Cardiovascular Safety and Sclerostin Inhibition
| Autor: | J C Forfar, Lorenz C. Hofbauer, Bente L. Langdahl |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Clinical Biochemistry Osteoporosis sclerostin Cardiovascular System Biochemistry chemistry.chemical_compound 0302 clinical medicine Endocrinology Bone Density Osteogenesis Osteoporosis Postmenopausal Bone Density Conservation Agents biology Antibodies Monoclonal Middle Aged medicine.anatomical_structure Cardiovascular Diseases RANKL Female Risk medicine.medical_specialty Romosozumab 030209 endocrinology & metabolism 03 medical and health sciences cardiovascular safety Osteoclast Internal medicine Product Surveillance Postmarketing medicine Humans Adverse effect Adaptor Proteins Signal Transducing Proportional Hazards Models romosozumab business.industry Biochemistry (medical) medicine.disease osteoporosis Clinical trial 030104 developmental biology Clinical Trials Phase III as Topic chemistry Heart Disease Risk Factors Relative risk biology.protein Sclerostin business Osteoporotic Fractures |
| Zdroj: | Langdahl, B L, Hofbauer, L C & Forfar, J C 2021, ' Cardiovascular Safety and Sclerostin Inhibition ', The Journal of clinical endocrinology and metabolism, vol. 106, no. 7, pp. 1845-1853 . https://doi.org/10.1210/clinem/dgab193 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgab193 |
| Popis: | Sclerostin, which is primarily produced by the osteocytes, inhibits the canonical Wnt pathway and thereby the osteoblasts and stimulates RANKL release by the osteocytes and thereby osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation of bone formation and inhibition of resorption. In clinical trials, romosozumab, an antibody against sclerostin, increases bone mineral density and reduces the risk of fractures compared with placebo and alendronate. The cardiovascular safety of romosozumab was adjudicated in 2 large clinical osteoporosis trials in postmenopausal women. Compared with placebo, the incidence of cardiovascular events was similar in the 2 treatment groups. Compared with alendronate, the incidence of serious cardiovascular events was higher in women treated with romosozumab. The incidence of serious cardiovascular adverse events was low and post hoc analyses should therefore be interpreted with caution; however, the relative risk seemed unaffected by preexisting cardiovascular disease or risk factors. Sclerostin is expressed in the vasculature, predominantly in vascular smooth muscle cells in the media. However, preclinical and genetic studies have not demonstrated any increased cardiovascular risk with continuously low sclerostin levels or inhibition of sclerostin. Furthermore, no potential mechanisms for such an effect have been identified. In conclusion, while there is no preclinical or genetic evidence of a harmful effect of sclerostin inhibition on cardiovascular safety, the evidence from the large clinical trials in postmenopausal women is conflicting. Romosozumab should therefore be used for the treatment of postmenopausal women with osteoporosis at high risk of fracture after careful consideration of the cardiovascular risk and the balance between benefits and risks. |
| Databáze: | OpenAIRE |
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