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Serum extracellular secreted antagonists of the canonical Wnt/β-catenin signaling pathway in patients with Cushing's syndrome.
MedLine Citation:
PMID:  23358608     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Patients with endogenous hypercortisolism have higher sclerostin, but do not differ in Dickkopf 1 (Dkk1) or secreted frizzled-related protein 1 (SFRP1) levels as compared to healthy control. INTRODUCTION: Endogenous Cushing's syndrome (CS), usually affecting young and otherwise healthy patients, is a good model to validate the effects of supraphysiological levels of glucocorticoids in humans. This study evaluates circulating levels of extracellular antagonists of the Wnt/β-catenin signaling pathway (sclerostin, Dkk1, SFRP1) in patients with CS versus healthy individuals. METHODS: Forty patients with clinically and biochemically evident CS and 40 sex-, age-, and body mass index-matched healthy subjects provided fasting serum samples for sclerostin, SFRP1 and Dkk1, along with bone turnover markers. RESULTS: Patients with CS had higher sclerostin levels (34.5 (30.3-37.1) pmol/L) versus healthy individuals (29.9 (24.3-36.8) pmol/L) (p = 0.032). Differences in sclerostin were due to the lack of lower sclerostin values rather than an increase in protein levels above the upper limits of the healthy control. The odds of sclerostin levels being higher than 30 pmol/L were greater in patients with CS as compared with the odds in healthy subjects (odds ratio = 3.81 95 % confidence interval 1.45-10.02) (p = 0.01). It coexisted with suppressed bone formation and unchanged bone resorption markers. Dkk1, SFRP1 did not differ from the control group. CONCLUSIONS: Of all the tested proteins (sclerostin, Dkk1, SFRP1), only sclerostin showed a significant difference when contrasting CS with healthy subjects. Hypercortisolism might prevent the down-regulation of sclerostin. Targeting sclerostin seems to be a promising therapeutic approach to treating osteoporosis in patients with CS.
Authors:
Z E Belaya; L Y Rozhinskaya; G A Melnichenko; A G Solodovnikov; N V Dragunova; A V Iljin; L K Dzeranova; I I Dedov
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-29
Journal Detail:
Title:  Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA     Volume:  -     ISSN:  1433-2965     ISO Abbreviation:  Osteoporos Int     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9100105     Medline TA:  Osteoporos Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The National Research Center for Endocrinology, ul. Dmitria Uljanova, 11, Moscow, 117036, Russia, jannabelaya@gmail.com.
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