Browsing by Author "Zivkovic, Vladimir (36783131300)"

Although seen frequently during dissections and autopsies, Hyperostosis frontalis interna (HFI) – a morphological pattern of the frontal bone thickening – is often ignored and its nature and development are not yet understood sufficiently. Current macroscopic classification defines four grades/stages of HFI based on the morphological appearance and size of the affected area; however, it is unclear if these stages also depict the successive phases in the HFI development. Here we assessed 3D-microarchitecture of the frontal bone in women with various degrees of HFI expression and in an age- and sex-matched control group, hypothesizing that the bone microarchitecture bears imprints of the pathogenesis of HFI and may clarify the phases of its development. Frontal bone samples were collected during routine autopsies from 20 women with HFI (age: 69.9 ± 11.1 years) and 14 women without HFI (age: 74.1 ± 9.7 years). We classified the HFI samples into four groups, each group demonstrating different macroscopic type or stage of HFI. All samples were scanned by micro-computed tomography to evaluate 3D bone microarchitecture in the following regions of interest: total sample, outer table, diploe and inner table. Our results revealed that, compared to the control group, the women with HFI showed a significantly increased bone volume fraction in the region of diploe, along with significantly thicker and more plate-like shaped trabeculae and reduced trabecular separation and connectivity density. Moreover, the inner table of the frontal bone in women with HFI displayed significantly increased total porosity and mean pore diameter compared to controls. Microstructural reorganization of the frontal bone in women with HFI was also reflected in significantly higher porosity and lower bone volume fraction in the inner vs. outer table due to an increased number of pores larger than 100 μm. The individual comparisons between the control group and different macroscopic stages of HFI revealed significant differences only between the control group and the morphologically most pronounced type of HFI. Our microarchitectural findings demonstrated clear differences between the HFI and the control group in the region of diploe and the inner table. Macroscopic grades of HFI could not be distinguished at the level of bone microarchitecture and their consecutive nature cannot be supported. Rather, our study suggests that only two different types of HFI (moderate and severe HFI) have microstructural justification and should be considered further. It is essential to record HFI systematically in human postmortem subjects to provide more data on the mechanisms of its development. © 2016 Anatomical Society

Although seen frequently during dissections and autopsies, Hyperostosis frontalis interna (HFI) – a morphological pattern of the frontal bone thickening – is often ignored and its nature and development are not yet understood sufficiently. Current macroscopic classification defines four grades/stages of HFI based on the morphological appearance and size of the affected area; however, it is unclear if these stages also depict the successive phases in the HFI development. Here we assessed 3D-microarchitecture of the frontal bone in women with various degrees of HFI expression and in an age- and sex-matched control group, hypothesizing that the bone microarchitecture bears imprints of the pathogenesis of HFI and may clarify the phases of its development. Frontal bone samples were collected during routine autopsies from 20 women with HFI (age: 69.9 ± 11.1 years) and 14 women without HFI (age: 74.1 ± 9.7 years). We classified the HFI samples into four groups, each group demonstrating different macroscopic type or stage of HFI. All samples were scanned by micro-computed tomography to evaluate 3D bone microarchitecture in the following regions of interest: total sample, outer table, diploe and inner table. Our results revealed that, compared to the control group, the women with HFI showed a significantly increased bone volume fraction in the region of diploe, along with significantly thicker and more plate-like shaped trabeculae and reduced trabecular separation and connectivity density. Moreover, the inner table of the frontal bone in women with HFI displayed significantly increased total porosity and mean pore diameter compared to controls. Microstructural reorganization of the frontal bone in women with HFI was also reflected in significantly higher porosity and lower bone volume fraction in the inner vs. outer table due to an increased number of pores larger than 100 μm. The individual comparisons between the control group and different macroscopic stages of HFI revealed significant differences only between the control group and the morphologically most pronounced type of HFI. Our microarchitectural findings demonstrated clear differences between the HFI and the control group in the region of diploe and the inner table. Macroscopic grades of HFI could not be distinguished at the level of bone microarchitecture and their consecutive nature cannot be supported. Rather, our study suggests that only two different types of HFI (moderate and severe HFI) have microstructural justification and should be considered further. It is essential to record HFI systematically in human postmortem subjects to provide more data on the mechanisms of its development. © 2016 Anatomical Society

Objectives: Alcoholic bone disease has been recognized in contemporary literature as a systemic effect of chronic ethanol consumption. However, evidence about the specific influence of alcoholic liver cirrhosis (ALC) on mandible bone quality is scarce. The aim of this study was to explore microstructural, compositional, cellular, and mechanical properties of the mandible in ALC individuals compared with a healthy control group. Materials and methods: Mandible bone cores of mаle individuаls with ALC (n = 6; age: 70.8 ± 2.5 yeаrs) and age-matched healthy controls (n = 11; age: 71.5 ± 3.8 yeаrs) were obtаined postmortem during аutopsy from the edentulous аlveolаr bone in the mandibular first molаr region аnd the mаndibulаr аngulus region of each individual. Micro-computed tomogrаphy wаs used to аssess bone microstructure. Analyses based on quаntitаtive bаckscаttered electron microscopy included the characterization of osteon morphology, osteocyte lаcunаr properties, and bone mаtrix minerаlizаtion. Composition of bone minerаl аnd collаgen phаses was assessed by Rаmаn spectroscopy. Histomorphometry wаs used to determine cellulаr аnd tissue chаrаcteristics of bone specimens. Vickers microhardness test was used to evaluate cortical bone mechanical properties. Results: The ALC group showed higher closed cortical porosity (volume of pores thаt do not communicаte with the sаmple surfаce) (p = 0.003) and smaller lacunar area in the trabecular bone of the molar region (p = 0.002) compared with the Control group. The trabecular bone of the angulus region showed lower osteoclast number (p = 0.032) in the ALC group. There were higher carbonate content in the buccal cortex of the molar region (p = 0.008) and lower calcium content in the trabecular bone of the angulus region (p = 0.042) in the ALC group. The cortical bone showed inferior mechanical properties in the ALC cortical bony sites (p < 0.001), except for the buccal cortex of the molar region (p = 0.063). There was no significant difference in cortical thickness between the groups. Conclusions: Bone quality is differentially altered in ALC in two bony sites and compartments of the mandible, which leads to impaired mechanical properties. Clinical relevance: Altered mandible bone tissue characteristics in patients with ALC should be considered by dental medicine professionals prior to oral interventions in these patients. Knowledge about mandible bone quality alterations in ALC is valuable for determining diagnosis, treatment plan, indications for oral rehabilitation procedures, and follow-up procedures for this group of patients. © 2024 Elsevier Inc.

Objectives: Alcoholic bone disease has been recognized in contemporary literature as a systemic effect of chronic ethanol consumption. However, evidence about the specific influence of alcoholic liver cirrhosis (ALC) on mandible bone quality is scarce. The aim of this study was to explore microstructural, compositional, cellular, and mechanical properties of the mandible in ALC individuals compared with a healthy control group. Materials and methods: Mandible bone cores of mаle individuаls with ALC (n = 6; age: 70.8 ± 2.5 yeаrs) and age-matched healthy controls (n = 11; age: 71.5 ± 3.8 yeаrs) were obtаined postmortem during аutopsy from the edentulous аlveolаr bone in the mandibular first molаr region аnd the mаndibulаr аngulus region of each individual. Micro-computed tomogrаphy wаs used to аssess bone microstructure. Analyses based on quаntitаtive bаckscаttered electron microscopy included the characterization of osteon morphology, osteocyte lаcunаr properties, and bone mаtrix minerаlizаtion. Composition of bone minerаl аnd collаgen phаses was assessed by Rаmаn spectroscopy. Histomorphometry wаs used to determine cellulаr аnd tissue chаrаcteristics of bone specimens. Vickers microhardness test was used to evaluate cortical bone mechanical properties. Results: The ALC group showed higher closed cortical porosity (volume of pores thаt do not communicаte with the sаmple surfаce) (p = 0.003) and smaller lacunar area in the trabecular bone of the molar region (p = 0.002) compared with the Control group. The trabecular bone of the angulus region showed lower osteoclast number (p = 0.032) in the ALC group. There were higher carbonate content in the buccal cortex of the molar region (p = 0.008) and lower calcium content in the trabecular bone of the angulus region (p = 0.042) in the ALC group. The cortical bone showed inferior mechanical properties in the ALC cortical bony sites (p < 0.001), except for the buccal cortex of the molar region (p = 0.063). There was no significant difference in cortical thickness between the groups. Conclusions: Bone quality is differentially altered in ALC in two bony sites and compartments of the mandible, which leads to impaired mechanical properties. Clinical relevance: Altered mandible bone tissue characteristics in patients with ALC should be considered by dental medicine professionals prior to oral interventions in these patients. Knowledge about mandible bone quality alterations in ALC is valuable for determining diagnosis, treatment plan, indications for oral rehabilitation procedures, and follow-up procedures for this group of patients. © 2024 Elsevier Inc.

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.

Context: The tumorigenic mechanisms involved in pituitary adenomas, especially of nonfunctional pituitary adenomas (NFAs), remains unclear. Various cell cycle inhibitors have been found to be underexpressedinpituitarytumors; however, Wee1 kinase, a nuclear protein that delays mitosis and was recently recognized as a tumor suppressor gene, has not been previously investigated in pituitary tumors. Objective: Our objective was to examine the expression of Wee1 in pituitary tumors and to identify microRNAs (miRs) that can regulate its expression. Design: Expression of Wee1 was examined by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Identification of miRs targeting the Wee1 3́-untranslated region was performed bymiRarray followed by expression analysis of identified miRs using qRT-PCR. Dual-luciferase assay and transient transfection of miRs into Hela cells followed by immunoblot analysis of Wee1 protein and cell proliferation analysis were carried out. Patients: A total of 57 pituitary tissue samples including 27 NFAs, 15 GH-producing adenomas with or without prolactin overproduction, and 15 normal pituitary glands were analyzed. Results: Wee1 protein expression was decreased in NFAs and GH-producing tumors with or without prolactin production, but no change in mRNA expression was observed with qRT-PCR. A specific subset of five miRNAs revealed by in silico target prediction was significantly overexpressed in NFA samples; three miRs (miR-128a, miR-155, and miR-516a-3p) targeted the 3′-untranslated region of the Wee1 transcript, and exogenous overexpression of these miRs inhibited Wee1 protein expression and HeLa cell proliferation. Conclusions: To our knowledge, this is the first report suggesting that regulation of Wee1 kinase by miRs may be linked to pituitary tumorigenesis. Copyright © 2010 by The Endocrine Society.

Context: The tumorigenic mechanisms involved in pituitary adenomas, especially of nonfunctional pituitary adenomas (NFAs), remains unclear. Various cell cycle inhibitors have been found to be underexpressedinpituitarytumors; however, Wee1 kinase, a nuclear protein that delays mitosis and was recently recognized as a tumor suppressor gene, has not been previously investigated in pituitary tumors. Objective: Our objective was to examine the expression of Wee1 in pituitary tumors and to identify microRNAs (miRs) that can regulate its expression. Design: Expression of Wee1 was examined by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Identification of miRs targeting the Wee1 3́-untranslated region was performed bymiRarray followed by expression analysis of identified miRs using qRT-PCR. Dual-luciferase assay and transient transfection of miRs into Hela cells followed by immunoblot analysis of Wee1 protein and cell proliferation analysis were carried out. Patients: A total of 57 pituitary tissue samples including 27 NFAs, 15 GH-producing adenomas with or without prolactin overproduction, and 15 normal pituitary glands were analyzed. Results: Wee1 protein expression was decreased in NFAs and GH-producing tumors with or without prolactin production, but no change in mRNA expression was observed with qRT-PCR. A specific subset of five miRNAs revealed by in silico target prediction was significantly overexpressed in NFA samples; three miRs (miR-128a, miR-155, and miR-516a-3p) targeted the 3′-untranslated region of the Wee1 transcript, and exogenous overexpression of these miRs inhibited Wee1 protein expression and HeLa cell proliferation. Conclusions: To our knowledge, this is the first report suggesting that regulation of Wee1 kinase by miRs may be linked to pituitary tumorigenesis. Copyright © 2010 by The Endocrine Society.

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/ Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within -214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas. © 2012 Society for Endocrinology.

C-type natriuretic peptide (CNP/Nppc) is expressed at high levels in the anterior pituitary of rats and mice and activates guanylyl cyclase B receptors (GC-B/ Npr2) to regulate hormone secretion. Mutations in NPR2/Npr2 can cause achondroplasia, GH deficiency, and female infertility, yet the normal expression profile within the anterior pituitary remains to be established in humans. The current study examined the expression profile and transcriptional regulation of NPR2 and GC-B protein in normal human fetal pituitaries, normal adult pituitaries, and human pituitary adenomas using RT-PCR and immunohistochemistry. Transcriptional regulation of human NPR2 promoter constructs was characterized in anterior pituitary cell lines of gonadotroph, somatolactotroph, and corticotroph origin. NPR2 was detected in all human fetal and adult pituitary samples regardless of age or sex, as well as in all adenoma samples examined regardless of tumor origin. GC-B immunoreactivity was variable in normal pituitary, gonadotrophinomas, and somatotrophinomas. Maximal transcriptional regulation of the NPR2 promoter mapped to a region within -214 bp upstream of the start site in all anterior pituitary cell lines examined. Electrophoretic mobility shift assays revealed that this region contains Sp1/Sp3 response elements. These data are the first to show NPR2 expression in normal human fetal and adult pituitaries and adenomatous pituitary tissue and suggest a role for these receptors in both pituitary development and oncogenesis, introducing a new target to manipulate these processes in pituitary adenomas. © 2012 Society for Endocrinology.

In 2011, small mass grave with completely skeletonized remains was discovered in Belgrade suburb. An eyewitness claimed that skeletons belonged to German soldiers killed in WWII. Anthropologists were engaged to investigate whether the skeletal remains correspond to the indicated German group or represent more recent case requiring court trial. Numerous dental restorations were noticed. Owing to the fact that different dental materials were used in dental practice at certain times, the aim of this study was to explore whether analysis of dental restorations could help in identification and estimation of time since death. Inductively coupled plasma optical emission spectrometry revealed that dental fillings corresponded to copper amalgam, conventional silver amalgam, silicophosphate cement, and zinc phosphate cement. Chemical results combined with anthropological and historical facts suggest that the individuals lived before the 1960s in country with well-developed dental service at that time. Therefore, chemical analysis of dental fillings was useful to distinguish between skeletal remains that are too old to be of forensic interest and the remains relevant to legal investigations. © 2013 American Academy of Forensic Sciences.

In 2011, small mass grave with completely skeletonized remains was discovered in Belgrade suburb. An eyewitness claimed that skeletons belonged to German soldiers killed in WWII. Anthropologists were engaged to investigate whether the skeletal remains correspond to the indicated German group or represent more recent case requiring court trial. Numerous dental restorations were noticed. Owing to the fact that different dental materials were used in dental practice at certain times, the aim of this study was to explore whether analysis of dental restorations could help in identification and estimation of time since death. Inductively coupled plasma optical emission spectrometry revealed that dental fillings corresponded to copper amalgam, conventional silver amalgam, silicophosphate cement, and zinc phosphate cement. Chemical results combined with anthropological and historical facts suggest that the individuals lived before the 1960s in country with well-developed dental service at that time. Therefore, chemical analysis of dental fillings was useful to distinguish between skeletal remains that are too old to be of forensic interest and the remains relevant to legal investigations. © 2013 American Academy of Forensic Sciences.

Purpose: The Roma constitute a large ethnic minority in Serbia, and are one of the poorest and most marginalized groups in Europe. Roma youth may be at high risk for hepatitis C, HIV, and other sexually transmitted infections, but little is known about the prevalence of these infectious diseases, HIV-related knowledge, and risky sexual behaviors in this vulnerable population. Methods: We used a respondent-driven sampling to conduct biobehavioral surveys of Roma youth (aged 15-24 years) in Belgrade and Kragujevac, and to document HIV-related knowledge and risky sexual behaviors, health-seeking behaviors, and seroprevalence of HIV, hepatitis C virus (HCV), and syphilis. Results: Four hundred eleven Roma youth participated in this study. One participant had HIV, four had HCV, and none had syphilis. Risky sexual behaviors were highly prevalent, especially among male subjects: 36.2% (Belgrade) and 45.1% (Kragujevac) had sexual debut before the age of 15 years; 53.9% (Belgrade) and 61.1% (Kragujevac) had more than one sexual partner in the past year; 11.5% (Belgrade) and 4.6% (Kragujevac) reported engaging in commercial sex; and 4.0% (Belgrade) and 3.2% (Kragujevac) reported having anal sex with other men. Among female subjects aged <25 years, 33.5% (Belgrade) and 25.7% (Kragujevac) reported having an abortion. One-quarter of all participants answered all five HIV knowledge questions correctly. Conclusions: Fortunately, the current prevalence of HIV, HCV, and syphilis is low; however, the high prevalence of reported risky behaviors suggests that Roma youth in Serbia are at high risk of contracting sexually transmitted infections. © 2013 Society for Adolescent Health and Medicine. All rights reserved.

To improve our understanding of hyperostosis frontalis interna (HFI), we investigated whether HFI was accompanied by changes in the postcranial skeleton. Based on head CT scan analyses, 103 postmenopausal women were divided into controls without HFI and those with HFI, in whom we measured the thickness of frontal, occipital, and parietal bones. Women in the study underwent dual energy x-ray absorptiometry to analyze the bone density of the hip and vertebral region and external geometry of the proximal femora. Additionally, all of the women completed a questionnaire about symptoms and conditions that could be related to HFI. Women with HFI had a significantly higher prevalence of headaches, neurological and psychiatric disorders, and a significantly lower prevalence of having given birth. Increased bone thickness and altered bone structure in women with HFI was localized only on the skull, particularly on the frontal bone, probably due to specific properties of its underlying dura. Bone loss in the postcranial skeleton showed the same pattern in postmenopausal women with HFI as in those without HFI. Recording of HFI in medical records can be helpful in distinguishing whether reported disorders occur as a consequence of HFI or are related to other diseases, but does not appear helpful in identifying women at risk of bone loss. © 2016 Taylor & Francis.

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.

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. © 2024 Oxford University Press. All rights reserved.

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.