COVID-19 and Bone Loss: A Review of Risk Factors, Mechanisms, and Future Directions

SARS-CoV-2 drove the catastrophic global phenomenon of the COVID-19 pandemic resulting in a multitude of systemic health issues, including bone loss. The purpose of this review is to summarize recent findings related to bone loss and potential mechanisms.

The early clinical evidence indicates an increase in vertebral fractures, hypocalcemia, vitamin D deficiencies, and a loss in BMD among COVID-19 patients. Additionally, lower BMD is associated with more severe SARS-CoV-2 infection. Preclinical models have shown bone loss and increased osteoclastogenesis. The bone loss associated with SARS-CoV-2 infection could be the result of many factors that directly affect the bone such as higher inflammation, activation of the NLRP3 inflammasome, recruitment of Th17 cells, the hypoxic environment, and changes in RANKL/OPG signaling. Additionally, SARS-CoV-2 infection can exert indirect effects on the skeleton, as mechanical unloading may occur with severe disease (e.g., bed rest) or with BMI loss and muscle wasting that has also been shown to occur with SARS-CoV-2 infection. Muscle wasting can also cause systemic issues that may influence the bone. Medications used to treat SARS-CoV-2 infection also have a negative effect on the bone. Lastly, SARS-CoV-2 infection may also worsen conditions such as diabetes and negatively affect kidney function, all of which could contribute to bone loss and increased fracture risk. SARS-CoV-2 can negatively affect the bone through multiple direct and indirect mechanisms. Future work will be needed to determine what patient populations are at risk of COVID-19-related increases in fracture risk, the mechanisms behind bone loss, and therapeutic options. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.