Changes in bone turnover markers and bone modulators during abatacept treatment

Abstract

Rheumatoid arthritis (RA) causes bone loss, only partly related to inflammation. The impact of RA treatments on bone metabolism and their ability to mitigate bone loss remains uncertain. The primary goal of our study was to examine the influence of abatacept on serum levels of markers and regulators involved in bone turnover. Secondary objectives included evaluating changes in bone mineral density (BMD), bone health parameters, erosions, and exploring potential correlations among these parameters. We conducted a prospective observational study on patients with active seropositive RA failure to biological disease modifying anti-rheumatic drugs initiating treatment with abatacept. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (modified Sharp van der Heijde score [mSvdH], bone health index [BHI] and metacarpal index [MCI]). Disease activity and glucocorticoid intake was monitored. 33 patients were enrolled in the study. We found a significant increase in markers of bone formation (B-ALP and P1nP) from baseline to M6 and M12. PTH increased significantly at M6 but not at M12. All other bone markers and modulators did not change. We found a significant decrease in BHI and MCI from baseline to M12 (median difference - 0.17 95% CI - 0.42 to - 0.10, p 0.001 and - 0.09 95% CI - 0.23 to - 0.07, respectively). BMD at femoral neck transitorily decreased at M6 (mean difference - 0.019 g/cm² 95% CI - 0.036 to - 0.001 p 0.04). BMD at total hip, lumbar spine and mSvdH score did not change significantly. P1nP delta at M12 correlated with delta mSvdH. Treatment with abatacept was associated with a significant increase in bone formation markers. The secondary and transient increase in PTH serum levels may be responsible of the transitory bone loss.

Figure 1

Changes in bone turnover markers (BTMs) in the study period. Changes were tested with mixed-effect model analysis for repeated measures (MMRM), p values are adjusted for multiple comparisons using the Tukey’s procedure.

Figure 2

Negative correlation between delta P1nP between baseline and M12 and delta Sharp van der Heijde (SvdH) between baseline and M12.

Figure 3

Changes in serum bone modulators in the study period. Changes were tested with mixed-effect model analysis for repeated measures (MMRM), p values are adjusted for multiple comparisons using the Tukey’s procedure.

Figure 4

Changes in bone mineral density (BMD) at lumbar spine, total hip and femoral neck in the lower panel. Changes were tested with mixed-effect model analysis for repeated measures (MMRM), p-values are adjusted for multiple comparisons using the Tukey’s procedure.

Figure 5

Changes in Sharp van der Heijde (SvdH) score, metacarpal index (MCI) and bone health index (BHI). Changes were tested with Wilcoxon signed-ranks test.