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Analysis on circulating sclerostin level according to estrogen status and investigation of the relationship between the factors of bone metabolism with sclerostin

Title
Analysis on circulating sclerostin level according to estrogen status and investigation of the relationship between the factors of bone metabolism with sclerostin
Other Titles
여성호르몬 상태에 따른 혈청 스클레로스틴의 변화와 골대사 관련인자와의 상관관계 분석
Issue Date
2012
Publisher
Graduate School, Yonsei University
Description
Dept. of Medicine/석사
Abstract
Bone formation and resorption is a complicated pathway that is involved by many mediators. There is a substance called sclerostin which is secreted by osteocytes, and acts on Wnt pathway leading to inhibition of bone formation. Many studies revealed that sclerostin is elevated in postmenopausal women, and with aging and the immobilization, and is decreased in primary hyperparathyroidism, estrogen or raloxifene treated patients after menopause. Aromatase inhibitor (AI) which reduces the conversion to estrogen is used in treatment of endocrine responsive breast cancer. As it lowers estrogen level, thus bone resorption and bone turnover rate are increased. The objective of the study was to analyze the changes in serum sclerostin levels in Korean women with endocrine-responsive breast cancer who were treated with AI and assess its relationship to absolute deficient estradiol, bone turnover markers and bone mineral density (BMD). We included postmenopausal women with endocrine-responsive breast cancer (n=90) treated with AI comparing with healthy premenopausal women (n=36). Patients with breast cancer were randomly assigned to take either 5 mg alendronate with 0.5 µg of calcitriol (n=46) or placebo (n=44) for 6 months. We analyzed serum sclerostin levels by along with routine chemistry, bone turnover markers including C-telopeptide (CTx) and osteocalcin, and BMD by dual X-ray absorptiometry. Premenopausal women were 28.0 years in average and postmenopausal women were 57.7 years in average. Postmenopausal women represented significantly higher sclerostin level compared with premenopausal women (27.8 ± 13.6 vs. 23.1 ± 4.8 pmol/L, p < 0.05). Baseline sclerostin was positively correlated with either lumbar spine or total hip BMD only in postmenopausal women (r = 0.218, and r = 0.233, p < 0.05, respectively). There were no significant correlations with other bone markers. Serum sclerostin levels increased 38.7% after the use of AI in placebo group compared to the alendronate group which showed slightly lesser increase about 24.4%. In our study, serum sclerostin level is increased along the absolute deficiency of residual estrogen in postmenopausal women with endocrine-responsive breast cancer on AI therapy. It significantly correlates with BMD at all sites with statistical significance. There need to be further studies in large numbers.
URI

http://ir.ymlib.yonsei.ac.kr/handle/22282913/134202
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 석사
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