Patryk Zarecki1, Matthias Hackl2, Johannes Grillari3, Miguel Debono4, Richard Eastell4. 1. Department of Oncology and Metabolism, University of Sheffield, England, United Kingdom. Electronic address: p.zarecki@sheffield.ac.uk. 2. TAmiRNA GmbH, Vienna, Austria. 3. TAmiRNA GmbH, Vienna, Austria; Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria; Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria. 4. Department of Oncology and Metabolism, University of Sheffield, England, United Kingdom.
Abstract
CONTEXT: Vertebral fractures are the hallmark of osteoporosis. MicroRNAs (miRNAs) are a prominent class of gene regulators likely to affect bone homeostasis, including bone remodelling and fracture healing by altering gene expression in bone cells. OBJECTIVE: This study sought to compare the levels of circulating miRNAs in older women with osteoporotic vertebral fractures, and/or low BMD and healthy controls, and to correlate miRNAs expression levels with BTMs. DESIGN: A single-site, case-control, observational, cross-sectional study at a university hospital. PARTICIPANTS: Altogether, 126 postmenopausal women belonging to four different groups were included: healthy (n=42), low BMD and no vertebral fractures (n=39), vertebral fractures and low BMD without a treatment (n=26), or receiving a treatment for osteoporosis (n=19). MAIN OUTCOME MEASURE: Serum samples from all participants were analyzed for 21 microRNA bone biomarkers. RESULTS: We identified 7 significantly (p<0.05) up-regulated miRNAs (miR-375, miR-532-3p, miR-19b-3p, miR-152-3p, miR-23a-3p, miR-335-5p, miR-21-5p) in patients with vertebral fractures and low BMD compared to low BMD and healthy individuals, regardless of osteoporosis treatment. No significant differences existed between low BMD and healthy controls. We observed 24 significant correlations (P<0.05) between miRNAs and BTMs (CTX, PINP, OC and bone ALP). CONCLUSIONS: Specific circulating miRNAs reflect the presence of osteoporotic vertebral fractures in postmenopausal women. They are unlikely to reflect low BMD, and more likely changes in bone quality or fracture healing. The effects of osteoporosis treatment on the selected miRNAs appear to be weaker than effects caused by vertebral fractures. The correlation between miRNAs and BTMs suggest that miRNAs may be involved in bone turnover or fracture healing.
CONTEXT: Vertebral fractures are the hallmark of osteoporosis. MicroRNAs (miRNAs) are a prominent class of gene regulators likely to affect bone homeostasis, including bone remodelling and fracture healing by altering gene expression in bone cells. OBJECTIVE: This study sought to compare the levels of circulating miRNAs in older women with osteoporotic vertebral fractures, and/or low BMD and healthy controls, and to correlate miRNAs expression levels with BTMs. DESIGN: A single-site, case-control, observational, cross-sectional study at a university hospital. PARTICIPANTS: Altogether, 126 postmenopausal women belonging to four different groups were included: healthy (n=42), low BMD and no vertebral fractures (n=39), vertebral fractures and low BMD without a treatment (n=26), or receiving a treatment for osteoporosis (n=19). MAIN OUTCOME MEASURE: Serum samples from all participants were analyzed for 21 microRNA bone biomarkers. RESULTS: We identified 7 significantly (p<0.05) up-regulated miRNAs (miR-375, miR-532-3p, miR-19b-3p, miR-152-3p, miR-23a-3p, miR-335-5p, miR-21-5p) in patients with vertebral fractures and low BMD compared to low BMD and healthy individuals, regardless of osteoporosis treatment. No significant differences existed between low BMD and healthy controls. We observed 24 significant correlations (P<0.05) between miRNAs and BTMs (CTX, PINP, OC and bone ALP). CONCLUSIONS: Specific circulating miRNAs reflect the presence of osteoporotic vertebral fractures in postmenopausal women. They are unlikely to reflect low BMD, and more likely changes in bone quality or fracture healing. The effects of osteoporosis treatment on the selected miRNAs appear to be weaker than effects caused by vertebral fractures. The correlation between miRNAs and BTMs suggest that miRNAs may be involved in bone turnover or fracture healing.
Authors: K Kerschan-Schindl; M Hackl; E Boschitsch; U Föger-Samwald; O Nägele; S Skalicky; M Weigl; J Grillari; P Pietschmann Journal: Calcif Tissue Int Date: 2021-01-11 Impact factor: 4.333
Authors: Maria Rosa Iaquinta; Carmen Lanzillotti; Chiara Mazziotta; Ilaria Bononi; Francesca Frontini; Elisa Mazzoni; Lucia Oton-Gonzalez; John Charles Rotondo; Elena Torreggiani; Mauro Tognon; Fernanda Martini Journal: Theranostics Date: 2021-04-30 Impact factor: 11.556