Biomarkers of bone metabolism may emerge as powerful tool to monitor and predict structural joint damage in patients with rheumatoid arthritis (RA). Based on rather large patients cohort, several bone biomarkers, i.e. biomarkers for bone resorption have been successfully correlated to bone damage visualized in conventional radiographs. We hypothesized that improvement of sensitivity for detection of joint damage by high resolution micro computed tomography (µCT) may allow to better correlate bone biomarkers and structural bone damage and allow to proof this link even in small cohorts of RA patients.
Forty RA patients received a simultaneous µCT scan and analysis of serum markers of bone resorption (collagen type1 crosslaps: CTX1, tartrate resistant acid phosphatase 5b:TRAP5b) and formation (bone alkaline phosphatase: BAP, osteocalcin) at baseline and one year follow up. Erosions (erosion count and score) as well as osteophytes (osteophyte count and score) detected by µCT in the metacarpophalangeal (MCP) joints 2-4 of the dominantly affected hand were recorded. Bone biomarkers were related to the imaging data by partial correlations including age, sex, disease duration, DAS 28 and autoantibody status.
All erosions and osteophytes detected at baseline were also visible at follow up with a slight progression in both numbers of erosions and of osteophytes (mean erosion count 5.112 ±7.120 at baseline versus 5.432 ±7.338 at follow up; mean osteophyte count 3.233 ±2.498 vs. 3.294 ±2.150 respectively). Erosion score did not change (5.001 ±7.452 vs. 5.002 ±6.907) whereas osteophyte score did increase (4.094 ±3.815 vs. 4.343 ±3.412). The mean levels (±SD) of bone metabolism parameters were as follows: CTX1 at baseline 0.354 ng/ml ±0.205 and 0.351 ng/ml ±0.220 at follow-up, tartat-resistent acid phosphatase 5b (±Trap5b) at baseline 2.464 U/l ±1.294, at follow-up 2.537 U/l ±1.134, BAP at baseline 19.360 E/l ±6.299, follow-up 19.731 E/l ±5,945 and osteocalcin 12.577 ng/ml ±7.791 vs. 11.600 ng/ml ±6,209. Bone erosions in the MCP joints detected by µCT were strongly correlated with the serum level of the osteoclast-specific protease TRAP5b, a marker for bone resorption and osteoclast activity at both baseline and 1-year follow-up (baseline: p=0.030, r= 0.426, follow-up: p=0.004, r=0.493). In contrast, osteophytes detected by µCT were strongly correlated to bone alkaline phosphatase being a marker for bone formation (baseline: p=0.022, r= 0.447, follow-up: p=0.004, r=0.499).
These data suggest that specific biomarkers of bone formation and bone resorption can be correlated to different forms of structural joint damage, such as bone erosions and osteophytes formation in patients with RA. Detailed assessment of structural bone changed in the joints by µCT allows a validation of bone biomarkers in patients with RA. Moreover, these data are stimulating for small proof-of-concepts studies with novel therapeutics, by suggesting that biomarkers can be related to structural bone damage even in small patient cohorts.
Disclosure: S. Aschenberg, None; S. Finzel, None; S. Schmidt, None; M. Englbrecht, None; J. Rech, None; G. Schett, None.