Endocrine Abstracts

Objective: Acromegaly (ACRO) is associated with abnormal bone remodeling and reduced volumetric bone mineral density (vBMD) at the lumbar spine and proximal femur. Circulating microRNAs (miRNAs) modulate the activity of osteoblasts and osteoclasts, and are currently being investigated as potential biomarkers of osteoporosis. The aims of our study were: 1) To identify differentially expressed miRNAs in the serum of five patients with active ACRO vs. healthy controls, and 2) To correlate selected miRNAs concentrations with altered bone parameters in 11 ACRO patients.

Patients and methods: Eleven patients with active ACRO (six females; mean age, 47.5±6.7 years; BMI, 27.2±3.8 kg/m²) and 11 age-, gender-, and BMI-matched controls were recruited. Analysis of differential expression of miRs was performed in 5 of them (5 males; mean age, 44.3±4.3; BMI, 26.2±2.8). Areal BMD (aBMD) at lumbar spine and femur was assessed through dual energy X-ray- absorptiometry (DXA); vBMD was measured by quantitative computed tomography (QCT). Serum miRNA levels were assessed by qPCR. Osteocalcin (OC), type 1 amino-terminal propeptide (P1NP) and carboxy-terminal collagen crosslinks (CTx) were measured using electrochemiluminescent immunoassay.

Results: Expression of miR-885-5p, miR-99a-5p, and miR-29a-3p was significantly higher, while that of miR-7-1-3p and miR-335-3p was significantly lower in the ACRO patients. Both miR-885-5p and miR-7-1-3p were inversely associated with femoral aBMD (r=−0.64, P=0.034 and r=−0.73, P=0.009, respectively), and trocantheric vBMD (r=−0.66; ρ=0.038 and ρ=0.67; P=0.023) in ACRO but not in the controls. They were also positively associated with P1NP (r=0.82, P=0.002 and r=0.79, P=0.004, respectively) and CTx (r=0.73, P=0.010 and r=0.68, P=0.019) in ACRO. MiR-99a-5p was inversely associated with femoral aBMD (r=−0.66, P=0.26) and positively associated with P1NP (r=0.83; P=0.001) and CTx (r=0.88, P<0.001) in ACRO only. The relationship between femoral aBMD and miR-99a-5p remained significant after adjusting for age and IGF-SDS (β=−0.52, P=0.012).

Conclusions: Circulating miRNAs may be one of the mechanisms whereby BMD is impaired, mainly at the femoral level. Further larger studies are needed to confirm these preliminary data.