New biomarkers of bone remodelling regulation in patients with acromegaly and endogenous hypercortisolism

Abstract

Background: Bone tissue is a non-classical endocrine organ, which produces at least two hormones: fibroblast growth factor 23 (FGF-23) and decarboxylated osteocalcin (OC). In addition to this, recent studies demonstrate that specific proteins involved in the paracrine regulation of bone remodelling can be measured in peripheral serum samples and may serve as additional biomarkers of bone metabolism.
 Aims: to evaluate the serum levels of biomarkers related to endocrine and paracrine function of bone tissue in patients with Cushings disease (CD) and acromegaly.
 Materials and methods: The study was conducted according to the cross-sectional case-control type. Fasting serum samples were taken between 810 a.m. from patients with CD, acromegaly and age-, sex- and BMI-matched healthy volunteers and stored at -40 C. Commercially available kits for enzyme-linked immunosorbent assay (ELISA) were used to determine the serum levels of FGF-23, co-factor (co-receptor) Klotho, cathepsin K, sclerostin, P1NP. Insulin-like growth factor-1 (IGF-1) was measured by the immunochemiluminescence assay, late-night (11 p.m.) salivary cortisol (LNSC) was evaluated using the electrochemiluminescence method. Non-parametric tests (the Kruskal-Wallis test and the Mann-Whitney test) were used to assess the differences between the groups of patients.
 Results: The study includes 78 patients, (37.6 years old, 95% CI 34.7540.46): 29 patients with CD (group 1), 22 with acromegaly (group 2), and 27 healthy individuals (group 3), matched by sex, age and BMI (p = 0.432, 0.373 and 0.725 between groups, respectively). LNSC in patients with CD and IGF-1 in patients with acromegaly were significantly higher compared to the control group (p = 0.004 and p 0.001, respectively). In patients with acromegaly, a statistically significant increase in FGF-23 (1.13 (0.78;1.49) vs 0.78 (0.54;1.09)) and phosphorus (1.38 (1.24;1.52) vs 1.16 (1.12;1.29)) (p = 0.01 and p 0.001, respectively) was observed along with increased levels of bone remodelling markers. In patients with CD, bone formation markers were suppressed, but differences in the levels of other biomarkers could not be identified.
 Conclusions: Acromegaly leads to hyperphosphatemia and increase in FGF-23, which is most likely due to the development of resistance to FGF-23, and the intensification of bone remodelling. With CD, another bone hormone, osteocalcin, is suppressed along with the suppression of P1NP.