The global COVID-19 pandemic has not only affected the respiratory system but has also had significant implications for bone health and musculoskeletal complications. Researchers from the Indiana University School of Medicine and Eastern Virginia Medical School have been investigating these effects and have made several noteworthy discoveries.
One of the key findings of their research is the increased risk of bone-related issues in COVID-19 patients. These complications include vertebral fractures, hypocalcemia (low calcium levels), vitamin D deficiencies, and reduced bone mineral density (BMD). Interestingly, lower BMD has been linked to more severe cases of SARS-CoV-2 infection, suggesting a potential connection between COVID-19 and bone health.
Furthermore, COVID-19 has been found to impact the musculoskeletal system, leading to joint pain, muscle pain, and an elevated risk of acute kidney injury. Factors such as obesity, age, and pre-existing conditions like diabetes can influence the severity of the disease. Additionally, COVID-19 can trigger a “cytokine storm,” which is associated with severe multiorgan dysfunction and complicates the clinical picture.
The post-acute sequelae of COVID-19 (PASC) can manifest in various ways, including kidney failure, inflammation markers, immune cell infiltration, and endothelial injury. The musculoskeletal system also contributes to PASC, with symptoms like myalgia (muscle pain), joint pain, sarcopenia (muscle loss), and heterotopic ossification (abnormal bone growth). Researchers are actively investigating the long-term and systemic effects of SARS-CoV-2 infection to better understand comorbidities and develop treatment options for COVID-19 survivors.
Observations from the pandemic have revealed alterations in mineral metabolism and bone turnover markers in COVID-19 patients. Hypocalcemia and reduced bone turnover have been observed, along with a higher prevalence of vertebral fractures. Even non-severe cases of COVID-19 show correlations between lower BMD and the severity of SARS-CoV-2 infection, indicating a broader impact on bone health.
In vitro and preclinical studies have provided insights into how SARS-CoV-2 directly affects bone cells. Human monocytes expressing the ACE2 receptor, used by the virus for cell entry, are potential targets for infection. Exposure to SARS coronavirus proteins increases osteoclastogenesis, indicating a direct impact on bone-related cells. Preclinical models involving genetically modified mice expressing human ACE2 show trabecular bone loss and increased osteoclastogenesis, regardless of disease severity.
The complex cellular mechanisms through which SARS-CoV-2 influences bone health involve inflammation, the NLRP3 inflammasome, Th17 cells, hypoxia, and indirect effects on bone through muscle weakness and nutritional deficiencies. Chronic inflammation can have detrimental effects on bone, and SARS-CoV-2 infection activates the NLRP3 inflammasome. Increased Th17 activity observed in COVID-19 contributes to the “cytokine storm” and may impact bone health. Hypoxia, present in severe COVID-19 cases, stimulates osteoclast formation. The RANK/RANKL/OPG signaling pathway plays a crucial role in osteoclastogenesis, and alterations in this pathway have been observed in COVID-19 patients. Systemic effects of COVID-19, such as muscle weakness, nutritional deficiencies, and steroid utilization, indirectly affect bone health.
Concurrent conditions like obesity, diabetes, acute kidney injury, and chronic kidney disease significantly influence the severity and outcomes of COVID-19. These conditions are associated with increased inflammatory markers and can contribute to increased osteoclast activity and bone resorption.
Future research aims to identify specific patient populations at higher risk of COVID-19-related fractures, unravel the mechanisms behind bone loss, and explore therapeutic options. Comparative studies on different SARS-CoV-2 variants and their unique impact on bone health are also needed. Understanding the intricate relationship between COVID-19 and bone health will guide future preventive and therapeutic strategies, offering hope for mitigating the long-term musculoskeletal effects of the ongoing pandemic.