Impaired Bone Microarchitecture in Premenopausal Women With Acromegaly: The Possible Role of Wnt Signaling

Abstract

Context: Acromegaly can impair bone integrity, increasing the risk of vertebral fractures (VFs).

Objective: To evaluate the impact of isolated GH/IGF-I hypersecretion on bone turnover markers, Wnt inhibitors, bone mineral density (BMD), microarchitecture, bone strength and vertebral fractures in female patients with acromegaly (Acro), compared with healthy control group (HC).

Design, setting, and patients: Cross-sectional study including 83 premenopausal women without any pituitary deficiency:18 acromegaly in remission (AcroR), 12 in group with active acromegaly (AcroA), and 53 HC. Serum procollagen type 1 N-terminal propeptide, β-carboxy-terminal crosslinked telopeptide of type 1 collagen, osteocalcin, sclerostin, and DKK1 were measured in blood samples. dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) and vertebral fractures evaluation were also assessed simultaneously.

Main outcome and results: AcroA showed significantly lower sclerostin and higher DKK1 compared with HC. On HR-pQCT of tibia and radius, Acro showed impairment of trabecular (area and trabecular number), increased cortical porosity, and increased cortical area and cortical thickness compared with HC. The only significant correlation found with HR-pQCT parameters was a positive correlation between cortical porosity and serum DKK1 (R = 0.45, P = 0.044). Mild VFs were present in approximately 30% of patients.

Conclusions: Eugonadal women with acromegaly without any pituitary deficiency showed increased cortical BMD, impairment of trabecular bone microstructure, and increased VF. Sclerostin was not correlated with any HR-pQCT parameters; however, DKK1 was correlated with cortical porosity in tibia (P = 0.027). Additional studies are needed to clarify the role of Wnt inhibitors on bone microarchitecture impairment in acromegaly.

Keywords: Wnt signaling pathway; acromegaly; bone microarchitecture; bone mineral density; growth hormone; vertebral fractures.