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01-01-2021 | Osteoporosis | Original Article

Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study

Authors: Cristiana Cipriani, Sara Piemonte, Luciano Colangelo, Viviana De Martino, Daniele Diacinti, Federica Ferrone, Valentina Piazzolla, Valeria Fassino, Luciano Nieddu, Salvatore Minisola, Jessica Pepe

Published in: Endocrine | Issue 1/2021

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.

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Title: Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study
Authors: Cristiana Cipriani
Sara Piemonte
Luciano Colangelo
Viviana De Martino
Daniele Diacinti
Federica Ferrone
Valentina Piazzolla
Valeria Fassino
Luciano Nieddu
Salvatore Minisola
Jessica Pepe
Publication date: 01-01-2021
Publisher: Springer US
Keywords: Osteoporosis
Osteoporosis
Arterial Occlusive Disease
Denosumab
Denosumab
Zoledronic Acid
Published in: Endocrine / Issue 1/2021
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-020-02483-2

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