Ex vivo analysis of cortical microarchitecture of the distal clavicle: implications for surgical management of fractures.

BACKGROUND: Cortical thickness and porosity are two main determinants of cortical bone strength. Thus, mapping variations in these parameters across the full width of the distal end of the clavicle may be helpful for better understanding the basis of distal clavicle fractures and for selecting optimal surgical treatment. METHODS: Distal ends of 11 clavicles (6 men, 5 women; age: 81.9 ± 15.1 years) were scanned by micro-computed tomography at 10-µm resolution. We first analyzed cortical thickness and porosity of each 500-µm-wide area across the superior surface of distal clavicle at the level of conoid tubercle in an antero-posterior direction. This level was chosen for detailed evaluation because previous studies have demonstrated its superior microarchitecture relative to the rest of the distal clavicle. Subsequently, we divided the full width of distal clavicle to three subregions (anterior, middle, and posterior) and analyzed cortical porosity, pore diameter, pore separation, and cortical thickness. RESULTS: We found the largest number of low-thickness and high-porosity areas in the anterior subregion. Cortical porosity, pore diameter, pore separation, and cortical thickness varied significantly among the three subregions (p < 0.001 p = 0.016, p = 0.001, p < 0.001, respectively). Cortex of the anterior subregion was more porous than that of the middle subregion (p < 0.001) and more porous and thinner than that of the posterior subregion (p < 0.001, p = 0.030, respectively). Interaction of site and sex revealed higher porosity of the anterior subregion in women (p < 0.001). The anterior subregion had larger pores than the middle subregion (p = 0.019), whereas the middle subregion had greater pore separation compared with the anterior (p = 0.002) and posterior subregions (p = 0.006). In general, compared with men, women had thinner (p < 0.001) and more porous cortex (p = 0.03) with larger cortical pores (p < 0.001). CONCLUSIONS: Due to high cortical porosity and low thickness, the anterior conoid subregion exhibits poor bone microarchitecture, particularly in women, which may be considered in clinical practice. LEVELS OF EVIDENCE: Level IV.

Lower microhardness along with less heterogeneous mineralization in the femoral neck of individuals with type 2 diabetes mellitus indicates higher fracture risk.

There is still limited understanding of the microstructural reasons for the higher susceptibility to fractures in individuals with type 2 diabetes mellitus (T2DM). In this study, we examined bone mineralization, osteocyte lacunar parameters, and microhardness of the femoral neck trabeculae in 18 individuals with T2DM who sustained low-energy fracture (T2DMFx: 78 ± 7 years, 15 women and 3 men) and 20 controls (74 ± 7 years, 16 women and 4 men). Femoral necks of the T2DMFx subjects were obtained at a tertiary orthopedic hospital, while those of the controls were collected at autopsy. T2DMFx individuals had lower trabecular microhardness (P = .023) and mineralization heterogeneity (P = .001), and a tendency to a lower bone area with mineralization above 95th percentile (P = .058) than the controls. There were no significant intergroup differences in the numbers of osteocyte lacunae per bone area, mineralized lacunae per bone area, and total lacunae per bone area (each P > .05). After dividing the T2DMFx group based on the presence of vascular complications (VD) to T2DMFxVD (VD present) and T2DMFxNVD (VD absent), we observed that microhardness was particularly reduced in the T2DMFxVD group (vs. control group, P = .02), while mineralization heterogeneity was significantly reduced in both T2DMFx subgroups (T2DMFxNVD vs. control, P = .002; T2DMFxVD vs. control, P = .038). The observed changes in mineralization and microhardness may contribute to the increased hip fracture susceptibility in individuals with T2DM.

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.

Deficiency of protein C or protein S as a possible cause of osteoporosis.

Proteins C and S are vitamin K-dependent anticoagulative factors that also exert a significant influence on bone quality. Clinical studies have linked the deficiency of proteins C and S to lower bone mineral density and the onset of femoral head osteonecrosis in children. Rare foundational studies analyzing this topic have demonstrated that activated protein C, upon binding to the endothelial protein C receptor expressed on the surface of osteoblasts, promotes osteoblast proliferation. It is also established that proteins C and S play crucial roles in proper collagen synthesis and in maintaining the number of osteoclasts and blood vessels. However, the association between protein C and/or S deficiency and the gradual onset of osteoporosis remains largely uninvestigated. Calculations based on data from peer-reviewed journals suggest that approximately one in every 10 individuals may develop osteoporosis due to congenital protein C or S deficiency. Moreover, when secondary causes of protein C and S deficiency are also considered, the proportion likely further increases. In this paper, we discuss the pathophysiological background of the potential relationship between protein C and S deficiency and the genesis of osteoporosis.

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.

Pediatric Anesthesia Providers' Perspective on the Real-Life Implementation of the Philips Visual Patient Avatar: A Qualitative Study.

The Philips Visual Patient Avatar represents an alternative method of patient monitoring that, according to computer-based simulation studies, enhances diagnostic accuracy and confidence and reduces workload. After its clinical integration, we assessed pediatric anesthesia providers' perspectives on this technology. This is a single-center qualitative study, conducted at the University Hospital Zurich using in-depth individual interviews. We aimed to identify the advantages and limitations of the Visual Patient Avatar in pediatric anesthesia and to assess children's and parents' reactions from caregivers' perspectives. Thematic analysis was used to identify the dominant themes. Fourteen members of the institution's pediatric anesthesia team were interviewed. The most prevalent themes were children's positive reactions towards the Visual Patient Avatar (92.9%) and enhanced speed in problem identification (71.4%). Additionally, 50% of participants reported finding the Visual Patient Avatar useful for diverting children's attention during anesthesia induction, and 50% suggested that its vital sign thresholds should be adaptable for different age groups. The study revealed that the Visual Patient Avatar was recognized as a tool in pediatric anesthesia, enabling prompt identification of underlying issues and receiving positive feedback from both children and parents. The most commonly voiced wish for improvement in the study was the ability to customize the Visual Patient Avatar's thresholds for different age groups.

Micropetrosis: Osteocyte Lacunar Mineralization in Aging and Disease.

PURPOSE OF REVIEW: As the importance of osteocytes for bone mineral homeostasis is increasingly recognized, there is growing interest in osteocyte cell death as a relevant indicator in various physiological and pathological conditions. Micropetrosis is an established term used to describe osteocyte lacunae that are filled with minerals following osteocyte death. While the early reports of micropetrosis were purely descriptive, there is now an increasing body of literature showing quantitative data on micropetrosis in various conditions such as aging, osteoporosis, immobilization, and diabetes, and in osteoporosis treatment (denosumab and bisphosphonates). This review summarizes quantitative findings on micropetrosis, with a particular emphasis on the recent advances in the field. RECENT FINDINGS: There is growing evidence that micropetrosis is more common in older, osteoporotic, and immobilized individuals, as well as in individuals with type 1 or type 2 diabetes. Denosumab and bisphosphonates seem to affect lacunar mineralization differently, where specifically bisphosphonates have been shown to prolong osteocyte viability and reduce micropetrosis. Despite continuous proceedings in the field of osteocyte-lacunar-network characteristics, more studies are necessary to further clarify the mechanisms of lacunar mineralization, the inter-site variability of micropetrosis accumulation, the relevance of micropetrosis in various diseases and conditions, and whether micropetrosis could be an indicator of bone fragility or a target for treatment.

Osteocyte apoptosis and cellular micropetrosis signify skeletal aging in type 1 diabetes.

Bone fragility is a profound complication of type 1 diabetes mellitus (T1DM), increasing patient morbidity. Within the mineralized bone matrix, osteocytes build a mechanosensitive network that orchestrates bone remodeling; thus, osteocyte viability is crucial for maintaining bone homeostasis. In human cortical bone specimens from individuals with T1DM, we found signs of accelerated osteocyte apoptosis and local mineralization of osteocyte lacunae (micropetrosis) compared with samples from age-matched controls. Such morphological changes were seen in the relatively young osteonal bone matrix on the periosteal side, and micropetrosis coincided with microdamage accumulation, implying that T1DM drives local skeletal aging and thereby impairs the biomechanical competence of the bone tissue. The consequent dysfunction of the osteocyte network hampers bone remodeling and decreases bone repair mechanisms, potentially contributing to the enhanced fracture risk seen in individuals with T1DM. STATEMENT OF SIGNIFICANCE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that causes hyperglycemia. Increased bone fragility is one of the complications associated with T1DM. Our latest study on T1DM-affected human cortical bone identified the viability of osteocytes, the primary bone cells, as a potentially critical factor in T1DM-bone disease. We linked T1DM with increased osteocyte apoptosis and local accumulation of mineralized lacunar spaces and microdamage. Such structural changes in bone tissue suggest that T1DM speeds up the adverse effects of aging, leading to the premature death of osteocytes and potentially contributing to diabetes-related bone fragility.

Experimental Analysis of Handcart Pushing and Pulling Safety in an Industrial Environment by Using IoT Force and EMG Sensors: Relationship with Operators' Psychological Status and Pain Syndromes.

Non-ergonomic execution of repetitive physical tasks represents a major cause of work-related musculoskeletal disorders (WMSD). This study was focused on the pushing and pulling (P&P) of an industrial handcart (which is a generic physical task present across many industries), with the aim to investigate the dependence of P&P execution on the operators' psychological status and the presence of pain syndromes of the upper limbs and spine. The developed acquisition system integrated two three-axis force sensors (placed on the left and right arm) and six electromyography (EMG) electrodes (placed on the chest, back, and hand flexor muscles). The conducted experiment involved two groups of participants (with and without increased psychological scores and pain syndromes). Ten force parameters (for both left and right side), one EMG parameter (for three different muscles, both left and right side), and two time-domain parameters were extracted from the acquired signals. Data analysis showed intergroup differences in the examined parameters, especially in force integral values and EMG mean absolute values. To the best of our knowledge, this is the first study that evaluated the composite effects of pain syndromes, spine mobility, and psychological status of the participants on the execution of P&P tasks-concluding that they have a significant impact on the P&P task execution and potentially on the risk of WMSD. The future work will be directed towards the development of a personalized risk assessment system by considering more muscle groups, supplementary data derived from operators' poses (extracted with computer vision algorithms), and cognitive parameters (extracted with EEG sensors).

Three-dimensional mapping of cortical porosity and thickness along the superolateral femoral neck in older women.

Although several studies have analyzed inter-individual differences in the femoral neck cortical microstructure, intra-individual variations have not been comprehensively evaluated. By using microCT, we mapped cortical pore volume fraction (Ct.Po) and thickness (Ct.Th) along the superolateral femoral neck in 14 older women (age: 77.1 ± 9.8 years) to identify subregions and segments with high porosity and/or low thickness-potential "critical" spots where a fracture could start. We showed that Ct.Po and Ct.Th significantly differed between basicervical, midcervical, and subcapital subregions of the femoral neck (p < 0.001), where the subcapital subregion showed the lowest mean Ct.Th and the highest mean Ct.Po. These cortical parameters also varied substantially with age and with the location of the analyzed microsegments along the individual's neck (p < 0.001), showing multiple microsegments with high porosity and/or low thickness. Although the highest ratio of these microsegments was found in the subcapital subregion, they were also present at other examined subregions, which may provide an anatomical basis for explaining the fracture initiation at various sites of the superolateral neck. Given that fractures likely start at structurally and mechanically weaker spots, intra-individual variability in Ct.Po and Ct.Th should be considered and the average values for the entire femoral neck should be interpreted with caution.

Pathogenesis of Pulmonary Calcification and Homologies with Biomineralization in Other Tissues.

Lungs often present tissue calcifications and even ossifications, both in the context of high or normal serum calcium levels. Precise mechanisms governing lung calcifications have not been explored. Herein, we emphasize recent advances about calcification processes in other tissues (especially vascular and bone calcifications) and discuss potential sources of calcium precipitates in the lungs, involvement of mineralization promoters and crystallization inhibitors, as well as specific cytokine milieu and cellular phenotypes characteristic for lung diseases, which may be involved in pulmonary calcifications. Further studies are necessary to demonstrate the exact mechanisms underlying calcifications in the lungs, document homologies in biomineralization processes between various tissues in physiological and pathologic conditions, and unravel any locally specific characteristics of mineralization processes that may be targeted to reduce or prevent functionally relevant lung calcifications without negatively affecting the skeleton.

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.

Expression of connexin-43 in surgical resections of primary tumor and lymph node metastases of squamous cell carcinoma and adenocarcinoma of the lung: a retrospective study.

Background: Connexins are transmembrane proteins forming gap junctions between the cells, which allow intercellular communication. Significance of gap junctions and connexins in lung carcinoma is not yet understood. The objective of the study was to investigate immunohistochemical expression and the localization of connexin-43 (Cx43) in primary lung carcinoma and its lymphatic metastases. Methods: Surgical specimens of excised tumors from 88 patients (45 men and 43 women, 61.9 ± 7.4 years) with lung carcinoma (52 adenocarcinoma (AC), 36 squamous cell carcinoma (SqCC)) who were operated on at the University Hospital "Bezanijska Kosa" in a five-year period (2012-2016) were used. We conducted immunohistochemical staining for Cx43 and measured the degree of expression (percentage of positive cells and staining intensity) as well as localization of Cx43 in primary tumor and in lymphatic metastases. Results: Immunohistochemical analysis of the primary tumors revealed that SqCC showed significantly higher percentage of tumor cells expressing Cx43 as well as higher staining intensity than AC (p < 0.001). Almost 70% of samples with SqCC showed high Cx43 expression, whereas AC showed no expression in more than 50% of cases. Localization of Cx43 expression was most often cytoplasmic (AC and SqCC) and combined membranous and cytoplasmic (SqCC) with very rare instances of nuclear localization (AC). Almost the same pattern in distribution, intensity, and localization of Cx43 expression was observed in the lymph node metastases; however, almost a third of AC cases changed the pattern of Cx43 expression in the metastasis compared to primary tumor. Conclusion: The results of this study showed that lung carcinomas express Cx43 in more than 65% of cases and that it was aberrantly localized (not membranous localization). We highlighted that SqCC expressed Cx43 more than did AC, both in primary tumor and lymphatic metastases. Further research is needed to establish whether Cx43 could be used as a prognostic biomarker in lung carcinoma.

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.

Vascular Complications in Individuals with Type 2 Diabetes Mellitus Additionally Increase the Risk of Femoral Neck Fractures Due to Deteriorated Trabecular Microarchitecture.

Individuals with diabetes mellitus type 2 (T2DM) have an increased risk of hip fracture, especially if vascular complications are present. However, microstructural origins of increased bone fragility in T2DM are still controversial. DXA measurement of the contralateral hip and three-dimensional microCT analyses of femoral neck trabecular microarchitecture were performed in 32 individuals (26 women and 6 men, 78 ± 7 years). The specimens were divided to two groups: T2DM individuals with hip fracture (DMFx, n = 18) and healthy controls (CTL, n = 14). DMFx group consisted of individuals with vascular complications (DMFx_VD, n = 8) and those without vascular complications (DMFx_NVD, n = 10). T-score was significantly lower in DMFx_VD and DMFx_NVD than in controls (p < 0.001). BV/TV, Tb.N, Tb.Sp, SMI, and FD varied among DMFx_NVD, DMFx_VD, and CTL groups (p = 0.023, p = 0.004, p = 0.008, p = 0.001, p = 0.007, respectively). Specifically, BV/TV of DMFx_VD was significantly lower than that of DMFx_NVD group (p = 0.020); DMFx_NVD group had higher Tb.N and lower Tb.Sp compared with DMFx_VD (p = 0.006, p = 0.012, respectively) and CTL (p = 0.026, p = 0.035, respectively). DMFx group and healthy controls showed similar BV/TV, Tb.Th, Tb.N, Tb.Sp, Conn.D, DA, and FD (p = 0.771, p = 0.503, p = 0.285, p = 0.266, p = 0.208, p = 0.235, p = 0.688, respectively), while SMI was significantly higher in controls (p = 0.005). Two distinct phenotypes of bone fragility were identified in T2DM patients: patients with vascular complications showed impaired trabecular microarchitecture, whereas bone fragility in the group without vascular complications was independent on trabecular microarchitecture pattern. Such heterogeneity among T2DM patients may explain contradicting literature data and may set a basis for further studies to evaluate fracture risk related to T2DM.

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 banding phenomenon: injury or hypostasis?

Correct interpretation of autopsy findings related to neck structures can be challenging and has tremendous legal importance. We describe a case of a 30-year-old man who was found dead in a hotel courtyard, facedown. The window of his hotel room on the 5th floor was wide open. Police investigation revealed that he was a gambler with many debts, leading them to suspect foul play. The body was transported for a forensic autopsy in a supine position. External examination showed multiple lacerations and contusions of the face and limbs, without signs of external neck injuries. Layer-by-layer neck dissection was unremarkable. Upon opening the pharynx and esophagus, dark purple discoloration of the pharyngeal mucosa could be seen, with a clearly defined margin to the pale circumferential appearance of the rest of the mucosa. To exclude possible tissue bruising due to potential neck compression, histological examination of the mucosa was carried out. Where the mucosa was purple in appearance, there was blood inside the blood vessels, while the vessels of the macroscopically pale mucosa were empty. After forensic autopsy and a detailed police investigation, the manner of death was ruled suicide. In the neck, differential diagnosis between hypostasis and bruising can be especially difficult in rapid, congestive deaths. Forensic pathologists have to be aware of many possible autopsy artifacts in this topographical region, one of those being "banding" of the esophagus. Herein we propose a possible pathophysiological mechanism behind this phenomenon.