Our study found an increase in serum sclerostin levels in RA patients compared to the healthy group (P = 0.001). This finding is confirmed by several studies such as El-Bakry et al study in Egypt which included 31 RA patients and showed an increase of serum levels of sclerostin when compared to 10 healthy controls (28), Gharbia et al. study Which was also conducted in Egypt and contained 40 RA patients and 40 healthy controls, (15), and Aydemir et al in Turkey in a study that comprised of 60 RA patients and 30 healthy controls (24).
In contrast, there was no significant difference in sclerostin levels between RA patients and the healthy group in several studies; We found this evident in Vargas et al study 2015 in Mexico that included 48 RA patients and 15 healthy controls where 50.98% of the RA patients in his study were at clinical remission. That study concluded that there was no role of sclerostin in the pathogenesis of rheumatoid arthritis (1). This was also displayed by the Aydemir study in Turkey 2020 that consisted of 60 RA patients that did not find an association between serum levels of sclerostin and disease activity. However, that study was conducted at a late stage of the disease (24). Fayed et al. study in 2019 also confirmed that serum sclerostin levels did not reflect its tissue concentration nor reflected changes in the microenvironment of the joints (14). Also, in another study by Mehaney et al. 2015 found that there was no correlation between sclerostin levels and DAS28. This also might be from 70% of the newly diagnosed cases receiving methotrexate at the time of the study and having only three of them (7.5%) not receiving any specific therapy (29). However, as sclerostin was associated with ACPA, which is known to be also associated with joint destruction, can be a confounding factor, causing our findings to be interpreted as sclerostin being directly associated with joints being affected.
We believe that the different previous findings might be from the previous studying being conducted at different stages of the disease in which the serum samples were taken. In addition, RA patients in these studies were of low disease activity or in the stage of clinical remission (29).
There was higher of mean levels of sclerostin in RA patients who had joint deformities compared to patients without deformities. This is believed to be from the effect of chondrocytes and osteoblasts surrounding the cartilage, which leads to an increase in serum sclerostin (28, 30).
Our study showed that serum sclerostin levels positively correlated with some inflammatory indicators, which were CRP, Anti-CCP, TJC, and DAS28. In contrast, there was not a significant association between serum Sclerostin levels and other variables, which were ESR, VAS, RF, and SJC.
The significant association between sclerostin and DAS28 was similar to other studies, such as El-Bakry in India (28), a Gharbia study in Egypt (15) and Megid et al. Study, which contained 50 RA patients and 20 healthy controls (Megid et al. 2019). This indicates that sclerostin probably plays an important role in the development of osteoporosis and it is influenced by the disease activity. Therefore, monitoring the disease activity is the main factor for the corrective local and systemic bone health in RA patients (15, 26).
No significant association was observed between serum sclerostin levels and anti-CCP in the Ghariba et al study which contradicted our study result. This might be due to the disproportion of ACPA positive RA patients (62.5%) compared to the proportion of ACPA positive patients in our study (82.5%) (15).
The presence of a correlation between serum sclerostin levels and the number of swollen joints is supported by the findings of two previous studies: El-Bakry in India (28) and Ghariba et al. study in Egypt 2020, which suggested that synovial cells and osteoblasts surrounding cartilage caused increased levels of circulating sclerostin (15).
Our study found similar findings to Dhakad et al. in India 2019 which did not find a significant association between ESR and sclerostin (17). However, this was different to Ibrahim et al. study in Egypt 2015 which found the correlation to be (r = 0.655) (30).
The ROC curve analysis to determine having a positive sclerostin result in cases and control demonstrated a cutoff value of 249.69 pg/ml (sensitivity 87.9%; specificity 93.3%). The study of El-bakry found that value to be (267ng/dl), with a sensitivity of 96.8%, and a specificity of 66.7% (28). Also, the 2019 study of Singh et al. in India demonstrated that value to be 394 pg/ml with a sensitivity of 100%, and a specificity of 90% (20).