الفهرس 
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Abstract
Chronic-inflammatory arthritis such as rheumatoid arthritis is characterized by joint inflammation creating a persistent phenomenon of bone matrix destruction, ultimately responsible for anatomical deformity, disability, functional impairment and decreased quality of life. Disease progress is determined by the time of diagnosis, early onset of therapy, disease activity, genetic factors, and autoantibodies positivity (Santos et al., 2018). Besides clinical and serological assessments, musculoskeletal ultrasound is now an important tool in the diagnosis and monitoring of disease progress. Ultrasound is suitable to measure both disease activity and structural damage. To justify the use of expensive medication such as biologics, it is essential to monitor treatment response. This can be accomplished by the measurement of disease activity by US using grey-scale and power Doppler mode for synovitis. It is also possible to visualize certain bone lesions such as erosions which represent structural damage (Aziz et al., 2015).
Dickkopf-1 is a cytokine induced mediators who shifts the normal balance between bone formation and resorption causing bone loss which is a pathological hallmark of RA and manifests as localized, peri-articular and systemic bone loss.
This study aimed to assess the level of DKK-1 in RA patients and its correlation between disease activity, disability and radiographic assessment. Also, we assessed the value of recent indices like US DAS in detecting synovitis and erosion.
Fifty rheumatoid arthritis patients were included in this study and were subjected to: full history taking, clinical examination, laboratory investigations (ESR, CRP, RF and ACPA), disability indices (HAQ-DI, functional status), and plain X-ray of both hand and feet to measure SENS. Moreover, we used US DAS which involves; GSUS H/E of 28 joints and PDUS of 22 joints to accurate assessment of activity. Structural damage was assessed by US recording of erosion by USEC and USER. Results of serum DKK-1 were also obtained for 25 healthy age- and sex-matched volunteers and served as controls.
Patients were grouped according to the cutoff values of US DAS into 3 groups (remission and low activity, moderate activity and high activity) and by DKK-1 level into two groups (normal and elevated level). The groups were compared as regards different clinical, laboratory, disability and imaging scores. We found a statistical significant difference between groups (US groups and DKK-1 level groups) in an increasing manner.
In this study, we found that US DAS had a significant positive correlation between different clinical disease activity and disability indices and imaging scores SENS. Also, we found that SENS had a significant positive correlation with disability indices. While, ultrasound -based assessment of disease activity is more accurate than clinical indices and SENS especially in detecting subclinical synovitis and erosions..
Our study found significantly positive correlation between DKK-1 and activity measures (DAS 28, VAS and duration of morning stiffness), laboratory investigations (ESR, CRP, RF and ACPA), disability (HAQ-DI, functional status) and US DAS, that reflects its relation to disease activity. In addition to, a significant positive correlation between DKK-1 and erosion score by SENS and USEC which may participate to structural damage ocurred in rheumatoid arthritis.
In Conclusion, Disease status can be evaluated in patients with RA by assessing one or more aspects of the disease using clinical indices, laboratory tests, or imaging scores. Musculoskeletal ultrasonographic scores are reliable and non-invasive methods complementary to standard clinical assessment for evaluating disease activity, subclinical synovitis and structural damage and its role in daily management and clinical trials. The results obtained demonstrates a relationship between increased levels of DKK1 and the increased disease activity, decrease in functional capacity of RA patients chronic structural damage suugesting its role in pathogenesis in RA.
We recommend the following:
• Routine use of clinical disease activity indices such as DAS 28-ESR, VAS and radiological follow-up in clinical practice as they allow easily and long-term monitoring of the disease status.
• Musculoskeletal ultrasonography is recommended for the routine use as a complementary method to clinical and laboratory evaluation for early and accurate detection of synovitis and erosions in rheumatoid arthritis patients and predict future flare.
• The serum levels of DKK1 in RA patients could be used as a marker of functional limitation and chronic damage over time. It may be a reliable biomarker of erosive arthritis detected by US in RA.
• The mechanism in which DKK-1 acts in RA is still controversial, so more studies are needed to prove its immune-modulatory role.
• Further studies should be planned for studying the application of anti Dkk-1 antibodies a treatment opinion for RA associated bone osteoporosis.