(A) Primary and secondary endpoints — by treatment
| (A) Primary endpoints | |||
| Standard-dose800 IU vitamin D3n=136 | High-dose2000 IU vitamin D3n=137 | P values * | |
| P value difference over time† | |||
| WOMAC function, operated knee P=0.94 | |||
| Baseline | 25.0 (23.3, 26.8) | 26.3 (24.6, 28.1) | 0.31 |
| 6 months | 9.9 (8.1, 11.6) | 10.8 (9.0, 12.5) | 0.49 |
| 12 months | 7.9 (6.1, 9.6) | 8.2 (6.4, 9.9) | 0.82 |
| 18 months | 7.2 (5.4, 9.0) | 8.0 (6.2, 9.8) | 0.56 |
| 24 months | 6.6 (4.8, 8.5) | 7.0 (5.2, 8.9) | 0.77 |
| Pacross time‡ | <0.0001 | <0.0001 | |
| WOMAC pain, operated knee P=0.97 | |||
| Baseline | 28.0 (26.1, 29.9) | 28.9 (27.0, 30.7) | 0.54 |
| 6 months | 9.1 (7.2, 11.0) | 10.0 (8.0, 11.9) | 0.52 |
| 12 months | 6.2 (4.3, 8.1) | 6.8 (4.9, 8.7) | 0.66 |
| 18 months | 5.7 (3.8, 7.7) | 6.3 (4.3, 8.3) | 0.70 |
| 24 months | 6.4 (4.4, 8.4) | 6.2 (4.2, 8.2) | 0.92 |
| Pacross time ‡ | <0.0001 | <0.0001 | |
| WOMAC function, contralateral knee P=0.36 | |||
| Baseline | 4.2 (2.8, 5.6) | 4.3 (2.9, 5.7) | 0.94 |
| 6 months | 6.1 (4.7, 7.5) | 4.6 (3.2, 6.0) | 0.15 |
| 12 months | 5.1 (3.7, 6.6) | 4.7 (3.2, 6.1) | 0.67 |
| 18 months | 5.3 (3.9, 6.8) | 5.3 (3.8, 6.7) | 0.94 |
| 24 months | 4.1 (2.6, 5.6) | 4.6 (3.1, 6.1) | 0.68 |
| Pacross time ‡ | 0.63 | 0.06 | |
| WOMAC pain, contralateral knee P=0.59 | |||
| Baseline | 4.7 (2.9, 6.4) | 4.6 (2.9, 6.4) | 0.98 |
| 6 months | 6.9 (5.1, 8.6) | 5.2 (3.5, 7.0) | 0.20 |
| 12 months | 6.4 (4.6, 8.2) | 5.2 (3.5, 7.0) | 0.37 |
| 18 months | 6.5 (4.7, 8.3) | 5.5 (3.7, 7.3) | 0.44 |
| 24 months | 6.5 (3.6, 7.3) | 5.8 (3.9, 7.6) | 0.84 |
| Pacross time ‡ | 0.19 | 0.80 | |
| Rate of falls (mean) | |||
| Baseline to 12 months | 0.53 (0.32, 0.83) | 0.45 (0.27, 0.72) | 0.27 |
| Baseline to 24 months | 1.07 (0.92, 1.23) | 1.05 (0.90, 1.21) | 0.84 |
| (B) Secondary endpoints | |||
| Least-square means | P values † | ||
| Standard-dose800 IU vitamin D3 | High-dose2000 IU vitamin D3 | ||
| P value difference over time* | |||
| Sit-to-stand performance in seconds P=0.09 | |||
| Baseline | 10.7 (10.2, 11.2) | 11.1 (10.6, 11.6) | 0.28 |
| 6 months | 9.7 (9.2, 10.1) | 9.3 (8.8, 9.8) | 0.32 |
| 12 months | 9.2 (8.7, 9.7) | 9.2 (8.7, 9.7) | 0.90 |
| 18 months | 9.2 (8.7, 9.7) | 9.0 (8.5, 9.5) | 0.48 |
| 24 months | 9.0 (8.5, 9.5) | 8.6 (8.1, 9.2) | 0.34 |
| Pacross time ‡ | <0.0001 | <0.0001 | |
| 4 m normal gait in seconds P=0.09 | |||
| Baseline | 4.3 (4.2, 4.4) | 4.4 (4.3, 4.5) | 0.13 |
| 6 months | 4.0 (3.9, 4.1) | 3.9 (3.8, 4.0) | 0.18 |
| 12 months | 3.8 (3.6, 3.9) | 3.7 (3.6, 3.8) | 0.47 |
| 18 months | 3.7 (3.6, 3.9) | 3.7 (3.6, 3.9) | 0.96 |
| 24 months | 3.7 (3.5, 3.8) | 3.7 (3.6, 3.8) | 0.44 |
| Pacross time ‡ | <0.0001 | <0.0001 | |
| StepWatch physical activity P=0.84 | |||
| Baseline | 41.6 (37.5, 45.7) | 42.0 (37.9, 46.1) | 0.89 |
| 12 months | 51.6 (47.4, 55.9) | 50.3 (46.1, 54.6) | 0.68 |
| 24 months | 49.1 (44.8, 53.4) | 48.6 (44.3, 52.9) | 0.48 |
| Pacross time ‡ | <0.0001 | <0.0001 | |
| Percentage of participants with radiographic progression of the non-operated knee | |||
| Baseline to 24 months | 31.3 (23.5, 40.4) | 30.5 (22.6, 39.6) | 0.88 |
In both treatment groups, we found significant within-group improvements for symptoms (WOMAC function and pain) in the operated knee, lower extremity function (sit-to-stand performance, 4 m normal gait) and physical activity. Also, in both treatment groups, we found no progression of symptoms (WOMAC function and pain) and an about 30% radiographic progression in the contralateral knee. For WOMAC symptoms, the number of patients followed in the 800 IU group at each time point was baseline=136, 6 months=130, 12 months=130, 18 months=123 and 24 months=115. The number of patients followed in the 2000 IU group at each time point was baseline=137, 6 months=129, 12 months=125, 18 months=118 and 24 months=111. For falls, all 273 participants are included in all analyses. All models included an indicator variable for treatment, time, and the interaction between treatment and time, and were adjusted for the preoperative WOMAC function score (<52 vs ≥52) in the operated knee, presence of osteoarthritis in the non-operated knee, hospital site, and baseline age, gender, body mass index and Charlson Comorbidity Index (score 0–37). Repeated-measures linear regression for WOMAC function and pain. Binomial regression model for the rate of falls—with same adjustments but without indicator variable time and without interaction assignment*time. Adjusting for five primary outcome variables, a Bonferroni-adjusted p value of 0.01 is required for statistical significance.
P values are two-sided. Statistical significance was set at p<0.05.
↵*P value for the treatment effect at each time point.
↵†P value for the overall treatment effect across the repeated measurements for WOMAC pain and function, sit-to-stand performance, 4 m normal gait in seconds and StepWatch physical activity.
↵‡P value for the change within treatment groups from 0 to 24 months.
WOMAC, Western Ontario and McMaster Universities Arthritis Index.