Endocrine Abstracts

JOINT2132

Osteocalcin (OC) is emerging as a hormone regulating metabolic/endocrine functions including glucose metabolism and energy homeostasis. OC displays different carboxylation status modulated by vitamin K with different biological activities. Here, we investigated the role of carboxylated (γ₃OC) and uncarboxylated (γ₀OC) osteocalcin using a human model of severe osteoporotic patients treated with teriparatide (TPT) and randomized to supplementation with metaquinone (MK-7) 375 microg/die. Sixty-five normoglycemic patients (60 females, 5 males, aged 73. 9±6. 0 years, BMI 24. 2±3. 8 kg/m², mean±SD) were enrolled, treated with 20 microg TPT daily sc and reevaluated after 18 months. Forty-three patients concluded the study, including 11 women supplemented with MK7 (TPT+MK-7). All patients experienced at least one fragility fractures (n = 3. 4±1. 9), while during the follow up incident vertebral morphometric deformities occurred just in one patient. TPT increased the circulating bone formation markers γ₃OC, γ₀OC, bone-specific alkaline phosphatase (BALP), as well as the bone resorption markers C-terminal telopeptide of type 1-collagen (β-CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b), while TPT reduced sclerostin. Of note, in patients treated with TPT+MK-7, circulating γ₃OC levels, but not γ₀OC, after 18 months were higher than those in non-supplemented patients (21. 1±13. 1 vs 12. 7±3. 7 ng/ml, P = 0. 0651; Δ +94. 1±0. 7% vs +34. 5±0. 5%, P = 0. 0313). TPT treatment significantly increased lumbar T-scores, with any difference in the amount of increase between the two groups (Δ17. 0±14. 0% vs 18. 3±15. 0%), while no changes were detected at neck and hip levels. By contrast, TPT+MK-7 induced a higher T-score Δ at hip level than TPT (22. 2±0. 5% vs 0. 4±0. 2%, P = 0. 0374). Long-term TPT as well as TPT+MK-7 did not prevent skeletal muscle mass reduction, evaluated as appendicular skeletal muscle index (ASMI; 5. 76±0. 82 vs 5. 51±0. 74 kg/m²; P = 0. 0018; Δ−3. 9% per year) and lean mass/height² (LMH; 14. 2±1. 6% vs 13. 9±1. 6%, P = 0. 0156) by DXA, as well as muscle strength loss by handgrip test (17. 5±5. 8 vs 15. 7±3. 9 kg, P = 0. 0715). Besides, the trunk/limb fat mass ratio increased, though circulating leptin levels decreased. Finally, TPT treatment induced a significant increase in insulin sensitivity evaluated by oral glucose tolerance test (OGIS index, 427. 7±82. 7 vs 474. 0±81. 4 µmol/min/m², P = 0. 0102). In Conclusions, long-term TPT increases γ₃OC and γ₀OC circulating levels and lumbar T-scores and prevents new fractures, improves peripheral insulin sensitivity and decreases leptin levels; however, it does not protect from aging-related loss of muscle mass and strength. MK-7 supplementation amplifies the TPT-induced increases of circulating γ₃OC levels and hip T-scores, but it does not affect glucose metabolism as well as body composition in normoglycemic severe osteoporotic elder patients.