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How Do MRI-Detected Subchondral Bone Marrow Lesions (BMLs) on Two Different MRI Sequences Correlate with Clinically Important Outcomes?

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Abstract

The aim of this study is to describe the association of bone marrow lesions (BMLs) present on two different MRI sequences with clinical outcomes, cartilage defect progression, cartilage volume loss over 2.7 years, and total knee replacement (TKR) over 13.3 years. 394 participants (50–80 years) were assessed at baseline and 2.7 years. BML presence at baseline was scored on T1-weighted fat-suppressed 3D gradient-recalled acquisition (T1) and T2-weighted fat-suppressed 2D fast spin-echo (T2) sequences. Knee pain, function, and stiffness were assessed using WOMAC. Cartilage volume and defects were assessed using validated methods. Incident TKR was determined by data linkage. BMLs were mostly present on both MRI sequences (86%). BMLs present on T2, T1, and both sequences were associated with greater knee pain and functional limitation (odds ratio = 1.49 to 1.70; all p < 0.05). Longitudinally, BMLs present on T2, T1, and both sequences were associated with worsening knee pain (β = 1.12 to 1.37, respectively; p < 0.05) and worsening stiffness (β = 0.45 to 0.52, respectively; all p < 0.05) but not worsening functional limitation or total WOMAC. BMLs present on T2, T1, and both sequences predicted site-specific cartilage defect progression (relative risk = 1.22 to 4.63; all p < 0.05) except at the medial tibial and inferior patellar sites. Lateral tibial and superior patellar BMLs present on T2, T1, and both sequences predicted site-specific cartilage volume loss (β = − 174.77 to − 140.67; p < 0.05). BMLs present on T2, T1, and both sequences were strongly associated with incident TKR. BMLs can be assessed on either T2- or T1-weighted sequences with no clinical predictive advantage of either sequence.

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Abbreviations

2D:

Two-dimensions

3D:

Three-dimensions

AOANJRR:

Association National Joint Replacement Registry

BML(s):

Bone marrow lesions

CI:

Confidence interval

CV:

Coefficient of variation percentage

GBD:

Global burden of disease

GRE:

Gradient-recalled echo

ICC:

Intra-class correlation coefficient

IW-FS:

Intermediate weighted fat saturation

MR:

Magnetic resonance

MRI:

Magnetic resonance imaging

OA:

Osteoarthritis

PD-FS:

Proton density fat saturation

RR:

Relative risk

SPGR:

Spoiled gradient-recalled acquisition in steady state

STIR:

Short tau inversion recovery

T1-w GRE:

T1-weighted fat-suppressed 3D gradient-recalled acquisition MRI

T2-w FSE:

T2-weighted fat-suppressed 2D fast spin-echo MRI

TASOAC:

Tasmanian Older Adult Cohort

TKR:

Total knee replacement

WOMAC:

Western Ontario and McMaster Universities OA Index

References

  1. Felson DT, Chaisson CE, Hill CL, Totterman SMS, Gale ME, Skinner KM et al (2001) The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med 134(7):541–549

    Article  PubMed  CAS  Google Scholar 

  2. Davies-Tuck ML, Wluka AE, Wang Y, English DR, Giles GG, Cicuttini F (2009) The natural history of bone marrow lesions in community-based adults with no clinical knee osteoarthritis. Ann Rheum Dis 68(6):904–908

    Article  PubMed  CAS  Google Scholar 

  3. Zhai G, Blizzard L, Srikanth V, Ding C, Cooley H, Cicuttini F et al (2006) Correlates of knee pain in older adults: tasmanian older adult cohort study. Arthritis Rheum 55(2):264–271

    Article  PubMed  Google Scholar 

  4. Dore D, Quinn S, Ding C, Winzenberg T, Zhai G, Cicuttini F et al (2010) Natural history and clinical significance of MRI-detected bone marrow lesions at the knee: a prospective study in community dwelling older adults. Arthritis Res Ther 12(6):R223

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wluka AE, Wang Y, Davies-Tuck M, English DR, Giles GG, Cicuttini FM (2008) Bone marrow lesions predict progression of cartilage defects and loss of cartilage volume in healthy middle-aged adults without knee pain over 2 years. Rheumatology 47(9):1392–1396

    Article  PubMed  CAS  Google Scholar 

  6. Dore D, Martens A, Quinn S, Ding C, Winzenberg T, Zhai G et al (2010) Bone marrow lesions predict site-specific cartilage defect development and volume loss: a prospective study in older adults. Arthritis Res Ther 12(6):R222

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wildi LM, Raynauld J-P, Martel-Pelletier J, Abram F, Dorais M, Pelletier J-P (2010) Relationship between bone marrow lesions, cartilage loss and pain in knee osteoarthritis: results from a randomised controlled clinical trial using MRI. Ann Rheum Dis 69(12):2118–2124

    Article  PubMed  Google Scholar 

  8. Tanamas SK, Wluka AE, Pelletier J-P, Pelletier JM, Abram F, Berry PA et al (2010) Bone marrow lesions in people with knee osteoarthritis predict progression of disease and joint replacement: a longitudinal study. Rheumatology 49(12):2413–2419

    Article  PubMed  Google Scholar 

  9. Scher C, Craig J, Nelson F (2008) Bone marrow edema in the knee in osteoarthrosis and association with total knee arthroplasty within a three-year follow-up. Skeletal Radiol 37(7):609–617

    Article  PubMed  PubMed Central  Google Scholar 

  10. Raynauld J-P, Martel-Pelletier J, Haraoui B, Choquette D, Dorais M, Wildi LM et al (2011) Risk factors predictive of joint replacement in a 2-year multicentre clinical trial in knee osteoarthritis using MRI: results from over 6 years of observation. Ann Rheum Dis 70(8):1382–1388

    Article  PubMed  Google Scholar 

  11. Hayashi D, Guermazi A, Kwoh CK, Hannon MJ, Moore C, Jakicic JM et al (2011) Semiquantitative assessment of subchondral bone marrow edema-like lesions and subchondral cysts of the knee at 3T MRI: a comparison between intermediate-weighted fat-suppressed spin echo and Dual Echo Steady State sequences. BMC Musculoskelet Disord 12(1):1–9

    Article  Google Scholar 

  12. Grande FD, Farahani SJ, Carrino JA, Chhabra A (2014) Bone marrow lesions: A systematic diagnostic approach. The Indian Journal of Radiology Imaging 24(3):279–287

    Article  PubMed  PubMed Central  Google Scholar 

  13. Duc SR, Koch P, Schmid MR, Horger W, Hodler J, Pfirrmann CWA (2007) Diagnosis of articular cartilage abnormalities of the knee: prospective clinical evaluation of a 3D water-excitation true FISP sequence. Radiology 243(2):475–482

    Article  PubMed  Google Scholar 

  14. Roemer FW, Hunter DJ, Guermazi A (2009) MRI-based semiquantitative assessment of subchondral bone marrow lesions in osteoarthritis research. Osteoarthr Cartil 17(3):414–415

    Article  PubMed  CAS  Google Scholar 

  15. Yoshioka H, Stevens K, Hargreaves BA, Steines D, Genovese M, Dillingham MF et al (2004) Magnetic resonance imaging of articular cartilage of the knee: comparison between fat-suppressed three-dimensional SPGR imaging, fat-suppressed FSE imaging, and fat-suppressed three-dimensional DEFT imaging, and correlation with arthroscopy. J Magn Reson Imaging 20(5):857–864

    Article  PubMed  Google Scholar 

  16. Hilfiker P, Zanetti M, Debatin JF, McKinnon G, Hodler J (1995) Fast spin-echo inversion-recovery imaging versus fast T2-weighted spin-echo imaging in bone marrow abnormalities. Invest Radiol 30(2):110–114

    Article  PubMed  CAS  Google Scholar 

  17. d’Anjou MA, Troncy E, Moreau M, Abram F, Raynauld JP, Martel-Pelletier J et al (2008) Temporal assessment of bone marrow lesions on magnetic resonance imaging in a canine model of knee osteoarthritis: impact of sequence selection. Osteoarthr Cartil 16(11):1307–1311

    Article  PubMed  Google Scholar 

  18. Mirowitz SA, Apicella P, Reinus WR, Hammerman AM (1994) MR imaging of bone marrow lesions: relative conspicuousness on T1-weighted, fat-suppressed T2-weighted, and STIR images. Am J Roentgenol 162(1):215–221

    Article  CAS  Google Scholar 

  19. Schmid MR, Hodler J, Vienne P, Binkert CA, Zanetti M (2002) Bone marrow abnormalities of foot and ankle: STIR versus T1-weighted contrast-enhanced fat-suppressed spin-echo MR imaging. Radiology 224(2):463–469

    Article  PubMed  Google Scholar 

  20. Raynauld J-P, Wildi LM, Abram F, Moser T, Pelletier J-P, Martel-Pelletier J (2013) Reliability and sensitivity to change of IW-TSE versus DESS magnetic resonance imaging sequences in the assessment of bone marrow lesions in knee osteoarthritis patients: Longitudinal data from the Osteoarthritis Initiative (OAI) cohort. J Biomed Sci Eng 6(03):9

    Article  Google Scholar 

  21. Wluka AE, Teichtahl AJ, Maulana R, Liu BM, Wang Y, Giles GG et al (2015) Bone marrow lesions can be subtyped into groups with different clinical outcomes using two magnetic resonance imaging (MRI) sequences. Arthritis Res Ther 17:270

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Altman RD, Gold GE (2007) Atlas of individual radiographic features in osteoarthritis, revised. Osteoarthritis Cartilage 15(Supplement 1):A1-A56

    Google Scholar 

  23. Dore D, Quinn S, Ding C, Winzenberg T, Jones G (2009) Correlates of subchondral BMD: a cross-sectional study. J Bone Miner Res 24(12):2007–2015

    Article  PubMed  Google Scholar 

  24. Shrout PE, Fleiss JL (1979) Intraclass correlations: uses in assessing rater reliability. Psychol Bull 86(2):420–428

    Article  PubMed  CAS  Google Scholar 

  25. Ding C, Garnero P, Cicuttini F, Scott F, Cooley H, Jones G (2005) Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown. Osteoarthr Cartil 13(3):198–205

    Article  PubMed  Google Scholar 

  26. Jones G, Glisson M, Hynes K, Cicuttini F (2000) Sex and site differences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life. Arthritis Rheum 43(11):2543–2549

    Article  PubMed  CAS  Google Scholar 

  27. Raynauld JP, Martel-Pelletier J, Berthiaume MJ, Labonte F, Beaudoin G, de Guise JA et al (2004) Quantitative magnetic resonance imaging evaluation of knee osteoarthritis progression over two years and correlation with clinical symptoms and radiologic changes. Arthritis Rheum 50(2):476–487

    Article  PubMed  Google Scholar 

  28. Raynauld JP, Kauffmann C, Beaudoin G, Berthiaume MJ, de Guise JA, Bloch DA et al (2003) Reliability of a quantification imaging system using magnetic resonance images to measure cartilage thickness and volume in human normal and osteoarthritic knees. Osteoarthr Cartil 11:351–360

    Article  PubMed  Google Scholar 

  29. Berthiaume MJ, Raynauld JP, Martel-Pelletier J, Labonte F, Beaudoin G, Bloch DA et al (2005) Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging. Ann Rheum Dis 64(4):556–563

    Article  PubMed  Google Scholar 

  30. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15(12):1833–1840

    PubMed  CAS  Google Scholar 

  31. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M et al (2014) The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 7(73):1323–1330

    Article  Google Scholar 

  32. Australian Orthopaedic Association National Joint Replacement Registry. Annual Report—2016. Adelaide: 2016 1445–3657

  33. Zhang M, Driban JB, Price LL, Lo GH, McAlindon TE (2015) Magnetic resonance image sequence influences the relationship between bone marrow lesions volume and pain: data from the Osteoarthritis initiative. Biomed Res Int 2015:5

    Google Scholar 

  34. Peterfy CG, Gold G, Eckstein F, Cicuttini F, Dardzinski B, Stevens R (2006) MRI protocols for whole-organ assessment of the knee in osteoarthritis. Osteoarthr Cartil 14(Supplement 1):95–111

    Article  Google Scholar 

  35. Thiryayi WA, Thiryayi SA, Freemont AJ (2008) Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage. Eur J Radiol 67(1):62–67

    Article  PubMed  CAS  Google Scholar 

  36. Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR (1988) Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 166(1):193–199

    Article  PubMed  CAS  Google Scholar 

  37. Zanetti M, Bruder E, Romero J, Hodler J (2000) Bone marrow edema pattern in osteoarthritic knees: correlation between MR imaging and histologic findings. Radiology 215(3):835–840

    Article  PubMed  CAS  Google Scholar 

  38. Muratovic D, Cicuttini F, Wluka A, Findlay D, Wang Y, Otto S et al (2015) Bone marrow lesions detected by specific combination of MRI sequences are associated with severity of osteochondral degeneration. Arthritis Res Ther 18(1):54

    Article  Google Scholar 

  39. Hill CL, Gill TK, Menz HB, Taylor AW (2008) Prevalence and correlates of foot pain in a population-based study: the North West Adelaide health study. J Foot Ankle Res 1:2-

    Article  PubMed  PubMed Central  Google Scholar 

  40. Carter KN, Imlach-Gunasekara F, McKenzie SK, Blakely T (2012) Differential loss of participants does not necessarily cause selection bias. Aust NZ J Public Health 36(3):218–222

    Article  Google Scholar 

  41. Morton SMB, Bandara DK, Robinson EM, Carr PEA (2012) In the 21st Century, what is an acceptable response rate? Aust NZ J Public Health 36(2):106–108

    Article  Google Scholar 

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Acknowledgements

We thank the participants who made this study possible, and Catrina Boon and Pip Boon for their role in collecting the data, and André Pelletier and Josée Thériault for their expertise in MRI reading.

Funding

This work was supported by the National Health and Medical Research Council of Australia; Tasmanian Community Fund; Masonic Centenary Medical Research Foundation; Royal Hobart Hospital Research Foundation; and Arthritis Foundation of Australia. The study sponsor had no role in the design of the study; the collection, analysis, and interpretation of the data; or the writing of the article and the decision to submit it for publication. The researchers work independently of their funders.

Availability of Data and Material

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Menzies Institute for Medical Research, University of Tasmania, Private Bag 23, Hobart, TAS, 7001, Australia

    Siti Maisarah Mattap, Dawn Aitken, Karen Wills, Laura Laslett, Changhai Ding & Graeme Jones

  2. Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM), Montreal, QC, Canada

    Jean-Pierre Pelletier & Johanne Martel-Pelletier

  3. Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR), Adelaide, SA, Australia

    Stephen E. Graves

  4. South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

    Michelle Lorimer

  5. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia

    Flavia Cicuttini

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  1. Siti Maisarah Mattap
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Contributions

All authors were involved in drafting the article or revising it for important intellectual content. All authors have approved the final manuscript. SMM (siti.mattap@utas.edu.au) and DA (dawn.aitken@utas.edu.au) take responsibility for the integrity of the work as a whole, from inception to finished article. KW participated in analysis and interpretation of the data, and critically revised the manuscript. LL participated in interpretation of the data, and critically revised the manuscript. SG and MH carried out data collection and critically revised the manuscript. CD, JP, and JM-P participated in the study planning, carried out data collection, and critically revised the manuscript. FC designed and carried out the study planning, participated in interpretation of data, and critically revised the manuscript. GJ designed and carried out the study planning, participated in analysis and interpretation of the analysis, and critically revised the manuscript.

Corresponding author

Correspondence to Siti Maisarah Mattap.

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Conflict of interest

Jean-Pierre Pelletier, Johanne Martel-Pelletier are shareholders in ArthroLab. Siti Maisarah Mattap, Dawn Aitken, Karen Wills, Laura Laslett, Changhai Ding, Stephen E. Graves, Michelle Lorimer, Flavia Cicuttini, Graeme Jones have declared no competing interests.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Southern Tasmanian Health and Medical Human Research Ethics Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All subjects gave informed written consent.

Additional information

Siti Maisarah Mattap and Dawn Aitken: Co-first author.

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Mattap, S.M., Aitken, D., Wills, K. et al. How Do MRI-Detected Subchondral Bone Marrow Lesions (BMLs) on Two Different MRI Sequences Correlate with Clinically Important Outcomes?. Calcif Tissue Int 103, 131–143 (2018). https://doi.org/10.1007/s00223-018-0402-8

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