Wnt10b and Wnt3a AS BIOMARKERS OF CHANGES IN THE REGULATION OF BONE METABOLISM IN PATIENTS WITH CUSHING’S DISEASE

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Abstract

Background: Endogenous hypercortisolism due to Cushing’s disease (CD) is complicated by low-traumatic fractures in 50% of cases. Modern technologies allow to study pathogenetic changes in the regulation of bone remodeling in hypercortisolism and to offer new serum biomarkers.

Aims: To evaluate levels of Wnt proteins related to bone remodeling regulation in serum samples from patients with CD.

Materials and methods: Fasting serum samples were taken and stored in aliquot at ≤-80 °C from 42 consecutive subjects with clinically evident and biochemically confirmed active CD and 42 healthy volunteers matched by age, sex and body mass index (BMI). Evaluation of the levels of Wnt proteins (Wnt3a, Wnt10b) was measured by immunochemiluminescence assay using the WNT3a SEL818Hu (USCN) and the WNT10b SEP553Hu (USCN). Twenty-four hours urine free cortisol (24hUFC) (60−413 nmol/24h) and bone turnover markers was measured by electrochemiluminescence assay on a Cobas 6000 Module e601 (Roche). At the time of enrollment all participants were questioned regarding any low traumatic fractures for the period of the disease. Patients underwent standard spinal radiographs in anterior-posterior and lateral positions of the vertebrae Th4−L4 (Axiom Icons R200 Siemens).

Results: The median (Ме Q25; Q75) age of patients with CD was 33 (21; 43) years with no difference among the groups, p=0.936; BMI ― 29 (23; 34) kg/m2, p=0.094 and without differences by sex, p=0.254. The median 24hUFC in subjects with CD ― 825 (301; 2077) nmol/24h was significantly higher as compared to the control group (p<0.001). We report increased levels of Wnt3a and Wnt10b in patients with CD: Wnt3а 0.15 (0.04; 0.23) ng/ml in patients with CD vs 0,04 (0.01; 0.13) ng/ml in control group (p=0.017) and Wnt10b 2621 (2226; 3688) pg/ml vs 1917 (1721; 2549) pg/ml (p=0.008).

Conclusions: The serum level of Wnt3a and Wnt10b reflects the intensity of Wnt-signaling dysregulation, and therefore they may be considered as biomarkers of bone remodeling deterioration in hypercortisolism.

About the authors

T. A. Grebennikova

Endocrinology Research Centre

Author for correspondence.
Email: Grebennikova@hotmail.com
ORCID iD: 0000-0003-1413-1549

Tatiana A. Grebennikova - MD.

Moscow

Russian Federation

Z. E. Belaya

Endocrinology Research Centre

Email: jannabelaya@gmail.com
ORCID iD: 0000-0002-6674-6441

Zhanna E. Belaya - MD, PhD.

Moscow

Russian Federation

A. G. Solodovnikov

Ural State Medical Academy

Email: dr.alexander.solodovnikov@gmail.com
ORCID iD: 0000-0002-4564-2168

Alexander G. Solodovnikov.

Ekaterinburg

Russian Federation

A. V. Ilyin

Medical Center FertiLab

Email: biochem@endocrincentr.ru
ORCID iD: 0000-0002-3259-4443

Alexander V. Ilyin - MD.

Moscow

Russian Federation

L. V. Nikankina

Endocrinology Research Centre

Email: larisanikan@rambler.ru
ORCID iD: 0000-0001-8303-3825

Larisa V. Nikankina - MD.

Moscow

Russian Federation

G. A. Melnichenko

Endocrinology Research Centre

Email: teofrast2000@mail.ru
ORCID iD: 0000-0002-5634-7877


Galina A. Melnichenko - MD, PhD, Professor.

Moscow

Russian Federation

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