Mechanisms Of Bone Remodeling Research Articles

Spatiotemporal characterization of microdamage accumulation and its targeted remodeling mechanisms in diabetic fatigued bone

The skeleton of type 1 diabetes mellitus (T1DM) has deteriorated mechanical integrity and increased fragility, whereas the mechanisms are not fully understood. Load-induced microdamage naturally occurs in bone matrix and can be removed by initiating endogenous targeted bone remodeling. However, the microdamage accumulation in diabetic skeleton and the corresponding bone remodeling mechanisms remain poorly understood. Herein, streptozotocin-induced T1DM rats and age-matched non-diabetic rats were subjected to daily uniaxial ulnar loading for 1, 4, 7, and 10 days, respectively. The SPECT/CT and basic fuchsin staining revealed significant higher-density spatial accumulation of linear and diffuse microdamage in diabetic ulnae than non-diabetic ulnae. Linear microcracks increased within 10-day loading in diabetic bone, whereas peaked at Day 7 in non-diabetic bone. Moreover, diabetic fatigued ulnae had more severe disruptions of osteocyte canaliculi around linear microcracks. Immunostaining results revealed that diabetes impaired targeted remodeling in fatigued bone at every key stage, including increased apoptosis of bystander osteocytes, decreased RANKL secretion, reduced osteoclast recruitment and bone resorption, and impaired osteoblast-mediated bone formation. This study characterizes microdamage accumulation and abnormal remodeling mechanisms in the diabetic skeleton, which advances our etiologic understanding of diabetic bone deterioration and increased fragility from the aspect of microdamage accumulation and bone remodeling.

Endothelium-dependent molecular mechanisms of articular cartilage and subchondral bone remodeling in conditions of cardiovascular comorbidity

Aim. To determine the expression level of endothelial factors (VEGF-A, CD34 + ) in the tissues of the joints in experimental arterial hypertension (AH), hyperlipidemia (HL) and their combination. Material and methods . An experimental study was conducted on 24 sexually mature males of outbred guinea pigs. All animals were divided into 4 groups of 6 animals each. In the first group, AH was reproduced by intramuscular injection of a hydrocartisone solution. HL in the second group was simulated by intraperitoneal injection 1 time in 3 weeks of Tween 80 and diet modification. In the third group, the combination of AH and GL was reproduced by injection of a hydrocartisone solution, Tween-80 and diet modification. On the 60-day animals were pull out of the experiment by euthanasia. Hock joint tissue sampling was performed, in which the expression of endothelial vascular growth factor A (VEGF-A), CD34 was determined using a peroxidase immunohistochemical reaction. Results. It was found that during experimental AH, expression of VEGF-A increased in the subchondral bone. In experimental HL, preferential induction of VEGF-A and CD34 in the articular cartilage and subchondral bone is observed. When combined with cardiovascular factors, the highest expression of the molecular mechanisms of cardiometabolic stress, including VEGF-A and CD34 is observed. Conclusion. The results indicate that cardiovascular factors affect the joint tissue. This allows us to make an assumption that the joint tissues belong to the target organs of cardiovascular diseases and make it possible to judge the important role of cardiovascular comorbidity in the pathogenesis of degenerative inflammatory joint diseases.

Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs.

Bone microenvironment provides growth and survival signals essential for osteosarcoma (OS) initiation and progression. OS cells regulate communications inside tumor microenvironment through different ways and, among all, tumor-derived exosomes support cancer progression and metastasis. To define the contribution of OS-derived exosomes inside the microenvironment, we investigated the effects induced in bone remodeling mechanism and tumor angiogenesis. We demonstrated that exosomes promoted osteoclasts differentiation and bone resorption activity. Furthermore, exosomes potentiated tube formation of endothelial cells and increased angiogenic markers expression. We therefore investigated the micro RNA (miRNA) cargo from exosomes and their parental cells by performing small RNA sequencing through NGS Illumina platform. Hierarchical clustering highlighted a unique molecular profile of exosomal miRNA; bioinformatic analysis by DIANA-mirPath revealed that miRNAs identified take part in various biological processes and carcinogenesis. Among these miRNAs, some were already known for their involvement in the tumor microenvironment establishment, as miR-148a and miR-21-5p. Enforced expression of miR-148a and miR-21-5p in Raw264.7 and hTert immortalized umbilical vein endothelial cells recapitulated the effects induced by exosomes. Overall, our study highlighted the importance of OS exosomes in tumor microenvironment also by a specific packaging of miRNAs.

Numerical Analysis of Electromechanically Driven Bone Remodeling Using the Open-source Software Framework.

Natural bone remodeling is the mechanism that regulates the relationship between bone morphology and external mechanical loads applied to it. This phenomenon has been studied extensively, including multiple numerical models that have been formulated to predict the density distribution and its evolution in several bone types. However, despite these models, bone remodeling mechanism under different stimuli is still not well understood. We implemented a recently proposed electromechanically driven bone remodeling model that encompasses both mechanical and therapeutic electrical stimuli using an open-source software framework, and studied a two-dimensional (2D) plate model and a femur bone model, respectively. For discretization, we employed the finite element method (FEM) for the spatial quantities and Euler scheme for the time derivatives. The simulation results demonstrate that the density distribution is changed under electrical stimulation, generally resulting in a greater mass deposition. This study supports the possibility of enhancing and accelerating the bone remodeling process via simultaneous application of electrical and mechanical stimulus.

Quantitative proteomics analysis of differentially expressed proteins in patients with sarco-osteoporosis and osteoporosis

Objective The differential expression of protein mass spectrum of patients with sarco-osteoporosis (SO) and osteoporosis (OP) was constructed to reveal the molecular mechanism of sarcopenia that facilitates the development of osteoporosis. Methods The samples of muscle tissues of patients with sarco-osteoporosis and osteoporosis were collected, and label free quantitative proteomic technique was used to analyze and identify the differentially expressed proteins between the two groups, and differential expressed proteins were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG). Results There were 1 507 differentially expressed proteins identified. Among them, 53 were significantly dysregulated, including 47 down-regulated proteins and 6 up-regulated ones. The GO analysis showed that differentially expressed proteins in SO group were mainly involved in the redox process, protein hydrolysis and metabolic process, and the main molecular functions were protein binding, adenosine triphosphate (ATP) binding and calcium binding. The most significant cellular structural difference between the SO and OP groups was total components located in the membrane. Based on KEGG pathway analysis, connexin 43 (Cx43), voltage dependent L-type calcium channel (VLCC), superoxide dismutase (SOD) were screened as candidate proteins which may be involved in the mechanism of bone remodeling of osteoporosis. Conclusion Cx43, VLCC, SOD may be associated with bone loss in patients with sarcopenia. Key words: Sarco-osteoporosis; Osteoporosis; Label-free quantitative proteomics; Bioinformatics analysis

Effect of Exercises on Quality of Life in Patients with Postmenopausal Osteoporosis - Randomized Trial.

BACKGROUND:Osteoporosis is a systemic skeletal disease characterised by a low bone density and microarchitectural deterioration of bone tissue leading to decrease of its strength and increased risk of fracture. Drug therapy decreases the risk of fracture, thus influencing on the mechanism of bone remodelling. Non-pharmacological interventions include specific exercises for osteoporosis that improve muscle strength and balance, decrease pain and improve quality of life.AIM:To compare the quality of life in patients with postmenopausal osteoporosis who practice exercises with those who do not practice on the beginning and after a year.MATERIJAL AND METHODS:A randomised Single-blind randomised controlled prospective trial study, which included 92 women with postmenopausal osteoporosis diagnosed and treated at the Institute of Physical Medicine and Rehabilitation in Skopje, Republic of Macedonia. Patients were randomly assigned to three groups: the first group of patients with exercises and physical modalities (gr. I), the second group with exercises (gr. II), and the third control group of patients who did not practice exercises (gr. III). Exercises were practised 3 times a week; each exercise was repeated for 5-8 times. Patients regularly took bisphosphonates, calcium and vitamin D. The follow-up period lasted for one year. Quality of life was determined with a specific questionnaire Qualeffo-41.RESULTS:The results showed, significant statistical difference in terms of pain, physical activity, social life, the perception of own health were shown between the groups (p < 0.0001), only in term of mental function were no significant (p < 0.3).CONCLUSION:Patients who practice exercises for osteoporosis have a significantly better quality of life than patients who do not perform exercises.

Bone remodeling effect of a chitosan and calcium phosphate-based composite.

Chitosan is a biocompatible polymer that has been widely studied for tissue engineering purposes. The aim of this research was to assess bone regenerative properties of an injectable chitosan and calcium phosphate-based composite and identify optimal degree of deacetylation (%DDA) of the chitosan polymer. Drill holes were generated on the left side of a mandible in Sprague-Dawley rats, and the hole was either left empty or filled with the implant. The animals were sacrificed at several time points after surgery (7–22 days) and bone was investigated using micro-CT and histology. No significant new bone formation was observed in the implants themselves at any time points. However, substantial new bone formation was observed in the rat mandible further away from the drill hole. Morphological changes indicating bone formation were found in specimens explanted on Day 7 in animals that received implant. Similar bone formation pattern was seen in control animals with an empty drill hole at later time points but not to the same extent. A second experiment was performed to examine if the %DDA of the chitosan polymer influenced the bone remodeling response. The results suggest that chitosan polymers with %DDA between 50 and 70% enhance the natural bone remodeling mechanism.

Sclerostin Modulation Holds Promise for Dental Indications.

Sclerostin modulation is a novel therapeutic bone regulation strategy. The anti-sclerostin drugs, proposed in medicine for skeletal bone loss may be developed for jaw bone indications in dentistry. Alveolar bone responsible for housing dentition share common bone remodeling mechanisms with skeletal bone. Manipulating alveolar bone turnover can be used as a strategy to treat diseases such as periodontitis, where large bone defects from disease are a surgical treatment challenge and to control tooth position in orthodontic treatment, where moving teeth through bone in the treatment goal. Developing such therapeutics for dentistry is a future line for research and therapy. Furthermore, it underscores the interprofessional relationship that is the future of healthcare.

Assessment of structural and functional condition of rats bone tissue under the influence of various parameters of vibration

Abstract Whole body vibration involves the exposure of the entire human body to direct contact with environmental vibration. Chronic mechanical vibrations, combined with the physical attributes of the human body, can amplify the incoming energy and present the potential for negative health effects. Vibration exposure can, thus, result in adverse health effects such as spinal injuries, abdominal neurological and cardiovascular disorders. These can manifest indirectly as an accident causal factor. The aim of our research is to study the impact of vibration fluctuations of different frequencies on the structural and functional condition and mechanisms of bone remodelling. An experimental study was, therefore, conducted on mature male rats. For assessment of bone metabolism in the venous blood of rats, osteocalcin level was determined, while fragments of rats’ lumbar vertebrae were subsequently taken for histologic examination. Our work revealed that with the increase of vibration frequency, an increase of osteocalcin level in the blood of experimental animals comes about. Moreover, we noted after terminating vibration fluctuations on the 56th day of the experiment, osteocalcin levels are gradually reduced. In addition, in the course of histological study of specimens of lumbar vertebrae bone tissue, even as early as of the 28th day of the experiment, evidences of acute impairment of the bone tissue and initial signs of its remodelling are clearly traced. Indeed, on the 56th day, the remodelling processes represented by enhanced regeneration in the zone of the cartilage plate, increased in proliferation activity. We also saw hyperplasia of chondrocytes, hypertrophy of the respective zones of cartilage tissue, zones of forming immature bone tissue on the areas of previous damage, focal replacement fibrosis and angiomatosis. Hence, with increasing vibratory acceleration of 0,5 g, the rate of bone metabolism grows, osteoblast activation processes are accelerated and the impairment of collagen and calcium loss is increased. All this leads subsequently to the occurrence of osteoporosis.

Multimethod Approach to the Early Postnatal Growth of the Mandible in Mice from a Zone of Robertsonian Polymorphism.

The western European house mouse (Mus musculus domesticus) shows high karyotypic diversity owing to Robertsonian translocations. Morphometric studies conducted with adult mice suggest that karyotype evolution due to these chromosomal reorganizations entails variation in the form and the patterns of morphological covariation of the mandible. However, information is much scarcer regarding the effect of these rearrangements on the growth pattern of the mouse mandible over early postnatal ontogeny. Here we compare mandible growth from the second to the eighth week of postnatal life between two ontogenetic series of mice from wild populations, with the standard karyotype and with Robertsonian translocations respectively, reared under the same conditions. A multi-method approach is used, including bone histology analyses of mandible surfaces and cross-sections, as well as geometric morphometric analyses of mandible form. The mandibles of both standard and Robertsonian mice display growth acceleration around weaning, anteroposterior direction of bone maturation, a predominance of bone deposition fields over ontogeny, and relatively greater expansion of the posterior mandible region correlated with the ontogenetic increase in mandible size. Nevertheless, differences exist between the two mouse groups regarding the timing of histological maturation of the mandible, the localization of certain bone remodeling fields, the temporospatial patterns of morphological variation, and the organization into two main modules. The dissimilarities in the process of mandible growth between the two groups of mice become more evident around sexual maturity, and could arise from alterations that Robertsonian translocations may exert on genes involved in the bone remodeling mechanism. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

Violations of cell-molecular mechanisms of bone remodeling under influence of glucocorticoids

The fact is disturbance of the processes of bone tissue remodeling leads to a change in the balance between synthesis and resorption of bone and the development of osteoporosis. The most common cause of secondary osteoporosis is the use of glucocorticoid therapy. The aim of this study is to investigate the cellular-molecular mechanisms of disturbance of the processes of bone remodeling regulation, reflected by hormones and intercellular mediators (for example parathyroid hormone, calcitonin, RANKL, osteoprotegerin, P-selectin, interleukin-17, transforming growth factor-β1, adiponectin and visfatin) on the background experimental glucocorticoid osteoporosis. The experimental study carried out in two groups of white female rats. Disturbance of bone tissue remodeling was verified by histological examination of the femoral head, vertebrae of the thoracic and lumbar spine of rats and the measurement of bone density. The study of the levels of hormones and intercellular mediators in the blood serum of animals was carried out by the method of enzyme immunoassay. The bone mineral density of the experimental group was reduced compared to the bone mineral density of the control group. The study of the histostructure of the femoral head and vertebrae in rats of the experimental group in comparison with the animals of the control group revealed changes in the structural organization of bone tissue, confirmed by histomorphometry, indicating inhibition of the processes of osteosynthesis. The article analyzes the nature of the involvement of hormones and cytokines in pathogenetic mechanisms of development of bone tissue disorders. The levels of cytokines RANKL, osteoprotegerin, interleukin-17 and calcitonin in the blood serum of animals of the group with the violation of bone tissue remodeling by glucocorticoids were higher than in intact animals. Serum levels of P-selectin, parathyroid hormone, transforming growth factor-β1, adiponectin and visfatin were lower than similar levels in animals from the control group. The use of glucocorticoids increases the expression of RANKL and inhibits the synthesis of osteoprotegerin, resulting in stimulation of bone resorption. The effect of glucocorticoids in the experimental model is realized by changing the production of the studied hormones, cytokines and adhesion molecules. These changes stimulate the apoptosis of osteoblasts and inhibit their proliferation and differentiation, which is another mechanism of bone loss. Correlations found during the study reflect the relationship in the system of regulation of bone tissue remodeling under the influence of glucocorticoids. A complex system for regulating bone remodeling, which includes many regulatory pathways and their interactions, requires further study.

Role and regulation of growth plate vascularization during coupling with osteogenesis in tibial dyschondroplasia of chickens

Tibial dyschondroplasia (TD) is the most-prevalent leg disorder in fast-growing chickens; it is intractable and characterized by abnormal endochondral bone formation of proximal tibial growth-plates (TGPs). Previous studies have shown that bone is a highly vascularized tissue dependent on the coordinated coupling between angiogenesis and osteogenesis, but the underlying mechanisms of bone formation and bone remodeling are poorly defined in TD chickens. Here, we observed that inhibition of vasculogenesis and angiogenesis remarkably impaired vascular invasion in the hypertrophic chondrocyte zone of the TGPs, resulting in the massive death of chondrocytes due to a shortage of blood vessels and nutrients. Moreover, the balance of the OPG (osteoprotegerin)/RANKL (receptor activator of nuclear factor-kB ligand) system is also severely disrupted during the osteogenesis process while coupling with angiogenesis, both of which eventually lead to abnormal endochondral bone formation in TD chickens. Thus, the process of vascular formation in endochondral bone appears to initiate the pathological changes in TD, and improvement of this process during coupling with osteogenesis may be a potential therapeutic approach to treat this intractable disease.

Mechanical bone remodelling: Comparative study of distinct numerical approaches

Bone is a complex living structure. Induced by its biomechanical environment, bone constantly adapts its internal and external structure, altering its mass and morphology. In this work, three distinct discretization techniques are combined with a mechanologic bone tissue remodelling algorithm, which describes the remodelling process by minimizing the strain energy density (SED) field. During an iterative remodelling process, bone tissue's mechanical properties are recurrently correlated with bone apparent density through a phenomenological law. The purpose of this study is to compare bone tissue remodelling solutions obtained with the Finite Element Method (FEM), the Radial Point Interpolation Method (RPIM) and the Natural Neighbour RPIM (NNRPIM). Thus, two numerical examples were analysed, namely a benchmark bone patch and a femur. On both examples, regardless the discretization technique, it was possible to accurately reproduce the trabecular bone architecture. Additionally, a comparison between each numerical method was performed. The model shown high adaptability, since, for every method, successful performances were obtained. Nevertheless, meshless solutions produced smoother and more accurate results, closer to real X-ray images.

Concentration of several osteotropic growth factors, markers of osteogenesis and biologically active molecules in the blood serum of patients with congenital pseudarthrosis of tibia during orthopaedic treatment with combined technologies

Congenital pseudarthrosis of tibia is a genetic, systemic pathology with impaired bone remodeling and unknown pathogenetic mechanisms. Orthopaedic treatment of the disease can fail in some cases. The process of bone remodeling is known to occur under control of local and systemic growth factors, and we sought to explore several osteotropic growth factors, markers of osteogenesis and biologically active molecules in the blood serum of patients with congenital pseudarthrosis of tibia. The study included 12 patients with congenital pseudarthrosis of tibia and anatomical shortening of 2.5±1.1 cm. The' age of patients ranged from 7 years to 18 years. Blood serum was used for enzyme immunoassay analysis. The own blood serum levels of 103 conditionally healthy individuals (of mean age of 13.0±0.27 years) were considered as the norm. Greater changes in the concentration were detected among vascular endothelial and transforming growth factors. The patients showed imbalance in serum TGF, low reparative potential of bone tissue due to osteoclast activation prevailing over differentiation of osteoblasts, progenitor and mesenchymal cells. Dynamics in serum concentration of IGF at the time of frame removal indicated to terminating osteoblast activation and collagen synthesis and concomitant active bone restructuring.

Calcitonin gene‑related peptide reduces Porphyromonasgingivalis LPS‑induced TNF‑α release and apoptosis in osteoblasts.

Periodontal diseases comprise mixed bacterial infections mainly caused by Gram‑negative anaerobic bacteria. Lipopolysaccharides (LPS) are important virulence factors and periodontal pathogens, which change local cytokine levels and promote osteoblast apoptosis, thereby leading to an imbalance in bone remodeling mechanisms and accelerating bone loss. Calcitonin gene‑related peptide (CGRP) is a vasoactive neuropeptide that is released from sensory nerves and has a positive effect on osteoblast proliferation and differentiation. In addition, this small molecule peptide is an important immune regulator in the inflammatory response. The aim of the present study was to assess the invitro effects of CGRP on Porphyromonas gingivalis (Pg)LPS‑induced osteoblast apoptosis. Osteoblast cultures were stimulated either with various concentrations of PgLPS (0, 25, 50, 100, 500 and 1,000ng/ml) for 48h or with 500ng/ml PgLPS for various lengths of time (0, 6, 12, 24, 48 and 72h). The PgLPS‑stimulated cells were pretreated with different concentrations of CGRP (0, 1, 10, 100 and 1,000nM) and cell viability and apoptotic rates were measured by Cell Counting kit‑8 assays and flow cytometry, respectively. CGRP, cleaved (c)‑Caspase‑8 and c‑Caspase‑3 protein expression levels were analyzed by western blotting. Changes in cytokine expression levels, which included tumor necrosis factor (TNF)‑α, interleukin (IL)‑1β, IL‑6, monocyte chemotactic protein (MCP)‑1 and MCP‑2, were measured by ELISA. PgLPS was demonstrated to inhibit osteoblast viability and promote apoptosis in a time‑ and concentration‑dependent manner. CGRP expression was revealed to reduce PgLPS‑induced cytostatic activity and apoptosis in osteoblasts. CGRP also suppressed the PgLPS‑induced release of TNF‑α and inhibited the activation of c‑Caspase‑3 and c‑Caspase‑8, thus preventing apoptosis in osteoblasts. CGRP may be an important neuropeptide in bone remodeling and may reduce osteoblast apoptosis in inflammatory conditions. These results may provide a solid foundation for CGRP to serve as a new target for the treatment of periodontitis.

Bone marrow cavity segmentation using graph-cuts with wavelet-based texture feature.

Emerging bioimaging technologies enable us to capture various dynamic cellular activities [Formula: see text]. As large amounts of data are obtained these days and it is becoming unrealistic to manually process massive number of images, automatic analysis methods are required. One of the issues for automatic image segmentation is that image-taking conditions are variable. Thus, commonly, many manual inputs are required according to each image. In this paper, we propose a bone marrow cavity (BMC) segmentation method for bone images as BMC is considered to be related to the mechanism of bone remodeling, osteoporosis, and so on. To reduce manual inputs to segment BMC, we classified the texture pattern using wavelet transformation and support vector machine. We also integrated the result of texture pattern classification into the graph-cuts-based image segmentation method because texture analysis does not consider spatial continuity. Our method is applicable to a particular frame in an image sequence in which the condition of fluorescent material is variable. In the experiment, we evaluated our method with nine types of mother wavelets and several sets of scale parameters. The proposed method with graph-cuts and texture pattern classification performs well without manual inputs by a user.

Mechanisms of Altered Bone Remodeling in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy of plasma cells proliferating in the bone marrow and it is associated with the osteolytic bone disease. About 70% of myeloma patients show the bone disease at diagnosis and 15–20% have pathologic fractures. The osteolytic disease is due to the altered bone remodeling with increased activity of osteoclasts, the bone resorbing cells, and the reduced activity of osteoblasts, the bone forming cells. In the bone marrow microenvironment, the deregulated activity of bone cells is due to the malignant plasma cells through the release of soluble molecules or cell-cell contact. Recently, the key role of osteocytes, the orchestrators of bone remodeling, and the adipocytes has been highlighted in MM-bone disease. In this review, we overview the mechanisms leading to increased bone resorption as well as suppressed osteoblast formation and activity in MM-bone disease, thus highlighting cytokines that will represent new therapeutic targets to improve bone health in MM-bone disease.

Estrogen inhibits starvation-induced apoptosis in osteocytes by a redox-independent process involving association of JNK and glutathione S-transferase P1-1.

Estrogen deficiency causes bone loss as a result of microdamage, oxidative stress, and osteocyte apoptosis. A relationship between oxidative stress‐induced apoptosis, c‐Jun N‐terminal kinase (JNK) activation, and expression of factors involved in bone remodeling has been demonstrated in osteocytes. However, the molecular regulation of these events in osteocytes treated with 17β‐estradiol (17β‐E2) remains unexplored. The MLO‐Y4 murine osteocyte‐like cell line was used as a model to study starvation‐induced apoptosis and ROS production during 17β‐E2 treatment. Expression of glutathione S‐transferase P1‐1 (GSTP1‐1), receptor activator kB ligand (RANKL), osteoprotegerin (OPG), sclerostin, and kinases activation were measured by western blot. In addition, the GSTP1‐1/JNK association was assessed by immunoprecipitation, and GSTP1‐1 involvement in the osteocyte response to 17β‐E2 was detected by specific siRNA transfection. 17β‐E2 prevents starvation‐induced apoptosis (DNA fragmentation and caspase activation), the increase in sclerostin expression and the RANKL/OPG ratio, which are all related to JNK activation due to oxidative stress in osteocytes. This occurs through GSTP1‐1 overexpression, which can inhibit JNK activation by formation of a GSTP1‐1/JNK complex. No early antioxidant action of 17β‐E2 has been found but the estrogen effect is similar to N‐acetylcysteine which, by increasing the intracellular redox state, maintains JNK bound to GSTP1‐1. Thus, the antiapoptotic and osteogenic effect of 17β‐E2 in MLO‐Y4 occurs by a redox‐independent process involving GSTP1‐1/JNK association. This study clarifies at molecular level the effect of 17β‐E2 on osteocyte activity and identifies a possible role of GSTP1‐1 and JNK activity in bone remodeling and repair mechanisms.

DIAGNOSIS AND TREATMENT OF PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AND RENAL INSUFFICIENCY. THERAPEUTIC POTENTIAL OF PARICALCITOL

A review of the literature is devoted to the issue of secondary hyperparathyroidism (SHPT) with underlying chronic renal failure. Initial manifestations of the disease can be observed even with a minimal decrease in the rate of glomerular filtration and are pathophysiologically associated with violations of normal metabolism of vitamin D with its conversion into D-hormone. SHPT pathogenesis is based on the D-hormone deprivation and triggering of pathophysiology mechanisms of bone remodelling, increased FRP-23, PTH, changes in the serum levels of calcium and phosphorus, which may further lead to significant changes in the bone tissue structure and cardiovascular complications. Active metabolites of vitamin D and vitamin D analogues (Paricalcitol) were developed for the replacement of active forms of vitamin D in conditions of D-hormone deficiency. Due to its chemical structure and pharmacokinetics, Paricalcitol is able to block the synthesis of parathyroid hormone to a greater extent and increase the absorption of calcium and phosphorus in the intestine to a lesser extent, which gives it advantages over pre-existing active metabolites

Clinical Management of Patients Older than 75 Years of Age With Fractures of the Proximal Femur

This paper presents a review of publications dedicated to the complex clinical management of patients older than 75 years of age who have had fractures of the proximal femur and presented signs of osteoporosis. Descriptive and analytical methods were used in the research. The work with the publications was performed by entering the relevant MeSH terms and subheadings in the search systems of databases. The study found that most researchers think that this problem still needs to be studied in the context of the search for effective clinical management strategies, including the surgical treatment as early as possible and the prescription of medications which influence bone remodeling mechanisms.