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.

Evidence of degraded BMD and geometry at the proximal femora in male patients with alcoholic liver cirrhosis.

UNLABELLED: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. INTRODUCTION: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. METHODS: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. RESULTS: After adjusting for age, body height, and weight, we found lower cross-sectional area (p = 0.005) and section modulus (p = 0.005), thinner cortex (p = 0.012), and higher buckling ratio (p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. CONCLUSION: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis.

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.