Table 2.
Generalized estimating equations (conducted on 20 imputed data sets) of the effect of ACPAs on baseline and longitudinal change in absolute BMD and Z scores and the association between ACPAs and the prevalence of osteopenia and osteoporosis over time*
| Dutch cohort | Swedish cohort | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Lumbar spine | Left hip (total hip) | Lumbar spine | Left hip (femoral neck) | |||||||||
| ACPA‐positive | ACPA‐negative | P | ACPA‐positive | ACPA‐negative | P | ACPA‐positive | ACPA‐negative | P | ACPA‐positive | ACPA‐negative | P | |
| Absolute BMD, g/cm2 | ||||||||||||
| Baseline EMM, (95% CI) | 1.01 (1.00, 1.03) | 1.05 (1.02, 1.08) | 0.03 | 0.92 (0.91, 0.93) | 0.95 (0.93, 0.97) | 0.01† | 1.10 (1.06, 1.14) | 1.13 (1.10, 1.17) | 0.12 | 0.85 (0.83, 0.88) | 0.90 (0.86, 0.94) | 0.22 |
| Yearly change, β (95% CI) | −0.002 (−0.004, 0.001) | 0.0004 (−0.004, 0.004) | 0.61 | −0.003 (−0.006, −0.001) | −0.004 (−0.008, 0.00002) | 0.89 | 0.003 (−0.002, 0.009) | 0.003 (−0.002, 0.009) | 0.95 | −0.003 (−0.007, 0.001) | −0.003 (−0.009, 0.002) | 0.92 |
| Z score | ||||||||||||
| Baseline EMM, (95% CI) | 0.32 (0.16, 0.47) | 0.62 (0.38, 0.86) | 0.04 | 0.18 (0.08, 0.29) | 0.48 (0.33, 0.63) | <0.01† | −0.15 (−0.36, 0.06) | 0.02 (−0.21, 0.26) | 0.13 | −0.22 (−0.45, 0.00) | −0.06 (−0.28, 0.17) | 0.12 |
| Yearly change, β (95% CI) | 0.038 (0.017, 0.058) | 0.060 (0.027, 0.094) | 0.43 | 0.008 (−0.007, 0.023) | 0.001 (−0.022, 0.025) | 0.37 | 0.035 (0.005, 0.064) | 0.033 (0.002, 0.064) | 0.93 | 0.004 (−0.026, 0.034) | 0.003 (−0.031, 0.037) | 0.98 |
| Prevalence of osteopenia, no. (%) | ||||||||||||
| Baseline | 94 (38.4) | 50 (37.6) | 0.48 | – | – | – | 37 (33.0) | 16 (20.2) | 0.04 | – | – | – |
| 5 years | 77 (43.8) | 31 (38.8) | 0.65‡ | – | – | – | 34 (38.6) | 25 (39.7) | – | – | – | – |
| 10 years | – | – | – | – | – | – | 26 (44.1) | 15 (32.6) | 0.56‡ | – | – | – |
| Prevalence of osteoporosis, no. (%) | ||||||||||||
| Baseline | 21 (8.6) | 9 (6.8) | 0.33 | – | – | – | 33 (29.5) | 26 (32.9) | 0.54 | – | – | – |
| 5 years | 14 (8.0) | 4 (5.0) | 0.66‡ | – | – | – | 28 (31.8) | 14 (22.2) | – | – | – | – |
| 10 years | – | – | – | – | – | – | 14 (23.7) | 12 (26.0) | 0.73‡ | – | – | – |
Models were adjusted for the following baseline variables: age, sex, body mass index, symptom duration, and smoking status. Models were also adjusted for the following longitudinal time‐varying measurements: Disease Activity Score, prednisone intake, Health Assessment Questionnaire score, C‐reactive protein levels, and serum 25‐hydroxyvitamin D levels (the latter only available for the Dutch cohort). Absolute bone mineral density (BMD) and Z score values are shown as point estimates with 95% confidence intervals (95% CIs) representing the estimated marginal means (EMMs) for baseline BMD and parameter estimates (β) for yearly change BMD. Osteopenia was defined as a T score between −2.5 (a value of −2.5 not included) and −1.0 (a value of −1.0 included) at any location, and osteoporosis was defined as a T score of less than or equal to −2.5 at any location. In the final generalized estimating equations model, osteopenia was defined as “at least osteopenia”, indicating a T score of less than or equal to −1.0, with a T score of more than −1.0 as reference. Osteoporosis was defined in a similar manner as osteopenia, with comparison groups using a T score of less than or equal to −2.5 versus a T score of more than −2.5 as reference. P values were calculated using Wald’s chi‐square test of model effects for anti–citrullinated protein antibodies (ACPAs) (e.g., baseline) and for the ACPA × time interaction (e.g., yearly change).
Difference between the groups remained significant after correction for multiple testing.
Yearly change P value with ACPA‐negative as reference group.