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

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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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Author contributions

C.C. and S.P. equally contributed to study design, data collection, analysis, drafting and revision of the manuscript. L.C., D.D. and V.P. contributed to data collection. V.D.M., F.F. and V.F. contributed to laboratory assessment. L.N. contributed to data analysis and revision of the manuscript. S.M. and J.P. contributed to data collection and analysis and final revision of the manuscript.

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  1. These authors contributed equally: Cristiana Cipriani, Sara Piemonte

Authors and Affiliations

  1. Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Cristiana Cipriani, Luciano Colangelo, Viviana De Martino, Federica Ferrone, Valentina Piazzolla, Salvatore Minisola & Jessica Pepe

  2. ASL ROMA 1, Distretto 2, via Tagliamento 19, 00198, Rome, Italy

    Sara Piemonte

  3. Department of Radiological Sciences, Oncology and Pathology, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Daniele Diacinti

  4. Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy

    Valeria Fassino

  5. Faculty of Economics, UNINT University, Via Cristoforo Colombo 200, 00147, Rome, Italy

    Luciano Nieddu

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Correspondence to Cristiana Cipriani.

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S.M. served as speaker for Abiogen, Amgen, Bruno Farmaceutici, Diasorin, Eli Lilly, Shire, Sandoz, Takeda. He served in advisory board of Abiogen, Kyowa Kirin, Pfizer, UCB. All other authors declare no conflict of interests.

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Cipriani, C., Piemonte, S., Colangelo, L. et al. Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study. Endocrine 71, 199–207 (2021). https://doi.org/10.1007/s12020-020-02483-2

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