Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopau
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ORIGINAL ARTICLE
Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study Cristiana Cipriani 1 Sara Piemonte2 Luciano Colangelo1 Viviana De Martino1 Daniele Diacinti3 Federica Ferrone1 Valentina Piazzolla1 Valeria Fassino4 Luciano Nieddu5 Salvatore Minisola1 Jessica Pepe1 ●
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Received: 28 May 2020 / Accepted: 26 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose We evaluated the early effect of denosumab on circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Methods Denosumab (60 mg) was administered subcutaneously every 6 months (m) in 27 women (mean age 75 ± 5 years) with postmenopausal osteoporosis and high cardiovascular risk for a total of 24 m. Zoledronic acid was administered in 6 age-matched women as a single intravenous dose. Serum levels of vascular cell adhesion protein 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E and P selectin, CD-40 ligand (CD40L), interleukin-6 (IL-6), matrix metalloproteinase (MMP) 1 and 9, monocyte chemoattractant protein-1 (MCP-1), fibrinogen (FBG), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline, 15 days (d), 2, 6 and 12 m after dosing. In the denosumab group, observation was extended to 24 m as secondary endpoint. Results Serum ICAM-1 levels showed significant increase in the zoledronic acid group (+18 ± 0.1%; p < 0.01) at 12 m. In the denosumab group, we observed a significant increase in serum CD40L (+2 ± 0.8%; p < 0.001), MMP-1 (+11 ± 0.4%, p < 0.02), and MMP-9 (+39.4 ± 0.8%, p < 0.01) at 24 m. There was a significant increase in serum FBG and hs-CRP in both groups at 12 m (denosumab:+2.2 ± 0.2% and +50.3 ± 1.6%; zoledronic acid: +9.4 ± 0.1 and +81.8 ± 0.8%; p < 0.01). No significant between-group differences were found. Conclusions 24-m treatment with denosumab has no effect on the circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Fluctuation of serum ICAM-1, CD40L, MMPs, FBG and hs-CRP can be ascribed to perturbation of immunological mechanisms stimulated by denosumab and zoledronic acid. Keywords Denosumab Atherosclerosis Postmenopausal Osteoporosis Cardiovascular ●
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These authors contributed equally: Cristiana Cipriani, Sara Piemonte * Cristiana Cipriani [email protected] 1
Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
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ASL ROMA 1, Distretto 2, via Tagliamento 19, 00198 Rome, Italy
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Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
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Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy
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Faculty of Economics, UNINT University, Via Cristoforo Colombo 200, 00147 Rome, Italy
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Introduction Osteoporosis is a comm
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