Bone Metabolism in SARS-CoV-2 Disease: Possible Osteoimmunology and Gender Implications

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 RANK-RANKL 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 RANK-RANKL 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.

Post-acute COVID-19 syndrome

“…So far, there is no evidence that COVID-19-associated diabetes can be reversed after the acute phase, nor that its outcomes differ in COVID-19 long haulers. COVID-19 also presents risk factors for bone demineralization related to systemic inflammation, immobilization, exposure to corticosteroids, vitamin D insufficiency and interruption of antiresorptive or anabolic agents for osteoporosis 190 .…”

Epidemiology and organ specific sequelae of post-acute COVID19: A narrative review

“…Home-isolation during lockdowns might decrease vitamin D levels and impair immunity (Appendix Table 2) [145]. Several patients have presented with abnormally low vitamin D and increased parathormone levels 8 weeks post COVID-19 onset, which may also have a clinically relevant impact on bone health (Table 2) [146,147].…”

Attenuation of COVID-19-induced cytokine storm in a young male patient with severe respiratory and neurological symptoms

“…The SARS-CoV‑2 also causes an activation of nuclear factor kappa-light-chain-enhancer of activated B‑cells (NF-κB) with subsequent bone resorption through direct activation of the receptor activator of NF-κB ligand (RANK-RANKL) system. Recent data suggest that this disease has the potential to act directly on bone resorption units with unfavorable long-term effects on bone metabolism (uncoupling) and a possibly increased risk of fragility fractures [ 11 ].…”