Background
Methods
Study patients
Symptoms as predictors of treatment response
Imaging characteristics at T0 as predictors of disease response
Statistical analysis
Results
Demographic, symptom and imaging characteristics at T0 and change in symptoms based on WOMAC scores
Total (n = 404)a | Low,b0 < WOMAC painc < 4(n = 118) | Moderate,4 ≤ WOMAC painc ≤ 7(n = 150) | High,WOMAC painc ≥ 8(n = 136) | Low vs Highp valued | Moderate vs Highp valued | |
---|---|---|---|---|---|---|
Subcohort | ||||||
Incidence | 47% (189) | 54% (64) | 50% (75) | 37% (50) | ||
Progression | 53% (215) | 46% (54) | 50% (75) | 63% (86) |
0.005
e
|
0.024
e
|
Injected knee | ||||||
Right | 50% (204) | 51% (60) | 51% (76) | 50% (68) | ||
Left | 50% (200) | 49% (58) | 49% (74) | 50% (68) | 0.893e | 0.910e |
Sex, male | 41% (165) | 46% (54) | 43% (65) | 34% (46) | 0.052e | 0.099e |
Age (years) | 66 ± 9 | 66 ± 9 | 66 ± 9 | 64 ± 9 | 0.140 | 0.190 |
(n = 364) | (n = 110) | (n = 134) | (n = 120) | |||
Body mass index | 30.39 ± 5.30 | 28.98 ± 4.48 | 30.74 ± 4.99 | 31.30 ± 6.07 |
0.002
| 0.353 |
Kellgren–Lawrence | (n = 208) | (n = 62) | (n = 78) | (n = 68) | ||
Grade 0, 1 | 15% (31) | 23% (14) | 14% (11) | 9% (6) | ||
Grade 2 | 26% (55) | 29% (18) | 26% (20) | 25% (17) | ||
Grade 3 | 35% (72) | 32% (20) | 33% (26) | 38% (26) | ||
Grade 4 | 24% (50) | 16% (10) | 27% (21) | 28% (19) | 0.088e | 0.769e |
(n = 226) | (n = 67) | (n = 86) | (n = 73) | |||
Joint space width (mm) | 3.34 ± 1.62 | 3.78 ± 1.79 | 3.23 ± 1.57 | 3.06 ± 1.45 |
0.010
| 0.430 |
Magnetic resonance imaging | ||||||
Cartilage volume (mm3) | (n = 239) | (n = 69) | (n = 92) | (n = 78) | ||
Global knee | 9371 ± 2788 | 10,196 ± 2356 | 9060 ± 2959 | 9009 ± 2813 |
0.002
| 0.917 |
Medial compartment | 4351 ± 1615 | 4861 ± 1515 | 4093 ± 1644 | 4205 ± 1582 |
0.008
| 0.670 |
Lateral compartment | 5020 ± 1490 | 5335 ± 1209 | 4967 ± 1627 | 4805 ± 1519 |
0.009
| 0.760 |
Bone marrow lesion (global knee) | (n = 246) | (n = 73) | (n = 92) | (n = 81) | ||
Presence | 42% (104) | 44% (32) | 36% (33) | 48% (39) | 0.592e | 0.102e |
Score | 1.97 ± 3.37 | 1.54 ± 2.54 | 1.86 ± 3.95 | 2.49 ± 3.28 | 0.090 | 0.058 |
Medial meniscus | (n = 248) | (n = 74) | (n = 95) | (n = 79) | ||
No extrusion | 64% (159) | 68% (50) | 67% (64) | 57% (45) | ||
Extrusion | 36% (89) | 32% (24) | 33% (31) | 43% (34) | 0.177e | 0.158e |
(n = 231) | (n = 67) | (n = 87) | (n = 77) | |||
Synovial fluid volume (ml) | 20.12 ± 13.59 | 17.43 ± 11.46 | 19.77 ± 13.25 | 22.86 ± 15.22 |
0.033
| 0.203 |
Total (n = 404)a | Low,b 0 < WOMAC painc < 4 (n = 118) | Moderate, 4 ≤ WOMAC painc ≤ 7 (n = 150) | High, WOMAC painc ≥ 8 (n = 136) | Low vs High p valued | Moderate vs High p valued | |
---|---|---|---|---|---|---|
WOMAC at T0 | ||||||
(n = 404) | (n = 118) | (n = 150) | (n = 136) | |||
Pain (0–20) | 6.13 ± 3.69 | 2.07 ± 0.80 | 5.37 ± 1.10 | 10.48 ± 2.19 |
< 0.001
|
< 0.001
|
(n = 390) | (n = 116) | (n = 146) | (n = 128) | |||
Function (0–68) | 19.27 ± 11.63 | 8.61 ± 5.53 | 18.46 ± 8.23 | 29.87 ± 9.55 |
< 0.001
|
< 0.001
|
(n = 404) | (n = 118) | (n = 150) | (n = 136) | |||
Stiffness (0–8) | 2.85 ± 1.68 | 1.84 ± 1.53 | 2.73 ± 1.38 | 3.85 ± 1.54 |
< 0.001
|
< 0.001
|
(n = 390) | (n = 116) | (n = 146) | (n = 128) | |||
Total (0–96) | 28.17 ± 15.80 | 12.49 ± 6.76 | 26.56 ± 9.32 | 44.23 ± 11.71 |
< 0.001
|
< 0.001
|
WOMAC change (T0 to T1) | (n = 404) | (n = 118) | (n = 150) | (n = 136) | ||
Pain | 0.28 ± 3.90 | 1.90 ± 2.81 | 1.25 ± 3.72 | −2.21 ± 3.71 |
< 0.001
|
< 0.001
|
Decrease ≥ 20% (responders) | 31% (125) | 19% (22) | 27% (40) | 46% (63) | ||
0% < decrease < 20% | 8% (31) | 0% (0) | 5% (7) | 18% (24) | ||
Stable = 0% (nonresponders) | 14% (55) | 14% (17) | 14% (21) | 13% (17) | ||
Increase > 0% (nonresponders) | 48% (193) | 67% (79) | 55% (82) | 24% (32) |
< 0.001
e
|
< 0.001
e
|
(n = 390) | (n = 116) | (n = 146) | (n = 128) | |||
Function | 0.95 ± 12.50 | 5.35 ± 9.84 | 2.56 ± 11.60 | −4.89 ± 13.50 |
< 0.001
|
< 0.001
|
(n = 404) | (n = 118) | (n = 150) | (n = 136) | |||
Stiffness | 0.18 ± 1.84 | 0.43 ± 1.53 | 0.29 ± 1.77 | −0.16 ± 2.10 |
0.010
|
0.032
|
(n = 390) | (n = 116) | (n = 146) | (n = 128) | |||
Total | 1.35 ± 16.71 | 7.62 ± 13.02 | 4.12 ± 15.43 | −7.50 ± 17.51 |
< 0.001
|
< 0.001
|
Total (n = 404)a | Low,b 0 < WOMAC painc < 4 (n = 118) | Moderate, 4 ≤ WOMAC painc ≤ 7 (n = 150) | High, WOMAC painc ≥ 8 (n = 136) | Low vs High p valued | Moderate vs High p valued | |
---|---|---|---|---|---|---|
(n = 311) | (n = 89) | (n = 119) | (n = 103) | |||
NSAIDs ± analgesics | 74% (230) | 74% (66) | 69% (82) | 80% (82) | 0.370 | 0.070 |
(n = 311) | (n = 89) | (n = 119) | (n = 103) | |||
Anti-bone remodeling | 17% (52) | 18% (16) | 18% (22) | 14% (14) | 0.404 | 0.324 |
(n = 404) | (n = 118) | (n = 150) | (n = 136) | |||
Steroid injections | 18% (72) | 12% (14) | 17% (26) | 24% (32) |
0.016
| 0.193 |
(n = 400) | (n = 117) | (n = 148) | (n = 135) | |||
Glucosamine ± chondroitin sulfate | 49% (194) | 56% (65) | 52% (77) | 39% (52) |
0.007
|
0.023
|
Responders and nonresponders
Total | High,a WOMAC painb ≥ 8 | ||||
---|---|---|---|---|---|
Responders and nonresponders (n = 112)c | Respondersd (n = 63) | Nonresponderse (n = 49) | p valuef | p valueg | |
Subcohort | |||||
Incidence | 34% (38) | 35% (22) | 33% (16) | ||
Progression | 66% (74) | 65% (41) | 67% (33) | 0.802h |
–
|
Injected knee | |||||
Right | 50% (56) | 46% (29) | 55% (27) | ||
Left | 50% (56) | 54% (34) | 45% (22) | 0.341h | – |
Sex, male | 33% (37) | 35% (22) | 31% (15) | 0.631h | – |
Age (years) | 64 ± 9 | 62 ± 8 | 67 ± 9 |
0.014
| – |
(n = 101) | (n = 58) | (n = 43) | |||
Body mass index | 31.23 ± 6.29 | 32.09 ± 6.04 | 30.06 ± 6.50 | 0.163 | – |
Kellgren–Lawrence | (n = 60) | (n = 34) | (n = 26) | ||
Grade 0, 1 | 10% (6) | 9% (3) | 12% (3) | ||
Grade 2 | 25% (15) | 26% (9) | 23% (6) | ||
Grade 3 | 37% (22) | 32% (11) | 42% (11) | ||
Grade 4 | 28% (17) | 32% (11) | 23% (6) | 0.812h | – |
(n = 61) | (n = 33) | (n = 29) | |||
Joint space width (mm) | 3.07 ± 1.46 | 3.37 ± 1.46 | 2.74 ± 1.42 | 0.102 | 0.150 |
Magnetic resonance imaging | |||||
Cartilage volume (mm3) | (n = 71) | (n = 42) | (n = 29) | ||
Global knee | 8746 ± 2554 | 9016 ± 2707 | 8354 ± 2306 | 0.196 | 0.263 |
Medial compartment | 4065 ± 1472 | 4334 ± 1455 | 3675 ± 1434 | 0.054 |
0.046
|
Lateral compartment | 4680 ± 1417 | 4682 ± 1517 | 4679 ± 1286 | 0.695 | 0.809 |
Bone marrow lesion (global knee) | (n = 72) | (n = 43) | (n = 29) | ||
Presence | 49% (35) | 51% (22) | 45% (13) | 0.598h | – |
Score | 2.47 ± 3.16 | 2.47 ± 3.25 | 2.47 ± 3.08 | 0.899 | 0.901 |
Medial meniscus | (n = 71) | (n = 41) | (n = 30) | ||
No extrusion | 58% (41) | 56% (23) | 60% (18) | ||
Extrusion | 42% (30) | 44% (18) | 40% (12) | 0.742h | – |
(n = 69) | (n = 40) | (n = 29) | |||
Synovial fluid volume (ml) | 22.95 ± 15.79 | 22.90 ± 16.63 | 23.01 ± 14.84 | 0.766 | 0.982 |
Total | High,b WOMAC paina ≥ 8 | ||||
---|---|---|---|---|---|
Responders and nonresponders (n = 112)c | Respondersd (n = 63) | Nonresponderse (n = 49) | p valuef | p valueg | |
WOMAC at T0 | |||||
(n = 112) | (n = 63) | (n = 49) | |||
Pain (0–20) | 10.44 ± 2.28 | 10.87 ± 2.37 | 9.88 ± 2.05 |
0.008
| 0.112 |
(n = 104) | (n = 62) | (n = 42) | |||
Function (0–68) | 29.93 ± 9.43 | 30.95 ± 8.93 | 28.41 ± 10.04 | 0.229 | 0.223 |
(n = 112) | (n = 63) | (n = 49) | |||
Stiffness (0–8) | 3.85 ± 1.50 | 3.87 ± 1.40 | 3.82 ± 1.64 | 0.966 | 0.364 |
(n = 104) | (n = 62) | (n = 42) | |||
Total (0–96) | 44.24 ± 11.67 | 45.63 ± 11.07 | 42.20 ± 12.36 | 0.146 | 0.163 |
WOMAC change (T0 to T1) | |||||
(n = 112) | (n = 63) | (n = 49) | |||
Pain | −2.41 ± 4.06 | −5.31 ± 2.84 | 1.33 ± 1.52 |
< 0.001
|
< 0.001
|
20% ≤ decrease < 40% | 59% (37) | ||||
Decrease > 40% | 41% (26) | ||||
(n = 104) | (n = 62) | (n = 42) | |||
Function | −5.30 ± 14.52 | −11.88 ± 10.99 | 4.42 ± 13.69 |
< 0.001
|
< 0.001
|
20% ≤ decrease < 40% | 44% (27) | ||||
Decrease > 40% | 21% (13) | ||||
(n = 112) | (n = 63) | (n = 49) | |||
Stiffness | −0.16 ± 2.16 | −0.75 ± 2.03 | 0.59 ± 2.10 |
< 0.010
|
< 0.001
|
20% ≤ decrease < 40% | 30% (19) | ||||
Decrease > 40% | 25% (16) | ||||
(n = 104) | (n = 62) | (n = 42) | |||
Total | −8.17 ± 18.97 | −17.95 ± 14.13 | 6.27 ± 15.76 |
< 0.001
|
< 0.001
|
20% ≤ decrease < 40% | 44% (27) | ||||
Decrease > 40% | 27% (17) |