Association of subchondral bone marrow lesion localization with weight-bearing pain in people with knee osteoarthritis: data from the Osteoarthritis Initiative

Koji Aso, Seyed Mohsen Shahtaheri, Daniel F McWilliams, David A Walsh, Koji Aso, Seyed Mohsen Shahtaheri, Daniel F McWilliams, David A Walsh

Abstract

Background: Subchondral bone marrow lesions (BMLs) detected on MRI in knee osteoarthritis (OA) are associated with knee pain. The prevalence and progression of subchondral BMLs are increased by mechanical knee load. However, associations of subchondral BML location with weight-bearing knee pain are currently unknown. In this study, we aim to demonstrate associations of subchondral BML location and size with weight-bearing knee pain in knee OA.

Methods: We analyzed 1412 and 582 varus knees from cross-sectional and longitudinal Osteoarthritis Initiative datasets, respectively. BML scores were semi-quantitatively analyzed with the MRI Osteoarthritis Knee Score for 4 subchondral regions (median and lateral femorotibial, medial and lateral patellofemoral) and subspinous region. Weight-bearing and non-weight-bearing pain scores were derived from WOMAC pain items. Correlation and negative binomial regression models were used for analysis of associations between the BML scores and pain at baseline and changes in the BML scores and changes in pain after 24-month follow-up.

Results: Greater BML scores at medial femorotibial and lateral patellofemoral compartments were associated with greater weight-bearing pain scores, and statistical significance was retained after adjusting for BML scores at the other 4 joint compartments and other OA features, as well as for non-weight-bearing pain, age, sex, and body mass index (BMI) (medial femorotibial; B = 0.08, p = 0.02. patellofemoral; B = 0.13, p = 0.01). Subanalysis revealed that greater medial femorotibial BML scores were associated with greater pain on walking and standing (B = 0.11, p = 0.01, and B = 0.10, p = 0.04, respectively). Lateral patellofemoral BML scores were associated with pain on climbing, respectively (B = 0.14, p = 0.02). Increases or decreases over 24 months in BML score in the medial femorotibial compartment were significantly associated with increases or decreases in weight-bearing pain severity after adjusting for non-weight-bearing pain, age, sex, baseline weight-bearing pain, BMI, and BML at the other 4 joint compartments (B = 0.10, p = 0.01).

Conclusions: Subchondral BML size at the medial femorotibial joint compartment was specifically associated with the severity and the change in weight-bearing pain, independent of non-weight-bearing pain, in knee OA. Specific associations of weight-bearing pain with subchondral BMLs in weight-bearing compartments of the knee indicate that BMLs in subchondral bone contribute to biomechanically induced OA pain.

Conflict of interest statement

D.A. Walsh: Grants from Versus Arthritis, while the study was being conducted; grants from Pfizer Ltd., other from Pfizer Ltd., personal fees from GlaxoSmithKline, outside the submitted work.

D. F. McWilliams: grants from Pfizer Ltd.

The remaining authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Subject selection from OAI database. n, number of participants included in the analysis
Fig. 2
Fig. 2
Delineation of subregional divisions for BML scoring. For BML scoring, the knee was divided into 4 articular sub-regions (medial and lateral femorotibial, and medial and lateral patellofemoral compartment) and subspinous region based on MOAKS; MFT, median femorotibial compartment; LFT, lateral femorotibial compartment; PF, patellofemoral compartment; S, subspinous region

References

    1. Stahl R, Jain SK, Lutz J, Wyman BT, Le Graverand-Gastineau MP, Vignon E, Majumdar S, Link TM. Osteoarthritis of the knee at 3.0 T: comparison of a quantitative and a semi-quantitative score for the assessment of the extent of cartilage lesion and bone marrow edema pattern in a 24-month longitudinal study. Skelet Radiol. 2011;40(10):1315–1327. doi: 10.1007/s00256-011-1156-9.
    1. Lo GH, McAlindon TE, Niu J, Zhang Y, Beals C, Dabrowski C, Le Graverand MP, Hunter DJ. Bone marrow lesions and joint effusion are strongly and independently associated with weight-bearing pain in knee osteoarthritis: data from the osteoarthritis initiative. Osteoarthr Cartil. 2009;17(12):1562–1569. doi: 10.1016/j.joca.2009.06.006.
    1. Driban JB, Price L, Lo GH, Pang J, Hunter DJ, Miller E, Ward RJ, Eaton CB, Lynch JA, McAlindon TE. Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker--longitudinal relationships with pain and structural changes: data from the osteoarthritis initiative. Arthritis Res Ther. 2013;15(5):R112. doi: 10.1186/ar4292.
    1. Hunter DJ, Gerstenfeld L, Bishop G, Davis AD, Mason ZD, Einhorn TA, Maciewicz RA, Newham P, Foster M, Jackson S, et al. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res Ther. 2009;11(1):R11. doi: 10.1186/ar2601.
    1. Kuttapitiya A, Assi L, Laing K, Hing C, Mitchell P, Whitley G, Harrison A, Howe FA, Ejindu V, Heron C, et al. Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Ann Rheum Dis. 2017;76(10):1764–1773. doi: 10.1136/annrheumdis-2017-211396.
    1. Beckwee D, Vaes P, Shahabpour M, Muyldermans R, Rommers N, Bautmans I. The influence of joint loading on bone marrow lesions in the knee: a systematic review with meta-analysis. Am J Sports Med. 2015;43(12):3093–3107. doi: 10.1177/0363546514565092.
    1. Felson DT, McLaughlin S, Goggins J, LaValley MP, Gale ME, Totterman S, Li W, Hill C, Gale D. Bone marrow edema and its relation to progression of knee osteoarthritis. Ann Intern Med. 2003;139(5 Pt 1):330–336. doi: 10.7326/0003-4819-139-5_Part_1-200309020-00008.
    1. Wildi LM, Raynauld JP, Martel-Pelletier J, Abram F, Dorais M, Pelletier JP. Relationship between bone marrow lesions, cartilage loss and pain in knee osteoarthritis: results from a randomised controlled clinical trial using MRI. Ann Rheum Dis. 2010;69(12):2118–2124. doi: 10.1136/ard.2009.127993.
    1. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. 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. 1988;15(12):1833–1840.
    1. Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI osteoarthritis knee score) Osteoarthr Cartil. 2011;19(8):990–1002. doi: 10.1016/j.joca.2011.05.004.
    1. Stratford PW, Kennedy DM, Woodhouse LJ, Spadoni GF. Measurement properties of the WOMAC LK 3.1 pain scale. Osteoarthr Cartil. 2007;15(3):266–272. doi: 10.1016/j.joca.2006.09.005.
    1. Aso K, Shahtaheri SM, Hill R, Wilson D, McWilliams DF, Walsh DA. Associations of symptomatic knee osteoarthritis with Histopathologic features in Subchondral bone. Arthritis Rheumatol. 2019;71(6):916–924. doi: 10.1002/art.40820.
    1. Wang J, Antony B, Zhu Z, Han W, Pan F, Wang X, Jin X, Liu Z, Cicuttini F, Jones G, et al. Association of patellar bone marrow lesions with knee pain, patellar cartilage defect and patellar cartilage volume loss in older adults: a cohort study. Osteoarthr Cartil. 2015;23(8):1330–1336. doi: 10.1016/j.joca.2015.02.018.
    1. Otsuki S, Nakajima M, Okamoto Y, Oda S, Hoshiyama Y, Iida G, Neo M. Correlation between varus knee malalignment and patellofemoral osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2016;24(1):176–181. doi: 10.1007/s00167-014-3360-3.
    1. Aso K, Shahtaheri SM, Hill R, Wilson D, McWilliams DF, Nwosu LN, Chapman V, Walsh DA. Contribution of nerves within osteochondral channels to osteoarthritis knee pain in humans and rats. Osteoarthr Cartil. 2020;28(9):1245–1254. doi: 10.1016/j.joca.2020.05.010.
    1. Lim YZ, Wang Y, Wluka AE, Davies-Tuck ML, Hanna F, Urquhart DM, Cicuttini FM. Association of obesity and systemic factors with bone marrow lesions at the knee: a systematic review. Semin Arthritis Rheum. 2014;43(5):600–612. doi: 10.1016/j.semarthrit.2013.10.006.
    1. Khan HI, Aitken D, Blizzard L, Ding C, Pelletier JP, Pelletier JM, Cicuttini F, Jones G. History of knee injury and MRI-assessed knee structures in middle- and older-aged adults: a cross-sectional study. Clin Rheumatol. 2015;34(8):1463–1472. doi: 10.1007/s10067-014-2758-0.
    1. Amano K, Pedoia V, Su F, Souza RB, Li X, Ma CB. Persistent biomechanical alterations after ACL reconstruction are associated with early cartilage matrix changes detected by quantitative MR. Orthop J Sports Med. 2016;4(4):2325967116644421. doi: 10.1177/2325967116644421.
    1. Antony B, Venn A, Cicuttini F, March L, Blizzard L, Dwyer T, Halliday A, Cross M, Jones G, Ding C. Correlates of knee bone marrow lesions in younger adults. Arthritis Res Ther. 2016;18:31. doi: 10.1186/s13075-016-0938-9.
    1. Englund M, Guermazi A, Roemer FW, Yang M, Zhang Y, Nevitt MC, Lynch JA, Lewis CE, Torner J, Felson DT. Meniscal pathology on MRI increases the risk for both incident and enlarging subchondral bone marrow lesions of the knee: the MOST study. Ann Rheum Dis. 2010;69(10):1796–1802. doi: 10.1136/ard.2009.121681.
    1. Hunter DJ, Zhang Y, Niu J, Goggins J, Amin S, LaValley MP, Guermazi A, Genant H, Gale D, Felson DT. Increase in bone marrow lesions associated with cartilage loss: a longitudinal magnetic resonance imaging study of knee osteoarthritis. Arthritis Rheum. 2006;54(5):1529–1535. doi: 10.1002/art.21789.
    1. Racunica TL, Teichtahl AJ, Wang Y, Wluka AE, English DR, Giles GG, O'Sullivan R, Cicuttini FM. Effect of physical activity on articular knee joint structures in community-based adults. Arthritis Rheum. 2007;57(7):1261–1268. doi: 10.1002/art.22990.
    1. Callaghan MJ, Parkes MJ, Hutchinson CE, Gait AD, Forsythe LM, Marjanovic EJ, Lunt M, Felson DT. A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions. Ann Rheum Dis. 2015;74(6):1164–1170. doi: 10.1136/annrheumdis-2014-206376.
    1. Hinman RS, Payne C, Metcalf BR, Wrigley TV, Bennell KL. Lateral wedges in knee osteoarthritis: what are their immediate clinical and biomechanical effects and can these predict a three-month clinical outcome? Arthritis Rheum. 2008;59(3):408–415. doi: 10.1002/art.23326.
    1. Bennell KL, Bowles KA, Payne C, Cicuttini F, Williamson E, Forbes A, Hanna F, Davies-Tuck M, Harris A, Hinman RS. Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial. BMJ. 2011;342:d2912. doi: 10.1136/bmj.d2912.
    1. Laslett LL, Dore DA, Quinn SJ, Boon P, Ryan E, Winzenberg TM, Jones G. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012;71(8):1322–1328. doi: 10.1136/annrheumdis-2011-200970.
    1. Vaysbrot EE, Osani MC, Musetti MC, McAlindon TE, Bannuru RR. Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthr Cartil. 2018;26(2):154–164. doi: 10.1016/j.joca.2017.11.013.
    1. Cai G, Laslett LL, Aitken D, Cicuttini F, March L, Hill C, Winzenberg T, Jones G. Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial. Ther Adv Musculoskelet Dis. 2019;11. 10.1177/1759720X19880054.
    1. Guymer E, Baranyay F, Wluka AE, Hanna F, Bell RJ, Davis SR, Wang Y, Cicuttini FM. A study of the prevalence and associations of subchondral bone marrow lesions in the knees of healthy, middle-aged women. Osteoarthr Cartil. 2007;15(12):1437–1442. doi: 10.1016/j.joca.2007.04.010.
    1. Wluka AE, Hanna F, Davies-Tuck M, Wang Y, Bell RJ, Davis SR, Adams J, Cicuttini FM. Bone marrow lesions predict increase in knee cartilage defects and loss of cartilage volume in middle-aged women without knee pain over 2 years. Ann Rheum Dis. 2009;68(6):850–855. doi: 10.1136/ard.2008.092221.
    1. Libicher M, Ivancic M, Hoffmann M, Wenz W. Early changes in experimental osteoarthritis using the Pond-Nuki dog model: technical procedure and initial results of in vivo MR imaging. Eur Radiol. 2005;15(2):390–394. doi: 10.1007/s00330-004-2486-y.
    1. Lefevre N, Klouche S, Sezer HB, Gerometta A, Bohu Y, Lefevre E. The “sleeper's sign” is valid and suggestive of a medial sub-meniscal flap tear. Knee Surg Sports Traumatol Arthrosc. 2019.
    1. Baker K, Grainger A, Niu J, Clancy M, Guermazi A, Crema M, Hughes L, Buckwalter J, Wooley A, Nevitt M, et al. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann Rheum Dis. 2010;69(10):1779–1783. doi: 10.1136/ard.2009.121426.
    1. Wang X, Jin X, Han W, Cao Y, Halliday A, Blizzard L, Pan F, Antony B, Cicuttini F, Jones G, et al. Cross-sectional and longitudinal associations between knee joint effusion synovitis and knee pain in older adults. J Rheumatol. 2016;eeeee43(1):121–130. doi: 10.3899/jrheum.150355.
    1. Moisio K, Eckstein F, Chmiel JS, Guermazi A, Prasad P, Almagor O, Song J, Dunlop D, Hudelmaier M, Kothari A, et al. Denuded subchondral bone and knee pain in persons with knee osteoarthritis. Arthritis Rheum. 2009;60(12):3703–3710. doi: 10.1002/art.25014.
    1. Zhu Z, Laslett LL, Jin X, Han W, Antony B, Wang X, Lu M, Cicuttini F, Jones G, Ding C. Association between MRI-detected osteophytes and changes in knee structures and pain in older adults: a cohort study. Osteoarthr Cartil. 2017;25(7):1084–1092. doi: 10.1016/j.joca.2017.01.007.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe