Decreased Mineral Density Research Articles

Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity

Breast cancer bone metastasis is a major cause of mortality in patients with advanced breast cancer. Although decreased mineral density is a known risk factor for bone metastasis, the underlying mechanisms remain poorly understood because studying the isolated effect of bone mineral density on tumor heterogeneity is challenging with conventional approaches. Moreover, mineralized biomaterials are commonly utilized for clinical bone defect repair, but how mineralized biomaterials affect the foreign body response and wound healing is unclear. Here, we investigate how bone mineral affects tumor growth and microenvironmental complexity in vivo by combining single-cell RNA-sequencing with mineral-containing or mineral-free decellularized bone matrices. We discover that the absence of bone mineral significantly influences fibroblast and immune cell heterogeneity, promoting phenotypes that increase tumor growth and alter the response to injury or disease. Importantly, we observe that the stromal response to bone mineral content depends on the murine tumor model used. While lack of bone mineral induces tumor-promoting microenvironments in both immunocompromised and immunocompetent animals, these changes are mediated by altered fibroblast phenotype in immunocompromised mice and macrophage polarization in immunocompetent mice. Collectively, our findings suggest that bone mineral density affects tumor growth by impacting microenvironmental complexity in an organism-dependent manner.

Rapamycin increases murine lifespan but does not reduce mineral volume in the Matrix GLA Protein (MGP) knockout mouse model of medial arterial calcification.

Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found that medial arterial calcification (MAC) is the primary cause of chronic limb ischemia below the knee. MAC involves calcification of the elastin fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA Protein (MGP) binds circulating calcium and inhibits vascular calcification. Mgp -/- mice develop severe MAC and die within 8 weeks of birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency in CD73 (ACDC) in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using Mgp -/- mice as a model. Mgp +/+ and Mgp -/- mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotypes and cellular functions. Rapamycin prolonged Mgp -/- mice lifespan, decreased mineral density in the arteries, and increased smooth muscle actin protein levels, however, calcification volume, vessel morphology, SMC proliferation, and autophagy flux were all unchanged. These findings suggest that rapamycin's effects in the Mgp -/- mouse are independent of the vascular phenotype.

Bone mineral density affects tumor growth by shaping microenvironmental heterogeneity.

Breast cancer bone metastasis is the leading cause of mortality in patients with advanced breast cancer. Although decreased mineral density is a known risk factor for bone metastasis, the underlying mechanisms remain poorly understood because studying the isolated effect of bone mineral density on tumor heterogeneity is challenging with conventional approaches. Here, we investigate how bone mineral content affects tumor growth and microenvironmental complexity in vivo by combining single-cell RNA-sequencing with mineral-containing or mineral-free decellularized bone matrices. We discover that the absence of bone mineral significantly influences fibroblast and immune cell heterogeneity, promoting phenotypes that increase tumor growth and alter the response to injury or disease. Importantly, we observe that the stromal response to matrix mineral content depends on host immunocompetence and the murine tumor model used. Collectively, our findings suggest that bone mineral density affects tumor growth by altering microenvironmental complexity in an organism-dependent manner.

Tissue Interactions in Dense Tissues of the Orofacial Region in Patients with Connective Tissue Dysplasia.

This study aimed to investigate the rate and quality of maturation of the mineral component of impacted teeth 38 and 48 and a fragment of the human lower jaw with connective tissue dysplasia (CTD) in different periods of postnatal ontogenesis. The study involved 102 males (76 with CTD and 26 without CTD), divided into age groups: 31-40, 41-50 and 51-60 years. For medical reasons, teeth 38 and 48 were removed from each patient, as well as a fragment of the alveolar part of the lower jaw in the projection of teeth 38 and 48 measuring 0.5 × 0.5 cm. The odontological parameters, the mineral density of the enamel and the lower jaw, the length and width of the enamel prisms, the spatial organisation of collagen fibrils and the dimensions of the bone plates of the lower jaw were determined. A decrease in optical density was observed at the age of 41-50 and 51-60 years with dysplasia, which indicated a decrease in mineral density and the presence of total areas of hypomineralisation relative to the age of 31-40 years. In the age groups of 41-50 and 51-60 years, pronounced sclerosis and deformation of the delimiting elements were observed at the border of the connective tissue structures and the periosteum. At the age of 31-40 years, the level of stratification of the bone plates was local; after 40 years, it was generalised. Progressive osteoporosis of the lower jaw and incomplete amelogenesis are obstacles to the correct and harmonious eruption of the lower 'wisdom' teeth after 30 years.

An evidence-based algorithmic approach to osteoporosis etiology verification on the example of a clinical case

Background. The importance of timely detection of osteoporosis in patients is conditioned by its severe consequences such as osteoporotic fractures. The disease can be both primary and related to the existing other pathology or to the therapy being carried out, i.e. secondary. In young patients, in most cases, osteoporosis is secondary in nature. Diagnosis verification requires doctor’s perseverance and knowledge. Purpose – is to demonstrate an algorithm of finding a possible cause of the osteoporosis development in a young person on the example of a clinical case. Materials and Methods. The medical history of a 32-year-old man is presented. The man was consulted a doctor with complaints of long-lasting aching pain in the back, stiffness in the morning in the thoracic spine and pain during movement, and was diagnosed with a compression fracture of the spine on the background of a decrease in bone mineral density. Results. The article describes the step-by-step algorithm of making a diagnosis by gradually excluding primary osteoporosis and possible causes of the secondary nature of the disease. Information about the possible mechanisms of osteoporosis formation in the most common conditions included to the differential diagnosis is given in the article. The described diagnostic search algorithm can be used in the practice of a doctor of any specialty. Conclusions. Making a diagnosis of osteoporosis must include a differential diagnosis of its forms with the establishment of the ethiology of this pathology. In young patients, in most cases, osteoporosis has secondary nature and requires a mandatory search for its cause by gradually and methodically excluding conditions that can lead to a decrease in the mineral density of bone tissue, including genetic ones. In practice, there are cases of idiopathic osteoporosis, when the examination does not allow to clearly establish the reasons that led to a decrease in bone density. Such cases require the special attention of doctors, because the diagnosis of the main disease that led to the development of osteoporosis in the future can be detected. In this case along with antiresorptive drugs, therapy of the condition, which is the root cause of the development of osteoporosis, is prescribed, if possible. The specified combined therapy will contribute to increasing the effectiveness of treatment and shortening its duration.

Минеральная плотность костной ткани у молодых пациентов с воспалительными заболеваниями кишечника

Inflammatory bowel diseases (IBD) are characterized by the development of various systemic manifestations. One of the significant extraintestinal manifestations of IBD is a decrease in mineral density (BMD) (demineralization) of bone tissue and osteoporosis (OP). The pathogenesis of decreased BMD is multifactorial: the activity of immune inflammation of the gastrointestinal mucosa, medication intake, malnutrition (low calcium intake), decreased muscle and fat mass, vitamin D deficiency, as well as other factors contribute to the development of osteoporosis in such patients. Despite various studies examining the prevalence of decreased BMD in patients with IBD, data vary widely, ranging from 17 to 77%. The purpose is to evaluate BMD, levels of bone resorption markers in young patients with IBD, and to evaluate the relationship between BMD and osteosynthesis markers. Materials and methods. 62 patients with a verified diagnosis of IBD were examined: 30 patients had Crohn’s disease (CD), 32 patients had ulcerative colitis (UC). All patients underwent a general clinical examination, a double-absorption X-ray densitometric study with determination of BMD and bone mineral content (BMC), as well as determination of bone resorption parameters — osteocalcin, Beta-Crosslaps (C-terminal telopeptides of type I collagen) and marker determination formation of bone matrix P1NP. The level of the mineral part of bone mass was measured using the bioimpedance method on the ABC-02 «MEDASS» apparatus. Results: Seven patients with IBD (11%) had low BMD for chronological age. The median values of BMD, osteocalcin, Beta-Crosslaps, and bone matrix formation marker P1NP in the general group of patients with IBD, as well as in the subgroups of patients with CD and UC are presented. A clinical example is presented. Conclusion. Diagnosis of osteoporosis in patients with IBD is difficult for several reasons. It is important to assess the presence of risk factors in conjunction with laboratory and instrumental examinations.

Combining Raman Microspectroscopy and X-ray Microcomputed Tomography for the Study of Bone Quality in Apolipoprotein-Deficient Animal Models.

Raman microspectroscopy and X-ray microcomputed tomography (micro-CT) were used for assessment of the quality of the femur and tibia bones in apolipoprotein-deficient mice compared to control littermates. The cortical and trabecular bone was investigated separately. Raman spectra revealed no differences in the bioapatite-to-collagenous matrix ratio of the cortical bone. The quantities of calcium and collagen, which were measured using atomic absorption spectrometry and thermogravimetric analysis, respectively, were also found to be equal in the two groups. Density and morphometric parameters, which were measured using micro-CT, verified the cortical mineral stability. Bone quality indices were measured using Raman spectra. A decreased collagen crosslink (trivalent-to-divalent) ratio revealed delayed maturation of the collagen network. Such a decrease has been reported in the literature to be connected to decreased bone strength. For the trabecular bone, micro-CT revealed severe osteoporosis in the knock-out group, which was evident from a decreased mineral density, trabecular thickness and increased bone surface/volume ratio. The trabecular bone was not accessible for Raman spectroscopy. According to these results, the cortical and trabecular femur bone is expected to exhibit proneness to fracturing, each for a different reason. A combination of the two techniques was regarded as necessary for an overall assessment of bone quality.

Problems of physical rehabilitation of movement disorders in the pathology of the hip joint in patients with the consequences of a cerebral stroke

The purpose of the work was to analyze the experience of foreign specialists regarding movement and structural disorders of the proximal part of the femur in patients with the consequences of stroke and their impact on the effectiveness of rehabilitation programs for hip joint pathology. To fulfill the goal, an analysis of foreign literary sources was carried out in modern databases: Google Scholar, Web of Science, PubMed, Medline, Cochrane, Pedro. The search depth is 22 years (from January 2000 to October 2021). The analysis of literature sources indicated that limitation of motor activity and axial loads in patients after acute cerebrovascular accident, in particular limitation of mobility in the hip joint, impairment of muscle strength and tone due to hemiparesis can lead to the development of osteoporosis. Particularly important from the point of view of adverse consequences is a decrease in mineral density and fractures of the proximal part of the femur. On the other hand, disturbed biomechanics of movements in the hip joint in persons with the consequences of a cerebral stroke, under the condition of axial load on the limb, can lead to the development of osteoarthritis of the hip joint. Osteoarthritis results in limited mobility of the hip joint, which leads to secondary immobilization of the hip joint and, as a result, can also lead to further osteoporosis. Existing disorders of neuromuscular control, muscle tone and strength, limitation of mobility of the hip joint, including due to spasticity, problems with static and dynamic balance, and, as a result, an increased risk of falling in patients with the consequences of a stroke, can negatively affect the recovery of motor functions, activity limitation, and, as a result, reduce the effectiveness of rehabilitation of patients after hip joint replacement. Existing movement disorders, as a result of a stroke, require the development and justification of new rehabilitation programs, including the use of modern technical means and virtual reality.

Comprehensive analysis of epigenetics mechanisms in osteoporosis.

Epigenetic modification pertains to the alteration of genetic-expression, which could be transferred to the next generations, without any alteration in the fundamental DNA sequence. Epigenetic modification could include various processes such as DNA methylation, histone alteration, non-coding RNAs (ncRNAs), and chromatin adjustment are among its primary operations. Osteoporosis is a metabolic disorder that bones become more fragile due to the decrease in mineral density, which could result in a higher risk of fracturing. Recently, as the investigation of the causal pathology of osteoporosis has been progressed, remarkable improvement has been made in epigenetic research. Recent literatures have illustrated that epigenetics is estimated to be one of the most contributing factors to the emergence and progression of osteoporosis. This dissertation primarily focuses on indicating the research progresses of epigenetic mechanisms and also the regulation of bone metabolism and the pathogenesis of osteoporosis in light of the significance of epigenetic mechanisms. In addition, it aims to provide new intelligence for the treatment of diseases related to bone metabolism.

Enamel Structure Defects in Kdf1 Missense Mutation Knock-in Mice.

The Keratinocyte differentiation factor 1 (KDF1) is reported to take part in tooth formation in humans, but the dental phenotype of Kdf1 mutant mice has not been understood. Additionally, the role of the KDF1 gene in dental hard tissue development is rarely known. In this study, we constructed a Kdf1 missense mutation knock-in mouse model through CRISPR/Cas9 gene-editing technology. Enamel samples from wildtypes (WT) and Kdf1 homozygous mutants (HO) were examined using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), an atomic force microscope (AFM) and Raman microspectroscopy. The results showed that a novel Kdf1 missense mutation (c. 908G>C, p.R303P) knock-in mice model was constructed successfully. The enamel of HO mice incisors appeared chalky and defective, exposing the rough interior of the inner enamel and dentin. Micro-CT showed that HO mice had lower volume and mineral density in their tooth enamel. In addition, declined thickness was found in the unerupted enamel layer of incisors in the HO mice. Using SEM and AFM, it was found that enamel prisms in HO mice enamel were abnormally and variously shaped with loose decussating crystal arrangement, meanwhile the enamel rods were partially fused and collapsed, accompanied by large gaps. Furthermore, misshapen nanofibrous apatites were disorderly combined with each other. Raman microspectroscopy revealed a compromised degree of order within the crystals in the enamel after the Kdf1 mutation. To conclude, we identified enamel structure defects in the Kdf1 missense mutation knock-in mice, which displayed fragmentary appearance, abnormally shaped prism structure, decreased mineral density, altered crystal ordering degree and chemical composition of the enamel layer. This may support the potential role of the KDF1 gene in the natural development of enamel.

Остеопороз у пацієнтів із хронічним панкреатитом – особливості діагностики

The purpose of the study was to determine the features of the development of osteoporotic bone changes in patients with fibrotic changes of the pancreas against the background of chronic pancreatitis. Materials and methods. 55 patients with chronic pancreatitis were examined. 30 examined were women, 25 were men. The average age of the patients was 47.3±3.5 years. To be included in the study, all patients were excluded from the presence of concomitant diseases. For female patients, preservation of menstrual function was a mandatory condition for inclusion in the study. The degree of fibrotic changes of the pancreas was established on the basis of conducting 2D shear wave elastometry with transcutaneous access by the shear wave method in the SWE mode. Determination of bone mineral density was carried out using a DEXXUM T X-ray densitometer by the method of dual-energy absorptiometry. Results and discussion. The severity of fibrotic changes in the pancreatic parenchyma also affected the prevalence of osteoporosis and osteopenia. Among patients with parenchyma density indicators corresponding to grade 3-4 of fibrotic changes, a decrease in bone mineral density was observed in 83% of examined patients, while among patients with grade 1-2 of such changes, osteoporosis and osteopenia were found in 34% (p = 0.003). In patients with fibrotic changes in the parenchyma of the pancreas, osteoporotic changes in the area of the lumbar vertebrae were noted in 55% of cases with reduced bone mineral density, an isolated decrease in the mineral density of the lumbar spine was diagnosed in 11 patients (28.2% of patients with a decrease in bone mineral density), 5 patients (12.8%) had a combination of a decrease in the mineral density of the spine with a decrease in the mineral density of the hip, the average T criterion of the vertebrae was -2.4±0.5, the average T criterion of the femoral neck was -2.6±0.36. In patients with fibrosis of the parenchyma of the pancreas of 1-2 stages bone mineral density decreased mainly to the level of osteopenia, with a combination of osteopenic changes in the lumbar spine and a decrease in hip mineral density. The average T criterion of vertebrae was -1.6±0.15, femoral neck -1.76±0.18 Conclusion. Patients with chronic pancreatitis are characterized by a high prevalence of osteoporosis and osteopenia. Patients with stages 3-4 of pancreatic fibrosis have a greater risk of developing this complication. The reduction of bone mineral density in patients with chronic pancreatitis is influenced not only by population risk factors, but also by the duration of pancreatitis. The severity of fibrotic changes in the pancreas affects the localization of changes in bone tissue

International standard measures during the AGBRESA bed rest study

The Artificial Gravity Bed Rest with European Space Agency (AGBRESA) study involved 2 campaigns of 60-day bed rest at 6° head down tilt in the:envihab facility in Cologne, Germany, in 2019. The objective was to determine whether centrifugation of supine subjects mitigates physiological changes that occur due to the exposure to the spaceflight analog of 6° head down tilt. A set of international standard measures was used to evaluate bone, muscle, nutritional status, ocular changes, and psychological state and to assess cardiovascular, sensorimotor, and immune systems functions. After 60 days of bed rest, the subjects who were not exposed to centrifugation had significant decreases in mineral density at the hip and lumbar spine, decreased muscle strength of the knee and ankle, reduced maximal aerobic capacity, orthostatic intolerance, and impaired balance and locomotion, as well as significant biochemical, immunological, and psychological alterations. A daily 30-min exposure to 1 Gz supine centrifugation at the center of mass (0.3 Gz at the head, 2 Gz at the feet) mitigated mineral density loss in the femur neck and lumbar spine; and lessened the effects of bed rest on aerobic capacity, biochemistry, and immunology. However, low statistical power could contribute to the non-significant effects that are reported.

Mineral density and chemical composition of the rats’ mandibles in experimental models of generalized periodontitis

The most severe and difficult to treat symptoms of generalized periodontitis associated with diabetes mellitus are changes in bone tissue. The aim of the research was to conduct a comparative study of the mineral density and chemical composition of the mandibular bone tissue in rats in the modeling of generalized periodontitis, which develops against the background of metabolic disorders in type 2 diabetes mellitus, and after additional use of strontium ranelate. The study was carried out on 24 white male Wistar rats weighing 230-250 g, divided into three groups, 8 animals in each (in I group streptozocin and nicotinamide were administered, in II group - additionally penicylamine, in III group – additionally strontium ranelate) and 6 intact rats were used as a control. According to data of computer tomography, it was found that in the control group the average values of the mineral density are 1450.0±125.0 HU, in I group – 1320.0±120.0 HU (p>0.05), in II group –1100.0±110.0 HU (p˂0.05), in III group –1400.0±137.0 HU (p>0.05). Thus, the most pronounced decrease in mineral density is observed in the case of the combined use of nicotinamide, streptozotocin and penicylamine, while strontium ranelate helps to normalize this indicator. According to atomic emission spectrometry, the mineralization index – the ratio of calcium / phosphorus – was 1.14 in the control group, 1.05 – in I, 1.0 – in II and 1.26 – in III. The strontium content in the samples of the III group exceeded the control values by almost two times (p˂0.001) in comparison with its significant decrease in the samples of the I and II groups (p˂0.05). An increase in the strontium content led to a decrease in the content of other elements, which is explained by the competitive substitution in apatite crystals. So, strontium ranelate activates remineralization of the bone component of the periodontium.

The 283 А>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>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.

Osteodensitometry as a method of early diagnosis of pathology of paraarticular tissues of the shoulder joint

Despite the significant prevalence of shoulder-scapular periarthrosis, methods of its early diagnosis remain insufficiently developed. The study aims to clarify the possibility of using osteodensitometry for early diagnosis of shoulder-scapular periarthrosis. We examined 70 men (the main group) with a diagnosis of shoulder-scapular periarthrosis without disorders of the function of the shoulder joints, which corresponded to the initial stage of the disease. The comparison group consisted of 78 patients with diagnosed osteoarthritis of the shoulder joints with moderate recurrent algic syndrome without limitation of the volume of movements; the control group consisted of 112 practically healthy men. The age of all examined men were 30-50 years. In addition to clinical and functional examination with neuro-orthopedic examination and radiography of the shoulder joints, the researchers conducted the mineral density of the bone tissue of the head of the humerus according to the results of digital radiography with a wedge-standard density. This method has a high accuracy in determining the mineral density of bone tissue, does not have an additional load and allows you to get the desired information. In the examined main group, in the absence of bone changes on the shoulder joint radiographs, experts have identified a significant decrease in the mineral density index in all zones of the upper sector, maximally expressed in the lateral zone of the humerus head in relation to the results of the control group. Patients in the comparison group also showed a significant decrease in this indicator in relation to the indicator of the control group. The decrease in bone mineral density in patients with osteoarthritis exceeded the decrease in similar indicators in individuals with shoulder-scapular periarthritis, however, there was no significant difference in these cases. The obtained results of the study allow us to conclude that the applied osteodensitometry makes it possible to detect a local decrease in bone mineral density in articular structures at the early stages of their formation, resulting from damage to the soft tissues of paraarticular structures, due to the unity of the response of the ligamentous-articular apparatus. Ethics. This study did not require the conclusion of the Ethics Committee.

Research of connective tissue dysplasia influence on teething

PurposeThis work aimed to study the rate and quality of maturation of the mineral component of retained teeth 3.8, 4.8 and lower jaw fragment of a human in connective tissue dysplasia in different periods of postpartum ontogenesis. MethodsThe study involved 102 men (76 with connective tissue dysplasia and 26 without connective tissue dysplasia) divided into groups by age: 31–40, 41–50, 51–60 years. One tooth 3.8, 4.8 and a fragment of the alveolar part of the lower jaw in the projection of teeth 3.8, 4.8 0.5*0.5 cm in size were extracted from each examinee for medical indications. ResultsLow optical density values are observed at the age of 41–50 years, at the age of 51–60 years, indicating decreased mineral density and the presence of total areas of hypomineralization from the age 31–40 years in connective tissue dysplasia. At the age of 41–50, 51–60 years, at the boundary of connective tissue structures and periosteum, a pronounced sclerosis and deformation of delineation elements were observed; at the age of 31–40 years, the indicated changes were less pronounced. At the age of 31–40 years, the level of bone plate dissection has a local character, after 40 years, it has a generalized character. ConclusionProgressive osteoporosis of the mandible and incomplete amelogenesis are an obstacle to the correct and harmonious teething of the lower wisdom teeth after the age of 30.

Toxic effects of thioacetamide-induced femoral damage in New Zealand white rabbits by activating the p38/ERK signaling pathway.

Thioacetamide (TAA) is widely used in the production of drugs, pesticides and dyeing auxiliaries. Moreover, it is a chemical that can cause liver damage and cancer. TAA has recently been identified to cause bone damage in animal models. However, the type of bone damage that TAA causes and its potential pathogenic mechanisms remain unclear. The toxic effects of TAA on the femurs of New Zealand white rabbits and the underlying toxicity mechanism were investigated in this study. Serum samples, the heart, liver, kidney and femurs were collected from rabbits after intraperitoneal injection of TAA for 5 months (100 and 200 mg/kg). The New Zealand white rabbits treated with TAA showed significant weight loss and femoral shortening. The activities of total bilirubin, total bile acid and gamma-glutamyl transpeptidase in the serum were increased following treatment with TAA. In addition, thinned cortical bone and significantly decreased trabecular thickness of TAA-treated rabbits was observed, which was accompanied by significantly decreased mineral density of the cortical and trabecular bone. Moreover, there was a significant decrease in modulus of elasticity and maximum load on bone stress in TAA-treated rabbits. The western blotting results showed that the expression of phosphorylated (p)-p38 and p-ERK in femur tissues of rabbits were increased after TAA administration. Collectively, these results suggested that TAA may lead to femoral damage in rabbits by activating the p38/ERK signaling pathway.

Phosphatidylserine liposomes containing curcumin inhibit bone loss in osteoporotic rats: A possible synergy through a common signaling pathway.

The present study aimed to investigate the effect of phosphatidylserine liposomes containing curcumin (PSLs-Cur) on the development of osteoporosis induced by glucocorticoids (GCs) in the rat model. PSL-Cur, phosphatidylserine (PSL), curcumin (Cur), and alendronate (AL) drugs as a positive control were administrated orally to evaluate the beneficial effects of 3-week treatments on osteoporotic rats. The biochemical and biomechanical properties of bone parameters as well as gene expression were evaluated in treated rats. Moreover, histomorphometric examinations were performed on the bone tissues of the animals. The results revealed that PSL-Cur oral administration caused a significant improvement in serum markers, mechanical strength, and OPG gene expression rather than PSL or Cur administration in osteoporotic rats. Also, PSL-Cur significantly increased the thickness and volume of cortical and trabecular bone mass in comparison with the untreated osteoporotic group. The results of this study indicated that PSL-Cur had a more inhibitory effect on bone loss induced by GCs compared to AL standard drug. Our findings suggested that PSL-loaded Cur may be an appropriate alternative therapy for glucocorticoid-induced osteoporosis. PRACTICAL APPLICATIONS: Osteoporosis is one of the most serious metabolic chronic diseases that causes fragile bone due to decreased mineral density and microarchitectural deterioration in humans. The osteoprotective effects of curcumin and phosphatidylserine, as a food spice and supplementary diet, respectively, have been shown, previously. However, the low bioavailability of curcumin (Cur) due to its poor absorption, rapid metabolism, and fast systemic elimination, limits its benefits. This deficit can be modified with phosphatidylserine liposome (PSL) formulation that facilitates the gastrointestinal delivery of Cur. Moreover, PSL is known as an osteoprotective agent that may make synergy effect with Cur against GC-induced osteoporosis. In this study, daily oral administration of phosphatidylserine liposomes containing curcumin (PSL-Cur) for 3weeks, considerably improved biochemical, biomechanical, and gene expression of bone parameters in the treated animals subjected to osteoporosis. PSL-Cur can significantly increase the thickness and volume of cortical and trabecular bone mass as well as the mechanical bone strength in animals. Experimental findings proposed PSL-Cur consumption as a proper and safe supplementary medication in the controlling of bone loss in patients with a high risk of osteoporosis.

Indicators of bone metabolism and bone mineral density in workers of a metallurgical plant

The mineral density of bone tissue and phosphorus and calcium metabolism are studied by ultrasound densitometry of the calcaneus using the apparatus Achilles+ (Lunar, USA) in 99 men working in foundry of the metallurgical alluminium works. The control group consisted of 87 healthy men of similar age. The prolonged effect of aerosols of aluminium, lead, nickel, chromium, manganese, copper is accompanied by more frequent decrease the mineral density of bone tissue, increase of incidence of osteoporosis. Workers of aluminium production are characterised by hyperphosphatemia and hyperphosphaturia resulting in insignificant decrease of parathyroid hormone secretion. The normal level of osteocalcin, alcaline phosphatase in the decreased mineral density of bone tissue shows oppression of the bone-formation process in workers.

Оптимізація антиостеопоротичної терапії у пацієнток із фіброзом печінки

The purpose of the study: to investigate the effect of zolendronic acid on bone mineral density in patients with osteoporosis and fibrotic changes of the liver due to steatohepatitis. Materials and methods. We examined 28 female patients with a mean age of 55.3±4.7 years with decreased bone mineral density, nonalcoholic steatohepatosis and liver fibrosis. All studied patients were in menopause duration of 7.8±3.5 years. For inclusion in the study, all patients were excluded from the presence of comorbidities. The degree of liver fibrosis was determined on the basis of 2D shear wave elastometry by transcutaneous access by the method of shear wave in the SWE mode. The study included patients with liver fibrosis F1 - F3 on METAVIR. Determination of bone mineral density was performed using an X-ray densitometer DEXXUM T by dual energy absorption. Results and discussion. The initial level of liver tissue stiffness in the studied patients was 8.52±1.12 kPa, which corresponded to the stage of fibrosis F2 - F3 according to METAVIR. Isolated decrease in lumbar spine mineral density was diagnosed in 20 patients, 8 patients had a combination of decreased spinal mineral density with decreased femoral mineral density, mean T vertebral T-test was -2.25±0.2, mean femoral neck T-test was -1, 9±0.3. In order to maintain and restore bone mineral density, these patients were advised to minimize the factors that contribute to bone loss, mainly by stopping alcohol and smoking. Patients were advised to exercise as much as possible under the supervision of a rehabilitologist, especially to do exercises aimed at improving the mechanics of the spine. One year after administration of 5 mg zolendronic acid intravenously and daily intake of 1500 mg calcium and 800 IU vitamin D the level of liver tissue stiffness in the studied patients was 7.69±1.14 kPa, which corresponded to the stage of fibrosis F2 - F3 according to METAVIR and not due to a moderate decrease in indicators, there was no statistically significant difference. Isolated decrease in lumbar spine mineral density was diagnosed in 19 patients, in 9 patients there was a combination of decrease in spinal mineral density with decrease in femur mineral density, the average criterion of T vertebrae was 1.1±0.3 (p=0.032), the average criterion of T femoral neck -0.9±0.3 (p=0.029). The study of the level of alaline transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyltranspeptidase did not reveal any abnormalities. After administration of zolendronic acid in 7 patients there was an increase in temperature to febrile levels within 2-3 days. None of the patients showed signs of bone fractures of any localization during the observation period. Conclusion. Thus, the administration of zolendronic acid to patients with decreased bone mineral density on the background of fibrous changes in liver tissue due to steatohepatitis is safe and highly effective