Serum extracellular secreted antagonists of the canonical Wnt/β-catenin signaling pathway in patients with Cushing’s syndrome

• Published in: Osteoporosis international Vol. 24; no. 8; pp. 2191 - 2199
• Main Authors: Belaya, Z. E., Rozhinskaya, L. Y., Melnichenko, G. A., Solodovnikov, A. G., Dragunova, N. V., Iljin, A. V., Dzeranova, L. K., Dedov, I. I.
• Format: Journal Article
• Language: English
• Published: London Springer London 01.08.2013
• Subjects: Adult; Biomarkers - blood; Bone Density - physiology; Bone Morphogenetic Proteins - blood; Bone Morphogenetic Proteins - physiology; Case-Control Studies; Cushing Syndrome - blood; Cushing Syndrome - complications; Cushing Syndrome - physiopathology; Endocrinology; Female; Femur Neck - physiopathology; Genetic Markers - physiology; Humans; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - physiology; Lumbar Vertebrae - physiology; Male; Medicine; Medicine & Public Health; Membrane Proteins - blood; Membrane Proteins - physiology; Middle Aged; Original Article; Orthopedics; Osteogenesis - physiology; Osteoporotic Fractures - blood; Osteoporotic Fractures - etiology; Osteoporotic Fractures - physiopathology; Osteoprotegerin - blood; RANK Ligand - blood; Rheumatology; Wnt Signaling Pathway - physiology; Young Adult; Dickkopf 1; Glucocorticoid-induced osteoporosis; Sclerostin; Cushing’s syndrome; Secreted frizzled-related protein 1
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-013-2268-y

Summary 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.