Sclerostin and OPG/RANK-L system take part in bone remodeling in patients with acromegaly

Introduction: Acromegaly is a disease characterized by enhanced bone turnover with persistently high vertebral fracture risk. Sclerostin is a glycoprotein, which acts as an inhibitor of bone formation and activates osteoclast-mediated bone resorption. The osteoprotegerin (OPG)/receptor activator for the nuclear factor κ B ligand (RANK-L) system is crucial for controlling bone metabolism.

Objective: The study aimed primarily at evaluating sclerostin, OPG, and RANK-L concentrations in patients at different stages of acromegaly activity. The secondary aim was to identify an association of sclerostin with the OPG/RANK-L system and bone mineral density (BMD).

Materials and methods: The study enrolled 126 patients aged 40 to 80 years, including 72 patients with acromegaly and 54 controls (CG). The acromegaly patients were further classified into the following subgroups: active acromegaly (AA), controlled acromegaly (CTA), and cured acromegaly (CA). Blood samples were taken from the participants to measure sclerostin, OPG, RANK-L, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Dual-energy X-ray absorptiometry was performed at the lumbar spine and hip.

Results: Significantly lower sclerostin concentrations were observed in acromegaly patients compared with CG (AA, CTA, CA, CTA+CA, AA+CTA+CA vs CG; p < 0.001). Significant differences in OPG concentrations were revealed between the following groups: CTA vs CA (p=0.002), CTA vs CG (p<0.001), CTA+CA vs. CG (p<0.001), and AA+CTA+CA vs. CG (p<0.001). There were no significant differences in RANK-L concentrations between studied groups, regardless of the adopted classification (p>0.05). There were no statistically significant correlations between sclerostin and GH/IGF-1 or BMD. In the AA+CTA+CA group, there was a statistically significant positive correlation between SCL and OPG concentrations (r=0.271; p=0.022). A significant negative correlation between SCL and RANK-L was found in the AA group (r=-0.738; p=0.046).

Conclusions: Patients with acromegaly have lower sclerostin concentrations than healthy controls, which may be a result of a compensatory mechanism to increased bone loss. The influence of the GH/IGF-I axis on bone remodeling may be mediated in part by the OPG/RANK-L system. The interaction between SCL and OPG/RANK-L system in acromegaly should be further elucidated.