Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis

Abstract

Objective. Autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts.Methods. Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations.Results. In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm 2 (95% confidence interval [95% CI] 0.91-0.93) versus 0.95 g/cm 2 (95% CI 0.93-0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08-0.29] versus 0.48 [95% CI 0.33-0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti-carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time.Conclusion. The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed.

Autoantibodies in Rheumatoid Arthritis – Laboratory and Clinical Perspectives

“…Studies of inception cohorts of patients with RA in Sweden demonstrated an association between ACPA and disease activity over time among those diagnosed in 1996-1999, but not in those diagnosed in 2006-2009 (116). Furthermore, whereas earlier studies reported a more pronounced general loss of bone mass in seropositive RA (117,118), more recent inception cohort studies did not demonstrate any difference in change of bone mineral density over time in ACPA positive compared to ACPA negative RA (119).…”

Impact of Anti-Citrullinated Protein Antibodies on Progressive Systemic Bone Mineral Density Loss in Patients With Early Rheumatoid Arthritis After Two Years of Treat-to-Target

“…The effects of early and intensive management on the epidemiology of OP in recent-onset RA remain poorly defined. Few studies have reported substantial stability of BMD in modern early RA populations (19,(32)(33)(34)(35), with the highest rates of bone loss being observed at the hip in the first two years after treatment start (35), especially in patients receiving glucocorticoids (36). Although the exact rates of BMD variations are not comparable across studies due to different demographic characteristics, anti-rheumatic treatments and use of prophylactic measures, our results confirm that early RA patients collectively undergo only minor changes in systemic BMD upon tightly controlled management.…”

“…Our results however do not implicitly assign a prominent role to ACPA, and we are aware that a number of important RA-related and non-related factors, such as disease activity, type of medications and duration of follow-up might mitigate or even contrast the association between autoantibodies and early bone loss found here. Accordingly, Amkreutz et al (19) recently failed to demonstrate significant relationships between ACPA and variations in BMD during five and ten years from treatment start in two independent populations of early RA and undifferentiated arthritis. However, also in this study, some possible differences seemed to arise, with the Swedish ACPA-positive sub-cohort showing a trend for reduced BMD at both the spine and the hip during the first two years, followed by further relative stabilization or even increase.…”

“…Accordingly, Amkreutz et al. ( 19 ) recently failed to demonstrate significant relationships between ACPA and variations in BMD during five and ten years from treatment start in two independent populations of early RA and undifferentiated arthritis. However, also in this study, some possible differences seemed to arise, with the Swedish ACPA-positive sub-cohort showing a trend for reduced BMD at both the spine and the hip during the first two years, followed by further relative stabilization or even increase.…”

“…We previously reported that ACPA-positive, treatment-naïve early RA patients already display reduced systemic bone mineral density (BMD) at presentation ( 17 ). Whether the negative impact of ACPA on bone continues over time after treatment institution remains largely unknown, and the few available studies have provided conflicting results ( 18 , 19 ). In light of the multiplicity of factors influencing bone remodeling in RA, such as cumulative disease activity ( 20 ) and use of different medications with opposite effects on bone ( 21 , 22 ), the net effect of ACPA, if any, could better emerge from prospective studies analyzing patient populations relatively homogeneous for disease duration and treatment.…”