MON-533 Irisin in Post-Menopausal Women with Primary Hyperparathyroidism: An Interplay between Irisin and Pth

Background: Irisin is a myokine able to ameliorate bone status, muscle atrophy and it influences also glucose and energy homeostasis. PTH is hormone able to exert several metabolic effects that may interact with irisin’s ones. No studies have investigated the biological relation between Irisin and PTH. Aim:To test the hypothesis that irisin and PTH mutually affect their biological action, we evaluated the FNDC5 mRNA expression in myotubes treated with PTH (1-34) and PTH-R mRNA expression in osteoblast treated with recombinant irisin. To confirm the in vivoimpact of PTH on irisin, we evaluated irisin serum concentration in post-menopausal women with primary hyperparathyroidism (PHPT) compared to age, sex and BMI matched control subjects with no impairment of calcium/phosphate metabolism. Methods: C2C12 myotubes were treated with 100nM of teriparatide for 3 and 8 hours or with 100nM of teriparatide for 6 days, refreshing medium every 48h. MC3T3-E1 osteoblastswere treated with 100 ng/ml r-Irisin for 8 hours. Teriparatide-treated myotubes, Irisin-treated osteoblasts and untreated controls were subjected to RNA extraction and qPCR analysis. In a cross-sectional, open-label trial, we enrolled 26 PHPT post-menopausal women and 31 age/BMI matched control subjects with no impairment of calcium/phosphate metabolism. Results:Both short (p=0.036) and continuous (p=0.006) teriparatide treatment on myotubes significantly decreased FNDC5 mRNA expression respect to untreated control. r-Irisinled to a 50% down regulation of PTH-R mRNA expression compared to untreated cell (p=0.029).Irisin was significantly lower in PHPT group compared to age/BMI-matched controls (4.5±1.1 vs 12±5.2 µg/mL, p<0.001). No significant correlation between Irisin and BMD or PTH was recorded in PHPT group. Conclusion: for the first time, our pre-clinical findings suggest the existence of interplay between PTH and irisin metabolism that seems to be confirmed by the significant reduction of irisin concentration in post-menopausal women with PHPT.