Skip to main content
Top

11-05-2018 | Osteoarthritis | Review | Article

The role of radiography and MRI for eligibility assessment in DMOAD trials of knee OA

Journal: Nature Reviews Rheumatology

Authors: Frank W. Roemer, C. Kent Kwoh, Daichi Hayashi, David T. Felson, Ali Guermazi

Publisher: Nature Publishing Group UK

Abstract

Currently, no disease-modifying osteoarthritis drugs (DMOADs) have been approved. Past clinical trials have failed for several reasons, including the commonly applied definition of eligibility based on radiographic assessment of joint structure. In the context of precision medicine, finding the appropriate patient for a specific treatment approach will be of increasing relevance. Phenotypic stratification by use of imaging at the time of determining eligibility for clinical trials will be paramount and cannot be achieved using radiography alone. Furthermore, identification of joints at high risk of rapid progression of osteoarthritis is needed in order to enable a more efficient DMOAD trial design. In addition, joints at high risk of collapse need to be excluded at screening. The use of MRI might offer advantages over radiography in this context. Technological advances and simplified image assessment address many of the commonly perceived barriers to the application of MRI to assessment of eligibility for DMOAD clinical trials.
Literature
1.
Karsdal, M. A. et al. The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study. Osteoarthritis Cartilage 18, 150–159 (2010).CrossRefPubMed
2.
Spector, T. D. et al. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res. Ther. 7, R625–R633 (2005).CrossRefPubMedPubMedCentral
3.
Alexandersen, P., Karsdal, M. A., Byrjalsen, I. & Christiansen, C. Strontium ranelate effect in postmenopausal women with different clinical levels of osteoarthritis. Climacteric 14, 236–243 (2011).CrossRefPubMed
4.
Reginster, J. Y. et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial. Ann. Rheum. Dis. 72, 179–186 (2013).CrossRefPubMed
5.
DiMasi, J. A., Grabowski, H. G. & Hansen, R. W. Innovation in the pharmaceutical industry: new estimates of R&D costs. J. Health Econ. 47, 20–33 (2016).CrossRefPubMed
6.
Kellgren, J. H. & Lawrence, J. S. Radiological assessment of osteo-arthrosis. Ann. Rheum. Dis. 16, 494–502 (1957).CrossRefPubMedPubMedCentral
7.
Hellio Le Graverand, M. P. et al. Considerations when designing a disease-modifying osteoarthritis drug (DMOAD) trial using radiography. Semin. Arthritis Rheum. 43, 1–8 (2013).CrossRefPubMed
8.
Guermazi, A. et al. Prevalence of abnormalities in knees detected by MRI in adults without knee osteoarthritis: population based observational study (Framingham Osteoarthritis Study). BMJ 345, e5339 (2012).CrossRefPubMedPubMedCentral
9.
Yusuf, E., Kortekaas, M. C., Watt, I., Huizinga, T. W. & Kloppenburg, M. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann. Rheum. Dis. 70, 60–67 (2011).CrossRefPubMed
10.
Hayashi, D. et al. Pre-radiographic osteoarthritic changes are highly prevalent in the medial patella and medial posterior femur in older persons: Framingham OA study. Osteoarthritis Cartilage 22, 76–83 (2014).CrossRefPubMed
11.
Hayashi, D., Jarraya, M., A., G. & Roemer, F. Frequency and fluctuation of susceptibility artifacts in the tibiofemoral joint space in painful knees on 3T MRI and association with meniscal tears, radiographic joint space narrowing and calcifications. Arthritis Rheum. 64, 1030 (2012).
12.
Nelson, A. E. et al. Differences in multijoint radiographic osteoarthritis phenotypes among African Americans and Caucasians: the Johnston County Osteoarthritis project. Arthritis Rheum. 63, 3843–3852 (2011).CrossRefPubMedPubMedCentral
13.
Bijlsma, J. W., Berenbaum, F. & Lafeber, F. P. Osteoarthritis: an update with relevance for clinical practice. Lancet 377, 2115–2126 (2011).CrossRefPubMed
14.
Deveza, L. A. et al. Knee osteoarthritis phenotypes and their relevance for outcomes: a systematic review. Osteoarthritis Cartilage 25, 1926–1941 (2017).CrossRefPubMed
15.
Kinds, M. B. et al. Influence of variation in semiflexed knee positioning during image acquisition on separate quantitative radiographic parameters of osteoarthritis, measured by Knee Images Digital Analysis. Osteoarthritis Cartilage 20, 997–1003 (2012).CrossRefPubMed
16.
Lawrence, J. S., Bremner, J. M. & Bier, F. Osteo-arthrosis. Prevalence in the population and relationship between symptoms and x-ray changes. Ann. Rheum. Dis. 25, 1–24 (1966).CrossRefPubMedPubMedCentral
17.
Hannan, M. T., Felson, D. T. & Pincus, T. Analysis of the discordance between radiographic changes and knee pain in osteoarthritis of the knee. J. Rheumatol. 27, 1513–1517 (2000).PubMed
18.
Neogi, T. et al. Association of joint inflammation with pain sensitization in knee osteoarthritis: the Multicenter Osteoarthritis Study. Arthritis Rheumatol. 68, 654–661 (2016).CrossRefPubMedPubMedCentral
19.
Neogi, T. et al. Association between radiographic features of knee osteoarthritis and pain: results from two cohort studies. BMJ 339, b2844 (2009).CrossRefPubMedPubMedCentral
20.
Baker, K. et al. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann. Rheum. Dis. 69, 1779–1783 (2012).CrossRef
21.
Kornaat, P. R. et al. Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology 239, 811–817 (2006).CrossRefPubMed
22.
Neogi, T. Structural correlates of pain in osteoarthritis. Clin. Exp. Rheumatol. 35 (Suppl. 107), 75–78 (2017).PubMed
23.
Zhang, Y. et al. Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. Arthritis Rheum. 63, 691–699 (2011).CrossRefPubMed
24.
Brandt, K. D. & Mazzuca, S. A. Lessons learned from nine clinical trials of disease-modifying osteoarthritis drugs. Arthritis Rheum. 52, 3349–3359 (2005).CrossRefPubMed
25.
Karsdal, M. A. et al. Osteoarthritis — a case for personalized health care? Osteoarthritis Cartilage 22, 7–16 (2014).CrossRefPubMed
26.
Karsdal, M. A. et al. OA phenotypes, rather than disease stage, drive structural progression — identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA. Osteoarthritis Cartilage 23, 550–558 (2015).CrossRefPubMed
27.
Roemer, F. W. et al. Prevalence of magnetic resonance imaging-defined atrophic and hypertrophic phenotypes of knee osteoarthritis in a population-based cohort. Arthritis Rheum. 64, 429–437 (2012).CrossRefPubMedPubMedCentral
28.
Yamamoto, T. & Bullough, P. G. Spontaneous osteonecrosis of the knee: the result of subchondral insufficiency fracture. J. Bone Joint Surg. Am. 82, 858–866 (2000).CrossRefPubMed
29.
Lecouvet, F. E. et al. Early irreversible osteonecrosis versus transient lesions of the femoral condyles: prognostic value of subchondral bone and marrow changes on MR imaging. AJR Am. J. Roentgenol. 170, 71–77 (1998).CrossRefPubMed
30.
Plett, S. K. et al. Femoral condyle insufficiency fractures: associated clinical and morphological findings and impact on outcome. Skeletal Radiol. 44, 1785–1794 (2015).CrossRefPubMed
31.
Hayashi, D., Guermazi, A. & Roemer, F. W. MRI of osteoarthritis: the challenges of definition and quantification. Semin. Musculoskelet. Radiol. 16, 419–430 (2012).CrossRefPubMed
32.
Roemer, F. W., Crema, M. D., Trattnig, S. & Guermazi, A. Advances in imaging of osteoarthritis and cartilage. Radiology 260, 332–354 (2011).CrossRefPubMed
33.
Fritz, J. et al. Three-dimensional CAIPIRINHA SPACE TSE for 5-minute high-resolution MRI of the knee. Invest. Radiol. 51, 609–617 (2016).CrossRefPubMed
34.
Fritz, J. et al. Simultaneous multislice accelerated turbo spin echo magnetic resonance imaging: comparison and combination with in-plane parallel imaging acceleration for high-resolution magnetic resonance imaging of the knee. Invest. Radiol. 52, 529–537 (2017).CrossRefPubMed
35.
Altahawi, F. F., Blount, K. J., Morley, N. P., Raithel, E. & Omar, I. M. Comparing an accelerated 3D fast spin-echo sequence (CS-SPACE) for knee 3-T magnetic resonance imaging with traditional 3D fast spin-echo (SPACE) and routine 2D sequences. Skeletal Radiol. 46, 7–15 (2017).CrossRefPubMed
36.
Schnaiter, J. W. et al. Diagnostic accuracy of an MRI protocol of the knee accelerated through parallel imaging in correlation to arthroscopy. Rofo 190, 265–272 (2018).CrossRefPubMed
37.
Peterfy, C. G. et al. Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage 12, 177–190 (2004).CrossRefPubMed
38.
Kornaat, P. R. et al. MRI assessment of knee osteoarthritis: Knee Osteoarthritis Scoring System (KOSS) — inter-observer and intra-observer reproducibility of a compartment-based scoring system. Skeletal Radiol. 34, 95–102 (2005).CrossRefPubMed
39.
Hunter, D. J. et al. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann. Rheum. Dis. 67, 206–211 (2008).CrossRefPubMed
40.
Roemer, F. W. et al. The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI — the MOST study. Semin. Arthritis Rheum. 42, 573–581 (2013).CrossRefPubMed
41.
Guermazi, A. et al. Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study. Ann. Rheum. Dis. 70, 805–811 (2011).CrossRefPubMed
42.
Niu, J. et al. Patterns of coexisting lesions detected on magnetic resonance imaging and relationship to incident knee osteoarthritis: the Multicenter Osteoarthritis Study. Arthritis Rheumatol. 67, 3158–3165 (2015).CrossRefPubMedPubMedCentral
43.
Waarsing, J. H., Bierma-Zeinstra, S. M. & Weinans, H. Distinct subtypes of knee osteoarthritis: data from the Osteoarthritis Initiative. Rheumatology 54, 1650–1658 (2015).CrossRefPubMedPubMedCentral
44.
Pelletier, J. P., Martel-Pelletier, J. & Abramson, S. B. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 44, 1237–1247 (2001).CrossRefPubMed
45.
Ayral, X., Pickering, E., Woodworth, T., Mackillop, N. & Dougados, M. Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis — results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthritis Cartilage 13, 361–367 (2005).CrossRefPubMed
46.
Roemer, F. W. et al. MRI-detected subchondral bone marrow signal alterations of the knee joint: terminology, imaging appearance, relevance and radiological differential diagnosis. Osteoarthritis Cartilage 17, 1115–1131 (2009).CrossRefPubMed
47.
Felson, D. T. et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann. Intern. Med. 134, 541–549 (2001).CrossRefPubMed
48.
Roemer, F. W. et al. Change in MRI-detected subchondral bone marrow lesions is associated with cartilage loss: the MOST study. A longitudinal multicenter study of knee osteoarthritis. Ann. Rheum. Dis. 68, 1461–1465 (2008).CrossRefPubMedPubMedCentral
49.
Felson, D. T. et al. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann. Intern. Med. 139, 330–336 (2003).CrossRefPubMed
50.
Englund, M., Roemer, F. W., Hayashi, D., Crema, M. D. & Guermazi, A. Meniscus pathology, osteoarthritis and the treatment controversy. Nat. Rev. Rheumatol. 8, 412–419 (2012).CrossRefPubMed
51.
Jarraya, M. et al. Meniscus morphology: does tear type matter? A narrative review with focus on relevance for osteoarthritis research. Semin. Arthritis Rheum. 46, 552–561 (2017).CrossRefPubMed
52.
Hunter, D. J. et al. The association of meniscal pathologic changes with cartilage loss in symptomatic knee osteoarthritis. Arthritis Rheum. 54, 795–801 (2006).CrossRefPubMed
53.
Sharma, L. et al. Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees. Arthritis Rheum. 58, 1716–1726 (2008).CrossRefPubMed
54.
Crema, M. D. et al. Factors associated with meniscal extrusion in knees with or at risk for osteoarthritis: the Multicenter Osteoarthritis study. Radiology 264, 494–503 (2012).CrossRefPubMedPubMedCentral
55.
Crema, M. D. et al. Is the atrophic phenotype of tibiofemoral osteoarthritis associated with faster progression of disease? The MOST study. Osteoarthritis Cartilage 25, 1647–1653 (2017).CrossRefPubMedPubMedCentral
56.
Roemer, F. W. et al. Risk factors for magnetic resonance imaging-detected patellofemoral and tibiofemoral cartilage loss during a six-month period: the joints on glucosamine study. Arthritis Rheum. 64, 1888–1898 (2012).CrossRefPubMed
57.
Roemer, F. W. et al. Tibiofemoral joint osteoarthritis: risk factors for MR-depicted fast cartilage loss over a 30-month period in the multicenter osteoarthritis study. Radiology 252, 772–780 (2009).CrossRefPubMedPubMedCentral
58.
Wilmot, A. S., Ruutiainen, A. T., Bakhru, P. T., Schweitzer, M. E. & Shabshin, N. Subchondral insufficiency fracture of the knee: a recognizable associated soft tissue edema pattern and a similar distribution among men and women. Eur. J. Radiol. 85, 2096–2103 (2016).CrossRefPubMed
59.
Allaire, R., Muriuki, M., Gilbertson, L. & Harner, C. D. Biomechanical consequences of a tear of the posterior root of the medial meniscus. Similar to total meniscectomy. J. Bone Joint Surg. Am. 90, 1922–1931 (2008).CrossRefPubMed
60.
Hein, C. N., Deperio, J. G., Ehrensberger, M. T. & Marzo, J. M. Effects of medial meniscal posterior horn avulsion and repair on meniscal displacement. Knee 18, 189–192 (2011).CrossRefPubMed
61.
LaPrade, C. M. et al. Altered tibiofemoral contact mechanics due to lateral meniscus posterior horn root avulsions and radial tears can be restored with in situ pull-out suture repairs. J. Bone Joint Surg. Am. 96, 471–479 (2014).CrossRefPubMed
62.
Marzo, J. M. & Gurske-DePerio, J. Effects of medial meniscus posterior horn avulsion and repair on tibiofemoral contact area and peak contact pressure with clinical implications. Am. J. Sports Med. 37, 124–129 (2009).CrossRefPubMed
63.
Schillhammer, C. K., Werner, F. W., Scuderi, M. G. & Cannizzaro, J. P. Repair of lateral meniscus posterior horn detachment lesions: a biomechanical evaluation. Am. J. Sports Med. 40, 2604–2609 (2012).CrossRefPubMed
64.
LaPrade, C. M. et al. Biomechanical consequences of a nonanatomic posterior medial meniscal root repair. Am. J. Sports Med. 43, 912–920 (2015).CrossRefPubMed
65.
Ra, H. J., Ha, J. K., Jang, H. S. & Kim, J. G. Traumatic posterior root tear of the medial meniscus in patients with severe medial instability of the knee. Knee Surg. Sports Traumatol. Arthrosc. 23, 3121–3126 (2015).CrossRefPubMed
66.
Henry, S. et al. Medial meniscus tear morphology and chondral degeneration of the knee: is there a relationship? Arthroscopy 28, 1124–1134.e2 (2012).CrossRefPubMed
67.
James, S. L., Panicek, D. M. & Davies, A. M. Bone marrow oedema associated with benign and malignant bone tumours. Eur. J. Radiol. 67, 11–21 (2008).CrossRefPubMed
68.
Ehara, S. et al. Peritumoral edema in osteoid osteoma on magnetic resonance imaging. Skeletal Radiol. 28, 265–270 (1999).CrossRefPubMed
69.
Podlipska, J. et al. Comparison of diagnostic performance of semi-quantitative knee ultrasound and knee radiography with MRI: Oulu Knee Osteoarthritis Study. Sci. Rep. 6, 22365 (2016).CrossRefPubMedPubMedCentral
70.
Bruyn, G. A. et al. An OMERACT reliability exercise of inflammatory and structural abnormalities in patients with knee osteoarthritis using ultrasound assessment. Ann. Rheum. Dis. 75, 842–846 (2016).CrossRefPubMed
71.
Hall, M. et al. Synovial pathology detected on ultrasound correlates with the severity of radiographic knee osteoarthritis more than with symptoms. Osteoarthritis Cartilage 22, 1627–1633 (2014).CrossRefPubMedPubMedCentral
72.
Parsons, M. A. et al. Increased 18F-FDG uptake suggests synovial inflammatory reaction with osteoarthritis: preliminary in-vivo results in humans. Nucl. Med. Commun. 36, 1215–1219 (2015).CrossRefPubMedPubMedCentral
73.
Mazzuca, S. A. et al. Severity of joint pain and Kellgren–Lawrence grade at baseline are better predictors of joint space narrowing than bone scintigraphy in obese women with knee osteoarthritis. J. Rheumatol. 32, 1540–1546 (2005).PubMed
74.
Guermazi, A., Hayashi, D., Roemer, F. W. & Felson, D. T. Osteoarthritis: a review of strengths and weaknesses of different imaging options. Rheum. Dis. Clin. North Am. 39, 567–591 (2013).CrossRefPubMed
75.
Omoumi, P., Mercier, G. A., Lecouvet, F., Simoni, P. & Vande Berg, B. C. CT arthrography, MR arthrography, PET, and scintigraphy in osteoarthritis. Radiol. Clin. North Am. 47, 595–615 (2009).CrossRefPubMed