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

Abstract

Purpose of Review 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. Recent Findings 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. Summary 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.

The Use of Artificial Intelligence in Writing Scientific Review Articles

“…The traditional methods of writing a review article were employed for the human-generated writing style [13,16,19]. Specifically, a comprehensive literature review was completed, and an outline of relevant topics was created to help guide the authors in organizing and focusing their review article.…”

“…(2) neural regulation of fracture healing [16][17][18]; and (3) COVID-19 and musculoskeletal health [19,20]. With this background, we hypothesized that the human paper would take the most time and require the fewest changes between the first and final drafts.…”

The Utility of AI in Writing a Scientific Review Article on the Impacts of COVID-19 on Musculoskeletal Health

“…To test this possibility in scientific writing, we created an experiment to see if the current state of LLMs, and more specifically ChatGPT 4.0, would be able to increase the efficiency of writing scientific review articles. To accomplish this, we first identified 3 topics of importance to the musculoskeletal research field: (1) COVID-19 and musculoskeletal health [ 4 , 5 ]; (2) the intersection of Alzheimer’s disease and bone [ 6 – 8 ]; and (3) the neural regulation of fracture healing [ 9 – 11 ]. We then implemented 3 approaches to write the first draft of review articles on each topic: (1) human only; (2) ChatGPT 4.0 only (AI-only or AIO); and (3) a combination of approaches 1 and 2 (AI-assisted or AIA).…”