Micro-scale vertebral features in postmenopausal women with alcohol-associated and metabolic-associated fatty liver disease: ex vivo bone quality analyses.

PURPOSE: Although epidemiological studies indicate increased fracture risk in women with alcohol-associated liver disease (AALD) and metabolic-associated fatty liver disease (MAFLD), data about their micro-scale bone features are still limited. We aimed to characterize bone quality changes in the anterior mid-transverse part of the first lumbar vertebral body collected from 32 adult postmenopausal females. Based on pathohistological assessment of the liver tissue, individuals were divided into AALD (n = 13), MAFLD (n = 9), and control group (n = 10). METHODS: We analyzed trabecular and cortical micro-architecture (using micro-computed tomography), bone mechanical properties (using Vickers microhardness tester), osteocyte lacunar network and bone marrow adiposity morphology (using optic microscopy). Data were adjusted to elude the covariant effects of advanced age and body mass index on our results. RESULTS: Our data indicated a minor trend toward deteriorated bone quality in MAFLD women, presented in impaired trabecular and cortical micro-architectural integrity, which could be associated with bone marrow adiposity alterations noted in these women. Additionally, we observed a significant decline in micro-architectural, mechanical, and osteocyte lacunar features in lumbar vertebrae collected from the AALD group. Lastly, our data indicated that vertebral bone deterioration was more prominent in the AALD group than in the MAFLD group. CONCLUSION: Our data suggested that MAFLD and AALD are factors that could play a part in compromised vertebral strength of postmenopausal women. Also, our data contribute to understanding the multifactorial nature of bone fragility in these patients and highlight the necessity for developing more effective patient-specific diagnostic, preventive, and therapeutic strategies.

The micro-structural analysis of lumbar vertebrae in alcoholic liver cirrhosis.

Although vertebral fracture is more common among alcoholic liver cirrhosis patients when compared to general population, current data on three-dimensional micro-architecture are scarce. Our study showed significant trabecular deterioration in lumbar vertebrae obtained from alcoholic liver cirrhosis donors, suggesting that they should be advised to undergo early-stage screening for osteoporosis. PURPOSE: Recent studies showed an increased incidence of vertebral fractures in alcoholic liver cirrhosis (ALC) patients, while data about vertebral micro-structure are still limited. The aim of this study was to compare trabecular and cortical micro-architecture of lumbar vertebrae between ALC patients and healthy age- and sex-matched controls. METHODS: Our study included lumbar vertebral samples of male cadaveric donors, divided into ALC (n = 20, age: 59 ± 6 years) and control group (n = 20, age: 59 ± 8 years). Following pathohistological verification of liver cirrhosis, trabecular and cortical bone micro-architecture was analyzed by micro-computed tomography (micro-CT). RESULTS: Micro-CT evaluation of the trabecular bone in lumbar vertebrae showed a significant decrease in bone volume fraction, trabecular thickness, trabecular number, and connectivity (p < 0.01). In contrast to trabecular deterioration, prominent alteration in cortical parameters was not observed in lumbar vertebrae of ALC patients (p > 0.05). CONCLUSIONS: Our data indicate that susceptibility to non-traumatic fractures in ALC patients could be explained by alterations in trabecular bone micro-architecture. Thus, we genuinely recommend osteological screening of the lumbar spine for all ALC patients in order to evaluate individual fracture risk. Graphical abstract.

Micro-morphological properties of osteons reveal changes in cortical bone stability during aging, osteoporosis, and bisphosphonate treatment in women.

SUMMARY: We analyzed morphological characteristics of osteons along with the geometrical indices of individual osteonal mechanical stability in young, healthy aged, untreated osteoporotic, and bisphosphonate-treated osteoporotic women. Our study revealed significant intergroup differences in osteonal morphology and osteocyte lacunae indicating different remodeling patterns with implications for fracture susceptibility. INTRODUCTION: Bone remodeling is the key process in bone structural reorganization, and its alterations lead to changes in bone mechanical strength. Since osteons reflect different bone remodeling patterns, we hypothesize that the femoral cortices of females under miscellaneous age, disease and treatment conditions will display distinct osteonal morphology and osteocyte lacunar numbers along with different mechanical properties. METHODS: The specimens used in this study were collected at autopsy from 35 female donors (young group, n = 6, age 32 ± 8 years; aged group, n = 10, age 79 ± 9 years; osteoporosis group, n = 10, age 81 ± 9 years; and bisphosphonate group, n = 9, age 81 ± 7 years). Von Kossa-modified stained femoral proximal diaphyseal sections were evaluated for osteonal morphometric parameters and osteocyte lacunar data. Geometrical indices of osteonal cross-sections were calculated to assess the mechanical stability of individual osteons, in terms of their resistance to compression, bending, and buckling. RESULTS: The morphological assessment of osteons and quantification of their osteocyte lacunae revealed significant differences between the young, aged, osteoporosis and bisphosphonate-treated groups. Calculated osteonal geometric indices provided estimates of the individual osteons' resistance to compression, bending and buckling based on their size. In particular, the osteons in the bisphosphonate-treated group presented improved osteonal geometry along with increased numbers of osteocyte lacunae that had been formerly impaired due to aging and osteoporosis. CONCLUSIONS: The data derived from osteons (as the basic structural units of the cortical bone) in different skeletal conditions can be employed to highlight structural factors contributing to the fracture susceptibility of various groups of individuals.

On the fracture behavior of cortical bone microstructure: The effects of morphology and material characteristics of bone structural components.

Bone encompasses a complex arrangement of materials at different length scales, which endows it with a range of mechanical, chemical, and biological capabilities. Changes in the microstructure and characteristics of the material, as well as the accumulation of microcracks, affect the bone fracture properties. In this study, two-dimensional finite element models of the microstructure of cortical bone were considered. The eXtended Finite Element Method (XFEM) developed by Abaqus software was used for the analysis of the microcrack propagation in the model as well as for local sensitivity analysis. The stress-strain behavior obtained for the different introduced models was substantially different, confirming the importance of bone tissue microstructure for its failure behavior. Considering the role of interfaces, the results highlighted the effect of cement lines on the crack deflection path and global fracture behavior of the bone microstructure. Furthermore, bone micromorphology and areal fraction of cortical bone tissue components such as osteons, cement lines, and pores affected the bone fracture behavior; specifically, pores altered the crack propagation path since increasing porosity reduced the maximum stress needed to start crack propagation. Therefore, cement line structure, mineralization, and areal fraction are important parameters in bone fracture. The parameter-wise sensitivity analysis demonstrated that areal fraction and strain energy release rate had the greatest and the lowest effect on ultimate strength, respectively. Furthermore, the component-wise sensitivity analysis revealed that for the areal fraction parameter, pores had the greatest effect on ultimate strength, whereas for the other parameters such as elastic modulus and strain energy release rate, cement lines had the most important effect on the ultimate strength. In conclusion, the finding of the current study can help to predict the fracture mechanisms in bone by taking the morphological and material properties of its microstructure into account.

Changes to the cell, tissue and architecture levels in cranial suture synostosis reveal a problem of timing in bone development.

Premature fusion of cranial sutures is a common problem with an incidence of 3-5 per 10,000 live births. Despite progress in understanding molecular/genetic factors affecting suture function, the complex process of premature fusion is still poorly understood. In the present study, corresponding excised segments of nine patent and nine prematurely fused sagittal sutures from infants (age range 3-7 months) with a special emphasis on their hierarchical structural configuration were compared. Cell, tissue and architecture characteristics were analysed by transmitted and polarised light microscopy, 2D-histomorphometry, backscattered electron microscopy and energy-dispersive-x-ray analyses. Apart from wider sutural gaps, patent sutures showed histologically increased new bone formation compared to reduced new bone formation and osseous edges with a more mature structure in the fused portions of the sutures. This pattern was accompanied by a lower osteocyte lacunar density and a higher number of evenly mineralised osteons, reflecting pronounced lamellar bone characteristics along the prematurely fused sutures. In contrast, increases in osteocyte lacunar number and size accompanied by mineralisation heterogeneity and randomly oriented collagen fibres predominantly signified woven bone characteristics in patent, still growing suture segments. The already established woven-to-lamellar bone transition provides evidence of advanced bone development in synostotic sutures. Since structural and compositional features of prematurely fused sutures did not show signs of pathological/defective ossification processes, this supports the theory of a normal ossification process in suture synostosis - just locally commencing too early. These histomorphological findings may provide the basis for a better understanding of the pathomechanism of craniosynostosis, and for future strategies to predict suture fusion and to determine surgical intervention.

Adolescent health in medieval Serbia: signs of infectious diseases and risk of trauma.

Although pattern of health in adults has been frequently assessed in past human populations, health status of adolescents as a distinct life stage has usually been overlooked. Inconsistency in number and meaning of recognised age categories in anthropological literature, as well as chronological age ranges used to define them, further complicate the interpretation of adolescent health. In this study, we analysed signs of pathological conditions on skeletal remains of 81 adolescents from a medieval site of Stara Torina (northern Serbia). Diagnostic palaeopathological procedures comprised gross examination, digital radiography, and histological analysis. Skeletal signs of anaemia such as cribra orbitalia and other porotic phenomena as well as signs of non-specific bone infection were observed frequently, while evidence of bone trauma was recorded in a very low percentage of individuals. In addition, we recorded two conditions relatively rarely observed in palaeopathological contexts: a case of skull and vertebral asymmetry indicative of congenital muscular torticollis, and a case of a fibrous cortical defect on distal femur. Comparison with available information from other medieval adolescent samples from Serbia demonstrated that while mortality was relatively constant throughout the sample, Stara Torina showed a much higher occurrence of bone disease. Characteristics of observed skeletal conditions, supported by available historical reports, suggest that the health of medieval adolescents in the examined population was most significantly affected by infectious processes.