Introduction
Methods
Study sample and treatment
Study design
Imaging of the knee
Symptoms
Outcomes
Statistical analyses
Results
Study sample and baseline characteristics
Baseline characteristics within the placebo group
Ext- (n = 86)
|
Ext+ (n = 26)
|
P
-value
| |
---|---|---|---|
Demographic and clinical
| |||
Age, years | 62 ± 8 | 65 ± 8 | 0.078 |
Female, n (%) | 57 (66%) | 19 (73%) | 0.515†
|
Body mass index, kg/m2
| 30 ± 4 | 29 ± 6 | 0.275 |
WOMAC | |||
Pain (0 to 100) | 37.7 ± 21.9 | 40.9 ± 20.0 | 0.340 |
Function (0 to 100) | 39.5 ± 22.4 | 38.3 ± 22.7 | 0.762 |
Stiffness (0 to 100) | 41.9 ± 24.5 | 46.4 ± 19.4 | 0.403 |
Total (0 to 300) | 120.6 ± 65.0 | 127.1 ± 56.6 | 0.654 |
VAS pain (0 to 100 mm) | 48.5 ± 25.2 | 54.3 ± 18.8 | 0.199 |
Imaging
| |||
Kellgren-Lawrence score, n (%) |
0.002
†
| ||
Grade 1 | - | - | |
Grade 2 | 64 (74%) | 11 (42%) | |
Grade 3 | 22 (26%) | 15 (58%) | |
Joint space width, mm | 3.61 ± 0.77 | 3.15 ± 0.51 |
0.004
|
Presence of BML in the medial compartment, n (%) | 18 (21%) | 12 (46%) |
0.011
†
|
MRI, mm3
| |||
Global knee
| 11256 ± 2968 | 10479 ± 2243 | 0.395 |
Femur | 7773 ± 2139 | 7398 ± 1465 | 0.697 |
Plateau | 3483 ± 897 | 3081 ± 830 | 0.109 |
Medial compartment
| 5324 ± 1435 | 5089 ± 1020 | 0.682 |
Medial femur | 3763 ± 1023 | 3619 ± 689 | 0.817 |
Medial plateau | 1562 ± 452 | 1470 ± 360 | 0.608 |
Ext- (n = 86)
|
Ext+ (n = 26)
| |||||
---|---|---|---|---|---|---|
BML- (n = 68)
|
BML+ (n = 18)
|
P
-value
|
BML- (n = 14)
|
BML+ (n = 12)
|
P
-value
| |
Demographic and clinical
| ||||||
Age, years | 61 ± 7 | 64 ± 10 | 0.493 | 65 ± 7 | 65 ± 10 | >0.999 |
Female, n (%) | 47 (69%) | 10 (56%) | 0.279†
| 9 (64%) | 10 (83%) | 0.275†
|
Body mass index, kg/m2
| 30 ± 4 | 30 ± 3 | 0.824 | 31 ± 7 | 27 ± 3 | 0.116 |
WOMAC | ||||||
Pain (0 to 100) | 37.4 ± 22.7 | 39.2 ± 19.0 | 0.587 | 48.5 ± 19.2 | 32.8 ± 18.2 |
0.053
|
Function (0 to 100) | 40.7 ± 22.5 | 35.5 ± 22.3 | 0.449 | 46.6 ± 22.6 | 28.7 ± 19.5 |
0.021
|
Stiffness (0 to 100) | 41.4 ± 26.3 | 43.7 ± 16.3 | 0.834 | 50.8 ± 17.5 | 41.4 ± 21.1 | 0.208 |
Total (0 to 300) | 120.9 ± 67.5 | 119.6 ± 55.8 | 0.871 | 149.4 ± 51.5 | 102.9 ± 53.5 |
0.024
|
VAS pain (0 to 100 mm) | 50.4 ± 25.6 | 41.3 ± 23.1 | 0.126 | 56.9 ± 17.2 | 51.3 ± 20.8 | 0.425 |
Imaging
| ||||||
Kellgren-Lawrence, n (%) |
0.039
†
| 0.391†
| ||||
Grade 1 | - | - | - | - | ||
Grade 2 | 54 (79%) | 10 (56%) | 7 (50%) | 4 (33%) | ||
Grade 3 | 14 (21%) | 8 (44%) | 7 (50%) | 8 (67%) | ||
Joint space width, mm | 3.68 ± 0.74 | 3.37 ± 0.85 | 0.125 | 3.28 ± 0.55 | 2.99 ± 0.42 | 0.207 |
MRI, mm3
| ||||||
Global knee
| 11247 ± 3151 | 11292 ± 2218 | 0.622 | 10930 ± 1749 | 9952 ± 2694 | 0.190 |
Femur | 7725 ± 2264 | 7956 ± 1621 | 0.321 | 7748 ± 1225 | 6989 ± 1664 | 0.129 |
Plateau | 3522 ± 943 | 3336 ± 700 | 0.803 | 3182 ± 591 | 2962 ± 1060 | 0.456 |
Medial compartment
| 5334 ± 1525 | 5288 ± 1065 | 0.746 | 5355 ± 841 | 4479 ± 1155 | 0.095 |
Medial femur | 3766 ± 1089 | 3752 ± 750 | 0.549 | 3818 ± 550 | 3388 ± 783 | 0.068 |
Medial plateau | 1568 ± 471 | 1537 ± 384 | >0.999 | 1538 ± 336 | 1390 ± 384 | 0.247 |
Baseline characteristics within the treatment groups
Strontium ranelate 1 g/day
|
Strontium ranelate 2 g/day
|
Placebo
|
P
-value
|
Placebo versus Strontium ranelate 1 g/day
|
Placebo versus Strontium ranelate 2 g/day
| |
---|---|---|---|---|---|---|
P
-value
|
P
-value
| |||||
Ext-
|
n = 94
|
n = 90
|
n = 86
| |||
Demographic and clinical
| ||||||
Age, years | 60 ± 7 | 63 ± 7 | 62 ± 8 |
0.045*
| 0.961** | 0.548** |
Female, n (%) | 63 (67%) | 61 (68%) | 57 (66%) | 0.978†
| ||
Body mass index, kg/m2
| 30.0 ± 5.0 | 29.8 ± 9.9 | 32.4 ± 8.1 | 0.187* | ||
WOMAC | ||||||
Pain (0 to100) | 40 ± 20 | 44 ± 21 | 38 ± 22 | 0.107* | ||
Function (0 to 100) | 42 ± 21 | 42 ± 24 | 40 ± 22 | 0.732* | ||
Stiffness (0 to 100) | 46 ± 23 | 48 ± 26 | 42 ± 24 | 0.294* | ||
Total (0 to 300) | 130 ± 59 | 132 ± 64 | 121 ± 65 | 0.446* | ||
VAS pain (0 to 100 mm) | 50 ± 22 | 54 ± 24 | 48 ± 25 | 0.204* | ||
Imaging
| ||||||
Kellgren-Lawrence, n (%) | 0.943†
| |||||
Grade 1 | - | - | - | |||
Grade 2 | 71 (76%) | 66 (73%) | 64 (74%) | |||
Grade 3 | 23 (24%) | 24 (27%) | 22 (26%) | |||
Joint space width, mm | 3.61 ± 0.82 | 3.67 ± 0.81 | 3.61 ± 0.77 | 0.707* | ||
Presence of BML, n (%) | 23 (24%) | 20 (22%) | 18 (21%) | 0.847†
| ||
MRI, mm3
| ||||||
Global knee
| 11256 ± 2920 | 11520 ± 3344 | 11256 ± 2968 | 0.911* | ||
Femur | 7759 ± 2121 | 8000 ± 2286 | 7773 ± 2139 | 0.750* | ||
Plateau | 3497 ± 886 | 3520 ± 1158 | 3483 ± 897 | 0.855* | ||
Medial compartment
| 5391 ± 1374 | 5547 ± 1577 | 5325 ± 1435 | 0.655* | ||
Medial femur | 3797 ± 1020 | 3937 ± 1098 | 3763 ± 1023 | 0.540* | ||
Medial plateau | 1594 ± 405 | 1610 ± 541 | 1562 ± 452 | 0.726* | ||
Ext+
|
n = 19
|
n = 15
|
n = 26
| |||
Demographic and clinical
| ||||||
Age, years | 61 ± 6 | 61 ± 8 | 65 ± 8 | 0.228* | ||
Female, n (%) | 7 (37%) | 9 (60%) | 19 (73%) |
0.051
†
|
0.045** | >0.999** |
Body mass index, kg/m2
| 30.7 ± 4.7 | 32.2 ± 6.4 | 29.3 ± 6.0 | 0.164* | ||
WOMAC | ||||||
Pain (0 to100) | 50 ± 21 | 50 ± 16 | 41 ± 20 | 0.320* | ||
Function (0 to 100) | 47 ± 21 | 45 ± 19 | 38 ± 23 | 0.593* | ||
Stiffness (0 to 100) | 52 ± 24 | 57 ± 17 | 46 ± 19 | 0.252* | ||
Total (0 to 300) | 147 ± 58 | 153 ± 46 | 127 ± 57 | 0.394* | ||
VAS pain (0 to 100 mm) | 56 ± 19 | 58 ± 19 | 54 ± 19 | 0.837* | ||
Imaging
| ||||||
Kellgren-Lawrence, n (%) | 0.158† | |||||
Grade 1 | - | - | - | |||
Grade 2 | 6 (32%) | 2 (13%) | 11 (42%) | |||
Grade 3 | 13 (68%) | 13 (87%) | 15 (58%) | |||
Joint space width (mm) | 2.91 ± 0.75 | 2.80 ± 0.35 | 3.15 ± 0.51 | 0.110* | ||
Presence of BML, n (%) | 8 (42%) | 3 (20%) | 12 (46%) | 0.232†
| ||
MRI, mm3
| ||||||
Global knee
| 12345 ± 3367 | 12838 ± 2972 | 10479 ± 2243 |
0.032* | 0.193** |
0.050** |
Femur | 8497 ± 2192 | 8962 ± 2100 | 7398 ± 1465 |
0.044* | 0.274** | 0.062** |
Plateau | 3848 ± 1281 | 3875 ± 1051 | 3081 ± 830 |
0.029* | 0.100** | 0.071** |
Medial compartment
| 5707 ± 1520 | 5845 ± 1305 | 5089 ± 1020 | 0.208* | ||
Medial femur | 4013 ± 958 | 4136 ± 945 | 3619 ± 689 | 0.176* | ||
Medial plateau | 1695 ± 624 | 1708 ± 397 | 1470 ± 360 | 0.295* |
Change in JSW and cartilage volume at 36 months in the placebo group
Ext- (n = 86)
|
Ext+ (n = 26)
|
P
-value
| ||||
---|---|---|---|---|---|---|
Joint space width loss
| ||||||
mm | -0.35 ± 0.61 | -0.76 ± 0.67 |
0.002
| |||
% | -10.36 ± 20.10 | -23.24 ± 19.23 |
0.0008
| |||
MRI (%)
| ||||||
Global knee
| -6.70 ± 2.78 | -8.02 ± 3.28 |
0.034
| |||
Femur | -6.15 ± 3.29 | -7.28 ± 2.91 | 0.171 | |||
Plateau | -7.80 ± 5.05 | -10.01 ± 5.79 |
0.005
| |||
Medial compartment
| -7.60 ± 4.63 | -10.40 ± 4.23 |
0.0005
| |||
Medial femur | -7.90 ± 4.76 | -10.89 ± 3.19 |
0.0002
| |||
Medial plateau | -6.77 ± 7.52 | -9.07 ± 8.74 |
0.012
| |||
BML- (n = 68)
|
BML+ (n = 18)
|
P
-value
|
BML- (n = 14)
|
BML+ (n = 12)
|
P
-value
| |
Joint space width loss
| ||||||
mm | -0.23 ± 0.55 | -0.77 ± 0.68 |
0.003
| -0.88 ± 0.82 | -0.61 ± 0.43 | 0.455 |
% | -5.79 ± 15.35 | -27.64 ± 26.29 |
0.002
| -25.44 ± 22.79 | -20.68 ± 14.62 | 0.589 |
MRI (%)
| ||||||
Global knee
| -6.75 ± 2.81 | -6.50 ± 2.71 | 0.227 | -6.89 ± 3.70 | -9.33 ± 2.19 | 0.066 |
Femur | -6.39 ± 3.36 | -5.26 ± 2.92 |
0.020
| -6.16 ± 2.97 | -8.57 ± 2.32 |
0.028
|
Plateau | -7.38 ± 4.15 | -9.40 ± 7.49 | 0.162 | -8.67 ± 7.12 | -11.57 ± 3.37 | 0.093 |
Medial compartment
| -7.08 ± 4.33 | -9.57 ± 5.29 | 0.090 | -9.69 ± 5.50 | -11.22 ± 1.90 | 0.103 |
Medial femur | -7.54 ± 4.90 | -9.26 ± 4.03 |
0.055
| -10.72 ± 4.08 | -11.08 ± 1.86 | 0.339 |
Medial plateau | -5.79 ± 5.68 | -10.46 ± 11.70 | 0.185 | -7.04 ± 10.97 | -11.45 ± 4.47 | 0.155 |
Loss of joint space width and cartilage volume linked to addition of one co-localized factor
|
P
-value
| |
---|---|---|
Joint space width loss
| ||
mm | 0.31 |
0.0004
|
% | -11.58 |
<0.0001
|
MRI (%)
| ||
Global knee
| -0.86 |
0.033
|
Femur | -0.53 | 0.239 |
Plateau | -1.97 |
0.007
|
Medial compartment
| -2.22 |
0.0005
|
Medial femur | -1.95 |
0.002
|
Medial plateau | -2.93 |
0.006
|
Effect of SrRan treatment at 36 months
SrRan 1 g/day
|
SrRan 2 g/day
|
Placebo
|
P
-value
|
Placebo versus
SrRan 1 g/day
|
Placebo versus
SrRan 2 g/day
| |
---|---|---|---|---|---|---|
n = 19
|
n = 15
|
n = 26
|
P
-value
|
P
-value
| ||
Joint space width loss
| ||||||
mm | -0.46 ± 0.45 | -0.41 ± 0.42 | -0.76 ± 0.67 | 0.085* | ||
% | -18.54 ± 19.69 | -14.67 ± 15.69 | -23.24 ± 19.23 | 0.228* | ||
MRI (%)
| ||||||
Global knee
| -7.66 ± 2.10 | -6.67 ± 2.56 | -8.02 ± 3.28 | 0.351* | ||
Femur | -7.70 ± 2.66 | -6.98 ± 4.26 | -7.28 ± 2.91 | 0.809* | ||
Plateau | -7.61 ± 3.79 | -5.74 ± 3.54 | -10.01 ± 5.79 |
0.003*
| 0.070** |
0.007**
|
Medial compartment
| -10.29 ± 3.68 | -9.14 ± 3.27 | -10.40 ± 4.23 | 0.119* | ||
Medial femur | -11.17 ± 4.25 | -10.72 ± 5.36 | -10.89 ± 3.19 | 0.290* | ||
Medial plateau | -8.13 ± 5.98 | -4.90 ± 5.19 | -9.07 ± 8.74 |
0.048*
| 0.708** | 0.081** |