Acute bone loss following SARS‐CoV‐2 infection in mice

Haudenschild, Anne K.; Christiansen, Blaine A.; Orr, Sophie; Ball, Erin E.; Weiss, Christopher M.; Liu, Hongwei; Fyhrie, David P.; Yik, Jasper H.N.; Coffey, Lark L.; Haudenschild, Dominik R.

doi:10.1002/jor.25537

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…Osteoclastogenesis was increased as determined by histological analysis. Another group also found losses in vertebral trabecular bone volume fraction and increases in osteoclastogenesis with SARS-CoV-2 infection using this mouse model [ 46 •]. Similar to this model, a different group has demonstrated trabecular bone loss within tibiae, femurs, and vertebrae of golden hamsters infected with SARS-CoV-2 [ 47 ••].…”

Section: In Vitro and Preclinical Work Indicating That Sars-cov-2 Inf...mentioning

confidence: 72%

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

Creecy,

Awosanya,

Harris

et al. 2024

Curr Osteoporos Rep

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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.

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Section: In Vitro and Preclinical Work Indicating That Sars-cov-2 Inf...mentioning

confidence: 72%

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

Creecy,

Awosanya,

Harris

et al. 2024

Curr Osteoporos Rep

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“…Further, a virally induced decrease in osteoblast-related alkaline phosphatase expression was also measured. Similarly, a recent study by Haudenschild et al [ 336 ] provided the first evidence that SARS-CoV-2 infection led to acute bone loss, increased osteoclast numbers, and thinner growth plates. This was speculated to occur via hyperinflammation and decreased mobility together with the direct effects of SARS-CoV-2 infection of bone cells.…”

Section: Sphingolipids Viral Host Cell Entry and Orthopedic Infectionmentioning

confidence: 90%

Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

Seal,

Hughes,

Wei

et al. 2024

IJMS

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The human skeleton is a metabolically active system that is constantly regenerating via the tightly regulated and highly coordinated processes of bone resorption and formation. Emerging evidence reveals fascinating new insights into the role of sphingolipids, including sphingomyelin, sphingosine, ceramide, and sphingosine-1-phosphate, in bone homeostasis. Sphingolipids are a major class of highly bioactive lipids able to activate distinct protein targets including, lipases, phosphatases, and kinases, thereby conferring distinct cellular functions beyond energy metabolism. Lipids are known to contribute to the progression of chronic inflammation, and notably, an increase in bone marrow adiposity parallel to elevated bone loss is observed in most pathological bone conditions, including aging, rheumatoid arthritis, osteoarthritis, and osteomyelitis. Of the numerous classes of lipids that form, sphingolipids are considered among the most deleterious. This review highlights the important primary role of sphingolipids in bone homeostasis and how dysregulation of these bioactive metabolites appears central to many chronic bone-related diseases. Further, their contribution to the invasion, virulence, and colonization of both viral and bacterial host cell infections is also discussed. Many unmet clinical needs remain, and data to date suggest the future use of sphingolipid-targeted therapy to regulate bone dysfunction due to a variety of diseases or infection are highly promising. However, deciphering the biochemical and molecular mechanisms of this diverse and extremely complex sphingolipidome, both in terms of bone health and disease, is considered the next frontier in the field.

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“…In this investigation, despite causing an abortive infection in precursor macrophages of osteoclasts, the SARS-CoV-2's ability to accelerate osteoclastogenesis and bone resorption is highlighted. Limited studies on the direct impact of SARS-CoV-2 on osteoclast susceptibility and differentiation, primarily conducted in rodent models, have provided insights (16,17,22,23). Studying SARS-CoV-2's impact on the skeletal system is challenging due to delayed onset, but lasting effects include bone metabolism disorders observed in COVID-19 patients (24,25).…”

Section: Discussionmentioning

confidence: 99%

The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts

Quarleri,

SVIERCZ,

JARMOLUK

et al. 2024

Preprint

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The COVID-19 pandemic has resulted in the loss of millions of lives, although a majority of those infected have managed to survive. Consequently, a set of outcomes, identified as long COVID, is now emerging. While the primary target of SARS-CoV-2 is the respiratory system, the impact of COVID-19 extends to various body parts, including the bone. This study aims to investigate the effects of acute SARS-CoV-2 infection on osteoclastogenesis, utilizing both ancestral and Omicron viral strains. Monocyte-derived macrophages (MDM), which serve as precursors to osteoclasts, were exposed to both viral variants. However, the infection proved abortive, even though ACE2 receptor expression increased post-infection, with no significant impact on cellular viability and redox balance. Both SARS-CoV-2 strains heightened osteoclast formation in a dose-dependent manner, as well as CD51/61 expression and bone resorptive ability. Notably, SARS-CoV-2 induced early pro-inflammatory M1 macrophage polarization, shifting towards an M2-like profile. Osteoclastogenesis-related genes (RANK, NFATc1, DC-STAMP, MMP9) were upregulated, and surprisingly, SARS-CoV-2 variants promoted RANKL-independent osteoclast formation. This thorough investigation illuminates the intricate interplay between SARS-CoV-2 and osteoclast precursors, suggesting potential implications for bone homeostasis and opening new avenues for therapeutic exploration in COVID-19.

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Acute bone loss following SARS‐CoV‐2 infection in mice

Cited by 9 publications

References 32 publications

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

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

Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection

The abortive SARS-CoV-2 infection of osteoclast precursors promotes their differentiation into osteoclasts

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