Osteomodulin deficiency in mice causes a specific reduction of transversal cortical bone size.

Skeletal growth, modeling and remodeling are regulated by various molecules, one of them being the recently identified osteoanabolic factor WNT1. We have previously reported that WNT1 transcriptionally activates the expression of Omd, encoding Osteomodulin (OMD), in a murine mesenchymal cell line, which potentially explained the skeletal fragility of mice with mutational WNT1 inactivation, since OMD has been shown to regulate type I collagen fibril formation in vitro. In the present study we confirmed the strong induction of Omd expression in a genome-wide expression analysis of transfected cells, and we obtained further evidence for Omd being a direct target gene of WNT1. To assess the in vivo relevance of this regulation, we crossed Omd-deficient mice with a mouse line harboring an inducible, osteoblast-specific Wnt1 transgene. After induction of Wnt1 expression for 1 or 3 weeks, the osteoanabolic potency of WNT1 was not impaired despite the Omd deficiency. Since current knowledge regarding the in vivo physiological function of OMD is limited, we next focused on skeletal phenotyping of wild-type and Omd-deficient littermates, in the absence of a Wnt1 transgene. Here we did not observe an impact of Omd deficiency on trabecular bone parameters by histomorphometry and µCT either. Importantly, however, male and female Omd-deficient mice at the ages of 12 and 24 weeks displayed a slender bone phenotype with significantly smaller long bones in the transversal dimension, while the longitudinal bone growth remained unaffected. Although mechanical testing revealed no significant changes explained by impaired bone material properties, atomic force microscopy of the femoral bone surface of Omd-deficient mice revealed moderate changes at the nanostructural level, indicating altered regulation of collagen fibril formation and aggregation. Taken together, our data demonstrate that, although OMD is dispensable for the osteoanabolic effect of WNT1, its deficiency in mice specifically modulates transversal cortical bone morphology.

We explored the physiological relevance of the protein Osteomodulin (OMD) that we previously found to be induced by the osteoanabolic molecule WNT1. While other studies have shown that OMD is involved in the regulation of collagen fibril formation in vitro, its function in vivo has not been investigated. We confirmed that OMD is directly regulated by WNT1 but surprisingly, when we bred mice lacking OMD with mice engineered to highly express WNT1, we found that the osteoanabolic effect of WNT1 was unaffected by the absence of OMD. Interestingly, mice lacking OMD did show differences in the shape of their bones, particularly in their width, despite no significant changes in bone density or length. Investigation of the bone matrix of mice lacking OMD at the nanostructural level indicated moderate differences in the organization of collagen fibrils. This study provided further insights into the effect of WNT1 on bone metabolism and highlighted a specific function of OMD in skeletal morphology.

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review.

Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.

TERT single nucleotide polymorphism rs2736098 but not rs2736100 is associated with telomere length in HIV-infected patients on cART.

BACKGROUND: Continuous application of "combination antiretroviral therapy" (cART) has transformed Human immunodeficiency virus (HIV) infection into a manageable chronic disease; however, due to lasting inflammation and cumulative toxicity, progressive pathophysiological changes do occur and potentially lead to accelerated aging, among others, contributing to telomere shortening. The single nucleotide polymorphisms (SNP) rs2736100 and rs2736098 are particularly important for human telomerase (TERT) gene expression. The objective of this study was to evaluate the effects of clinical parameters and single nucleotide polymorphisms in TERT (rs2736100 and rs2736098) on telomere length in HIV-infected patients. METHODS AND RESULTS: This cross-sectional study included 176 patients diagnosed with HIV infection. Relative telomere length (RTL) was determined by real-time polymerase chain reaction (qPCR), whereas genotyping was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis (PCR-RFLP). The mean age of the patients (p = .904), time since HIV diagnosis (p = .220), therapy-related variables such as the cART regimen (0.761), and total cART duration (p = .096) did not significantly affect RTL. TERT rs2736100 genotype showed no association with RTL. However, TERT rs2736098 heterozygotes (GA) had significantly longer telomeres (P = .049) than both homozygotes (GG and AA). CONCLUSIONS: Our findings support the fact that cellular aging in HIV-infected patients is influenced by the TERT rs2736098 polymorphism.

Improved femoral micro-architecture in adult male individuals with overweight: fracture resistance due to regional specificities.

BACKGROUND: It is still unclear whether femoral fracture risk is positively or negatively altered in individuals with overweight. Considering the lack of studies including men with overweight, this study aimed to analyze regional specificities in mechano-structural femoral properties (femoral neck and intertrochanteric region) in adult male cadavers with overweight compared to their normal-weight age-matched counterparts. METHODS: Ex-vivo osteodensitometry, micro-computed tomography, and Vickers micro-indentation testing were performed on femoral samples taken from 30 adult male cadavers, divided into the group with overweight (BMI between 25 and 30 kg/m2; n = 14; age:55 ± 16 years) and control group (BMI between 18.5 and 25 kg/m2; n = 16; age:51 ± 18 years). RESULTS: Better quality of trabecular and cortical microstructure in the inferomedial (higher trabecular bone volume fraction, trabecular thickness, and cortical thickness, coupled with reduced cortical pore diameter, p < 0.05) and superolateral femoral neck (higher trabecular number and tendency to lower cortical porosity, p = 0.043, p = 0.053, respectively) was noted in men with overweight compared to controls. Additionally, the intertrochanteric region of men with overweight had more numerous and denser trabeculae, coupled with a thicker and less porous cortex (p < 0.05). Still, substantial overweight-induced change in femoral osteodensitometry parameters and Vickers micro-hardness was not demonstrated in assessed femoral subregions (p > 0.05). CONCLUSIONS: Despite the absence of significant changes in femoral osteodensitometry, individuals with overweight had better trabecular and cortical femoral micro-architecture implying higher femoral fracture resistance. However, the microhardness was not significantly favorable in the individuals who were overweight, indicating the necessity for further research.

Age-at-death estimation based on micro-CT assessment of pubic symphysis: Potentially new methodological approach.

BACKGROUND: Although various methods for age-at-death estimation of skeletal remains are available, this is still an unsolved issue in forensic anthropology, especially concerning elderly individuals. Moreover, the lack of population-specific methods often made age-at-death estimation unreliable in other populations. AIM: Our study aimed to examine whether micro-computed tomography (micro-CT) analysis of pubic bone samples obtained from the contemporary Serbian population could be used in anthropological and forensic practice for age-at-death estimation. METHODOLOGY: This study encompassed 62 pubic samples obtained from 26 adult male and 36 adult female cadaveric donors (age range: 22-91 years). Initially, staging according to the Suchey-Brooks phases was performed by two experienced investigators, followed by micro-CT assessment of pubic bone trabecular and cortical compartments (spatial resolution of the scans was 10 µm). RESULTS: Our results revealed an age-associated decline in trabecular and cortical micro-architecture of elderly male and female individuals, with the most prominent changes present in trabecular bone volume fraction and total porosity of the anterior and posterior cortical surface of the pubic bone. Those parameters were used to generate age-at-death estimation equations. One sample t-test did not reveal a significant difference between estimated age-at-death and real (known) age-at-death in the overall sample (mean absolute error [MAE] of 4.76 years), female (MAE of 9.66 years) and male cadaveric donors (MAE of 6.10 years, p > 0.05). CONCLUSION: Our data indicated that micro-architectural features of trabecular and cortical compartments of pubic bone could potentially be applied as an additional reliable method for age-at-death estimation in the Serbian population.

Association between Combination Antiretroviral Therapy and Telomere Length in People Living with Human Immunodeficiency Virus.

Long-term exposure to combination antiretroviral therapy (cART) may be associated with accelerated ageing. Telomere length is considered to be reliable aging biomarker. The aim of this study was to compare patients' relative telomere length (RTL) between and within different cART classes and to estimate the impact of certain HIV-related variables on RTL. The study was conducted in 176 HIV-infected male patients receiving cART, with ≤50 copies HIV RNA/mL plasma. RTL was determined from mononuclear cells by quantitative polymerase chain reaction. Standard statistical tests and unsupervised machine learning were performed. The mean RTL was 2.50 ± 1.87. There was no difference (p = 0.761) in RTL between therapeutic groups: two nucleoside reverse transcriptase inhibitors as the backbone treatment, combined with either integrase inhibitor, protease inhibitor, or non-nucleoside reverse transcriptase inhibitor (NNRTI). Machine learning results suggested duration of HIV infection, CD4+ T-cell count, and cART, including NNRTI, as potentially significant variables impacting RTL. Kendall's correlation test excluded duration of HIV infection (p = 0.220) and CD4+ T-cell count (p = 0.536) as significant. The Mann-Whitney test confirmed that cART containing NNRTI impacted RTL (p = 0.018). This was the first study to show that patients using efavirenz within cART had significantly shorter telomeres than patients using nevirapine.

Testing of Different Scanning Protocols Used for Precise 3D-printing of Mandibular Models.

Multidetector computed tomography (MDCT) is often necessary to manufacture 3D-printed medical models (MMs) required for mandibular restoration due to trauma or malignant tumor. Although cone-beam computed tomography (CBCT) is a preferable method of mandibular imaging, additional scanning is often unjustified. To test whether a single radiologic protocol could be used for mandibular reconstructions, the human mandible was scanned with 6 MDCT and 2 CBCT protocols and later 3D-printed using a fused-deposition modelling technique. Then, we assessed linear measures on the mandible and compared them with MDCT/CBCT digital scans and 3D-printed MMs. Our data revealed that CBCT0.25 was the most precise protocol for manufacturing 3D-printed mandibular MMs, which is expected considering its voxel size. However, we noted that CBCT0.35 and Dental2.0H60s MDCT protocols were of comparable accuracy, indicating that this MDCT protocol could be a single radiologic protocol used to scan both donor and recipient regions required for mandibular reconstruction.

Bone loss in chronic liver diseases: Could healthy liver be a requirement for good bone health?

Given that the liver is involved in many metabolic mechanisms, it is not surprising that chronic liver disease (CLD) could have numerous complications. Secondary osteoporosis and increased bone fragility are frequently overlooked complications in CLD patients. Previous studies implied that up to one-third of these individuals meet diagnostic criteria for osteopenia or osteoporosis. Recent publications indicated that CLD-induced bone fragility depends on the etiology, duration, and stage of liver disease. Therefore, the increased fracture risk in CLD patients puts a severe socioeconomic burden on the health system and urgently requires more effective prevention, diagnosis, and treatment measures. The pathogenesis of CLD-induced bone loss is multifactorial and still insufficiently understood, especially considering the relative impact of increased bone resorption and reduced bone formation in these individuals. It is essential to note that inconsistent findings regarding bone mineral density measurement were previously reported in these individuals. Bone mineral density is widely used as the "golden standard" in the clinical assessment of bone fragility although it is not adequate to predict individual fracture risk. Therefore, microscale bone alterations (bone microstructure, mechanical properties, and cellular indices) were analyzed in CLD individuals. These studies further support the thesis that bone strength could be compromised in CLD individuals, implying that an individualized approach to fracture risk assessment and subsequent therapy is necessary for CLD patients. However, more well-designed studies are required to solve the bone fragility puzzle in CLD patients.

Hip structure analysis and femoral osteodensitometry in aged postmenopausal women with hip osteoarthritis and femoral neck fracture.

PURPOSE: Osteoarthritis (OA), osteoporosis, and bone fractures are frequent aging-related conditions. Regardless of the growing research interest in the effects of hip OA on femoral fracture risk, data about the region specificity of osteodensitometric and hip structure analysis (HSA) parameters of the proximal femora are lacking in aged postmenopausal women with hip OA compared to individuals with femoral neck fragility fracture. METHODS: This study included 76 postmenopausal women admitted for total hip arthroplasty due to non-traumatic femoral neck fracture (FN_Fx group, n = 39) and hip osteoarthritis (OA group, n = 37). RESULTS: Osteodensitometric parameters differed significantly between the OA and FN_Fx groups, depicting lower bone mineral density in the FN_Fx group (p < 0.05). The most significant increase in these parameters was registered in the intertrochanteric region of the OA group. Moreover, the OA-induced changes in HSA-derived parameters displayed significant regional heterogeneity, with the intertrochanteric region showing the most notable difference between OA and FN_Fx group. CONCLUSION: Our data may indicate that OA displayed the most prominent positive effect on the intertrochanteric femoral region, revealing the regional heterogeneity in structural geometry and biomechanical indices of proximal femora in OA individuals. Since we did not observe significant differences in the femoral neck region, we may speculate that OA does not have a substantial protective effect on the femoral neck fracture risk in aged postmenopausal women.

Micro-scale assessment of bone quality changes in adult cadaveric men with congestive hepatopathy.

Congestive hepatopathy (CH) is a chronic liver disease (CLD) caused by impaired hepatic venous blood outflow, most frequently resulting from congestive heart failure. Although it is known that heart failure and CLDs contribute to increased risk for age-related fractures, an assessment of CH-induced skeletal alterations has not been made to date. The aim of our study was to characterize changes in bone quality in adult male cadavers with pathohistologically confirmed CH compared with controls without liver disease. The anterior mid-transverse part of the fifth lumbar vertebral body was collected from 33 adult male cadavers (age range 43-89 years), divided into the CH group (n = 15) and the control group (n = 18). We evaluated trabecular and cortical micro-architecture and bone mineral content (using micro-computed tomography), bone mechanical competence (using Vickers micro-hardness tester), vertebral cellular indices (osteocyte lacunar network and bone marrow adiposity), and osteocytic sclerostin and connexin 43 expression levels (using immunohistochemistry staining and analysis). Deterioration in trabecular micro-architecture, reduced trabecular and cortical mineral content, and decreased Vickers microhardness were noted in the CH group (p < 0.05). Reduced total number of osteocytes and declined connexin 43 expression levels (p < 0.05) implied that harmed mechanotransduction throughout the osteocyte network might be present in CH. Moreover, elevated expression levels of sclerostin by osteocytes could indicate the role of sclerostin in mediating low bone formation in individuals with CH. Taken together, these micro-scale bone alterations suggest that vertebral strength could be compromised in men with CH, implying that vertebral fracture risk assessment and subsequent therapy may need to be considered in these patients. However, further research is required to confirm the clinical relevance of our findings.

Increased Cortical Porosity, Reduced Cortical Thickness, and Reduced Trabecular and Cortical Microhardness of the Superolateral Femoral Neck Confer the Increased Hip Fracture Risk in Individuals with Type 2 Diabetes.

Individuals with diabetes mellitus type 2 (T2DM) have approximately 30% increased risk of hip fracture; however, the main cause of the elevated fracture risk in those subjects remains unclear. Moreover, micromechanical and microarchitectural properties of the superolateral femoral neck-the common fracture-initiating site-are still unknown. We collected proximal femora of 16 men (eight with T2DM and eight controls; age: 61 ± 10 years) at autopsy. After performing post-mortem bone densitometry (DXA), the superolateral neck was excised and scanned with microcomputed tomography (microCT). We also conducted Vickers microindentation testing. T2DM and control subjects did not differ in age (p = 0.605), body mass index (p = 0.114), and femoral neck bone mineral density (BMD) (p = 0.841). Cortical porosity (Ct.Po) was higher and cortical thickness (Ct.Th) was lower in T2DM (p = 0.044, p = 0.007, respectively). Of trabecular microarchitectural parameters, only structure model index (p = 0.022) was significantly different between T2DM subjects and controls. Control group showed higher cortical (p = 0.002) and trabecular bone microhardness (p = 0.005). Increased Ct.Po and decreased Ct.Th in T2DM subjects increase the propensity to femoral neck fracture. Apart from the deteriorated cortical microarchitecture, decreased cortical and trabecular microhardness suggests altered bone composition of the superolateral femoral neck cortex and trabeculae in T2DM. Significantly deteriorated cortical microarchitecture of the superolateral femoral neck is not recognized by standard DXA measurement of the femoral neck.

'CT and CT image-based texture image analysis in radiological diagnostics of allergic fungal rhinosinusitis'.

BACKGROUND: This prospective study is focused on evaluating radiological properties of AFRS. We analysed specific CT features related to the presence of AFRS, as well as explored the possible usefulness of the texture image analysis (TIA) as an additional diagnostical parameter. METHODS: The CT images of maxillary sinuses of 37 adult patients diagnosed with chronic rhinosinusitis were analysed for homogeneity, high-attenuation areas, density of the soft tissue mass, bony wall thickness and density. TIA included assessment of uniformity, contrast, homogeneity and entropy of sinus content. RESULTS: In the F+ group, soft tissue mass was significantly more non-homogeneous, high-attenuation areas were more prevalent, while soft tissue densities were higher. The sinus wall showed a tendency towards decreased thickness and significantly higher density in the F+ group. Among TIA parameters only homogeneity was significantly lower in the F+ group. CONCLUSIONS: Presence of fungi should be suspected when the sinus is filled with a non-homogenous soft tissue content of a high CT density not necessarily presented as clearly visible hyperattenuation material. Additional criteria in radiological diagnostics of AFRS should encompass assessment of sinus bony wall density. TIA may serve as a tool for quantitative assessment of subjective CT features such as homogeneity of the soft tissue mass for investigative purposes. However, other TIA parameters showed limited potential.

The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets.

Previous studies suggested that osteocyte lacunar network disruption could play a role in the complex pathophysiology of bone changes in aging and disease. Considering that particular research interest is lacking, we aimed to assess alcoholic liver cirrhosis (ALC)-induced changes in osteocyte lacunar network and bone marrow adiposity. Immunohistochemistry was conducted to assess changes in the micro-morphology of osteocyte lacunar network and bone marrow adiposity, and expression of connexin 43 and sclerostin in vertebral and femoral samples collected from 40 cadaveric men (age range between 44 and 70 years) divided into ALC group (n = 20) and control group (n = 20). Furthermore, the assessment of the potential association between bone changes and the severity of the hepatic disorder (given by Knodell's pathohistologic scoring) was conducted. Our data revealed fewer connexin 43-positive osteocytes per vertebral and femoral bone area (p < 0.01), suggesting defective signal transduction among osteocytes in ALC individuals. Moreover, we found an ALC-induced increase in the number of adipocytes in the vertebral bone marrow (p = 0.038). Considering significant associations between the severity of liver tissue disturbances and impaired functionality of osteocyte lacunar network (Pearson's correlation analyses, p < 0.05), we may assume that timely treatment of the liver disease may delay bone impairment. ALC induced an increase in osteocytic sclerostin expression (p < 0.001), suggesting its role in mediating low bone formation among ALC individuals. Hence, medicaments targeting low bone formation may be beneficial to attenuate the bone changes among ALC patients. However, future clinical studies are required to verify the therapeutic utility of these findings.

Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility.

Although increased hip fracture risk is noted in patients with alcoholic liver disease (ALD), their femoral microstructural and mechanical properties were not investigated previously. The present study aimed to analyze the associations between subregional deteriorations in femoral mechano-structural properties and clinical imaging findings to explain increased femoral fracture risk among ALD patients. This study analyzed proximal femora of 33 male cadaveric donors, divided into ALD (n = 13, 57 ± 13 years) and age-matched control group (n = 20, 54 ± 13 years). After pathohistological verification of ALD stage, DXA and HSA measurements of the proximal femora were performed, followed by micro-CT and Vickers microindentation of the superolateral neck, inferomedial neck, and intertrochanteric region. Bone mineral density and cross sectional area of the femoral neck were deteriorated in ALD donors, compared with healthy controls (p < 0.05). Significant ALD-induced degradation of trabecular and cortical microstructure and Vickers microhardness reduction were noted in the analyzed femoral regions (p < 0.05). Still, the most prominent ALD-induced mechano-structural deterioration was noted in intertrochanteric region. Additionally, more severe bone alterations were observed in individuals with an irreversible stage of ALD, alcoholic liver cirrhosis (ALC), than in those with an initial ALD stage, fatty liver disease. Observed osteodensitometric and mechano-structural changes illuminate the basis for increased femoral fracture risk in ALD patients. Additionally, our data suggest bone strength reduction that may result in increased susceptibility to intertrochanteric femoral fracture in men with ALD. Thus, femoral fracture risk assessment should be advised for all ALD patients, especially in those with ALC.

The comparison of age- and sex-specific alteration in pubic bone microstructure: A cross-sectional cadaveric study.

BACKGROUND: The burden of age-associated fragility fracture of the pelvis has gradually amplified over the years. Commonly used clinical tools cannot fully explain age-associated fracture risk increase, and microstructural analysis could be required to elucidate pubic bone strength decline in elderly. MATERIAL AND METHODS: The study sample encompassed 46 pubic bones obtained from cadaveric donors divided into a young women (<45 years, n = 11), aged women (>60 years, n = 11), young men (<45 years, n = 12) and aged men group (>60 years, n = 12). Micro-computed tomography was used to evaluate the cortical and trabecular microstructure of pubic bone samples. RESULTS: Apart from age-associated loss in quantitative trabecular parameters, significant alteration of micro-CT parameters that more closely reflect internal trabecular microarchitectural complexity may contribute to pubic bone strength decline in men and women of advanced age (p < 0.05). Additionally, decreased cortical thickness and increased Ct.Po, Po.Dm and Po.N were found in the anterior and posterior cortical surface of pubic bone samples from the aged individuals (p < 0.05). The more pronounced alteration was noted in aged female donors, illustrated in a significant deterioration trend of the Tb.N, Tb.Sp, and thinner posterior cortical surface with decreased pore spacing (p < 0.05). CONCLUSION: Our data suggest that age-associated deterioration in trabecular and cortical pubic bone micro-architecture could unravel a morphological basis for decreased pubic bone strength and increased pubic bone fragility, which leads to fracture predilection in the elderly women. Thus, the individual fracture risk assessment should be advised in the elderly, with a particular accent on aged women.

The severity of hepatic disorder is related to vertebral microstructure deterioration in cadaveric donors with liver cirrhosis.

Patients with liver cirrhosis (LC) commonly suffer from osteoporosis and vertebral fracture, but data about their vertebral micro-architectural changes are still limited. This study aimed to evaluate the potential differences in trabecular micro-architecture of lumbar vertebrae between male LC patients and healthy controls, in relation to etiology and pathohistological scoring of the liver disorder. After pathohistological examination of liver tissue, micro-computed tomography was performed on the vertebral samples included into: alcoholic liver cirrhosis group (ALC; n = 16; age: 59 ± 8 years), non-alcoholic liver cirrhosis group (non-ALC; n = 15; age: 69 ± 10 years) and control group (n = 16; age: 58 ± 6 years). Our data showed significant impairment of the trabecular microstructure in the lumbar vertebrae from LC donors, regardless of the alcoholic/non-alcoholic origin of liver disorder, as illustrated by lower BV/TV, Tb.Th, and Tb.N compared with controls (p < .05). Moreover, depredation in trabecular micro-architecture was inversely associated with pathohistological scores (p < .05), indicating that severity of liver disorder could be an important predictor of reduced vertebral strength in LC. We noticed significant micro-architectural deterioration in the trabecular compartment of the lumbar vertebrae of male individuals with alcoholic and non-alcoholic LC, which was associated with the severity of the liver disease. Thus, clinical assessment of fracture risk should be advised for all LC patients, regardless of the alcoholic origin of liver cirrhosis. Additionally, adequate and timely treatment of liver disorder may decelerate the progression of bone impairment in LC patients.

Effect of Betaine Supplementation on Liver Tissue and Ultrastructural Changes in Methionine-Choline-Deficient Diet-Induced NAFLD.

Nonalcoholic fatty liver disease (NAFLD) represents a hepatic manifestation of metabolic syndrome. The aim of this study was to examine the effect of betaine on ultrastructural changes in the mouse liver with methionine- and choline-deficient (MCD) diet-induced NAFLD. Male C57BL/6 mice were divided into groups: Control-fed with standard chow, BET-standard chow supplemented with betaine (1.5% w/v drinking water), MCD-fed with MCD diet, and MCD + BET-MCD diet with betaine supplementation for 6 weeks. Liver samples were taken for pathohistology and transmission electron microscopy. The MCD diet-induced steatosis, inflammation, and balloon-altered hepatocytes were alleviated by betaine. MCD diet induced an increase in mitochondrial size versus the control group (p < 0.01), which was decreased in the betaine-treated group. In the MCD diet-fed group, the total mitochondrial count decreased versus the control group (p < 0.01), while it increased in the MCD + BET group versus MCD (p < 0.01). Electron microscopy showed an increase in the number of autophagosomes in the MCD and MCD + BET group versus control, and a significant difference in autophagosomes number was detected in the MCD + BET group by comparison with the MCD diet-treated group (p < 0.05). Betaine decreases the number of enlarged mitochondria, alleviates steatosis, and increases the number of autophagosomes in the liver of mice with NAFLD.

Comparative Analysis of Femoral Macro- and Micromorphology in Males and Females With and Without Hyperostosis Frontalis Interna: A Cross-Sectional Cadaveric Study.

We hypothesized that subjects with hyperostosis frontalis interna (HFI), which represents local, endocranial thickening of the frontal bone, would express extra-calvarial manifestations of this condition. Therefore, we compared femoral bone mineral density, geometry, and microarchitecture of males and females with HFI to those without this condition as well as between males and females with HFI. The sample was taken from human donor cadavers, 38 males (19 with and 19 without HFI) and 34 females (17 with and 17 without HFI) that were age-matched within the same sex. The specimens of femoral bones were scanned using microcomputed tomography and dual-energy X-ray absorptiometry (DXA). Parameters of hip structure analysis (HSA) were calculated from data derived from DXA scans. Females with HFI had increased cortical bone volume fraction and their cortical bone was less porous compared to females without HFI. Males with HFI showed microarchitectural differences only with the trabecular bone. They had increased bone volume fraction and decreased trabecular separation compared to males without HFI, although with borderline significance. These microarchitectural changes did not have significant impact on femoral geometry and bone mineral density. The same, still unknown etiological factor behind HFI might be inducing changes at the level of bone microarchitecture at a remote skeletal site (femoral bone), in both sexes. These alterations still do not have the magnitude to induce obvious, straightforward overall increase of bone mineral density measured by DXA. HFI could be a systemic phenomenon that affects both males and females in a similar manner.

Micro-computed Tomography Study of Frontal Bones in Males and Females with Hyperostosis Frontalis Interna.

Hyperostosis frontalis interna (HFI) represents irregular thickening of the endocranial surface of the frontal bone, mostly seen in postmenopausal females. The microarchitecture of this condition is poorly studied. The aim of this cross-sectional autopsy study was to investigate and compare microarchitectural structure of the frontal bone affected with HFI in both sexes and to test whether HFI severity could be distinguished at the microarchitectural level. The sample was taken from human donor cadavers, 19 males (61 ± 15 years old) and 17 females (75 ± 15 years old). After classification of HFI severity (type A, B, C or D), samples of the frontal bone were taken and scanned using micro-computed tomography. Bone volume fraction was higher and total porosity lower only in the outer table of males with HFI, compared to females with HFI. Mean total sample thickness differed only between males with HFI type A and D. Bone microarchitecture between males and females with corresponding HFI types (e.g., male with type A versus female with type A) differed only in HFI type C regarding the fractal dimension of diploe. The degree of anisotropy differed between HFI subtypes in males, but the post hoc analysis revealed no significant differences between individual groups. Other microarchitectural parameters did not differ among males with different HFI subtypes, as well in females, in any part of the frontal bone. There is no difference in microarchitectural structure of the frontal bone between males and females with HFI, in general aspect and within corresponding HFI subtypes. HFI severity could not be distinguished at the microarchitectural level, neither in males nor in females.