Bone worse after COVID - several studies

Note: COVID
   ==> deactivates Vitamin D Receptor
     ==> reduced Vitamin D for both bone cells and for gut cells to get Calcium

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Effect of COVID-19 pandemic on lifestyle and bone mineral density in young adults - Nov 2023

Am J Hum Biol . 2023 Nov 22:e24009. doi: 10.1002/ajhb.24009
Darina Falbová 1, Viktória Kovalčíková 1, Radoslav Beňuš 1, Simona Sulis 1, Lenka Vorobeľová 1

Objectives: This study investigates the relationships between the COVID-19 pandemic, lifestyle factors, and their impact on bone mineral density in the radius forearm bone and the total bone mineral content in young adults from Slovakia.

Methods: We assessed 773 Slovak young adults aged 18 to 30 years, divided into subgroups on their pandemic status. bone mineral density (BMD) was analyzed by the QUS device (Sunlight MiniOmni™), and bone mineral content (BMC) and fat mass (FM) were measured by InBody 770 bioimpedance analyzer. Finally, linear regression analysis tested the associations.

Results: Statistically significant lower speed of sound (SOS) along the length of the forearm radius bone and Z-score values was determined in participants during the COVID-19 pandemic than before it, and statistically significant lower BMC values were observed in the male group during COVID-19 than beforehand. Regression analysis confirmed the negative pandemic effect in the following indices: SOS (p < .001 for women and p = .035 for men), Z-score (p < .001 for women and p = .003 for men), and BMC (p = .024 for men). Vitamin D was a further significant SOS predictor in women at p = .029, but this association was not detected in men. In contrast, the significant male BMC predictors were pandemic presence (p = .028), physical activity (p = .028), and fat mass percentage (p = .001).

Conclusions: Significant COVID-19 pandemic effects on bone tissue were determined on bone mass density in the radius forearm bone and the total bone mineral content. These effects establish that the pandemic had a negative impact on both their bone quality and health.

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Long-term implications of COVID-19 on bone health: pathophysiology and therapeutics - July 2022

Inflammation Research volume 71, pages1025–1040 (2022)
Leena Sapra, Chaman Saini, Bhavuk Garg, Ranjan Gupta, Bhupendra Verma, Pradyumna K. Mishra & Rupesh K. Srivastava

Background
SARS-CoV-2 is a highly infectious respiratory virus associated with coronavirus disease (COVID-19). Discoveries in the field revealed that inflammatory conditions exert a negative impact on bone metabolism; however, only limited studies reported the consequences of SARS-CoV-2 infection on skeletal homeostasis. Inflammatory immune cells (T helper—Th17 cells and macrophages) and their signature cytokines such as interleukin (IL)-6, IL-17, and tumor necrosis factor-alpha (TNF-α) are the major contributors to the cytokine storm observed in COVID-19 disease. Our group along with others has proven that an enhanced population of both inflammatory innate (Dendritic cells—DCs, macrophages, etc.) and adaptive (Th1, Th17, etc.) immune cells, along with their signature cytokines (IL-17, TNF-α, IFN-γ, IL-6, etc.), are associated with various inflammatory bone loss conditions. Moreover, several pieces of evidence suggest that SARS-CoV-2 infects various organs of the body via angiotensin-converting enzyme 2 (ACE2) receptors including bone cells (osteoblasts—OBs and osteoclasts—OCs). This evidence thus clearly highlights both the direct and indirect impact of SARS-CoV-2 on the physiological bone remodeling process. Moreover, data from the previous SARS-CoV outbreak in 2002–2004 revealed the long-term negative impact (decreased bone mineral density—BMDs) of these infections on bone health.

Methodology
We used the keywords “immunopathogenesis of SARS-CoV-2,” “SARS-CoV-2 and bone cells,” “factors influencing bone health and COVID-19,” “GUT microbiota,” and “COVID-19 and Bone health” to integrate the topics for making this review article by searching the following electronic databases: PubMed, Google Scholar, and Scopus.

Conclusion
Current evidence and reports indicate the direct relation between SARS-CoV-2 infection and bone health and thus warrant future research in this field. It would be imperative to assess the post-COVID-19 fracture risk of SARS-CoV-2-infected individuals by simultaneously monitoring them for bone metabolism/biochemical markers. Importantly, several emerging research suggest that dysbiosis of the gut microbiota—GM (established role in inflammatory bone loss conditions) is further involved in the severity of COVID-19 disease. In the present review, we thus also highlight the importance of dietary interventions including probiotics (modulating dysbiotic GM) as an adjunct therapeutic alternative in the treatment and management of long-term consequences of COVID-19 on bone health.
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Vitamin D status (clipped from PDF)

An active form of vitamin D (1,25-dihydroxy vitamin D) is responsible for the regulation of calcium and phosphate metabolism. Several studies reported that lower levels of vitamin D enhance the development of multiple immune- related diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), type 1 diabetes (T1D), and COVID-19. It has been observed that older patients with vitamin D deficiency (< 30 nmol/L) showed higher D-dimer levels and were found to be associated with worse outcomes of COVID-19 infection [43]. Consistent with this, a study recently dem­onstrated that COVID-19-positive patients with vitamin D levels > 30 ng/ml showed lower levels of D-dimer, CRP, and shorter hospital stays in contrast to COVID-19 patients with severe vitamin D deficiency (< 10 ng/ml) [44]. Thus, these studies suggest that vitamin D levels may be employed as a prognosis indicator. A clinical trial (NCT04344041): COVIT-TRIAL is a randomized clinical trial where a high­risk elderly population was supplemented with vitamin D and the outcome of the trial described that a high dose of vitamin D is found to be an effective and immediately approachable treatment for COVID-19 [45]. Furthermore, a vitamin D deficiency’s secondary effect is a disturbance in the process of bone mineralization, which results in bone loss, muscle weakness, and the onset of osteoporosis, which may eventually progress to osteomalacia [46]. Notably, the majority of patients admitted to ICU and dying concomi­tantly suffered from hypovitaminosis D. In agreement with this, a study showed that decreased serum vitamin D lev­els were linked to an increase in mortality in critically ill patients infected with SARS-CoV-2 [47]. Vitamin D is also a key modulator of the renin-angiotensin system which is exploited by the SARS-CoV-2 to enter the host cells [48]. In addition, vitamin D controls the immune system via dampening the pro-inflammatory immune response along with enhancing the anti-inflammatory immune response, anti-microbial peptides (AMPs), along with activating the macrophages thereby exhibiting the potential to destroy the SARS-CoV-2. According to a study, a feedback loop between vitamin D deficiency and the COVID-19-linked coagulopathy enhances platelet activation, which heightens thrombosis 49. Notably, vitamin D insufficiency and low platelet count have been connected to illnesses that cause pathological bone loss, such as osteoporosis, and have also been proven to play a critical role in the metabolism of min­erals and the preservation of bone health. Thus, to prevent the pathological bone loss caused by the SARS-CoV-2 infec­tion, it is crucial to monitor both platelet count and vitamin D levels.

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The Impact of COVID-19 in Bone Metabolism: Basic and Clinical Aspects - 2022

Horm Metab Res 2022; 54(08): 540-548 DOI: 10.1055/a-1825-9641 PDF is behind a paywall
Elena Tsourdi , Lorenz C. Hofbauer , Martina Rauner

The use of standard procedures for the diagnosis of osteoporosis and assessment of fracture risk significantly decreased during the COVID-19 pandemic, while the incidence of fragility fractures was mostly unaltered.
Both COVID-19 per se and its treatments are associated with a negative impact on bone health.
Preclinical models show that mice infected with SARS-CoV2 even without symptoms display loss of trabecular bone mass two weeks post infection, due to increased numbers of osteoclasts. Osteoporosis medications do not aggravate the clinical course of COVID-19, while preclinical data suggests possible beneficial effects of some therapies.
While vitamin D deficiency is clearly associated with a worse clinical course of COVID-19, evidence of improved patient outcome with vitamin D supplementation is lacking. Osteoporosis treatment should not be generally discontinued, and recommendations for substituting therapies are available. Osteoporosis therapies do not interfere with the efficacy or side-effect profiles of COVID-19 vaccines and should not be stopped or indefinitely delayed because of vaccination.

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Vitamin D and Platelets: A Menacing Duo in COVID-19 and Potential Relation to Bone Remodeling - Sept 2021

Int. J. Mol. Sci. 2021, 22(18), 10010; https://doi.org/10.3390/ijms221810010
by Francesca Salamanna 1ORCID,Melania Maglio 1,*ORCID,Maria Sartori 1ORCID,Maria Paola Landini 2 and Milena Fini 1

Global data correlate severe vitamin D deficiency with COVID-19-associated coagulopathy, further suggesting the presence of a hypercoagulable state in severe COVID-19 patients, which could promote thrombosis in the lungs and in other organs. The feedback loop between COVID-19-associated coagulopathy and vitamin D also involves platelets (PLTs), since vitamin D deficiency stimulates PLT activation and aggregation and increases fibrinolysis and thrombosis. Vitamin D and PLTs share and play specific roles not only in coagulation and thrombosis but also during inflammation, endothelial dysfunction, and immune response. Additionally, another ‘fil rouge’ between vitamin D and PLTs is represented by their role in mineral metabolism and bone health, since vitamin D deficiency, low PLT count, and altered PLT-related parameters are linked to abnormal bone remodeling in certain pathological conditions, such as osteoporosis (OP).

Hence, it is possible to speculate that severe COVID-19 patients are characterized by the presence of several predisposing factors to bone fragility and OP that may be monitored to avoid potential complications. Here, we hypothesize different pervasive actions of vitamin D and PLT association in COVID-19, also allowing for potential preliminary information on bone health status during COVID-19 infection.
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