Statins, bone formation and osteoporosis: Hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis

Adiponectin and Its Effects on Acute Leukemia Cells: An Experimental and Bioinformatics Approach

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. It is known that deregulation of adipokine pathways is probably implicated in the ontogenesis of ALL. The present work aims at investigating the role of adiponectin and its effects on an ALL cell line. The CCRF-CEM cells were used as a model. Cells have been treated with adiponectin, with different concentrations up to 72 h. Cytotoxicity and cell cycle distribution were investigated for all concentrations using flow cytometry. Selected concentrations were also used for additional microarray analysis, using a small gene set of cancer-related genes. Lower and higher adiponectin concentrations did not produce an inhibition of proliferation, as well as an increase in cell death. It was found that adiponectin regulated differentially genes, such as CD22, CDH1, IFNG, LCK, MSH2, SPINT2, and others. At the same time, it appeared that adiponectin-related gene expression was more active on chromosomes 18 and 1. Machine learning classification algorithms showed that several genes were grouped together indicating common regulatory mechanisms. The present study showed that adiponectin is able to induce gene differential expression in leukemic cells in vitro, suggesting a possible role in the progression of leukemia. It is also an indication that more studies are required in order to further understand the role of adiponectin and adipokines in general in the role of human neoplasms. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

Systems Approaches in the Common Metabolomics in Acute Lymphoblastic Leukemia and Rhabdomyosarcoma Cells: A Computational Approach

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

The effect of treatment and bone metabolic factors on fracture incidence in patients with thalassemia-induced osteoporosis: An observational study

Background: Thalassemia Major (TM) is a hereditary disease caused by defective globin synthesis. Because of the significant increase in life expectancy, these patients suffer from various health conditions, including endocrinopathies and low bone mineral density. Aim: The aim of the present study was to evaluate the fracture incidence regarding the markers of bone metabolism, bone mineral density and treatment of osteoporosis as well as the treatment of comorbidities. Methods: Sixty-four patients with TM (32 men and 32 women) participated in a cross-sectional study design. The patients were recruited from “Aghia Sofia” Children’s Hospital and evaluated using dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results: The statistical analysis of markers of bone metabolism in relation to fractures revealed no statistical significance. However, statistical analysis of bone mineral density and markers of bone metabolism in relation to fractures was also not significant. Conclusions: In TM patients, fractures are not related to bone mineral density. Maybe some other conditions are the cause, haemosidirosis, drugs, comorbid conditions. © 2020 Bentham Science Publishers

The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review

Background and Objectives: The association between diabetes mellitus and increased risk of bone fractures has led to the investigation of the impact of antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP1RAs) are a relatively novel and promising class of anti-hyperglycemic drugs. In addition to their blood glucose lowering action, GLP1RAs seem to have additional pleiotropic properties such as a beneficial skeletal effect; although the underlying mechanisms are not completely understood. The present systematic review summarizes current evidence about GLP1RAs and their effects on bone metabolism and fracture. Methods: An extensive literature search was conducted based on electronic databases namely, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL) through October 2019 to January 2020 for articles related to bone mineral density, diabetes mellitus and GLP1RAs. We included articles published in English. Finally, we included four randomized controlled trials, three meta-analyses, a case-control study and a population-based cohort analysis. Results: Based on the articles included, the animal studies indicated the salutary skeletal effects of GLP1RAs in opposition to what has been commonly observed in human studies, showing that these agents have no impact on bone mineral density (BMD) and the turnover markers. Moreover, it was demonstrated that GLP1 was not associated with fracture risk as compared to other anti-hyperglycemic drugs. Conclusions: Findings from this systematic review have demonstrated the neutral impact of GLP1RAs on BMD. Moreover, further double-blind randomized controlled trials are needed to draw more meaningful and significant conclusions on the efficacy of GLP1RAs on BMD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland