Bone Tissue Quality Research Articles

Osteogenic tailoring of oriented bone matrix organization using on/off micropatterning for osteoblast adhesion on titanium surfaces.

Titanium (Ti) implants are well known for their mechanical reliability and chemical stability, crucial for successful bone regeneration. Various shape control and surface modification techniques to enhance biological activity have been developed. Despite the crucial importance of the collagen/apatite bone microstructure for mechanical function, antimicrobial properties, and biocompatibility, precise and versatile pattern control for regenerating the microstructure remains challenging. Here, we developed a novel osteogenic tailoring stripe-micropatterned MPC-Ti substrate that induces genetic-level control of oriented bone matrix organization. This biomaterial was created by micropatterning 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer onto a titanium (Ti) surface through a selective photoreaction. The stripe-micropatterned MPC-Ti substrate establishes a distinct interface for cell adhesion, robustly inducing osteoblast cytoskeleton alignment through actin cytoskeletal alignment, and facilitating the formation of a bone-mimicking-oriented collagen/apatite tissue. Moreover, our study revealed that this bone alignment process is promoted through the activation of the Wnt/β-catenin signaling pathway, which is triggered by nuclear deformation induced by strong cellular alignment guidance. This innovative material is essential for personalized next-generation medical devices, offering high customizability and active restoration of the bone microstructure. STATEMENT OF SIGNIFICANCE: This study demonstrates a novel osteogenic tailoring stripe-micropatterned MPC-Ti substrate that induces osteoblast alignment and bone matrix orientation based on genetic mechanism. By employing a light-reactive MPC polymer, we successfully micropatterned the titanium surface, creating a biomaterial that stimulates unidirectional osteoblast alignment and enhances the formation of natural bone-mimetic anisotropic microstructures. The innovative approach of regulating cell adhesion and cytoskeletal alignment activates the Wnt/β-catenin signaling pathway, crucial for both bone differentiation and orientation. This study presents the first biomaterial that artificially induces the construction of mechanically superior anisotropic bone tissue, and it is expected to promote functional bone regeneration by enhancing bone differentiation and orientation-targeting both the quantity and quality of bone tissue.

Impaired Bone Tissue Quality Associated with Inflammation in HIV-Immunological Non-Responders: A Cross-Sectional Analysis.

People with HIV (PWH) with poor immune response despite adequate antiretroviral treatment (ART) are susceptible to non-AIDS-related health issues. This study seeks to evaluate bone quality in Immunological Non-Responders (INRs) in comparison to those with proper immune response (IRs) using in vivo microindentation to quantify bone quality, in addition to conventional bone mineral density (BMD) evaluations. A cross-sectional study was conducted at Hospital del Mar in Barcelona from January 2019 to June 2023. Participants were matched in a 1:2-ratio (INRs:IR) based on age, sex, body mass index (BMI), and ART. Participants underwent bone quality assessment using in vivo microindentation, BMD and analysis of bone turnover and inflammation markers. Statistical analyses involved multivariable regression to adjust for potential confounding variables. A total of 159 PWH were included, 53 INRs and 106 IRs. INRs had worse bone quality, with lower median Bone Material Strength index (BMSi) compared to IRs (79 (76-87) vs. 86 (82-89); p<0.001), and similar BMD. INRs shown increased high-sensitive C-Reactive Protein levels with lower 25-(OH)-Vitamin D3. A significant negative correlation between inflammation and bone quality was found, especially noticeable in INRs. Multivariable linear regression shown that INR status is a major predictor of decreased bone quality, regardless of conventional risk factors. INRs condition is significantly associated with higher inflammatory levels, which may contribute to a deleterious effect on bone quality as measured by in vivo microindentation. Further studies are needed to confirm these results and to focus on non-AIDS comorbidities in this subgroup of PWH.

The cemented stem in hip arthroplasty - state of the art technique and recommendations.

The indication for femoral stem cementation should be made on a patient-specific basis, taking physical activity, femoral geometry, and bone tissue quality into account. Age alone should not be the sole justification for cementation. The Dorr classification can serve as decision support for whether a cemented fixation should be used. Femoral neck fractures should generally be cemented. Familiarize yourself with the applied stem philosophy. Force-closed stems typically have a polished surface that allows for subsidence, especially in the first 2 years postoperatively. Stems following the shape-closed philosophy have rougher surfaces and do not allow subsidence. There are various types of cement that differ in viscosity and can be categorized accordingly. These cement types go through four temperature-dependent phases: mixing phase, waiting phase, working phase, and curing phase. Rough implants should be implanted quickly, using wetter cement. For a polished stem, the cement should be slightly firmer. To avoid complications like bone cement implantation syndrome, it is essential to adhere to the state-of-the-art retrograde cementation technique, which recommends pulsatile lavage and vacuum mixing of the cement. Additionally, cement restrictors and pressurizers are used. A thorough understanding of cementation techniques is crucial to ensure a favorable outcome with a uniformly thick cement mantle that encompasses the entire stem. Incorrect cementing can lead to the premature failure of the endoprosthesis.

Endoscopic and percutaneous denervation of facet joints in the treatment of patients with degenerative lumbar deformities: comparative analysis

Background. At present, degenerative lumbar scoliosis is considered as the severest form of degenerative diseases of the spine. As a rule, it occurs at the final stage of the disease development. Advanced age of the patients, high comorbidity and poor bone tissue quality increase risk of complications development at any stage of the treatment. All things considered, the majority of specialists continue their search for minimally invasive surgeries able to improve the life quality of patients with such pathology. Aim of the study — comparative analysis of the surgical treatment results of patients with degenerative lumbar deformities operated using percutaneous and endoscopic denervation techniques. Methods. The study enrolled 58 patients: 42 (72.4%) women and 16 (27.6%) men. Median age accounted for 64 (60-69) years, minimum follow-up period — 2 years. In 28 cases, we performed endoscopic denervation of the lumbar facet joints at the apex of the deformity on both sides (group A), in 30 cases — percutaneous radiofrequency denervation in the appropriate volume (group В). Evaluation of the treatment effectiveness was based on the dynamics of pain syndrome (VAS), patients’ quality of life (ODI), as well as on the frequency of complications and repeated surgical interventions. Results. Mean operative duration and radiation exposure were significantly higher in endoscopic intervention (p0.001). Group A showed an earlier reduction in back pain syndrome compared to group B (p0.001). Assessment of patients’ life quality by ODI showed a high degree of correlation with the level of back pain syndrome. Significant complications of the surgical treatment were not revealed in any patient of both groups. Repeated denervation was performed during the two-year follow-up period in 18 patients (60%) of group B and in 2 patients (7.1%) of group A (p0.001). Analysis of the factors associated with the efficacy of percutaneous denervation showed the significance of deformation magnitude in the frontal plane. Efficiency of percutaneous treatment decreased at the deformity value of 30° and more with a sensitivity of 77% and specificity of 67%. Conclusions. A more pronounced decrease in the intensity of back pain syndrome with preservation of the effect during the whole period of follow-up was noted in patients after endoscopic denervation. However, this was accompanied by a longer duration of intervention and radiation load. According to our data, low efficacy of percutaneous denervation is due to the use of this technique in patients with severe deformity of the lumbar spine.

Anti-inflammatory, antiosteoporotic, and bone protective effect of hydroxysafflor yellow A against glucocorticoid-induced osteoporosis in rats.

Osteoporosis is a common condition worldwide, affecting millions of people. Women are more commonly affected than men, and the risk increases with age. Inflammatory reaction plays a crucial role in the expansion of osteoporosis. Osteoporosis is characterized by a gradual decline in bone density and bone tissue quality, which increases fragility and raises the risk of fractures. We scrutinized the anti-osteoporosis effect of hydroxysafflor yellow A (HYA) against glucocorticoid-induced osteoporosis (GIOP) in rats. In-silico study was carried out on EGFR receptor (PDBID: 1m17), Estrogen Alpha (PDB id: 2IOG), MTOR (PDB id: 4FA6), RANKL (PDB id: 1S55), and VEGFR2 (PDB id: 1YWN) protein. For this investigation, Sprague-Dawley (SD) rats were used, and they received an oral dose of HYA (5, 10, and 20 mg/kg, b.w.) along with a subcutaneous injection of dexamethasone (0.1 mg/kg/day) to induce osteoporosis. The biomechanical, bone parameters, antioxidant, cytokines, inflammatory, nutrients, hormones, and urine parameters were estimated. HYA treatment significantly suppressed the body weight and altered the organ weight. HYA treatment remarkably suppressed the level of alkaline phosphatase, acid phosphatase, and improved the level of bone mineral density (total, proximal, mild, and dis). HYA treatment restored the level of calcium (Ca), phosphorus (P), estradiol (E2), and parathyroid hormone near to the normal level. HYA treatment remarkably altered the level of biomechanical parameters, antioxidant, cytokines, urine, and inflammatory parameters. HYA treatment altered the level of osteoprotegerin (OPG), receptor activator of nuclear factor kappa beta (RANKL) and RANKL/OPG ratio. The result clearly showed the anti-osteoporosis effect of HYA against GIOP-induced osteoporosis in rats via alteration of antioxidant, cytokines, inflammatory, and bone protective parameters.

Technical and Biological Reliability of pQCT Measured Bone and Muscle Tissue Quality Across the Age-Span

Introduction: Reliable peripheral quantitative computed tomography (pQCT) assessment is essential to the accurate longitudinal reporting of bone and muscle quality. However, the between-day reliability of pQCT and the influence of age on outcome reliability is currently unknown.Objective: To quantify the same- and between-day reliability of morphological pQCT at proximal and distal segments of the forearm, shank, and thigh, and explore the influence of participant body size, age, and sex on outcome reliability.Methods: Men and women (49 % female, 18-85 years, n=72-86) completed two consecutive-day pQCT testing sessions, where repeat measurements were conducted on day-one for technical error, and between-day for biological error quantification. Testing was undertaken following best practice body composition testing guidance, including standardized presentation and consistent time-of-day.Results: All measurements of bone were classified as having ‘good’ to ‘excellent’ reliability [intraclass correlation coefficient (r=0.786- 0.999], as were measurements of muscle area (ICC r=0.991-0.999) and total fat (r=0.996-0.999). However, between- and same-day muscle density measurements at the thigh and forearm were classified as ‘poor’ (r=0.476) and ‘moderate’ (r=0.622), respectively. Likewise, intramuscular fat area at the thigh was classified as ‘moderate’ (r=0.737) for between-day measurement. Biological error was inflated compared to technical error by an average of 0.4 % for most measurements. Error values tended to increase proportionally with the amount of tissue quantified and males had significantly greater biological error for measurement of distal tibial bone (p<0.002) and trabecular area (p<0.002). Biological error was inflated among older adults for measurement of forearm muscle density (p<0.002).Conclusions: Most pQCT outcomes can be implemented with confidence, especially outcomes that assess bone area and density at any of the radial, tibial, and femoral sites investigated herein. However, it is important to account for the influence of biological measurement error in further studies, especially for muscle and intramuscular fat outcomes derived by pQCT.

Bone turnover markers and muscle decay indicator in patients with proximal femur fracture - a case-control study.

Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the injury. Handy and readily accessible biochemical tests would be useful to assess the musculoskeletal system condition in daily practice. The aim of the study was to determine whether there is any relation between muscle decay and fracture of the proximal femur and to assess bone quality in elderly patients. In the study 22 patients who represented the treatment group were hospitalized due to proximal femur fracture. Eighteen patients from the control group with no fracture in their history were admitted to the Internal Medicine Department. Anyone treated for osteoporosis, immune disease affecting protein balance, neoplasm, mental illness, heart failure, or myocardial infarction was excluded from the study. In every case a blood sample from an elbow vein was drawn, collected in EDTA-K2 tubes, and then centrifuged to separate plasma from the whole blood. Subsequently, the concentrations of C-terminal cross-linked telopeptide of type I collagen (CTX-I), sex hormone binding globulin (SHBG) and creatine kinase (CK) in plasma were determined using commercial enzyme-linked immunosorbent assays. The CK plasma concentration differed between the patient groups (p = 0.011). The SHBG plasma concentration was significantly higher in the treatment group (p = 0.006), whereas a slight difference in CTX-I plasma concentration between the groups was found (p = 0.038). No significant correlations between plasma CK, SHBG or CTX-I were found (p > 0.05). Creatine kinase is actually not an appropriate marker for the clinical assessment of muscle tissue quality in patients with or at risk of proximal femur fracture. Analyzing the quality of bone tissue, we can conclude it was poorer in patients with proximal femur fracture than in the control group.

Special aspects of total hip arthroplasty in patients with proximal femur pseudarthrosis

IntroductionThe rate of proximal femur fractures (PFF) in the structure of musculoskeletal system injuries among all fractures of long bones ranges from 3.9 to 18%. According to Russian Ministry of Health 2020 data, the incidence of femoral fractures in Russia was up to 61 cases per 100,000 population (90,000 per year); and femoral neck fractures incidence was 4 times higher among people over 75 years of age. The choice of surgical technique and the fixator used depend on many factors, such as fracture location and its nature, the age of the patient, comorbidities, and the quality of bone tissue. Internal osteosynthesis, is the current treatment method of choice for extra-articular proximal femur fracture, but every treatment method has its limitations. a significant number of complications caused by technical errors, vicious union or nonunion with the subsequent development of false joints, the development of femoral head aseptic necrosis, which leads to coxarthrosis and persistent pain syndrome. To solve the above-described problems, it is necessary to use a conversion surgery - total hip replacement. Objectiveslong-term analysis of the results of total hip replacement in patients with proximal femur pseudarthrosis. MethodsThe study was based on clinical and laboratory data analysis and on the results of total hip arthroplasty (THA) in 45 patients aged 56–84 years (mean age 68.3), including 32 (71.1%) women and 13 (26.1%) men. 12 patients initially received conservative treatment, and 33 patients received initial surgical treatment using various metal osteosynthesis procedures. The time from osteosynthesis or from the moment of injury to admission to the hospital for hip arthroplasty ranged from 12 to 30 months. All patients, before conversion arthroplasty and after discharge, were repeatedly invited to the clinical diagnostic department for a clinical examination and for assessment using rating scales. 3, 6 and 12 months after the surgery, pain syndrome and patient quality of life were assessed using the following questionnaire scales: Harris Hip Score, MOS SF-36, VAS. The maximum follow-up period ranged from 12 to 60 months. ResultsBased on the results obtained, patients of all 4 groups after conversion arthroplasty noted a significant quality of life improvement, a decrease in pain severity and functional results improvement. This was probably due to the presence of a severe limitation of range of movements in the joint, intense pain, absence of support ability of the extremity, as well as low operative efficacy expectations.In 1 (2%) patient, acute PJI was diagnosed in the early postoperative period, followed by sepsis and death.In 4 patients (9%) the result was considered unsatisfactory. At 1 year of follow-up after surgery, they complained of pain and claudication in the operated joint.3 (6%) patients underwent reduction of dislocation. ConclusionsStrict adherence to the recommended treatment algorithm for patients with proximal femur pseudarthrosis made it possible to achieve good treatment results in 90% of surgically treated patients. An important step in the treatment of this patients is a careful preoperative planning with thorough assessment of bone tissue quality and muscles condition in the proximal femur area, allowing to choose the optimal endoprosthesis components.

Metals accumulation affects bone and muscle in osteoporotic patients: A pilot study

Osteoporosis is the most common bone disease, characterized by decreased bone mineral density (BMD) and often associated to decreased muscle mass and function. Metal exposure plays a role in the pathophysiology of osteoporosis and affects also muscle quality. The aim of this study was to assess the association between metal levels in bone and muscle samples and the degeneration of these tissues. A total of 58 subjects (30 male and 28 female) was enrolled and classified in osteoporotic (OP, n = 8), osteopenic (Ope, n = 30) and healthy (CTR, n = 20) subjects, according to BMD measures. Femoral head bone samples and vastus lateralis muscle samples were collected during hip arthroplasty surgeries. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed increased levels of Al, Cd and Pb in OP and Ope bone tissue compared to CTR subjects (p = 0.04, p = 0.005 and p = 0.01, respectively). Whereas, increased levels of Co, Cd and Pb were measured in OP and Ope muscle tissues, compared to CTRs (p < 0.001, p = 0.02 and p = 0.01, respectively). In addition, Al, Cd and Pb levels in bone and Cd and Co levels in muscle were negatively correlated with BMD. A negative association among Co, Cd, Cr and Hg levels and muscle fibers diameter was also observed in muscle tissues. This study assessed that metal exposure can affects bone and muscle tissue quality and may contribute to the onset and progression of musculoskeletal diseases such as osteoporosis. Therefore, it is important to implement metal exposure assessment and their impact on disease development, in order to manage and prevent metal accumulation effects on bone and muscle quality.

THE IMPACT OF METABOLISM DYSREGULATION IN SCAFFOLD-GUIDED LARGE-VOLUME BONE REGENERATION

The ability of the body to constantly maintain metabolism homeostasis while fulling the heightened energy and macromolecule demand is crucial to ensure successful tissue healing outcomes. Studies investigating the local metabolic environment during healing are scarce to date. Here, using Type 2 Diabetes (T2D) as a study model, we investigate the impact of metabolism dysregulation on scaffold-guided large-volume bone regeneration. Our study treated wild-type or T2D rats with 5 mm critical-sized femoral defects with 3D-printed polycaprolactone (PCL) scaffolds with 70% porosity. Metabolomics was leveraged for a holistic view of metabolism alteration as healing progress and correlated to regenerated bone tissue volume and quality assessed using micro-computed tomography (µ-CT), histology, and immunohistology. Semi-targeted metabolomics analysis indicated dysregulation in the glycolysis and TCA cycle – the main energy production pathways, in T2D compared to healthy animals. The abundance of metabolites substrates, i.e., amino acids – for protein/ extracellular matrix synthesis was also affected in T2D. Tissue-level metabolites observations aligned with morphological observation with less newly formed bone observed in T2D than wild-type rats. This study enlightens the metabolism landscape during scaffold-guided large-volume bone regeneration in wild-type vs. T2D to further guide the personalization of the scaffold to drive successful regeneration.

The Role of Traditional Chinese Medicines in the Treatment of Osteoporosis.

Osteoporosis (OP) represents a substantial public health issue and is associated with increasing rates of morbidity and mortality. It is characterized by reduced bone mineral density, deterioration of bone tissue quality, disruption of the microarchitecture of bones, and compromised bone strength. These changes may be attributed to the following factors: intercellular communication between osteoblasts and osteoclasts; imbalanced bone remodeling; imbalances between osteogenesis and adipogenesis; imbalances in hormonal regulation; angiogenesis; chronic inflammation; oxidative stress; and intestinal microbiota imbalances. Treating a single aspect of the disease is insufficient to address its multifaceted nature. In recent decades, traditional Chinese medicine (TCM) has shown great potential in the treatment of OP, and the therapeutic effects of Chinese patent drugs and Chinese medicinal herbs have been scientifically proven. TCMs, which contain multiple components, can target the diverse pathogeneses of OP through a multitargeted approach. Herbs such as XLGB, JTG, GSB, Yinyanghuo, Gusuibu, Buguzhi, and Nvzhenzi are among the TCMs that can be used to treat OP and have demonstrated promising effects in this context. They exert their therapeutic effects by targeting various pathways involved in bone metabolism. These TCMs balance the activity of osteoblasts (bone-forming cells) and osteoclasts (bone-resorbing cells), and they exhibit anti-inflammatory, immunomodulatory, anti-oxidative, and estrogen-like functions. These multifaceted mechanisms underlie the efficacy of these herbs in the management and treatment of OP. Herein, we examine the efficacy of various Chinese herbs and Chinese patent drugs in treating OP by reviewing previous clinical trials and basic experiments, and we examine the potential mechanism of these therapies to provide evidence regarding the use of TCM for treating OP.

Analysis of Bone Mineral Density, Bone Tissue Quality Index (TBS) and Salt Transport in Patients with Nephrolithiasis

The objective: to determine the bone mineral density (BMD), bone tissue quality index (TBS) and to analyze the salt transport in patients with and without urolithiasis. Materials and methods. For qualitatively assess of crystalluria, a study of salt transport was conducted. Evaluation of the structural and functional state of bone tissue was performed on the basis of the Ukrainian Osteoporosis Center of the State University “Institute of Gerontology named after D. F. Chebotareva of National Academy of Sciences of Ukraine” by X-ray absorptiometry of the “Hologic Discovery” apparatus. 80 persons (15 men and 65 women) were included in the study, the average age of the patients was 58 years. Study participants were divided into two groups depending on the presence of urolithiasis. I group (n=32) included patients without urolithiasis with somatic diseases in the remission stage, who had no signs of exclusion criteria. Osteoporosis was diagnosed in 9 (28.1%) women of this group. Patients with urolithiasis were included in the II group (n=48). Osteoporosis was diagnosed in 18 (37.5%) women and 3 (6.25%) men in this group. Results. It was established that 21 (26.2%) patients had BMD within the normal range, 29 (36.3%) patients had BMD abnormalities within the limits of osteopenia, and 30 (37.6%) patients had osteoporosis, namely: 27 (33.8%) women and 3 (3.8%) men. Analysis of BMD status demonstrated that normal densitometric values were comparable in both groups (31.2% without urolithiasis and 22.9% patients with nephrolithiasis; p&gt;0.05). The incidence of osteopenia in patients with urolithiasis (33.3%) and without urolithiasis (40.7%) and the number of cases of detected osteoporosis also did not significantly differ (43.8% and 28.1%, respectively; p&gt;0.05). During X-ray absorptiometry it was found that the TBS bone quality index was significantly lower in patients with urolithiasis (p&lt;0.05). A comparative analysis of salt transport demonstrated that blood uric acid levels in patients with urolithiasis were significantly higher (p=0.02) than those in patients without nephrolithiasis. Conclusions. The results of the study indicate the need for ultrasound examination of the kidneys and salt transport when checking BMD in patients at risk of osteoporosis for early diagnosis of nephrolithiasis and correction of crystalluria. Since a decrease in TBS even with a normal BMD is also an increased risk factor for bone fractures, its timely identification and correction are extremely important in patients with nephrolithiasis. The obtained data indicate the need to conduct a correlational analysis of risk factors in the group of patients with nephrolithiasis, in particular, the influence of the state of the bone system, the TBS indicator and crystalluria.

Pertimbangan pemasangan implan gigi pada pasien lanjut usia

Background: The elderly population is a group of people who are vulnerable have tooth loss so it is common to use of dental implant for replace it. Unfortunately, decreased function and changes in the condition of the tissues of the oral cavity and alveolar bones due to the aging process are often make installation of implant more complicated. Futhermore, in the elderly often found systemic diseases such as hypertension, diabetes mellitus, osteoporosis or cardiovascular diseases that affect the installation of implants. But if the quality and quantity of alveolar bone and soft tissue are adequate accompanied by a healthy elderly condition, it is possible that implant placement will be succesfull.&#x0D; Case Report: A 69-years-old male patient attended a clinic to replace his missing right lower teeth with permanent denture. After undergoing several examinations, it was decided to perform dental implant on tooth 46, diameter 3.8 mm and length 10.5 mm with a cemented-screw type PFM crown. The implant and PFM crown were successfully placed in tooth 46 and patients were comfortable with the implant without any complaints of pain.&#x0D; Conclusion: chronological age by itself is suggested as one of the risk factors for success, but it would not be a contraindication as long as the condition of the alveolar bone is adequate and systemic disease is well controlled.

Factors affecting chicken bone strength

Purpose: to study the accumulated data on the genetic determinism of the Kostyak fortress and discuss the possibility of their use to improve poultry farming.In both meat-type and egg-type poultry, bone strength is an important characteristic of animal welfare, on which largely depends the economic efficiency. The lack of strength is expressed by bone fragility, deformations or fractures occurring both at certain technologies of animal housing and at processing of poultry products, which is accompanied by economic losses. The quality and strength of bone tissue is formed, in addition to housing conditions, by a complex set of interactions of structural, physiological, nutritional and architectural components. The study of poultry bone strength is also complicated by reproduction peculiarities. Egg laying determines some features of osteogenesis, including medullary bone formation, which deposit calcium for eggshell formation. To date, the actual assessment of bone strength occurs postmortem, by measuring bone mineral density and breaking strength. Both methods do not allow using the evaluated animals in breeding to improve bone strength, therefore the study of genetic determinants of this trait is a relevant research task. The use of modern information analysis based on DNA technologies is a necessary step for identification of candidate genes controlling bone strength, because of their ability to increase selection efficiency in poultry. This review discusses the available results of genome-wide association studies (GWAS) for bone strength in birds, as well as existing data on the relationship of bone strength with traits such as egg production and age at first lay.

Toward the use of MRI measurements of bound and pore water in fracture risk assessment.

The current clinical assessment of fracture risk lacks information about the inherent quality of a person's bone tissue. Working toward an imaging-based approach to quantify both a bone tissue quality marker (tissue hydration as water bound to the matrix) and a bone microstructure marker (porosity as water in pores), we hypothesized that the concentrations of bound water (Cbw) are lower and concentrations of pore water (Cpw) are higher in patients with osteoporosis (OP) than in age- and sex-matched adults without the disease. Using recent developments in ultrashort echo time (UTE) magnetic resonance imaging (MRI), maps of Cbw and Cpw were acquired from the uninjured distal third radius (Study 1) of 20 patients who experienced a fragility fracture of the distal radius (Fx) and 20 healthy controls (Non-Fx) and from the tibia mid-diaphysis (Study 2) of 30 women with clinical OP (low T-scores) and 15 women without OP (normal T-scores). In Study 1, Cbw was significantly lower (p=0.0018) and Cpw was higher (p=0.0022) in the Fx than in the Non-Fx group. In forward stepwise, logistic regression models using Bayesian Information Criterion for selecting the best set of predictors (from imaging parameters, age, BMI, and DXA scanner type), the area-under-the-receiver operator characteristics-curve (AUC with 95% confidence intervals) was 0.73 (0.56, 0.86) for hip aBMD (best predictors without MRI) and 0.86 (0.70, 0.95) for the combination of Cbw and Cpw (best predictors overall). In Study 2, Cbw was significantly lower (p=0.0005) in women with OP (23.8±4.3 1H mol/L) than in women without OP (29.9±6.4 1H mol/L); Cpw was significantly higher by estimate of 2.9 1H mol/L (p=0.0298) with clinical OP, but only when accounting for the type of UTE-MRI scan with 3D providing higher values than 2D (p<0.0001). Lastly, Cbw, but not Cpw, was sensitive to bone forming osteoporosis medications over 12-months. UTE-MRI-derived measurements of bound and pore water concentrations are potential, aBMD-independent predictors of fracture risk.

Склеростин-залежні механізми формування остеопорозу у хворих цукровим діабетом 2 типу та ожирінням

при обстеженні 103 пацієнтів на цукровий діабет 2 типу (ЦД), що у 83 випадкахперебігав на тлі збільшеної маси тіла або ожиріння, було встановлено вірогідне збільшеннявмісту склеростину у сироватці крові, яке мало пряму кореляційну залежність з індексоммаси тіла. Висловлено припущення, що зміни даного глікопротеїну, який входить до групиантагоністів кісткових морфогенетичних білків, відбуваються внаслідок багатьох процесів ворганізмі: збільшення синтезу ФНП-α адипоцитами, ендотелієм судин, клітинами нейроглії натлі пре- та менопаузи, що сприяє порушенню мінеральної щільності кісткової тканини, тобтоформуванню остеопорозу. Ендокринний остеопороз становить найбільшу групу вторинногоостеопорозу, провідною причиною якого є цукровий діабет 2 типу. В разі наявності ЦД 2 типу,який перебігає на тлі ожиріння, формуються умови до розвитку остеопоротичних станів, одниміз механізмів розвитку яких може виступати глікопротеїн склеростин. Метою дослідженнястало визначення структурно-функціонального стану кісткової тканини шляхом дослідженнявмісту склеростину у хворих на цукровий діабет 2 типу, що перебігає на тлі топографічнихособливостей розподілу жирової тканини. До роботи було залучено 103 хворих на ЦД 2 типу,який у 83 випадках перебігав в поєднанні з надлишковою вагою або ожирінням (основна група). Догрупи порівняння увійшло 20 хворих на ЦД 2 типу, що був діагностований у пацієнтів з незмінениміндексом маси тіла (ІМТ). Вік хворих коливався від 31 до 55 років та в середньому по групах складав43±4,6 років та 44,1±2,1 роки відповідно. В обох групах хворих переважали чоловіки 44 (53%) та11 (55%) осіб. Тривалість захворювання реєструвалась в межах від 1 до 13 років. Визначеннярозподілу жирової тканини в організмі досліджували за допомогою ваг для характеристикискладу тіла - OMRON BF511 (Японія). Ідентифікували вміст вісцеральної жирової тканини(ВЖТ) та підшкірної жирової тканини (ПЖТ). Активність склеростину в сироватці крові&#x0D; визначали імуноферментним методом з використанням комерційних тест-систем «Biomedi-ca» (США) згідно інструкції на імуноферментному аналізаторі «Labline-90» (Австрія). Обробку&#x0D; отриманих даних здійснювали методом варіаційної статистики за допомогою ліцензійногопрограмного забезпечення Stata 10 («StatSoft Inc.», США). Перевірка на нормальність розподілуданих виконувалася за допомогою критерію Шапіро-Уілка. Для параметрів з нормальнимрозподілом розраховували середню величину (M) ± стандартну помилку середньої (m). Отриманірезультати розглядалися як статистично значущі при p&lt;0,05. В результаті було визначено, щозбільшення ІМТ супроводжувалось підвищенням показника склеростину. Тобто, виявлені зміниглікопротеїну, який входить до групи антагоністів кісткових морфогенетичних білків, дають змогу припустити порушення процесу диференціації остеобластів. Тобто, як ЦД 2 типу, такі кількісна зміна жирової тканини з її перерозподілом, негативно впливають на метаболізмкісткової тканини. Так, перебіг цукрового діабету супроводжується збільшенням активностіпрозапальних цитокінів, а саме, ФНП-α – складового цитокінового каскаду жирової тканини.Цей феномен також пов’язують із залученням до процесу судин (ендотеліальні клітинипродукують даний цитокін), нервової тканини (залучення клітин нейроглії) та метаболічнимизсувами в організмі. Окрім того F.Xu та співавт. в експерименті доведено, що остеокластогенезпригнічується при гіперглікемічних та гіперінсулінемічних станах. Тобто, у хворих на ЦД призбільшенні ІМТ складається негативний «тандем» через додаткове надходження з багатьохклітин ФНП-α та збільшення синтезу склеростину, що не тільки «запускає» процес порушеннямінеральної щільності кісткової тканини (МЩКТ), але й підтримує його впродовж всьогоперебігу захворювання. Також певна роль відводиться віковому аспекту обстежених хворихна ЦД (середній вік менопаузи у здорових жінок нашої країни становить 45 років), що такожсприяє пригніченню кісткового метаболізму. В такому разі збільшення активності склеростинув поєднанні з негативним фоном (ожиріння, період менопаузи) можна розглядати як один ізмеханізмів формування остеопоротичних змін. При цьому поєднуються механізми первинного тавторинного ОП, що посилює і прискорює процес порушення архітектоніки кістки. Тому можназробити висновки, що у хворих на цукровий діабет 2 типу у поєднанні з ожирінням виникаютьумови до зниження якості кісткової тканини через уповільнення кісткового метаболізму, щосприяє формуванню остеопоротичних станів.

Trabecular Bone Microarchitecture Evaluation in an Osteoporosis Mouse Model.

Bone microstructure refers to the arrangement and quality of bone tissue at the microscopic level. Understanding the bone microstructure of the skeleton is crucial for gaining insight into the pathophysiology of osteoporosis and improving its treatment. However, handling bone samples can be complex due to their hard and dense properties. Secondly, specialized software makes image processing and analysis difficult. In this protocol, we present a cost-effective and easy-to-use solution for trabecular bone microstructure analysis. Detailed steps and precautions are provided. Micro-CT is a non-destructive three-dimensional (3D) imaging technique that provides high-resolution images of trabecular bone structure. It allows for the objective and quantitative evaluation of bone quality, which is why it is widely regarded as the gold standard method for bone quality assessment. However, histomorphometry remains indispensable as it offers crucial cellular-level parameters, bridging the gap between two-dimensional (2D) and 3D assessments of bone specimens. As for the histologic techniques, we chose to decalcify the bone tissue and then perform traditional paraffin embedding. In summary, combining these two methods can provide more comprehensive and accurate information on bone microstructure.

CHANGES IN THE DENSITY AND COMPOSITION OF BONE TISSUE AND ALVEOLAR BONE ATROPHY IN RATS WITH HYPOTHIREOSIS AND CORRECTION WITH A COMPLEX OF MINERALS AND VITAMINS

Problem. For diseases of the thyroid gland, it is advisable to use hormone replacement therapy. However, numerous consequences of an overdose of L‑thyroxine drugs are known. The use of a preventive complex based on minerals, vitamins and quercetin can be an alternative to replacement therapy for correcting the consequences of disorders of the musculoskeletal system in thyroid diseases. Goal. The purpose of the work is an experimental study of the osteoprotective effectiveness of a complex of vitamins and minerals in rats with hypothyroidism. Method. In the experiment, 36 rats were used, which were divided into three groups: 12 intact, 12 animals that were simulated with hypothyroidism, and 12 rats that, against the background of hypothyroidism, were administered a preventive complex daily. The experiment on modeling hypothyroidism and its prevention lasted 4 months. Mandibles, lumbar vertebrae and femurs of rats of both sexes were isolated. Morphometric parameters were studied in vertebrae and femurs: density, content of mineral and organic components of bone tissue. The degree of atrophy of the alveolar process was determined in the jaws of the animals. Main results. Modeling hypothyroidism in rats caused a significant decrease in femoral bone density in males by 2.2% and in females by 1.7%, had no effect on lumbar vertebral density, and significantly increased alveolar process atrophy in males by 22.2% and in females by 15. 8%. The decrease in the density of the femur bone was due to a decrease in the content of the mineral component of bone tissue by 4.5–7.2%. The use of a preventive complex containing vitamins, minerals and quercetin led to an increase in the density of femurs to the level of healthy animals, increased the density of the lumbar vertebrae by 2.2–3.1%, and reduced atrophy of the alveolar process of the jaws in females by 21.5% and in males by 31.4%. Deterioration of the quality of bone tissue in thyroid insufficiency, as well as the osteotropic effectiveness of the prophylactic complex in conditions of hypothyroidism, were more pronounced in males. Conclusions. The conducted studies showed the development of dystrophic processes in the jaws and femurs of rats against the background of a deficiency of thyroid hormones and the positive effect of a complex of vitamins and minerals, which effectively stopped the atrophy of the alveolar process of the jaws and the decrease in the density of the femurs, and also increased the density of the lumbar vertebrae of rats with hypothyroidism.

Changes in Bone Quality after Treatment with Etelcalcetide.

Secondary hyperparathyroidism is associated with osteoporosis and fractures. Etelcalcetide is an intravenous calcimimetic for the control of hyperparathyroidism in patients on hemodialysis. Effects of etelcalcetide on the skeleton are unknown. In a single-arm, open-label, 36-week prospective trial, we hypothesized that etelcalcetide improves bone quality and strength without damaging bone-tissue quality. Participants were 18 years or older, on hemodialysis ≥1 year, without calcimimetic exposure within 12 weeks of enrollment. We measured pretreatment and post-treatment areal bone mineral density by dual-energy X-ray absorptiometry, central skeleton trabecular microarchitecture by trabecular bone score, and peripheral skeleton volumetric bone density, geometry, microarchitecture, and estimated strength by high-resolution peripheral quantitative computed tomography. Bone-tissue quality was assessed using quadruple-label bone biopsy in a subset of patients. Paired t tests were used in our analysis. Twenty-two participants were enrolled; 13 completed follow-up (mean±SD age 51±14 years, 53% male, and 15% White). Five underwent bone biopsy (mean±SD age 52±16 years and 80% female). Over 36 weeks, parathyroid hormone levels declined 67%±9% ( P < 0.001); areal bone mineral density at the spine, femoral neck, and total hip increased 3%±1%, 7%±2%, and 3%±1%, respectively ( P < 0.05); spine trabecular bone score increased 10%±2% ( P < 0.001); and radius stiffness and failure load trended to a 7%±4% ( P = 0.05) and 6%±4% increase ( P = 0.06), respectively. Bone biopsy demonstrated a decreased bone formation rate (mean difference -25±4 µ m 3 / µ m 2 per year; P < 0.01). Treatment with etelcalcetide for 36 weeks was associated with improvements in central skeleton areal bone mineral density and trabecular quality and lowered bone turnover without affecting bone material properties. The Effect of Etelcalcetide on CKD-MBD (Parsabiv-MBD), NCT03960437.

Lipid Peroxidation as a Possible Factor Affecting Bone Resorption in Obese Subjects-Preliminary Research.

Oxidative stress, which promotes bone catabolism, also affects the quality of bone tissue. We aimed to assess the impact of metabolic disorders and oxidant-antioxidant imbalance associated with primary obesity on bone resorption and formation processes. Anthropometric parameters, metabolic variables, oxidative stress indicators (malondialdehyde, vitamins A and E, uric acid, superoxide dismutase, catalase, glutathione peroxidase, type 1 paraoxonase, iron-reducing plasma antioxidant power) and markers of bone turnover (type I procollagen N-terminal propeptide and the type I collagen C-terminal cross-linked telopeptide; P1NP and CTX) were assessed in 108 Polish participants. Under the influence of oxidative stress, both enzymatic and non-enzymatic defense mechanisms were stimulated in obese subjects, especially in women, who had increased lipid peroxidation and activity of catalase (particularly in first-degree obesity) and decreased vitamin E concentration. The process of lipid peroxidation, as well as the weakening of the bone formation, was strongly manifested in women at a BMI range of 35.0-39.9 kg/m2 but not at BMI > 40.0 kg/m2, but it had a comprehensive negative impact on bone turnover in obese men. Obesity and its degree of advancement significantly affected the decrease in the concentration of the marker of bone formation-P1NP-only in the plasma of women. Excessive body weight had no effect on the value of the bone resorption marker in plasma, regardless of gender. Our results confirm the existence of the "obesity paradox" in the aspect of bone tissue metabolism and suggest that a specific body weight threshold changed the molecular response of the tissue.