In contrast to the significant improvement in the understanding of the pathogenesis and treatment of PsA in the last ten years, there is only little known regarding the impact of clinical features on structural and radiological damage. To close this gap, the aim of our retrospective study was to quantify clinical parameters which influence periarticular mineralization of the metacarpal bones and finger JSD in PsA-patients.
In our study, a decrease in DXR-BMD was found for both disease duration and elevated CRP. In addition, prednisone use was associated with a decreased DXR-BMD. However, these parameters did not have an impact on JSD and Z-score. Furthermore, we demonstrated a decrease in DXR-BMD and JSDMCP as well as JSDPIP under therapy with bDMARDs.
Computer-aided techniques including DXR and CAJSA serve as innovative tools in the quantification of radiological damage (5, 6, 13). The computer-based structural analysis of hand radiographs offers significant advantages in the quantification of radiographic damage in inflammatory arthritis (e. g. RA and PsA) in comparison with conventional scoring of hand radiographs (6, 13-15). Mainly, the computer-based measurement of DXR-BMD (coefficient of variation: 0.13% - 1.50%) and CAJSA-JSD (coefficient of variation: 0.38 – 0.66%) provide a high reproducibility, compared to standard scoring methods for the detection of radiographic damage (e. g. reproducibility of the van der Heijde modification of the Sharp Score: 1.8 – 3.8%) (16-18). Therefore, detailed changes of bone structure and JSD are noticeable, especially with regard to the detection of treatment effects, and represent markers for structural damage (13-15).
The present study evaluated the influence of clinical features such as disease duration, inflammatory activity, prednisone use, and other different treatment strategies on structural parameters of the hands as measured by DXR-BMD and finger JSD in PsA-patients.
In our study, PsA-patients with a disease duration of more than ten years showed a significantly reduced DXR-BMD (- 6.6%), JSDMCP (- 11.5%), and Z-ScoreMCP (- 0.43). This is in accordance with previous data, which revealed an increase of erosive bone changes in PsA, depending on disease duration as measured with high-resolution peripheral quantitative computed-tomography (HR-pQCT) (24). In this context, the results of our study revealed a significant influence of age on DXR-BMD and finger JSD in PsA patients which has also been shown in healthy subjects (19-21). Simon et al. reported a lower volumetric articular BMD of the MCP-joints, measured by HR-pQCT in PsA-patients, compared with healthy subjects (22). In addition, patients with RA showed a significantly reduced DXR-BMD (- 20.7%) and JSD of MCP-joints (- 18.9%) versus a healthy control group (12, 23). Sex had an additional impact on DXR-BMD, whereas JSD was not influenced. As demonstrated before, the DXR-BMD in healthy women is significantly lower (-12.8%) versus healthy men (19).
Inflammatory activity is strongly associated with radiographic damage in PsA (25). Regarding inflammatory activity as measured by CRP levels, PsA-patients with increased CRP values showed a reduced DXR-BMD (- 0.7%). The linear regression models yielded a significant impact of CRP on DXR-BMD. Furthermore, Wu et al. reported a significant bone loss of the second and third metacarpal bone head, quantified by HR-pQCT in association with elevated CRP values in PsA-patients (26). These results highlight the strong interaction of inflammatory activity and demineralization of metacarpal bones in inflammatory arthritis which was also published for RA (27, 28). Additionally, CRP served as an independent predictor of radiographic progression in PsA (29). At the time of initial diagnosis, elevated CRP levels were associated with new erosions as a marker for radiographic progression (30).
In our study, JSD-parameters assessed with CAJSA were not influenced by CRP. In accordance with these results, a longitudinal study showed that an elevated baseline CRP was not related to joint space narrowing, as quantified by van der Heijde-modified total Sharp score for PsA (33).
We demonstrated, that treatment with prednisone was associated with a significant reduction of DXR-BMD (- 6.6%). A negative correlation between the change of DXR-BMD over 24 months and the use of corticosteroids (r = - 0.27; P < 0.005) was also observed by Hoff et al. (10). These results indicate that corticosteroids can lead to a demineralization of metacarpal bones. The JSD-parameters in our study revealed no significant changes in association with prednisone treatment. Bond et al. showed an increase of radiological damage, assessed with the Steinbrocker staging system under corticosteroids (31), where the Steinbrocker method represented a composite score including the quantification of periarticular demineralisations, erosions, joint space narrowing and ankyloses.
Recently published studies showed periarticular demineralization (6, 9, 10, 24, 25) and severity-dependent bone loss in patients with PsA (6). Additionally, finger joint space narrowing represented a common radiographic hallmark for structural damage in PsA (26, 27). In summary, both parameters reflected PsA-associated radiographic damage (6, 27). In the present study, treatment with bDMARDs resulted in a significant lower DXR-BMD (- 6.6%), JSDMCP (- 11.5%), and Z-scoreMCP (- 0.83), compared to csDMARDs and NSAIDs. Concerning DXR-BMD and CAJSA-JSD as radiographic markers of damage and disease severity (5, 8), bDMARDs-treated patients in our study showed more structural damage, which is explainable with the advanced course of the disease. According to the updated recommendations of the European League Against Rheumatism (EULAR) for the treatment of PsA, this led to the treatment with bDMARDs (32).
Additionally, radiographic damage in PsA is a potential risk factor for disease progression. In our study, DXR-BMD was influenced by inflammatory activity, prednisone use, and treatment with DMARDs. In contrast, the reduction of JSD measured by CAJSA-JSD was only significantly affected by DMARDs. Consequently, JSD serves as parameter for monitoring treatment with DMARDs. Therefore, both DXR-BMD and JSD represent radiographic damage under different aspects.
As a result, patients with an accentuated radiographic damage should be treated earlier with bDMARDs to avoid radiographic structural damage. In this case, the use of csDMARDs should be critically questioned, whereas bDMARDs revealed also higher response rates and reduced radiographic progression in PsA (33). Radiographic damage and progression correlated with the Health Assessment Questionnaire (HAQ) as outcome marker for disability (34).
Our study is potentially limited by the cross-sectional design. Further investigations are needed to verify these results in a longitudinal study design. However, the present study offered the first insights of the influence of clinical features on DXR-BMD and JSD as surrogate markers of radiographic damage in PsA patients.