A practical approach for anabolic treatment of bone fragility with romosozumab

• Published in: Journal of endocrinological investigation 2024-11, Vol.47 (11), p.2649-2662
• Main Authors: Cianferotti, L., Cipriani, C., Palermo, A., Viapiana, O., Zavatta, G., Mazziotti, G.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Anabolic Agents - therapeutic use; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Bone Density - drug effects; Bone Density Conservation Agents - therapeutic use; Endocrinology; Female; Humans; Internal Medicine; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Osteoporosis - drug therapy; Osteoporotic Fractures - prevention & control; Short Review
• ISSN: 1720-8386; 1720-8386
• DOI: 10.1007/s40618-024-02395-2

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.