Browsing by Author "Jadzic, Jelena (57217214308)"

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. © 2023 Elsevier B.V.

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. ©The Author(s) 2023.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility. © 2024 by the authors.

This study aimed to perform microstructural characterization of the increased fragility of human bone in type 2 diabetes mellitus (T2DM) by exploring the matrix mineralization and osteocyte lacunar density at the superolateral femoral neck—the typical fracture-initiating site. Postmortem specimens of the full-length superolateral femoral neck from 16 elderly men with T2DM and age-matched non-DM controls were examined using backscattered-electron microscopy in terms of mineralization parameters and parameters of osteocyte lacunar density. The T2DM and control groups did not differ in age and body mass index (p > 0.05). In the endocortical region, T2DM was associated with a lower degree of mineralization (lower CaMean: p = 0.04), a higher proportion of extremely low-mineralized areas (higher CaLow: p = 0.027), and greater mineralization heterogeneity (higher CaWidth: p = 0.003) relative to controls. However, there were no significant intergroup differences in mineralization parameters in the periosteal region. In the endocortical region, T2DM showed lower unmineralized (p = 0.006) and total osteocyte lacunar number (Lc.N) per bone area (B.Ar) (p = 0.018) coupled with a higher percentage of mineralized lacunae (%Mn.Lc) relative to controls (p = 0.05). In the periosteal region, only Lc.N/B.Ar was lower in T2DM (p = 0.004). As for the trabecular compartment, T2DM was associated with lower trabecular CaMean (p = 0.048) and higher trabecular CaLow and CaWidth (p = 0.005, p = 0.007). Altered pattern of mineralization in the cortical (especially in the endocortical region) and trabecular compartments of the superolateral femoral neck and reduced cortical osteocyte lacunar density are structural hallmarks of bone fragility in T2DM. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.

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. © 2022 Wiley-VCH GmbH.

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. © 2024 Baishideng Publishing Group Inc. All rights reserved.

Skeletal porous lesions such as cribra orbitalia (CO) have long been of interest to bioanthropologists worldwide, mainly due to their high prevalence in osteological material. Previous studies considered CO as an external morphological manifestation, and therefore, research has mainly focused on visible (macroscopic) CO patterns. However, the understanding of CO-induced micro-scale bone changes is still scarce. Therefore, we performed high-resolution micro-computed tomography imaging to investigate three-dimensional CO-induced micro-architectural patterns in non-adults, with a particular focus on the correlation between macroscopic and micro-architectural orbital features. Cortical and trabecular micro-architectural changes in the orbital roof were analyzed in non-adults younger than 15 years, using orbital roof samples with and without macroscopic traces of CO (n = 28). A widely accepted five-grade macroscopic CO scoring system was applied to analyze CO severity. Areas affected with CO (area 1) and areas without macroscopic CO traces (area 2) were analyzed separately. The conducted high-resolution analysis showed that cortical and trabecular micro-architecture varied with CO presence, lesion severity (CO grade), and the analyzed area. Inter-grade comparisons suggested that most of the analyzed micro-architectural parameters were not significantly different between adjacent CO grades. Based on the micro-architectural evaluation of areas 1 and 2, the porous lesions were much more extensive than revealed by gross examination. In addition, micro-architectural differences were particularly pronounced in younger non-adults. In summary, our pilot study suggests that the macroscopic examination of CO reflects only the tip of the iceberg, as the micro-architectural changes seem to be much larger than macroscopically identified. Research Highlights: Cribra orbitalia (CO) represents orbital porous lesions. A high-resolution microscopic assessment of CO-induced changes in non-adults was done by micro-computed tomography. The microarchitecture was affected by CO presence, CO grade, area, and age. © 2024 Wiley Periodicals LLC.

Skeletal porous lesions such as cribra orbitalia (CO) have long been of interest to bioanthropologists worldwide, mainly due to their high prevalence in osteological material. Previous studies considered CO as an external morphological manifestation, and therefore, research has mainly focused on visible (macroscopic) CO patterns. However, the understanding of CO-induced micro-scale bone changes is still scarce. Therefore, we performed high-resolution micro-computed tomography imaging to investigate three-dimensional CO-induced micro-architectural patterns in non-adults, with a particular focus on the correlation between macroscopic and micro-architectural orbital features. Cortical and trabecular micro-architectural changes in the orbital roof were analyzed in non-adults younger than 15 years, using orbital roof samples with and without macroscopic traces of CO (n = 28). A widely accepted five-grade macroscopic CO scoring system was applied to analyze CO severity. Areas affected with CO (area 1) and areas without macroscopic CO traces (area 2) were analyzed separately. The conducted high-resolution analysis showed that cortical and trabecular micro-architecture varied with CO presence, lesion severity (CO grade), and the analyzed area. Inter-grade comparisons suggested that most of the analyzed micro-architectural parameters were not significantly different between adjacent CO grades. Based on the micro-architectural evaluation of areas 1 and 2, the porous lesions were much more extensive than revealed by gross examination. In addition, micro-architectural differences were particularly pronounced in younger non-adults. In summary, our pilot study suggests that the macroscopic examination of CO reflects only the tip of the iceberg, as the micro-architectural changes seem to be much larger than macroscopically identified. Research Highlights: Cribra orbitalia (CO) represents orbital porous lesions. A high-resolution microscopic assessment of CO-induced changes in non-adults was done by micro-computed tomography. The microarchitecture was affected by CO presence, CO grade, area, and age. © 2024 Wiley Periodicals LLC.

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. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s) under exclusive licence to SICOT aisbl.

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. [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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. [Figure not available: see fulltext.] © 2023, The Author(s), under exclusive licence to Springer Nature Limited.

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. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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. © 2021 Elsevier Inc.

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. © 2021 Elsevier Inc.

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. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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. © 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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 this 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. © The Author(s) 2024.

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. © 2023 Lippincott Williams and Wilkins. All rights reserved.

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. © 2022 Anatomical Society.