Decreased Serum Wnt Antagonist Levels in Patients With Active Acromegaly

Endocr Pract. 2022 May;28(5):515-520. doi: 10.1016/j.eprac.2022.01.011. Epub 2022 Feb 2.

Abstract

Objective: The Wnt signaling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients.

Methods: We recruited 77 patients recently diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. At baseline and posttreatment, Wnt antagonists (sclerostin [SOST], dickkopf-related protein 1 [DKK-1], and Wnt inhibitory factor 1 [WIF-1]), bone turnover markers (osteocalcin, procollagen type 1 N-terminal propeptide [P1NP], and C-terminal telopeptide of type 1 collagen [CTX]) and the bone remodeling index were investigated.

Results: Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodeling index than controls (P < .01). Serum SOST, DKK-1, and WIF-1 levels were significantly decreased in patients compared to controls (all P < .01). Serum SOST and WIF-1 levels were negatively correlated with growth hormone levels; SOST levels were positively correlated with WIF-1. After treatment, serum bone turnover markers and the bone remodeling index decreased, while SOST and WIF-1 significantly increased (P < .05). DKK-1 levels did not change compared to baseline (P > .05). In biochemically controlled patients, SOST and WIF-1 levels and bone turnover markers were restored and did not differ from those of the control participants (all P > .05).

Conclusion: Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists is a compensatory mechanism to counteract increased bone fragility in active acromegaly.

Keywords: Wnt antagonists; acromegaly; bone turnover markers; growth hormone; insulin-like growth factor 1.

MeSH terms

  • Acromegaly* / blood
  • Adaptor Proteins, Signal Transducing* / blood
  • Biomarkers / blood
  • Bone Morphogenetic Proteins / blood
  • Case-Control Studies
  • Genetic Markers
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood
  • Osteocalcin / blood
  • Peptide Fragments / blood
  • Procollagen / blood
  • Wnt Proteins* / antagonists & inhibitors
  • Wnt Proteins* / blood
  • Wnt Signaling Pathway*

Substances

  • Adaptor Proteins, Signal Transducing
  • BGLAP protein, human
  • Biomarkers
  • Bone Morphogenetic Proteins
  • DKK1 protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • Peptide Fragments
  • Procollagen
  • SOST protein, human
  • WIF1 protein, human
  • Wnt Proteins
  • procollagen Type I N-terminal peptide
  • Osteocalcin