Evaluating the role of serum sclerostin as an indicator of activity and damage in Egyptian patients with rheumatoid arthritis: university hospital experience

Elgohary, Rasmia; Fawzy, Mary

doi:10.1007/s10067-019-04878-7

Cited by 17 publications

(18 citation statements)

References 48 publications

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“…These results would be aligned with those indicating that an increase of sclerostin would contribute to the inhibition of osteogenesis. A recent study has shown a positive correlation between FGF23 and sclerostin levels in patients with rheumatic arthritis, suggesting a link between FGF23, reduced Wnt activity, and bone demineralization in these patients [87]. Evenepoel et al found that sclerostin but not Dkk1 participate in alterations of mineral metabolism related to CKD [79,81].…”

Section: Fgf23-klotho and Wnt In Bonementioning

confidence: 99%

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

Muñoz‐Castañeda

Rodelo-Haad

Mier

et al. 2020

Toxins

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Fibroblast Growth Factor 23 (FGF23) and Klotho play an essential role in the regulation of mineral metabolism, and both are altered as a consequence of renal failure. FGF23 increases to augment phosphaturia, which prevents phosphate accumulation at the early stages of chronic kidney disease (CKD). This effect of FGF23 requires the presence of Klotho in the renal tubules. However, Klotho expression is reduced as soon as renal function is starting to fail to generate a state of FGF23 resistance. Changes in these proteins directly affect to other mineral metabolism parameters; they may affect renal function and can produce damage in other organs such as bone, heart, or vessels. Some of the mechanisms responsible for the changes in FGF23 and Klotho levels are related to modifications in the Wnt signaling. This review examines the link between FGF23/Klotho and Wnt/β-catenin in different organs: kidney, heart, and bone. Activation of the canonical Wnt signaling produces changes in FGF23 and Klotho and vice versa; therefore, this pathway emerges as a potential therapeutic target that may help to prevent CKD-associated complications.

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Section: Fgf23-klotho and Wnt In Bonementioning

confidence: 99%

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

Muñoz‐Castañeda

Rodelo-Haad

Mier

et al. 2020

Toxins

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“…32 Eleven studies examining the association between serum sclerostin, and carotid intima media thickness were identified. [33][34][35][36][37][38][39][40][41][42][43] Seven studies showed a positive association, [33][34][35][36][37][38][39] one study showed a negative association, 40 and 3 studies showed no association [41][42][43] between high serum sclerostin concentration and greater carotid artery intima-media ratio (Table 1). One study investigated postmenopausal women with type 2 diabetes and reported a negative correlation between serum sclerostin concentration and severity of carotid artery intimamedia ratio.…”

Section: Human Blood Samplesmentioning

confidence: 99%

Role of Sclerostin in Cardiovascular Disease

Golledge

Thanigaimani

2022

ATVB

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Sclerostin is most recognized for its role in controlling bone formation but is also expressed in the heart, aorta, coronary, and peripheral arteries. This review summarizes research on sclerostin’s role in cardiovascular disease. Rodent studies have found sclerostin to be expressed at sites of arterial calcification. In contrast, aortic sclerostin was reported to be downregulated in a mouse model of abdominal aortic aneurysm, and transgenic upregulation or administration of sclerostin was found to prevent abdominal aortic aneurysm and atherosclerosis formation. Sclerostin deficiency was reported to stimulate cardiac rupture in one rodent model. In humans, 7 of 11 studies reported a significant association between high serum sclerostin and high carotid intima media thickness. Ten of 15 studies reported a significant association between high serum sclerostin and severe arterial calcification. Twelve of 14 studies reported a significant association between high serum sclerostin and high arterial stiffness or atherosclerosis severity. Four of 9 studies reported a significant association between high serum sclerostin and high risk of cardiovascular events. A meta-analysis of randomized controlled trials suggested that administration of the sclerostin blocking antibody romosozumab did not significantly increase the risk of major adverse cardiovascular events (risk ratio, 1.14 [95% CI, 0.83–1.57]; P =0.54) or cardiovascular death (risk ratio, 0.92 [95% CI, 0.53–1.59]; P =0.71). Human genetic studies reported variants predisposing to low arterial sclerostin expression were associated with a high risk of cardiovascular events. Overall, past research suggests a cardiovascular protective role of sclerostin but findings have been inconsistent, possibly due to variations in study design, the unique populations and models studied, and the heterogeneous methods used.

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“…However, that study was conducted at a late stage of the disease (24). Fayed et al study in 2019 also con rmed that serum sclerostin levels did not re ect its tissue concentration nor re ected 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.…”

Section: Discussionmentioning

confidence: 96%

“…Another inhibitor of that pathway is TNF-alpha, which also increases during in ammation and therefore RA. TNF-alpha stimulates osteoclasts and leads to an increase of the expression of DKK-1, another inhibitor of the Wnt pathway, and plays an important role in the stimulation of sclerostin production (14,21,26).…”

Section: Introductionmentioning

confidence: 99%

“…There is a need to nd other biomarkers that may help to assess disease activity, con rm early diagnosis, identify high risk patients, and allow to start of intensive therapy (4,8). Recent research has focused on biomarkers that may play a prominent role in RA pathogenesis, mainly sclerostin, which is an antagonist of wingless (Wnt) signaling pathway (14,15). Wnt/β-catenin pathway is crucial to control osteoblast differentiation, which leads to bone formation (16,17).…”

Section: Introductionmentioning

confidence: 99%

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The role of sclerostin in rheumatoid arthritis in a Syrian population: a potential indicator of disease activity in newly-diagnosed patients

Hussein

Kakaje

Aboukhais

2022

Preprint

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Background: Rheumatoid arthritis (RA) is an autoimmune disease that can cause irreversible joint deformities and bone erosions. Criteria to diagnose RA includs many laboratory tests with variable sensitivity and specificity. Sclerostin, a Wnt inhibitor, could be associated with the reduced bone formation in RA. This study aims to measure sclerostin level and its association with RA and its activity.Materials and methods: This study contained fifty-eight RA cases and thirty controls who were age and sex matched. All laboratory tests were conducted on both groups, including sclerostin which was measured by enzyme-linked immunosorbent assay (ELISA). The disease activity was assessed using disease activity scores (DAS28).Results: Our results showed that sclerostin levels were significantly higher in RA patients compared to control (p<0.001) but were significantly lower than RA patients with joint deformities (0.026). Sclerostin levels also correlated with CRP (r=0.328, p=0.012), Anti-CCP (r=0.418, p=0.001), tender joint count (r=0.293, p=0.025), and DAS28 (r=0.26, p=0.047). There was not a significant association with other variables such as ESR, and rheumatoid factor. By using receiver operating characteristic (ROC) curve, the best cut-off value of sclerostin was 249.69 pg/ml which showed (AUC 0.910, sensitivity 87.9%; specificity 93.3%) and [Odd Ratio (OR) Value & P-value: 102, P< 0.0001].Conclusion: Sclerostin can be used in addition to other parameters to diagnose RA as it was associated with RA with good sensitivity and specificity. It was also associated in early joint destruction and tenderness.

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Evaluating the role of serum sclerostin as an indicator of activity and damage in Egyptian patients with rheumatoid arthritis: university hospital experience

Cited by 17 publications

References 48 publications

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

Role of Sclerostin in Cardiovascular Disease

The role of sclerostin in rheumatoid arthritis in a Syrian population: a potential indicator of disease activity in newly-diagnosed patients

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