism by dynamic [18] F fluoride ion PET: correlation with bone histomorphometry. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2001;42(7):1091–100.

    CAS  Google Scholar 

  15. Messa C, Goodman WG, Hoh CK, et al. Bone metabolic activity measured with positron emission tomography and [18F] fluoride ion in renal osteodystrophy: correlation with bone histomorphometry. J Clin Edocrinol Metab. 1993;77(4):949–55.

    CAS  Google Scholar 

  16. • Dyke JP. MRI and PET. In: Aaron RK, editor. Skeletal circulation in clinical practice. Singapore: World Scientific; 2016. p. 117–38. Description of the techniques and uses of dynamic imaging in OA bone.

    Chapter  Google Scholar 

  17. Aaron RK, Dyke JP, Ciombor DM, et al. Perfusion abnormalities in subchondral bone associated with marrow edema, osteoarthritis, and avascular necrosis. Ann N Y Acad Sci. 2007;1117:124–37.

    Article  PubMed  Google Scholar 

  18. Lee JH, Dyke JP, Ballon D, et al. Subchondral fluid dynamics in a model of osteoarthritis: use of dynamic contrast-enhanced magnetic resonance imaging. Osteoarthr Cartil. 2009;17(10):1350–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brix G, Semmler W, Port R, et al. Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging. J Comput Assist Tomogr. 1991;15(4):621–8.

    Article  CAS  PubMed  Google Scholar 

  20. Tofts PS, Brix G, Buckley DL, et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J Magn Reson Imaging. 1999;10(3):223–32.

    Article  CAS  PubMed  Google Scholar 

  21. Tsai PH, Lee HS, Siow TY, et al. Abnormal perfusion in patellofemoral subchondral bone marrow in the rat anterior cruciate ligament transection model of post-traumatic osteoarthritis: a dynamic contrast-enhanced magnetic resonance imaging study. Osteoarthr Cartil. 2016;24(1):129–33.

    Article  PubMed  Google Scholar 

  22. Wang YX, Griffith JF, Deng M, et al. Compromised perfusion in femoral head in normal rats: distinctive perfusion MRI evidence of contrast washout delay. Br J Radiol. 2012;85(1016):e436–41.

    Article  PubMed  PubMed Central  Google Scholar 

  23. • Dyke JP, Synan M, Ezell P, et al. Characterization of bone perfusion by dynamic contrast-enhanced magnetic resonance imaging and positron emission tomography in the Dunkin-Hartley guinea pig model of advanced osteoarthritis. J Orthop Res. 2015;33(3):366–72. Demonstration of the uses of dynamic and functional imaging to describe bone and circulatory physiology

    Article  PubMed  Google Scholar 

  24. van Dijke CF, Peterfy CG, Brasch RC, et al. MR imaging of the arthritic rabbit knee joint using albumin-(Gd-DTPA) 30 with correlation to histopathology. Magn Reson Imaging. 1999;17(2):237–45.

    Article  PubMed  Google Scholar 

  25. Frost ML, Siddique M, Blake GM, et al. Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography. J Bone Miner Res. 2011;26(5):1002–11.

    Article  CAS  PubMed  Google Scholar 

  26. Piert M, Zittel TT, Machulla HJ, et al. Blood flow measurements with [(15)O] H2O and [18F] fluoride ion PET in porcine vertebrae. J Bone Miner Res. 1998;13(8):1328–36.

    Article  CAS  PubMed  Google Scholar 

  27. Temmerman OP, Raijmakers PG, Heyligers IC, et al. Bone metabolism after total hip revision surgery with impacted grafting: evaluation using H2 15O and [18F] fluoride PET; a pilot study. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging. 2008;10(5):288–93.

    Article  Google Scholar 

  28. Lee JH, Dyke JP, Ballon D, et al. Assessment of bone perfusion with contrast-enhanced magnetic resonance imaging. Orthop Clin North Am. 2009;40(2):249–57.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kiaer T, Dahl B, Lausten G. Partial pressures of oxygen and carbon dioxide in bone and their correlation with bone-blood flow: effect of decreased arterial supply and venous congestion on intraosseous oxygen and carbon dioxide in an animal model. J Orthop Res. 1992;10(6):807–12.

    Article  CAS  PubMed  Google Scholar 

  30. Kiaer T, Gronlund J, Jensen B, et al. Effects of variation in systemic blood pressure on intraosseous pressure, PO2, and PCO2. J Orthop Res. 1990;8(4):618–22.

    Article  CAS  PubMed  Google Scholar 

  31. Kiaer T, Dahl B, Lausten GS. The relationship between inert gas wash-out and radioactive tracer microspheres in measurement of bone blood flow: effect of decreased arterial supply and venous congestion on bone blood flow in an animal model. J Orthop Res. 1993;11(1):28–35.

    Article  CAS  PubMed  Google Scholar 

  32. Kiaer T, Pedersen NW, Kristensen KD, et al. Intra-osseous pressure and oxygen tension in avascular necrosis and osteoarthritis of the hip. J Bone Joint Surg Br. 1990;72(6):1023–30.

    CAS  PubMed  Google Scholar 

  33. Kiaer T, Gronlund J, Sorensen KH. Subchondral pO2, pCO2, pressure, pH, and lactate in human osteoarthritis of the hip. Clin Orthop Relat Res. 1988;229:149–55.

    Google Scholar 

  34. Kiaer T. Bone perfusion and oxygenation. Animal experiments and clinical observations. Acta Orthop Scand Suppl. 1994;257:1–41.

    CAS  PubMed  Google Scholar 

  35. Imhof H, Breitenseher M, Kainberger F, et al. Degenerative joint disease: cartilage or vascular disease? Skelet Radiol. 1997;26(7):398–403.

    Article  CAS  Google Scholar 

  36. Imhof H, Sulzbacher I, Grampp S, et al. Subchondral bone and cartilage disease: a rediscovered functional unit. Investig Radiol. 2000;35(10):581–8.

    Article  CAS  Google Scholar 

  37. Watt I. Osteoarthritis revisited—again! Skelet Radiol. 2009;38(5):419–23.

    Article  Google Scholar 

  38. Pedersen NW, Kiaer T, Kristensen KD, et al. Intraosseous pressure, oxygenation, and histology in arthrosis and osteonecrosis of the hip. Acta Orthop Scand. 1989;60(4):415–7.

    Article  CAS  PubMed  Google Scholar 

  39. Warren SM, Steinbrech DS, Mehrara BJ, et al. Hypoxia regulates osteoblast gene expression. J Surg Res. 2001;99(1):147–55.

    Article  CAS  PubMed  Google Scholar 

  40. Dodd JS, Raleigh JA, Gross TS. Osteocyte hypoxia: a novel mechanotransduction pathway. Am J Phys. 1999;277(3 Pt 1):C598–602.

    CAS  Google Scholar 

  41. Steinbrech DS, Mehrara BJ, Saadeh PB, et al. Hypoxia increases insulinlike growth factor gene expression in rat osteoblasts. Ann Plast Surg. 2000;44(5):529–34. discussion 534-525

    Article  CAS  PubMed  Google Scholar 

  42. Hillsley MV, Frangos JA. Bone tissue engineering: the role of interstitial fluid flow. Biotechnol Bioeng. 1994;43(7):573–81.

    Article  CAS  PubMed  Google Scholar 

  43. Wong SY, Evans RA, Needs C, et al. The pathogenesis of osteoarthritis of the hip. Evidence for primary osteocyte death. Clin Orthop Relat Res. 1987;214:305–12.

    Google Scholar 

  44. Tanaka SM, Sun HB, Roeder RK, et al. Osteoblast responses one hour after load-induced fluid flow in a three-dimensional porous matrix. Calcif Tissue Int. 2005;76(4):261–71.

    Article  CAS  PubMed  Google Scholar 

  45. McAllister TN, Frangos JA. Steady and transient fluid shear stress stimulate NO release in osteoblasts through distinct biochemical pathways. J Bone Miner Res. 1999;14(6):930–6.

    Article  CAS  PubMed  Google Scholar 

  46. Wadhwa S, Choudhary S, Voznesensky M, et al. Fluid flow induces COX-2 expression in MC3T3-E1 osteoblasts via a PKA signaling pathway. Biochem Biophys Res Commun. 2002;297(1):46–51.

    Article  CAS  PubMed  Google Scholar 

  47. Burr DB. The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998;10(3):256–62.

    Article  CAS  PubMed  Google Scholar 

  48. Lavigne P, Benderdour M, Lajeunesse D, et al. Subchondral and trabecular bone metabolism regulation in canine experimental knee osteoarthritis. Osteoarthr Cartil. 2005;13(4):310–7.

    Article  CAS  PubMed  Google Scholar 

  49. Lahm A, Kreuz PC, Oberst M, et al. Subchondral and trabecular bone remodeling in canine experimental osteoarthritis. Arch Orthop Trauma Surg. 2006;126(9):582–7.

    Article  CAS  PubMed  Google Scholar 

  50. Westacott CI, Webb GR, Warnock MG, et al. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum. 1997;40(7):1282–91.

    Article  CAS  PubMed  Google Scholar 

  51. Hilal G, Martel-Pelletier J, Pelletier JP, et al. Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum. 1998;41(5):891–9.

    Article  CAS  PubMed  Google Scholar 

  52. Martel-Pelletier J, Faure MP, McCollum R, et al. Plasmin, plasminogen activators and inhibitor in human osteoarthritic cartilage. J Rheumatol. 1991;18(12):1863–71.

    CAS  PubMed  Google Scholar 

  53. Pelletier JP, Mineau F, Faure MP, et al. Imbalance between the mechanisms of activation and inhibition of metalloproteases in the early lesions of experimental osteoarthritis. Arthritis Rheum. 1990;33(10):1466–76.

    Article  CAS  PubMed  Google Scholar 

  54. Sanchez C, Deberg MA, Piccardi N, et al. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthr Cartil. 2005;13(11):988–97.

    Article  CAS  PubMed  Google Scholar 

  55. Sanchez C, Deberg MA, Piccardi N, et al. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthr Cartil. 2005;13(11):979–87.

    Article  CAS  PubMed  Google Scholar 

  56. Prasadam I, van Gennip S, Friis T, et al. ERK-1/2 and p38 in the regulation of hypertrophic changes of normal articular cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts. Arthritis Rheum. 2010;62(5):1349–60.

    Article  CAS  PubMed  Google Scholar 

  57. • Goldring SR, Goldring MB. Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk. Nat Rev Rheumatol. 2016;12(11):632–44. This study summarizes current information on bone-cartilage crosstalk

    Article  PubMed  Google Scholar 

  58. Suri S, Walsh DA. Osteochondral alterations in osteoarthritis. Bone. 2012;51(2):204–11.

    Article  PubMed  Google Scholar 

  59. Lyons TJ, McClure SF, Stoddart RW, et al. The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces. BMC Musculoskelet Disord. 2006;7:52.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Simkin P, Peterson J. The cartilage/bone interface is permeable to saline under phsyiologic articular pressures. Osteoarthr Cartil. 2001;9(Supp 2):S4.

    Google Scholar 

  61. Arkill KP, Winlove CP. Solute transport in the deep and calcified zones of articular cartilage. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2008;16(6):708–14.

    Article  CAS  Google Scholar 

  62. Pan J, Wang B, Li W, et al. Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone. 2012;51(2):212–7.

    Article  PubMed  Google Scholar 

  63. Tami AE, Schaffler MB, Knothe Tate ML. Probing the tissue to subcellular level structure underlying bone’s molecular sieving function. Biorheology. 2003;40(6):577–90.

    CAS  PubMed  Google Scholar 

  64. Knothe Tate ML. “Whither flows the fluid in bone?” an osteocyte’s perspective. J Biomech. 2003;36(10):1409–24.

    Article  PubMed  Google Scholar 

  65. Wang L, Fritton SP, Weinbaum S, et al. On bone adaptation due to venous stasis. J Biomech. 2003;36(10):1439–51.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Karsdal MA, Leeming DJ, Dam EB, et al. Should subchondral bone turnover be targeted when treating osteoarthritis? Osteoarthr Cartil. 2008;16(6):638–46.

    Article  CAS  PubMed  Google Scholar 

  67. Mapp PI, Avery PS, McWilliams DF, et al. Angiogenesis in two animal models of osteoarthritis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2008;16(1):61–9.

    Article  CAS  Google Scholar 

  68. Walsh DA, Bonnet CS, Turner EL, et al. Angiogenesis in the synovium and at the osteochondral junction in osteoarthritis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2007;15(7):743–51.

    Article  CAS  Google Scholar 

  69. Ashraf S, Walsh DA. Angiogenesis in osteoarthritis. Curr Opin Rheumatol. 2008;20(5):573–80.

    Article  PubMed  Google Scholar 

  70. Murata M, Yudoh K, Masuko K. The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society. 2008;16(3):279–86.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, Warren Alpert Medical School of Brown University, 100 Butler Drive, Providence, RI, 02906, USA

    Roy K. Aaron & Jennifer Racine

  2. Department of Radiology, Weill Cornell Medicine Citigroup Biomedical Imaging Center , 516 E 72nd Street, New York, NY, 10021, USA

    Jonathan P. Dyke

Authors
  1. Roy K. Aaron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jennifer Racine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonathan P. Dyke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roy K. Aaron.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Osteoarthritis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aaron, R.K., Racine, J. & Dyke, J.P. Contribution of Circulatory Disturbances in Subchondral Bone to the Pathophysiology of Osteoarthritis. Curr Rheumatol Rep 19, 49 (2017). https://doi.org/10.1007/s11926-017-0660-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-017-0660-x

Keywords

Search

Navigation