Background/Purpose:  Glucocorticoids are widely used to treat a variety of diseases, including systemic autoimmune diseases. Although glucocorticoids improve the outcome for patients with these diseases, various side effects of long-term treatment, such as osteoporosis, have become an important problem. Glucocorticoids decrease bone density through multiple mechanisms by inhibition of bone formation and by enhancement of bone resorption. Recently, the identification of the Wnt/β-catenin signaling pathway has led to considerable interest as one of the mechanism of osteoporosis in postmenopausal women. Wnt/β-catenin signaling pathway is mediated by Wnt3a and plays an important role in bone formation. Sclerostin and Dickkopf1 (Dkk-1) have been identified as antagonists of Wnt signaling. Therefore the purpose of this study is to clarify the clinical significance of the Wnt signaling pathway by measuring the serum levels of sclerostin, Dkk-1, Wnt3a and bone turnover markers in patients with recent onset of glucocorticoid therapy.

Methods: Patients were recruited at Toho University Omori Medical Center. This study was approved by the Ethics Committee of the Medical Center. Forty patients (25 females [14 postmenopausal],  55.2 ± 2.9 yr [mean ± SD]) with systemic autoimmune diseases (vasculitis syndrome 16, systemic lupus erythematosus 12, polymyositis / dermatomyositis 9, and adult-onset Still’s disease 3) who received initial glucocorticoid  therapy with prednisolone daily (30-60 mg) were prospectively enrolled in this study. Their mean bone mineral density at starting of prednisolone therapy was 0.944 g/cm2. Mean C -reactive protein was 4.08 ± 0.51 (S.D.) mg/dl. Regular doses of bisphosphonates (alendronate or risedronate) were co-administered in all patients. We measured serum sclerostin, Dkk-1, Wnt3a and bone turnover markers at 0, 1, 2, 3 and 4 weeks after start of glucocorticoid therapy.

Results: Serum sclerostin level was significantly (p<0.05) increased from 1st to 2nd weeks after starting of glucocorticoid therapy in comparison to previous value. Serum Dkk-1 level had a tendency to decrease, but there was no significant difference. Serum Wnt3a level had a trend to decrease after glucocorticoid therapy. Serum bone formation markers, osteocalcin and procollagen type I N-terminal peptide, decreased from 1st to 4th weeks, whereas bone alkaline phosphatase did not change. Serum bone resorption markers, tartrate-resistant acid phosphatase isoform 5b and N-telopeptide crosslinked of type I collagen did not change.

Conclusion: We found that glucocorticoid therapy caused increased level of serum sclerostin and a trend of decreased Wnt3a level. It is suggested that suppression of Wnt/β-catenin signaling pathway might, at least in part, be a cause of severe osteoporosis in patients with systemic autoimmune diseases under glucocorticoid therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/significance-of-serum-marker-levels-of-wnts-catenin-signaling-pathway-in-patients-with-systemic-autoimmune-diseases-under-glucocorticoid-therapy-a-prospective-study/