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A practical approach for anabolic treatment of bone fragility with romosozumab

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Abstract

Background

Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management.

Methods

The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures.

Results

Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent.

Conclusions

Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

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The authors did not receive support from any organization for the submitted work.

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Authors and Affiliations

  1. Bone Metabolic Diseases Unit, Department of Experimental and Clinical Biomedical Sciences, University Hospital of Florence, University of Florence, Florence, Italy

    L. Cianferotti

  2. Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy

    C. Cipriani

  3. Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy

    A. Palermo

  4. Unit of Metabolic Bone and Thyroid Disorders, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy

    A. Palermo

  5. Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy

    O. Viapiana

  6. Division of Endocrinology and Diabetes Prevention and Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    G. Zavatta

  7. Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, Bologna, Italy

    G. Zavatta

  8. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, 420090, Pieve Emanuele, MI, Italy

    G. Mazziotti

  9. Endocrinology, Diabetology and Andrology Unit, Osteoporosis and Bone Diseases Section, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy

    G. Mazziotti

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  1. L. Cianferotti
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  2. C. Cipriani
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  3. A. Palermo
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  4. O. Viapiana
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  5. G. Zavatta
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  6. G. Mazziotti
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Correspondence to G. Mazziotti.

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Conflict of interest

Luisella Cianferotti received fees for consultancy from UCB and fees for lectures from Abiogen Pharma and Bruno Farmaceutici. Cristiana Cipriani served as speaker for Abiogen and in advisory board of IBSA. Andrea Palermo received founds for clinical Studies from, Ascendis Pharma and Takeda, fees for lectures from Amgen, UCB, Bruno Farmaceutici, Theramex, educational Grants from Bruno Farmaceutici, UCB and Amgen. Ombretta Viapiana received fees for consultancy from UCB, Grunenthal, Angelini and fees for lectures from Amgen, Eli Lilly, Galapagos, BMS. Guido Zavatta received fees for lectures from Abiogen Pharma and Bruno Farmaceutici. Gherardo Mazziotti received fees for consultancy and preceptorship from Amgen-UCB and Sanofi and fees for lectures from Theramex and Recordati. Gherardo Mazziotti and Luisella Cianferotti serve as Associate Editors for Journal of Endocrinological Investigation.

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Cianferotti, L., Cipriani, C., Palermo, A. et al. A practical approach for anabolic treatment of bone fragility with romosozumab. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02395-2

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