Changes In Bone Metabolism Research Articles

Long-Term Changes in Bone Density and Bone Metabolism After Gastric Bypass Surgery: a Retrospective Cohort Study.

Patients with severe obesity submitted to Roux-en-Y gastric bypass (RYGB) are at risk of developing long-term hypovitaminosis D and secondary hyperparathyroidism (SHPT) as well as osteometabolic disease. This study aimed to evaluate calcium-vitamin D-PTH axis and bone mineral density (BMD) changes from post-RYGB patients who were followed-up until a median of 5 years. Vitamin D deficiency was defined as 25-hydroxyvitamin D <20 ng/mL and SHPT as PTH >68 pg/mL, in patients with normal serum creatinine and calcium. BMD was estimated by dual-energy X-ray absorptiometry (DXA, g/cm2). We included 127 post-RYGB patients (51±10.6 years, 87.4% self-declared White, 91.3% female, 52.8% postmenopausal). Vitamin D deficiency prevalence was the highest (41.5%) in the second year and the lowest (21.2%) in the third year (p<0.05). SHPT prevalence was 65.4% in the second year and increased to 83.7% in the sixth year (p<0.05). Patients with low BMD in lumbar, femoral neck, and total proximal femur were older and presented menopausal status more frequently than normal BMD group (p<0.05). Older age was a risk marker for altered BMD in femoral neck (OR=1.185; 95% CI 1.118-1.256) and in total proximal femur (OR=1.158; 95% CI 1.066-1.258), both after adjusting for follow-up and excess weight loss. After 5 years, most bariatric patients presented calcium-vitamin D-PTH axis disruption, in which SHPT was more frequent than hypovitaminosis D. Older patients and menopausal women presented higher rates of low BMD, and older age was a risk marker, especially for low BMD in femoral sites.

Dynamics of the Expression of Bone Homeostasis Genes in the Developmet of Aseptic Necrosis of the Femoral Head in the Experiment

The pathogenesis of a number of diseases is characterized by a violation of the regulation of bone homeostasis, with the progressive development of osteodestruction. At the same time, an active study of the mechanisms leading to a shift in the balance of osteoreparative and osteoresorption directions of osteogenesis is underway. The determination of molecular and cellular patterns affecting the dynamics of changes in bone metabolism is a significant task among a wide range of specialists. Such research works allow us to propose algorithms for targeted therapeutic effects on various key links in the pathogenesis of osteodestruction. The study analyzed the expression of genes involved in maintaining bone homeostasis, changes in the histological picture under experimental conditions, depending on the time elapsed since the induction of aseptic necrosis. The result of the work showed the heterogeneity of the development of osteodestruction in an experiment on Wistar rats, with a surgically created focus of hypoperfusion of the femoral head against the background of increased intra-articular pressure. In the first two weeks of the development of aseptic necrosis, the expression of the hif1a gene was most actively determined, which can be considered from the position of a trigger for further disruption of bone metabolism. At the same time, the concentration of m-RNA of osteogenesis and osteoresorption genes was reduced. The most active osteolytic processes according to electron microscopy data, increases in the expression of osteoclastogenesis induction genes were observed at 6 weeks of the experiment. The osteoreporative orientation of bone metabolism gradually increased from the beginning of the study and 2 months after the manifestation of avascular necrosis of the femoral head, active osteoblasts, increased expression of bone matrix genes, osteoblastogenesis were determined. Thus, the development of osteodestruction is an extremely heterogeneous process, with dynamically changing molecular patterns depending on time, determining the activity of signaling pathways of bone metabolism.

Quantification of bone metabolic activity in the natural course of fractural lesions measured by quantitative SPECT/CT.

While increased uptake at the bone fractural site gradually decreases over time on bone scans, the rate of change has not been quantitatively evaluated. The purpose of this study was to quantify the extent of bone metabolic changes in fractural lesions on bone SPECT/CT. We reviewed bone scans acquired by dedicated SPECT/CT and chose those scans in which quantitative SPECT/CT of the same range was acquired twice or more. We set the region of interest on lesions of bone fracture and degeneration, and measured the maximum standardized uptake value (SUVmax). From the SUVmax of lesions and the interval between scans, a value for 30-day change in SUVmax was calculated as ∆SUVmax30d. The relationship between preSUVmax, SUVmax for the first scan of the comparison, and ∆SUVmax30d was evaluated utilizing a linear least-squares method. Furthermore, we assessed the ability to differentiate between fracture and degeneration using receiver operating characteristics (ROC) analysis and the Mann-Whitney U test. All cases were then categorized into five groups according to preSUVmax. Values of p <0.05 were considered statistically significant. We investigated 175 scans from 60 patients and analyzed scan combinations for 157 fractural lesions and 266 degenerative lesions. The relationship between preSUVmax of fractural lesions and ∆SUVmax30d was approximated as ∆SUVmax30d =-0.15×preSUVmax +1.35 (R 2=0.60, p<0.0001). Area under the curves for all cases, 30≤ preSUVmax, 20≤ preSUVmax <30, 15≤ preSUVmax <20, 10≤ preSUVmax <15, and preSUVmax <10 were 0.73, 0.89, 0.86, 0.80, 0.91, and 0.59, respectively. Median ∆SUVmax30d was significantly lower at fractural lesions than at degenerative lesions (-0.62 vs -0.04; p <0.0001). As for analyses of groups divided by preSUVmax, all median ∆SUVmax30d for fractural lesions were significantly lower than those of degenerative lesions except for the group with preSUVmax <10. The increased uptake at the fractural bone lesion observed in the quantitative bone SPECT/CT gradually decreased at the rate of SUV 0.15 per month, which showed a different trend with degenerative change.

Exercise maintains bone homeostasis by promoting osteogenesis through STAT3

Bone exhibits changes in density, strength, and microarchitecture in relation to mechanical loading mediated by exercise. Appropriate exercise maintains bone homeostasis, while the absence of exercise leads to disuse bone loss. However, the acting mechanism of mechanotransduction in bone remains unclear. We performed the running-wheel exercise and tail suspension model to study the effects of exercise on bone metabolism, and found that osteoblastic Signal transducer and activator of transcription 3 (STAT3) activity was closely related to exercise-induced bone mass and metabolism changes. With the Flexcell tension-loading system in vitro, mechanical force promoted STAT3 activity, which was accompanied by increased osteoblastic differentiation of the bone marrow mesenchymal stem cells (BMSCs). In contrast, the inhibition of STAT3 phosphorylation blocked force-induced osteoblastic differentiation. Furthermore, pharmacological inactivation of STAT3 impaired the increase in exercise-induced bone mass and osteogenesis. With an inducible conditional deletion mouse model, we found that the osteoblast lineage-specific Stat3 deletion could also block force-induced osteoblastic differentiation in vitro and impair exercise-promoted bone mass and osteogenesis in vivo. This confirmed the crucial role of osteoblastic STAT3 in exercise-mediated bone metabolism. Finally, colivelin, a STAT3 agonist, promoted osteoblastic differentiation in vitro and partly rescued exercise loss-induced disuse bone loss by improving osteogenesis in the tail suspension model. Taken together, our study revealed the essential role of STAT3 in maintaining exercise-mediated bone homeostasis. In addition, STAT3 might act as a potential target for osteoporosis caused by exercise loss.

Relationship to Bariatric Surgery and their Gastrointestinal Hormones: how we Weight Loss?

Obesity is a disease related to severe metabolic comorbidities due to the high accumulation of body fat. In the context of this pandemic, bariatric surgery is the most effective treatment for the long-term resolution of the disease, having both structural and anatomic and hormonal effects on the gastrointestinal tract. The hormones analyzed in this review are cholecystokinin, secrete, gastrin, glucagon-like peptide 1 (GLP-1), peptide YY, pancreatic polypeptide, leptin, adiponectin, ghrelin, glucose, cholesterol, gastric inhibitory peptide, insulin, and glucagon. After bariatric procedures, changes in vitamins and micronutrients are also observed, which can lead to anemia, changes in coagulation, bone metabolism, neurological, and immunological deficiencies.

Approach to the Patient: Management of Parathyroid Diseases Across Pregnancy.

Taking care of patients with parathyroid disorders during pregnancy requires consideration of the physiological fundamental changes in bone and mineral metabolism occurring in these women. Diagnostic and therapeutic procedures regarding primary hyperparathyroidism (PHPT) and hypoparathyroidism significantly differ from the nonpregnant population. PHPT should preferably be cured by parathyroidectomy before pregnancy since in women with hypercalcemic PHPT, maternal and fetal pregnancy complications seem to increase according to the degree of hypercalcemia. Parathyroidectomy, if needed during pregnancy, is preferentially performed in the second trimester. Conservative treatment is recommended for milder cases and is mainly restricted to hydration, with only limited evidence regarding drug treatment. Women with hypoparathyroidism can be informed that there are no major concerns regarding disease-associated infertility and that the risk of pregnancy complications is low if the disease is properly managed. Regular active surveillance is recommended, as requirements for calcium and active vitamin D may change during the course of pregnancy in either direction, with an overall trend for rather reduced doses. Any woman suffering from parathyroid disorders during pregnancy requires further surveillance in the postpartum period and during lactation, as there is an increased risk of hypercalcemia after delivery. Newborns of mothers with parathyroid diseases should, depending on disease severity, be carefully monitored for calcium levels in the first days (to weeks) after delivery since intrauterine exposure to hyper- or hypocalcemia may impact their postnatal regulation of calcium metabolism.

Bone metabolism during strict head-down tilt bed rest and exposure to elevated levels of ambient CO2

Astronauts on the International Space Station are exposed to levels of atmospheric carbon dioxide (CO2) above typical terrestrial levels. We explored the possibility that increased levels of ambient CO2 further stimulate bone resorption during bed rest. We report here data from 2 ground-based spaceflight analog studies in which 12 male and 7 female subjects were placed in a strict 6° head-down tilt (HDT) position for either 30 days at 0.5% ambient CO2 or 60 days with nominal environmental exposure to CO2. Bone mineral density (BMD) and bone mineral content (BMC) were determined using dual-energy X-ray absorptiometry (DXA). Blood and urine were collected before and after HDT for biochemical analysis. No change was detected in either BMD or BMC, as expected given the study duration. Bone resorption markers increased after bed rest as expected; however, elevated CO2 had no additive effect. Elevated CO2 did not affect concentrations of minerals in serum and urine. Serum parathyroid hormone and 1,25-dihydroxyvitamin D were both reduced after bed rest, likely secondary to calcium efflux from bone. In summary, exposure to 0.5% CO2 for 30 days did not exacerbate the typical bone resorption response observed after HDT bed rest. Furthermore, results from these strict HDT studies were similar to data from previous bed rest studies, confirming that strict 30–60 days of HDT can be used to evaluate changes in bone metabolism. This is valuable in the continuing effort to develop and refine efficacious countermeasure protocols to mitigate bone loss during spaceflight in low-Earth orbit and beyond.

Coronary artery calcification in patients with advanced chronic kidney disease

IntroductionCardiovascular disease (CVD) is associated with higher morbidity and mortality rates in patients with chronic kidney disease (CKD). Studies have shown that vascular calcification is a major predictor of CVD. Vascular calcification in the CKD population is associated with various risk factors, and changes in bone and mineral metabolism have been linked to an increased risk of atherosclerosis. Therefore, we aimed to investigate the correlation between vascular calcification and bone metabolism, which is necessary to improve the survival and prognosis of patients with CKD.MethodsWe included 146 patients with CKD who received coronary artery calcification (CAC) scores at our hospital from May 2017 to November 2018. Spearman rank correlation analysis, Mann–Whitney U test, and Kaplan–Meier method were used to analyze laboratory data and all-cause mortality.ResultsIn the 146 patients, chronic glomerulonephritis accounted for the most common cause of CKD, at approximately 39.0%. Spearman rank correlation analysis on the factors influencing vascular calcification in patients with CKD showed that CAC score was significantly and positively correlated with C-reactive protein, N-terminal/midregion osteocalcin (N-MID), N-terminal peptide of type 1 procollagen (P1NP), β-cross-linked C-telopeptide of type 1 collagen (β-CTx), and parathyroid hormone (P = 0.0423, P = 0.0432, P = 0.0235, P = 0.0061, P < 0.0001, respectively). Serum calcium levels were positively correlated with N-MID, P1NP, β-CTx, and iPTH (r = 0.19, r = 0.24, r = 0.21, r = 0.21, respectively), and serum phosphorus levels were positively correlated with N-MID, P1NP, β-CTx, and iPTH (r = 0.50, r = 0.37, r = 0.50, r = 0.55, respectively). However, no difference was found in CVC scores among patients with CKD in different stages and receiving different treatments. In the Kaplan–Meier analysis of all-cause hospitalization and mortality rates, patients with CAC > 400 had a higher risk.ConclusionWe found that the primary cause of CKD is glomerulonephritis, and the CAC score is positively correlated with inflammatory and bone metabolism markers, with a higher risk of all-cause mortality and cardiovascular hospitalization when the CAC score is greater than 400.

The Dietary and Non-Dietary Management of Osteoporosis in Adult-Onset Celiac Disease: Current Status and Practical Guidance.

Impaired bone mineral density (BMD) is a frequent complication of adult-onset celiac disease (CeD). This is usually due to malabsorption of nutrients, changes in bone metabolism in association with inflammation, and to a lesser extent, decreased overall physical health and mobility. This review aims to highlight the current status concerning surveillance, prevention, and treatment strategies for bone disease in CeD. A practical guidance on these matters is suggested. The available published research on the prevention and treatment of decreased BMD in relation to CeD is scarce. In general, publications were based on expert opinions or extrapolation from studies on postmenopausal women or inflammatory bowel disease. Optimal dietary treatment and an adequate supply of calcium and vitamin D are the cornerstones for the reduction in fracture risk in patients with CeD. In adults with low BMD or fragility fractures, CeD needs to be considered and specifically approached. When osteoporosis is documented, start treatment with an antiresorptive agent; these agents are proven to result in a long-term reduction in fracture risk in high-risk individuals. However, there are some important differences between the management of male and female patients, particularly premenopausal women, that need to be addressed. In patients with persisting diarrhea and malabsorption, parenteral medications may be preferable. Future research specifically focusing on celiac disease and the associated disorders in bone mineralization is mandatory to provide evidence-based recommendations in this field.

Spatial metabolomics reveals upregulation of several pyrophosphate-producing pathways in cortical bone of Hyp mice.

Patients with the renal phosphate-wasting disease X-linked hypophosphatemia (XLH) and Hyp mice, the murine homolog of XLH, are characterized by loss-of-function mutations in phosphate-regulating endopeptidase homolog X-linked (PHEX), leading to excessive secretion of the bone-derived phosphotropic hormone FGF23. The mineralization defect in patients with XLH and Hyp mice is caused by a combination of hypophosphatemia and local accumulation of mineralization-inhibiting molecules in bone. However, the mechanism by which PHEX deficiency regulates bone cell metabolism remains elusive. Here, we used spatial metabolomics by employing matrix-assisted laser desorption/ionization (MALDI) Fourier-transform ion cyclotron resonance mass spectrometry imaging (MSI) of undecalcified bone cryosections to characterize in situ metabolic changes in bones of Hyp mice in a holistic, unbiased manner. We found complex changes in Hyp bone metabolism, including perturbations in pentose phosphate, purine, pyrimidine, and phospholipid metabolism. Importantly, our study identified an upregulation of several biochemical pathways involved in intra- and extracellular production of the mineralization inhibitor pyrophosphate in the bone matrix of Hyp mice. Our data emphasize the utility of MSI-based spatial metabolomics in bone research and provide holistic in situ insights as to how Phex deficiency-induced changes in biochemical pathways in bone cells are linked to impaired bone mineralization.

DYNAMICS OF MMP8 AND OSTEOPONTIN CONTENT IN ORAL LIQUID OF PATIENTS WITH ORAL DISEASES IN THE PRESENCE OF ONCOPATHOLOGY

According to WHO, breast cancer is one of the most common forms of cancer in women. In 2020, 2.3 million women were diagnosed with breast cancer and 685,000 deaths from the disease were reported worldwide. This research aims to study the dynamics of the concentration of MMP8, osteopontin, and Ca2+ ions, as well as the pH level in patients with breast cancer during chemotherapy and specific dental treatment. Materials and methods. The study involved 60 patients, both men and women. All respondents were divided into groups by their oncological diseases: group 1 consisted of 20 patients with stage II and III breast cancer after chemotherapy, without prior dental treatment, group 2 comprised 20 patients with breast cancer after chemotherapy, with previous dental treatment, the control group included 20 people without cancer and dental pathology. Results and discussion. Dental diseases in patients of both groups were manifested by significant changes in bone metabolism, which was accompanied with sharp rise of MMP8 concentration in oral fluid during reducing osteopontin concentration. It is worth noting that the above pathobiochemical changes occurred against the background of a fall in the Ca2+ ion content and a pH shift towards the acidic side. The increase in Ca2+ is associated with a decrease in MMP8 level and the elevation in pH and osteoponine. In turn, the pH has medium power feedback with MMP8 and a direct relationship of medium force with osteoponin. MMP8 and osteopontin are associated with strong feedback, that is, an increase in the level of one of them can be displayed about reducing osteopontin. Conclusion. This study has established a statistically significant increase in MMP 8 against the background of the reducing concentration of osteoponitis. Pathobiochemical changes in bone tissue were found against the background of significant loss of Ca2+ ions and pH. Dental treatment for this category of patients has led to the improvement in the concentration of these markers. The data obtained justifies the necessity of their use as diagnostic markers and laboratory screening of the effectiveness of dental treatment in patients of this category.

Silymarin prevents iron overload induced bone loss by inhibiting oxidative stress in an ovariectomized animal model

Silibinin (SIL) has been used extensively for its hepatoprotective properties and antioxidant properties, including bone health. Iron overload can inhibit osteogenic proliferation and differentiation and promote bone loss. However, whether SIL can reverse the harmful effects of iron overload inovariectomized (OVX) rats and the mechanism is not clear. Therefore, this study intends to investigate the effect of SIL on bone mass and bone metabolism in iron overload rats and also explore the role of SIL on osteogenic differentiation of MC3T3-E1.RT-qPCR was used to measure the transcribe of target genes. Furthermore, alizarin red staining, alkaline phosphatase staining, immunofluorescence and CCK-8 assay were conducted to detect cell viability and target protein expression, osteogenic function. The OVX rat model with iron overload was set up to investigate bone reconstruction.Our results demonstrated that SIL promotes the proliferation and differentiation of osteoblasts, increases the ALP secretion and mineralization ability of osteoblasts, and enhances the transcribe and expression of target genes including OC, Runx-2, SOD2 and SIRT1 in an iron overload environment. In addition, it was confirmed that systemic SIL administration inhibits bone loss in OVX rats with iron overload and changes bone metabolism and oxidative stress status. Further study has shown that iron overload exerts its harmful function by accelerating bone turnover-mediated changes in higher bone metabolism to worsen osteoporosis. SIL can inhibit the unfriendly effects of iron overload, and by modifying bone metabolism and oxidative stress levels, the results contribute to clinical prevention and treatment of the progression of postmenopausal osteoporosis.

Mast Cells and Vitamin D Status: A Clinical and Biological Link in the Onset of Allergy and Bone Diseases.

The immune system is made up by an extremely composite group of cells, whose regulated and harmonious activity is fundamental to maintain health. The mast cells are an essential effector of inflammatory response which is characterized by a massive release of mediators accumulated in cytoplasmic secretory granules. However, beyond the effects on immune response, mast cells can modify bone metabolism and are capable of intervening in the genesis of pathologies such as osteoporosis and osteopenia. Vitamin D is recognized to induce changes in bone metabolism, but it is also able to influence immune response, suppressing mast cell activation and IgE synthesis from B cells and increasing the number of dendritic cells and IL-10-generating regulatory T cells. Vitamin D deficit has been reported to worsen sensitization and allergic manifestations in several different experimental models. However, in clinical situations, contradictory findings have been described concerning the correlation between allergy and vitamin D deficit. The aim of this review was to analyze the close relationships between mast cells and vitamin D, which contribute, through the activation of different molecular or cellular activation pathways, to the determination of bone pathologies and the onset of allergic diseases.

Structural and Metabolic Changes in Bone.

Simple SummaryBone is an extremely metabolically active tissue that is regenerated and repaired over its lifetime by bone remodeling. Most bone diseases are caused by abnormal restructure processes that undermine bone structure and mechanical strength and trigger clinical symptoms, such as pain, deformity, fracture, and abnormalities of calcium and phosphate homoeostasis. The article examines the main aspects of bone development, anatomy, structure, and the mechanisms of cell and molecular regulation of bone remodeling.As an essential component of the skeleton, bone tissue provides solid support for the body and protects vital organs. Bone tissue is a reservoir of calcium, phosphate, and other ions that can be released or stored in a controlled manner to provide constant concentration in body fluids. Normally, bone development or osteogenesis occurs through two ossification processes (intra-articular and intra-chondral), but the first produces woven bone, which is quickly replaced by stronger lamellar bone. Contrary to commonly held misconceptions, bone is a relatively dynamic organ that undergoes significant turnover compared to other organs in the body. Bone metabolism is a dynamic process that involves simultaneous bone formation and resorption, controlled by numerous factors. Bone metabolism comprises the key actions. Skeletal mass, structure, and quality are accrued and maintained throughout life, and the anabolic and catabolic actions are mostly balanced due to the tight regulation of the activity of osteoblasts and osteoclasts. This activity is also provided by circulating hormones and cytokines. Bone tissue remodeling processes are regulated by various biologically active substances secreted by bone tissue cells, namely RANK, RANKL, MMP-1, MMP-9, or type 1 collagen. Bone-derived factors (BDF) influence bone function and metabolism, and pathophysiological conditions lead to bone dysfunction. This work aims to analyze and evaluate the current literature on various local and systemic factors or immune system interactions that can affect bone metabolism and its impairments.

Wnt Inhibitors and Bone Mineral Density in Patients with Graves' Disease Treated with Antithyroid Drugs: A Preliminary Prospective Study.

This study aimed to investigate the association of Wnt inhibitors with thyroid hormones, bone turnover markers, and bone mineral density (BMD) in patients with newly diagnosed Graves’ disease (GD) at the beginning of the antithyroid treatment and after a follow-up period of one year. The study included 37 patients with newly diagnosed GD who were treated with antithyroid drugs (ATD). At baseline and after one year, thyroid hormones and thyroid-stimulating hormone (TSH), serum concentrations of sclerostin, and Dickkopf-1 (DKK1) were measured by an enzyme-linked immunosorbent assay (ELISA). In addition, BMD was measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover including osteocalcin (OC), beta-cross laps (β-CTX), and deoxypyridinoline (DPD) were determined. After one year of ATD therapy sclerostin levels were significantly decreased (p < 0.001), whereas DKK1 levels were significantly increased (p = 0.01). In addition, BMD of the lumbar spine, total hip, and femoral neck was significantly improved (p < 0.001), accompanied by an increase in OC, β-CTX, and DPD concentrations (p < 0.001). At baseline, sclerostin levels were positively associated with free triiodothyronine (FT3). Following ATD therapy, a positive correlation was observed between FT3 and DKK1 (p = 0.003), whereas a negative correlation was found between TSH and DKK1 (p = 0.04). Correlation analysis demonstrated no association of the sclerostin and DKK1 with other bone remodeling biomarkers OC, β-CTX, or DPD. Also, no significant correlation between sclerostin or DKK1 and T-score or BMD of the lumbar spine, hip, and femoral neck was observed at both time points. Conclusion: Observed differences in sclerostin and DKK1 serum following GD treatment indicate involvement of Wnt inhibitors in the etiopathogenesis of bone loss associated with hyperthyroidism. Furthermore, both sclerostin and DKK1 are involved in the reversal of changes in bone metabolism following ATD therapy, thus presenting potentially valuable bone remodeling markers worth further investigation.

Human psychophysiology in Antarctica

Antarctica is a natural laboratory for scientists and an adventure destination for tourists. It has challenging yet beautiful landscape. Due to extreme environment and isolation, wintering over in Antarctica is still challenging, even with advancement in accommodations. Polar scientists have focused on the aspects of Antarctica according to their specialty. For example, psychologists have highlighted polar psychology; likewise, physiologists and other allied human biologists have pointed-out to biochemistry, immunology, and stress biology. A researcher new to Antarctica gets confused to encounter diverse literature of different domains. These reasons require a review on the scientific aspects of wintering-over in Antarctica to enlighten first time readers. Journal articles from PubMed and Google Scholar (up to 2021) were searched with the search terms “Antarctica,” in combination with the words “human physiology” and “human psychology”. Vivid direct quotes of early explorers of the heroic age of polar expeditions are described and 53 articles were finally selected. The human psychophysiology points of discussion in this narrative review are geomagnetism, circadian rhythm, immunity, hypoxia, bone metabolic changes, acute mountain sickness, and stress biology concerning extended stay in Antarctica.

Bone Disease and New Prevention Frontiers Chapter One: Osteoporosis

In this first chapter, we describe different Osteopathies of degenerative or inflammatory nature related to the ageing of people. We are going to give a brief description of the pathogenic processes responsible for bone diseases, with a particular focus on osteoporosis and we will present various options and proposals for the prevention and treatment of changes in bone metabolism with medicines and food supplements. We are going to devote particular attention to the effects of Silicon in these pathologies, until now poorly considered, and we will propose our own formulation composed of Organic Silicon plus trace elements. We have treated a large number of patients, osteopenics or osteoporotics and we have obtained good and encouraging results with this innovative formulation. We therefore consider the proposal presented here to be a valid alternative to traditional pharmacological treatment, with respect to which it has the double advantage of equal effectiveness and absolute absence of side effects.

The 283 А&gt;G (BsmI) VDR gene polymorphism as a predictor of osteoporosis complicated by chronic pyelonephritis in aluminum production workers

Introduction. In the structure of the morbidity of workers in the aluminum industry the leading place are occupied by bone and joint pathology and disorders of mineral metabolism, caused by prolonged exposure to toxic fluoride compounds. The study of the molecular genetic basis for the development of changes in bone metabolism and concomitant pathology of the kidneys in chronic occupational intoxication with fluorine compounds will make it possible to establish an associative relationship between the polymorphism of certain genes and the likelihood of developing these diseases. The aim of the study was to determine the significance of detecting BsmI VDR polymorphism as a predictor of osteoporosis associated with chronic kidney disease in workers of the main professions of aluminum production on the basis of clinical and genetic analysis. Materials and methods. Based on molecular-genetic and clinical methods, a comprehensive study of the prevalence of fluorine osteopathy was carried out with the determination of bone density parameters in 217 workers in the main professions of aluminum smelting under conditions of chronic exposure to high doses of fluorine on the body and in the comparison group (57 individuals) without occupational pathology. Results. When examining workers, it was established that the frequency of registration of BsmI VDR polymorphism genotypes corresponded to the Hardy-Weinberg law. It was determined that the GG VDR genotype is a predictor of osteoporosis (p=0,0034), and carriers of the AA genotype are resistant to its development (p=0,0001). An associative relationship of the heterozygous AG VDR genotype with the development of chronic occupational intoxication with fluorine compounds was revealed (p=0,0232). It has been shown that osteoporosis associated with chronic kidney disease is associated with the G allele of the GG VDR genotype. Conclusions. In the structure of professional pathology of metallurgists employed in the production of aluminum, against the background of hyperplastic changes in bone tissue due to an increase in its mass, there is a significant decrease in mineral density (p=0,0047). The allelic specificity of the VDR gene associated with the development of toxic osteopathies was revealed. The GG genotype is associated with the development of osteoporosis. A high degree of association of the AG genotype (p=0,0232) with fluoride intoxication was shown. Osteoporosis associated with chronic kidney disease is associated with the GG VDR genotype and the G allele of the 283 A&gt;G (BsmI) VDR polymorphism, which determines progressive disorders of mineral metabolism and aggravates the course of fluorosis in workers. Ethics. The examination of aluminum production workers was carried out in the hospital of the Research Institute for Complex Problems of Hygiene and Occupational Diseases in strict accordance with the ethical principles of conducting scientific and medical research with human participants, developed on the basis of the Helsinki Declaration by the World Medical Association "Ethical principles of conducting scientific medical research with human participants" with amendments of 2013, "Rules of Clinical Practice in the Russian Federation" approved by the Order of the Ministry of Health of the Russian Federation No. 266 dated 06/19/2003. The collection of clinical history data was carried out during an oral questionnaire face to face with a written informed consent to participate in the study and analysis of medical histories according to 025/u-87 form.

Abstract 6318: Effects of per- and polyfluoroalkyl substances on bone marrow adipose environment: Potential implications for bone metastatic cancers

Abstract Bone is a site of metastasis from several tumor types including prostate cancer (PCa). Metastatic PCa is lethal, largely due to the complex nature of bone microenvironment, and the functional cross-talk between bone-resident cells and tumor cells that favors therapy evasion. We have shown previously that age- and obesity-induced changes in the bone microenvironment, specifically increased marrow adiposity, promote tumor adaptation in bone. Numerous studies have also linked the disruption in bone homeostasis with aggressive tumor phenotype. Whether environmental toxicants with propensity to accumulate in bone can modulate bone microenvironment to support tumor growth and progression is, however, not known. Per- and polyfluoroalkyl substances (PFAS) are “forever” chemicals with very long half-lives and ability to accumulate in bone. Limited reports have linked PFAS exposure with adipocyte differentiation and osteoclast activation, but their specific effects on bone are not known. It is also unclear whether the exposure to PFAS can directly impact metastatic tumor cells. Here, we hypothesized that PFAS contribute to metastatic progression by impacting both the tumor and its microenvironment. Specifically, we aimed to establish that exposure to PFAS promotes adipogenesis and osteoclastogenesis, creating microenvironment conducive to tumor growth. We also sought to determine whether direct effects of PFAS exposure on tumor cells lead to activation of growth and survival signaling that drives aggressive phenotype in bone. Our data show that 12-week exposure of mice to a cocktail of 5 PFAS chemicals (PFOS, PFOA, PFNA, PFHxS, and GenX) increases the number of adipocytes in the tibia and augments expression of adipogenesis-associated genes, such as FABP4 and adiponectin. RNAseq analyses of tibia from mice exposed to PFAS chemicals for 3 and 6 weeks indicate changes in bone metabolism and turnover, results supported by in vitro osteoclastogenesis assays. Mass spectrometry analyses of bone extracts from PFAS cocktail exposed mice reveal that the compound with highest concentration in bone is PFHxS. Interestingly, our in vitro assays employing bone marrow derived mesenchymal cells show that PFHxS can activate peroxisome proliferator-activated receptor (PPAR) signaling, leading to an increase in adipogenesis. Studies examining the direct impact of long term PFHxS as well as PFAS cocktail exposure on in vitro PCa cultures and progression of intratibially implanted PCa tumors are currently ongoing. Our findings to date indicate that changes in bone marrow microenvironment induced by PFAS chemicals have a potential to disrupt the balance between osteoblasts and adipocytes, promote marrow adipogenesis and osteoclastogenesis, and activate specific signaling pathways in tumor cells that support growth and survival. Citation Format: Laimar C. Garmo, Mackenzie K. Herroon, Shane Mecca, Alexis Wilson, Michael C. Petriello, Izabela Podgorski. Effects of per- and polyfluoroalkyl substances on bone marrow adipose environment: Potential implications for bone metastatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6318.

Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis

Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that trigeminal ganglia (TG) Nav1.8+ nociceptors regulate bone metabolism changes in response to AP. A selective ablation of nociceptive neurons in Nav1.8Cre/Diphtheria toxin A (DTA)Lox mouse line was used to evaluate the development and progression of AP using murine model of infection-induced AP. Ablation of Nav1.8+ nociceptors had earlier progression of AP with larger osteolytic lesions. Immunohistochemical and RNAscope analyses demonstrated greater number of macrophages, T-cells, osteoclast and osteoblast precursors and an increased RANKL:OPG ratio at earlier time points among Nav1.8Cre/ DTALox mice. There was an increased expression of IL-1α and IL-6 within lesions of nociceptor-ablated mice. Further, co-culture experiments demonstrated that TG neurons promoted osteoblast mineralization and inhibited osteoclastic function. The findings suggest that TG Nav1.8+ neurons contribute to modulation of the AP development by delaying the influx of immune cells, promoting osteoblastic differentiation, and decreasing osteoclastic activities. This newly uncovered mechanism could become a therapeutic strategy for the treatment of AP and minimize the persistence of osteolytic lesions in refractory cases.Graphical abstract