Bone Metabolism in SARS-CoV-2 Disease: Possible Osteoimmunology and Gender Implications
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REVIEW PAPER
Bone Metabolism in SARS-CoV-2 Disease: Possible Osteoimmunology and Gender Implications Gianmaria Salvio 1 & Claudio Gianfelice 1 & Francesca Firmani 1 & Stefano Lunetti 1 & Giancarlo Balercia 1 & Gilberta Giacchetti 1 Accepted: 18 August 2020 # The Author(s) 2020
Abstract Even though inflammatory conditions are known to exert adverse effects on bone metabolism, there are no published data regarding SARS-CoV-2 infection and subsequent fracture risk. We present a brief review of the molecular mechanisms linking inflammatory diseases to increased fracture risk/osteoporosis and of the therapeutic strategies that can prevent bone resorption in patients with inflammatory disease, focusing on the RANK-RANKL system. We also make some considerations on gender differences in infection response and on their implications for survival and for the consequences of COVID-19. Several inflammatory cytokines, especially IL-1, IL-6, and TNF-α, stimulate osteoclast activity, favoring bone resorption through the RANKRANKL system. Data from the previous SARS-CoV outbreak suggest that the present disease also has the potential to act directly on bone resorption units, although confirmation is clearly needed. Even though the available data are limited, the RANKRANKL system may provide the best therapeutic target to prevent bone resorption after COVID-19 disease. Vitamin D supplementation in case of deficiency could definitely be beneficial for bone metabolism, as well as for the immune system. Supplementation of vitamin D in case of deficiency could be further advantageous. In COVID-19 patients, it would be useful to measure the bone metabolism markers and vitamin D. Targeting the RANK-RANKL system should be a priority, and denosumab could represent a safe and effective choice. In the near future, every effort should be made to investigate the fracture risk after SARS-CoV-2 infection. Keywords Osteoporosis . Fracture risk . COVID-19 . SARS-CoV-2 . Denosumab
Introduction In early December 2019, a novel coronavirus emerged in Wuhan City (Hubei Province, China). It subsequently spread throughout the country and eventually through the world. The virus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can easily reach the lower respiratory tract, causing a bilateral pneumonia (coronavirus infectious disease, COVID-19) characterized by a high mortality rate [1]. According to the information reported in the World Health Organization website, by May 18, the number of laboratory-confirmed cases of
* Gilberta Giacchetti [email protected] 1
Division of Endocrinology, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Via Conca 71, Umberto I Hospital, 60126 Ancona, Italy
COVID-19 worldwide had climbed to 4,660,870 and 313,403 patients had died. In Italy, on the same day, the number of laboratory-confirmed COVID-19 cases was 226,699; average patient age was 62 years (52.1% men, 47.9% women). As SARS-CoV-2 infection predominantly affects older people [2], o
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