Denosumab's Therapeutic Effect for Future Osteosarcopenia Therapy : A Systematic Review and Meta-Analysis.

BACKGROUND: Osteosarcopenia, a combination of osteopenia/osteoporosis and sarcopenia, is a common condition among older adults. While numerous studies and meta-analyses have been conducted on the treatment of osteoporosis, the pharmacological treatment of osteosarcopenia still lacks evidence. Denosumab, a human monoclonal antibody, has shown encouraging results for the treatment of osteosarcopenia. Our systematic review and meta-analysis aimed to investigate the potential dual role of denosumab as an anti-resorptive agent and for other beneficial muscle-related effects in patients with osteosarcopenia, and to evaluate whether denosumab can be a treatment of choice compared to bisphosphonate. METHODS: Relevant literature was collated from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Google Scholar databases. The primary outcome was denosumab's effect on lumbar spine bone mineral density (LS BMD), handgrip strength, and gait speed change. The secondary outcome was the effect of denosumab on appendicular lean mass (ALM). The outcomes were presented as mean difference (MD). A random effects model was used in the analysis to represent the population. The risk of bias was assessed using funnel plots. RESULTS: Out of the 3,074 studies found, four full-text studies met the inclusion criteria, including 264 and 244 participants in the intervention and control groups, respectively. Regarding a primary outcome, our meta-analysis showed that denosumab showed no significant differences in LS BMD and gait speed changes compared to other agents-MD=0.37, 95% confidence interval (CI), -0.35 to 0.79; p=0.09 and MD=0.11; 95% CI, -0.18 to 0.40; p=0.46, respectively. Denosumab had a significant effect on handgrip strength change compared to standard agents-MD=5.16; 95% CI, 1.38 to 18.94; p=0.007, based on the random effects model. CONCLUSIONS: Denosumab was better than bisphosphonate and placebo in improving muscle strength (handgrip strength). Therefore, denosumab may be favored in individuals with osteosarcopenia to improve muscular performance and reduce fall risk.

Sedentary Lifestyle of Older Adults and Its Associated Factors: A Multicentre Cross-Sectional Study During COVID-19 Pandemic in Indonesia.

BACKGROUND: COVID-19 is here to stay, and humans ought to decide how to adapt. We aimed to describe lifestyle changes during COVID-19 pandemic, and to determine the prevalence and factors associated with sedentary lifestyle among older adults. METHODS: We obtained data from community-dwelling older adults aged ≥60 years. We presented the data descriptively and used multivariate analysis to assess the association between Physical Activity Scale for the Elderly (PASE) -based sedentary lifestyle and other variables in several tertiary geriatric centres. RESULTS: Among 601 participants, 21.1% had sedentary lifestyle. Ethnic groups with the highest prevalence of sedentary lifestyle were Minang, Balinese, and Sundanese. Changes related to food intake, body weight, and physical activity were seen in a small proportion of older adults. Sun exposure habit was described. Sedentary lifestyle was associated with less consumption of food (OR 2.59, 95% CI 1.07-6.30), weight loss (OR 3.00, 95% CI 1.64-5.48), and higher intensity of snacking (OR 0.45, 95% CI 0.20-0.99). CONCLUSION: During COVID-19 pandemic, one out of five older adults had sedentary lifestyle, which was positively associated with less consumption of food and weight loss, and negatively associated with higher intensity of snacking. The prevalence of sedentary lifestyle varied across ethnic groups. Adequate and appropriate food intake may be crucial to keep older adults active, preventing them from entering vicious cycle of malnutrition, sarcopenia, and frailty.

Convalescent Plasma in Older Adults with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Among all patients infected with coronavirus disease 2019 (COVID-19), the older adult population was the most affected, with 80%-90% of fatalities occurring in this group. The effectiveness of convalescent plasma (CP) in older adults is considerably more restricted than that in adults, resulting in a demand for data on the efficacy of therapeutic CP in older adults. This meta-analysis of updated literature examined the effect of CP in older adults with COVID-19. METHODS: Relevant literature was identified from studies indexed in the Cochrane, PubMed, and Google Scholar databases between December 2019 and April 2022. The primary outcome was all-cause mortality. Risk estimates were pooled using a random-effects model. The risk of bias was assessed by regression-based Egger test using the relative risk (RR) and upper and lower confidence intervals (CIs) of the three included studies. RESULTS: Among 377 studies identified, three full-text studies that included 1,038 patients met the inclusion criteria. The results of our meta-analysis showed that CP administration lowered the mortality risk in older adults with COVID-19 (RR=0.47; 95% CI, 0.26-0.86; p=0.01; I2=0%, p<0.81). CP therapy was more useful if delivered early in the course of the disease (within 72 hours of onset) and in less severe stages of the disease. Mortality tended to be lower in the high-titer group. CONCLUSIONS: CP treatment was significantly associated with a lower risk of mortality in older adults with COVID-19 than in patients not administered CP. The timing of CP administration is critical since earlier treatment after disease onset was associated with a better prognosis.

Appropriate Timing and Type of Physical Training in Patients with COVID-19 for Muscle Health and Quality of Life: A Systematic Review.

Physical activity is beneficial to modulate immune system function and has inverse relationship to ARDS linked with SARS-CoV-2. Physical activity consists of daily activity and physical training. Studies regarding effect of physical training on patients with COVID-19 are controversial. This systematic review aims to investigate physical training on muscle health and QOL in patients with COVID-19. The literature review was carried out using keywords: (Exercise) AND (COVID) AND (Muscle) AND (Observational Study) in several databases of PubMed and Cochrane Central Register of Controlled Trials (CENTRAL). All references were reviewed using critical appraisal Newcastle Ottawa Scale (NOS) and Centre for Evidence-Based Medicine (CEBM) checklist. The studies were subsequently screened for reporting exercise, muscle, and COVID-19. The descriptions of the extracted data are guided by Preferred Reporting Items for Systematic Reviews (PRISMA) statement with GRADE approach. This study is registered in PROSPERO: ID CRD42021295188. Six studies pooled and entered review synthesis. Studies were reviewed using critical appraisal by NOS and CEBM. Two clinical trial studies and four observational designs were selected. Our result showed physical training improved patients' outcomes in the acute phase, critical phase, and post-COVID-19 phase. Multiple types of physical trainings were suggested by those studies, and most of them showed beneficial effects to patients with COVID-19 in different phases. The level of evidence by GRADE was downgraded, and further investigations are needed to establish guidelines and strong recommendation for a specific stage of COVID-19.

Importance of Sclerostin as Bone-Muscle Mediator Crosstalk.

Loss of bone and muscle mass is a frequent aging condition and has become a growing public health problem. The term "osteosarcopenia" denotes close links between bone and muscle. Mechanical exercise was once thought to be the only mechanism of crosstalk between muscle and bone. Sclerostin is an important player in the process of unloading-induced bone loss and plays an important role in mechanotransduction in the bone. Furthermore, bones and muscles are categorized as endocrine organs because they produce hormone-like substances, resulting in "bone-muscle crosstalk." Sclerostin, an inhibitor of bone development, has recently been shown to play a role in myogenesis. This review discusses the importance of sclerostin in bone-muscle crosstalk.

Molecular Mechanism of -Acute Sarcopenia in Elderly Patient with COVID - 19.

Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Case fatality rate has been on the rise among older adults. Muscle loss is a consequence of several chronic diseases (chronic sarcopenia) and recent theory also suggested that acute sarcopenia may caused by acute significant stressor such as an acute illness, surgery, infections, trauma or burns including COVID-19 infection leading to further muscle loss in elderly. Cytokine storm, the hallmark of COVID-19 pathogenesis will induce various pro-inflammatory cytokine such as IL-1 and IL-6 causing acute sarcopenia by activating negative regulators like NF-κB, atrogin-1, MURF-1. Long standing chronic inflammation also known as inflammaging along with acute inflammation during COVID-19 in elderly will cause reticulum endoplasmic and mitochondria stress activating caspase and finally increase both cytosolic and nuclear levels of AIF and EndoG to induce acute sarcopenia. Several precipitating factors shared same molecular pathway like physical inactivity and hormonal dysregulation which act through IGF-1-AKT-mTOR pathway. Physical inactivity during COVID-19 infection also induced myostatin and Atrogin-1/ MaFbx/ MuRF pathway. This review provides recent research advances dealing with molecular pathway modulating muscle mass in acute sarcopenia during COVID-19 infection.