Ultrasonographic echo intensity in the medial femoral cartilage is enhanced prior to cartilage thinning in women with early mild knee osteoarthritis

233

1.

Casula V, Hirvasniemi J, Lehenkari P, Ojala R, Haapea M, Saarakkala S, et al. (2016) Association between

234

quantitative MRI and ICRS arthroscopic grading of articular cartilage. Knee Surg Sports Traumatol Arthrosc

235

24(6):2046-2054

236

2.

Harkey MS, Blackburn JT, Davis H, Sierra-Arevalo L, Nissman D, Pietrosimone B (2017) Ultrasonographic

237

assessment of medial femoral cartilage deformation acutely following walking and running. Osteoarthritis

238

Cartilage 25(6):907-913

239

3.

echo intensity associates with arthroscopic cartilage damage. Ultrasound Med Biol 47(1):43-50

240

241

4.

5.

Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics

33(1):159-174

244

245

Koo TK, Li MY (2016) A guideline of selecting and reporting intraclass correlation coefficients for reliability

research. J Chiropr Med 15(2):155-163

242

243

Harkey MS, Little E, Thompson M, Zhang M, Driban JB, Salzler MJ (2021) Femoral cartilage ultrasound

6.

MacKay JW, Low SBL, Smith TO, Toms AP, McCaskie AW, Gilbert FJ (2018) Systematic review and meta-

246

analysis of the reliability and discriminative validity of cartilage compositional MRI in knee osteoarthritis.

247

Osteoarthritis Cartilage 26(9):1140-1152

248

7.

Imaging Med Surg 3(3):162-174

249

250

Matzat SJ, van Tiel J, Gold GE, Oei EH (2013) Quantitative MRI techniques of cartilage composition. Quant

8.

Migliore A, Gigliucci G, Alekseeva L, Avasthi S, Bannuru RR, Chevalier X, et al. (2019) Treat-to-target

251

strategy for knee osteoarthritis. International technical expert panel consensus and good clinical practice

252

statements. Ther Adv Musculoskelet Dis 11:1759720x19893800

253

9.

osteoarthritis of the knee using 3-Tesla magnetic resonance imaging. Pol J Radiol 84:e549-e564

254

255

10.

Moller I, Bong D, Naredo E, Filippucci E, Carrasco I, Moragues C, et al. (2008) Ultrasound in the study and

monitoring of osteoarthritis. Osteoarthritis Cartilage 16 Suppl 3:S4-7

256

257

Mittal S, Pradhan G, Singh S, Batra R (2019) T1 and T2 mapping of articular cartilage and menisci in early

11.

Okano T, Filippucci E, Di Carlo M, Draghessi A, Carotti M, Salaffi F, et al. (2016) Ultrasonographic

258

evaluation of joint damage in knee osteoarthritis: feature-specific comparisons with conventional

259

radiography. Rheumatology (Oxford) 55(11):2040-2049

260

12.

Pamukoff DN, Vakula MN, Holmes SC, Shumski EJ, Garcia SA (2020) Body mass index moderates the

261

association between gait kinetics, body composition, and femoral knee cartilage characteristics. J Orthop

262

Res 38(12):2685-2695

263

13.

Reichenbach S, Yang M, Eckstein F, Niu J, Hunter DJ, McLennan CE, et al. (2010) Does cartilage volume

264

or thickness distinguish knees with and without mild radiographic osteoarthritis? The Framingham Study.

265

Ann Rheum Dis 69(1):143-149

266

14.

Saarakkala S, Waris P, Waris V, Tarkiainen I, Karvanen E, Aarnio J, et al. (2012) Diagnostic performance of

267

knee ultrasonography for detecting degenerative changes of articular cartilage. Osteoarthritis Cartilage

268

20(5):376-381

269

15.

thickness: A comparison between ultrasound and magnetic resonance imaging methods. Knee 24(2):217-223

270

271

16.

Scuderi GR, Bourne RB, Noble PC, Benjamin JB, Lonner JH, Scott WN (2012) The new Knee Society Knee

Scoring System. Clin Orthop Relat Res 470(1):3-19

272

273

Schmitz RJ, Wang HM, Polprasert DR, Kraft RA, Pietrosimone BG (2017) Evaluation of knee cartilage

17.

Stefanik JJ, Guermazi A, Roemer FW, Peat G, Niu J, Segal NA, et al. (2016) Changes in patellofemoral and

274

tibiofemoral joint cartilage damage and bone marrow lesions over 7 years: the Multicenter Osteoarthritis

275

Study. Osteoarthritis Cartilage 24(7):1160-1166

276

18.

Stehling C, Liebl H, Krug R, Lane NE, Nevitt MC, Lynch J, et al. (2010) Patellar cartilage: T2 values and

277

morphologic abnormalities at 3.0-T MR imaging in relation to physical activity in asymptomatic subjects

278

from the osteoarthritis initiative. Radiology 254(2):509-520

279

19.

Surowiec RK, Lucas EP, Ho CP (2014) Quantitative MRI in the evaluation of articular cartilage health:

280

reproducibility and variability with a focus on T2 mapping. Knee Surg Sports Traumatol Arthrosc

281

22(6):1385-1395

282

20.

Taniguchi M, Ikezoe T, Kamitani T, Tsuboyama T, Ito H, Matsuda S, et al. (2021) Extracellular-to-

283

intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis:

284

results from the Nagahama Study. Clin Rheumatol 40(7):2889-2896

285

21.

Taniguchi N, Matsuda S, Kawaguchi T, Tabara Y, Ikezoe T, Tsuboyama T, et al. (2015) The KSS 2011 reflects

286

symptoms, physical activities, and radiographic grades in a Japanese population. Clin Orthop Relat Res

287

473(1):70-75

288

289

22.

Vannini F, Spalding T, Andriolo L, Berruto M, Denti M, Espregueira-Mendes J, et al. (2016) Sport and early

osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis. Knee Surg

10

Sports Traumatol Arthrosc 24(6):1786-1796

290

291

23.

Wirth W, Hunter DJ, Nevitt MC, Sharma L, Kwoh CK, Ladel C, et al. (2017) Predictive and concurrent

292

validity of cartilage thickness change as a marker of knee osteoarthritis progression: data from the

293

Osteoarthritis Initiative. Osteoarthritis Cartilage 25(12):2063-2071

294

24.

Yamagata M, Taniguchi M, Tateuchi H, Kobayashi M, Ichihashi N (2021) The effects of knee pain on knee

295

contact force and external knee adduction moment in patients with knee osteoarthritis. J Biomech

296

123:110538

297

298

11

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Tables

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Table 1 Participant demographic characteristics

Age, y

Control

Early OA

Grade 2

68.3±11.0

Height, cm

vs

eOA

vs 2

Weight, kg

p=0.033

Knee ROM, °

vs

151.0±6.0

eOA

vs 2

vs 3

p=0.014

vs 3

p=0.001

vs 4

p=0.008

vs 4

p<0.001

vs 2

n.s.

vs 2

n.s.

n.s.

vs 2

n.s.

vs

eOA

vs 2

vs 3

n.s.

vs 3

n.s.

vs 4

p=0.045

vs 4

n.s.

n.s.

154.3±5.9 vs eOA

n.s.

47.8±4.5

n.s.

n.s.

153.4±4.0 vs 2

n.s.

vs 3

n.s.

vs 3

n.s.

vs 3

n.s.

vs 3

n.s.

vs 4

p=0.018

vs 4

n.s.

vs 4

n.s.

vs 4

p<0.001

vs 3

n.s.

155.0±5.7 vs 3

n.s.

vs 3

n.s.

vs 3

n.s.

vs 4

n.s.

vs 4

n.s.

vs 4

n.s.

vs 4

p<0.001

n.s.

155.3±5.5 vs 4

n.s.

vs 4

n.s.

vs 4

p<0.001

Grade 3

72.6±7.3

vs 4

Grade 4

75.9±8.9

152.6±7.1 -

55.3±8.7

56.8±9.7

57.2±10.5 -

146.4±6.5

n.s.

66.3±11.4 vs 2

72.4±8.4

54.8±8.9

n.s.

145.4±7.4

140.3±7.4

129.2±11.3 -

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Total

71.9±8.9

154.3±5.9

54.8±9.3

141.9±11.1

Data are presented as mean ± standard deviation. Bold text indicates a significant difference in the Sidak post hoc test.

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OA: osteoarthritis, ROM: range of motion, eOA: early OA, 2: grade 2, 3: grade 3, 4: grade 4, n.s.: not significant

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304

305

306

307

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Table 2 Comparison of the femoral cartilage ultrasonographic outcomes between knees with varying OA grades

Control

Early OA

Grade 2

LS thickness, mm

vs

1.4±0.1

n.s.

eOA

vs 2

n.s.

ST thickness, mm

vs

1.6±0.1

n.s.

eOA

vs 2

p=0.02

26.5±2.4

vs eOA

n.s.

vs 2

n.s.

p=0.001

vs 3

p=0.001

vs 3

p=0.04

vs 3

n.s.

vs 4

p<0.001

vs 4

p=0.009

vs 4

p<0.001

vs 4

n.s.

vs 2

n.s.

1.4±0.1 vs 2

n.s.

24.5±3.0 vs 2

n.s.

1.5±0.1 vs 2

n.s.

29.7±2.9

vs 3

p=0.003

vs 3

p=0.015

vs 3

n.s.

vs 3

n.s.

vs 4

p=<0.001

vs 4

n.s.

vs 4

p<0.001

vs 4

n.s.

31.9±1.7 vs 3

n.s.

1.3±0.1 vs 3

vs 3

n.s.

vs 4

n.s.

vs 4

p<0.001

vs 4

n.s.

36.5±2.1 vs 4

n.s.

1.3±0.1 vs 4

p=0.004

32.1±2.1

vs 4

n.s.

32.0±2.2

1.2±0.1 vs 3

1.0±0.1 vs 4

n.s.

p<0.001

n.s.

n.s.

Grade 4

0.8±0.1 34.6±2.1 0.9±0.1 309

Data are shown as mean ± standard error. Bold text indicates a significant difference in the Sidak post hoc test.

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ST echo intensity, a.u.

vs 3

vs 4

Grade 3

LS echo intensity, a.u.

vs

23.5±2.4

n.s.

eOA

vs 2

p=0.049

32.0±1.6

OA: osteoarthritis, LS: longitudinal sagittal, ST: suprapatellar transverse, eOA: early OA, 2: grade 2, 3: grade 3, 4: grade 4, n.s.: not significant, a.u.: arbitrary unit

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312

313

314

315

316

Figures

317

Fig. 1 Ultrasonographic image of the femoral cartilage

318

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a. Longitudinal and b. transverse images. The region inside the yellow line represents the area analyzed. The transverse

320

images were manually segmented using a previously described method [3]. The intercondylar zone was defined as the

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middle 25% of the image, centered at the deepest point of the intercondylar notch. The medial femoral zone was defined

322

as the portion to the right side of the intercondylar zone. In this study, we analyzed only the medial compartment.

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Fig. 2 Unadjusted thickness and echo intensity of the femoral medial cartilage in each group

325

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The top and bottom line represent the maximum and minimum values of cartilage thickness and echo intensity,

327

respectively. The top and bottom line of the boxes represent the third and first quartiles, and the line in the boxes represent

328

the median. LS : longitudinal sagittal, ST : suprapatellar transverse

Supplemental file 1 Differences of femoral cartilage ultrasound outcomes between knee OA grade

LS thickness, mm

vs control

vs early OA

vs grade 2

vs grade 3

LS echo intensity, a.u.

ST thickness, mm

ST echo intensity, a.u.

difference

95% CI

P value

difference

95% CI

P value

difference

95% CI

P value

difference

95% CI

P value

early OA

0.02

-0.33 to 0.38

>0.99

0.99

-9.84 to 11.81

>0.99

-0.08

-0.44 to 0.28

>0.99

3.15

-7.44 to 13.75

0.99

grade 2

-0.21

-0.48 to 0.07

0.28

8.44

0.05 to 16.87

0.049

-0.31

-0.59 to -0.03

0.02

5.43

-2.79 to 13.65

0.47

grade 3

-0.43

-0.73 to -0.13

0.001

13.05

3.86 to 22.24

0.001

-0.31

-0.62 to -0.006

0.04

5.57

-3.48 to 14.62

0.57

grade 4

-0.66

-0.97 to -0.36

<0.001

11.11

1.84 to 20.38

0.009

-0.68

-0.99 to -0.37

<0.001

5.45

-3.85 to 14.75

0.64

grade 2

-0.24

-0.56 to 0.09

0.35

7.45

-2.46 to 17.36

0.29

-0.23

-0.56 to 0.10

0.37

2.28

-7.40 to 11.95

>0.99

grade 3

-0.45

-0.80 to -0.10

0.003

12.06

1.49 to 22.64

0.015

-0.24

-0.59 to 0.12

0.44

2.42

-7.97 to 12.81

>0.99

grade 4

-0.69

-1.04 to -0.33

<0.001

10.13

-0.52 to 20.77

0.07

-0.61

-0.97 to -0.25

<0.001

2.30

-8.32 to 12.91

>0.99

grade 3

-0.22

-0.47 to 0.03

0.13

4.61

-2.94 to 12.16

0.58

-0.004

-0.26 to 0.25

>0.99

0.14

-7.59 to 7.31

>0.99

grade 4

-0.45

-0.70 to -0.20

<0.001

2.67

-4.90 to 10.25

0.98

-0.37

-0.63 to -0.11

0.001

0.02

-7.64 to 7.68

>0.99

grade 4

-0.23

-0.51 to 0.04

0.17

-1.94

-10.32 to 6.44

>0.99

-0.37

-0.66 to -0.08

0.004

-0.12

-8.68 to 8.44

>0.99

Post hoc analyses with the Sidak correction after the general linear model were performed to compare cartilage thickness and echo intensity in two portions of the femoral medial

condyle among knee OA grades. Bold font indicates a statistically significant difference. OA: osteoarthritis; LS: longitudinal-sagittal; ST: suprapatellar transverse; difference: adjusted

mean difference; CI: confidence interval

...