Browsing by Author "Milovanovic, Petar (25927301300)"

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

Background: Cameriere’s method has been tested in many populations and is widely accepted for dental age estimation. Aim: To establish a new formula for age estimation by measurement of open apices of mandibular teeth based on Cameriere’s European formula. Subjects and methods: Panoramic radiographs of 333 healthy Serbian children aged 5–14 years were analysed by two independent researchers. The new formula–Belgrade Age Formula (BAF)–was created and tested on the same Serbian sample. Furthermore, BAF was tested on the Serbian validation sample of 126 children and 2115 Italian children aged 5–14 years. Results: In the Serbian sample, the residuals of the BAF and European formula demonstrated that BAF is significantly better in age estimation than the European formula. No significant difference was found in females from the Serbian validation sample between dental and chronological age when BAF was applied. For males, the BAF and European formula had similar accuracy. In the Italian sample, the mean differences between estimated and real age for the European formula were −0.214 ± 0.934 and 0.109 ± 0.773 for females and males, respectively, while for BAF these differences were 0.182 ± 0.951 and −0.195 ± 0.923 for females and males, respectively. Conclusion: BAF was found to be accurate in the Serbian and Italian populations. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Background: Cameriere’s method has been tested in many populations and is widely accepted for dental age estimation. Aim: To establish a new formula for age estimation by measurement of open apices of mandibular teeth based on Cameriere’s European formula. Subjects and methods: Panoramic radiographs of 333 healthy Serbian children aged 5–14 years were analysed by two independent researchers. The new formula–Belgrade Age Formula (BAF)–was created and tested on the same Serbian sample. Furthermore, BAF was tested on the Serbian validation sample of 126 children and 2115 Italian children aged 5–14 years. Results: In the Serbian sample, the residuals of the BAF and European formula demonstrated that BAF is significantly better in age estimation than the European formula. No significant difference was found in females from the Serbian validation sample between dental and chronological age when BAF was applied. For males, the BAF and European formula had similar accuracy. In the Italian sample, the mean differences between estimated and real age for the European formula were −0.214 ± 0.934 and 0.109 ± 0.773 for females and males, respectively, while for BAF these differences were 0.182 ± 0.951 and −0.195 ± 0.923 for females and males, respectively. Conclusion: BAF was found to be accurate in the Serbian and Italian populations. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Background. Age- and sex-specific 3D bone structure patterns in human radii and tibiae were investigated with respect to individuals' osteodensitometric status to unravel associations with site-specific fracture occurrences and underlying loading patterns. Methods. A sample of 385 patients (121 men and 264 women, age range: 23-91 years) were investigated. The patients were classified according to dual X-ray absorptiometry T-scores in three groups: control (n = 60), osteopenia (n = 160), and osteoporosis (n = 165). Bone architecture and geometry were assessed by high-resolution peripheral quantitative computed tomography of the cortical and trabecular compartments in distal radii and tibiae. Results. We found site-dependent age- and sex-related trends regarding bone architecture and geometry. Females displayed more pronounced age-related changes than males. Specifically, female radii showed both cortical and trabecular structural deterioration with aging, whereas the tibiae demonstrated exclusively cortical deterioration. The mean cortical perimeter revealed a significant age-related increase for both sexes even after adjusting for body height and weight, which suggests that periosteal expansion can be observed in both the tibia and also in the radius. Osteopenia and osteoporosis cases did not reveal higher cortical perimeters in comparison to controls. Conclusions. The tomographic assessment of bone structure further clarifies the architectural basis for increased bone fragility at distal radii and tibiae with advanced age leading to fracture predilection in females. Our findings may represent a morphological link to epidemiological data on age-dependent fracture incidences. Our data support the presence of periosteal apposition at both skeletal sites despite different loading magnitudes, and challenges the view on periosteal expansion just as a compensatory mechanism to counterbalance bone loss. © 2015 The Author.

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

There is an increasing interest in bone nano-structure, the ultimate goal being to reveal the basis of age-related bone fragility. In this study, power spectral density (PSD) data and fractal dimensions of the mineralized bone matrix were extracted from atomic force microscope topography images of the femoral neck trabeculae. The aim was to evaluate age-dependent differences in the mineralized matrix of human bone and to consider whether these advanced nano-descriptors might be linked to decreased bone remodeling observed by some authors and age-related decline in bone mechanical competence. The investigated bone specimens belonged to a group of young adult women (n = 5, age: 20-40 years) and a group of elderly women (n = 5, age: 70-95 years) without bone diseases. PSD graphs showed the roughness density distribution in relation to spatial frequency. In all cases, there was a fairly linear decrease in magnitude of the power spectra with increasing spatial frequencies. The PSD slope was steeper in elderly individuals (-2.374 vs. -2.066), suggesting the dominance of larger surface morphological features. Fractal dimension of the mineralized bone matrix showed a significant negative trend with advanced age, declining from 2.467 in young individuals to 2.313 in the elderly (r = 0.65, P = 0.04). Higher fractal dimension in young women reflects domination of smaller mineral grains, which is compatible with the more freshly remodeled structure. In contrast, the surface patterns in elderly individuals were indicative of older tissue age. Lower roughness and reduced structural complexity (decreased fractal dimension) of the interfibrillar bone matrix in the elderly suggest a decline in bone toughness, which explains why aged bone is more brittle and prone to fractures. © 2012 The Authors Journal of Anatomy © 2012 Anatomical Society.

Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6 ± 11.5. yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>. 10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover. © 2013 Elsevier Inc.

Osteoclasts are unique cells capable of bone resorption and therefore have become a major target in osteoporosis treatment strategies. Bisphosphonates suppress bone turnover via interference with the internal enzymatic cell system of osteoclasts leading to cytoskeletal disruption. This mechanism found its clinical relevance in reducing bone resorption, stabilizing bone mass and reducing fracture risk in osteoporosis patients. However, knowledge about specific in vivo changes in osteoclast cell morphology and function is still insufficient. We examined osteoclasts in 23 paired bone biopsies from osteoporosis patients (18 males, 5 females; age: 52.6 ± 11.5. yrs) under nitrogen-containing bisphosphonate administration with a mean treatment duration of three years. Formalin-fixed, undecalcified sections were assessed by qualitative and quantitative bone histomorphometry, where the osteoclast morphology, nuclei, distribution, location as well as resorption parameters were investigated to obtain information about cell function and viability. After three years of treatment, resorption parameters decreased significantly while the number of osteoclasts remained unchanged. Out of 23 patients, nine developed previously termed "giant-osteoclasts" with increased size, numerous nuclei (>. 10 nuclei/Oc) and oftentimes detachment from the bone surface. These cells frequently had pycnotic nuclei and other morphological signs suggestive of osteoclast apoptosis. Characteristic large-sized osteoclasts were uniquely found in patients treated with nitrogen-containing bisphosphonates, thus being clearly distinguishable from giant-osteoclasts in other bone disorders such as Paget disease, secondary hyperparathyroidism or osteopetrosis. The resorption indices of large-sized osteoclasts, specifically the eroded perimeter and erosion depth, revealed significantly reduced values but not an entirely inhibited resorption capability. Bisphosphonate-osteoclasts' viability and affinity to bone seem significantly disturbed while the apoptotic process may be prolonged for a yet unknown period of time in favor of maintaining a low bone turnover. © 2013 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.

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.

Cement lines are known as thin peripheral boundaries of the osteons. With a thickness below 5 μm their composition of inorganic and organic compounds has been a matter of debate. Here, we hypothesized that cement lines become hypermineralized and their degree of mineralization is not constant but related to the tissue age of the osteon. Therefore, we analyzed the calcium content of osteons and their corresponding cement lines in a range of different tissue ages reflected by osteonal mineralization levels in femoral cortical bone of both postmenopausal women with osteoporosis and bisphosphonate-treated cases. Quantitative backscattered electron imaging (qBEI) showed that cement lines are hypermineralized entities with consistently higher calcium content than their corresponding osteons (mean calcium content: 29.46 ± 0.80 vs. 26.62 ± 1.11 wt%; p < 0.001). Micro-Raman spectroscopy complemented the qBEI data by showing a significantly higher phosphate/amide I ratio in the cement lines compared to the osteonal bone (8.78 ± 0.66 vs. 6.33 ± 0.58, p < 0.001), which was both due to an increased phosphate peak and a reduced amide I peak in cement lines. A clear positive correlation of cement line mineralization and the mineralization of the osteon was observed (r = 0.839, p = 0.003). However, the magnitude of the difference between cement line and osteonal calcium content decreased with increased osteonal calcium content (r = −0.709, p < 0.001), suggesting diverging mineralization dynamics in these osseous entities. The number of mineralized osteocyte lacunae per osteon bone area correlated positively with both osteonal and cement line calcium content (p < 0.01). The degree of mineralization of cement lines may represent another tissue-age related phenomenon, given that it strongly relates to the osteonal mineralization level. Understanding of the cement lines' mineralization and their changes in aging and disease states is important for predicting crack propagation pathways and fracture resistance mechanisms in human cortical bone. © 2018 Elsevier Inc.

Cement lines are known as thin peripheral boundaries of the osteons. With a thickness below 5 μm their composition of inorganic and organic compounds has been a matter of debate. Here, we hypothesized that cement lines become hypermineralized and their degree of mineralization is not constant but related to the tissue age of the osteon. Therefore, we analyzed the calcium content of osteons and their corresponding cement lines in a range of different tissue ages reflected by osteonal mineralization levels in femoral cortical bone of both postmenopausal women with osteoporosis and bisphosphonate-treated cases. Quantitative backscattered electron imaging (qBEI) showed that cement lines are hypermineralized entities with consistently higher calcium content than their corresponding osteons (mean calcium content: 29.46 ± 0.80 vs. 26.62 ± 1.11 wt%; p < 0.001). Micro-Raman spectroscopy complemented the qBEI data by showing a significantly higher phosphate/amide I ratio in the cement lines compared to the osteonal bone (8.78 ± 0.66 vs. 6.33 ± 0.58, p < 0.001), which was both due to an increased phosphate peak and a reduced amide I peak in cement lines. A clear positive correlation of cement line mineralization and the mineralization of the osteon was observed (r = 0.839, p = 0.003). However, the magnitude of the difference between cement line and osteonal calcium content decreased with increased osteonal calcium content (r = −0.709, p < 0.001), suggesting diverging mineralization dynamics in these osseous entities. The number of mineralized osteocyte lacunae per osteon bone area correlated positively with both osteonal and cement line calcium content (p < 0.01). The degree of mineralization of cement lines may represent another tissue-age related phenomenon, given that it strongly relates to the osteonal mineralization level. Understanding of the cement lines' mineralization and their changes in aging and disease states is important for predicting crack propagation pathways and fracture resistance mechanisms in human cortical bone. © 2018 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.

[No abstract available]

Objective: To assess dental age and deviations of dental from chronological age according to the Willems and Cameriere methods (European formula) in patients with cleft lip and/or cleft palate (CL/P) and compare it with control group. Design: Retrospective cross-sectional study. Setting: Clinic of Orthodontics. Participants: Sixty-nine patients with CL/P between 6 and 15 years of age (55 with unilateral and 14 with bilateral CL/P) with 148 panoramic radiographs. The same number of radiographs was examined in the age-matched control group. Main Outcome Measures: Estimation and comparison of dental age and differences of dental from chronological age in relation to the type of cleft, sex, and age in the group of patients with and without CL/P according to Willems and Cameriere method. Results: No significant intersex and intergroup differences were found in deviations of dental from chronological age according to Cameriere method (P >.05). Significant difference in deviation of dental from chronological age was found between the patients with and without CL/P according to Willems method (P <.001). Conclusion: Cameriere European formula for dental age estimation, which is not influenced by sex and tooth morphology, showed similar dental development of children with and without CL/P. However, Willems method detected that deviation of dental from chronological age significantly differed between children with and without clefts. © American Cleft Palate-Craniofacial Association. All rights reserved 2021.

Objective: To assess dental age and deviations of dental from chronological age according to the Willems and Cameriere methods (European formula) in patients with cleft lip and/or cleft palate (CL/P) and compare it with control group. Design: Retrospective cross-sectional study. Setting: Clinic of Orthodontics. Participants: Sixty-nine patients with CL/P between 6 and 15 years of age (55 with unilateral and 14 with bilateral CL/P) with 148 panoramic radiographs. The same number of radiographs was examined in the age-matched control group. Main Outcome Measures: Estimation and comparison of dental age and differences of dental from chronological age in relation to the type of cleft, sex, and age in the group of patients with and without CL/P according to Willems and Cameriere method. Results: No significant intersex and intergroup differences were found in deviations of dental from chronological age according to Cameriere method (P >.05). Significant difference in deviation of dental from chronological age was found between the patients with and without CL/P according to Willems method (P <.001). Conclusion: Cameriere European formula for dental age estimation, which is not influenced by sex and tooth morphology, showed similar dental development of children with and without CL/P. However, Willems method detected that deviation of dental from chronological age significantly differed between children with and without clefts. © American Cleft Palate-Craniofacial Association. All rights reserved 2021.

Aims: To test the applicability of European formula for dental maturity estimation in non-adults on Serbian sample and compare its accuracy with Willems’ age estimation method. Materials and methods: Panoramic radiographs of 423 children (192 boys and 231 girls) aged between 5 to 15 were evaluated. Willems’ method and European formula were applied to estimate dental age. Intra-class correlation (ICC) coefficients between estimated age and chronological age for each method and sex were reported separately. Furthermore, the percentage of individuals with estimated age within error range of ±0.5 year was calculated. Results: Total sample was divided into three groups (<7 years, 7–13 years, ≥13 years). In individuals younger than 7 years, the highest ICC coefficients were achieved with European formula (0.609 in girls and 0.487 in boys). Willems’ method showed better ICC coefficients in individuals older than 13 years (0.378 in girls and 0.600 in boys). In individuals between 7 and 13 years, ICC coefficients were between 0.800 and 0.900 with both methods European formula estimated the age in 47.6% of girls and 42.5% of boys within error range of ±0.5 year. Willems’ method reported similar results (45.4% in girls and 40.4% in boys). Conclusions: The Willems’ method is more appropriate for individuals older than 13 years. European formula gives better results for individuals younger than 7 years. In individuals between 7 and 13 years there is no significant difference between European formula and Willems’ method, yet, European formula was found to be slightly more accurate. © 2018 Elsevier B.V.

Abstract: Ectopic calcifications occur in tendons, ligaments, entheses, muscles, and fasciae, and are often associated with pain and inflammation. In clinical settings, these calcifications are commonly treated by physical therapy and/or surgical interventions. However, there is not enough understanding of pharmacological treatments as primary cures, supportive therapy to physical or surgical treatment, or even preventive measures to avoid or diminish the development of ectopic calcifications. Here, we summarize preclinical and clinical evidence for pharmacological candidates for treatment/prevention of ectopic calcification in the context of painful syndromes in the musculoskeletal field. Specifically, we discuss the potential mechanisms of nonsteroidal anti-inflammatory drugs, corticosteroids, H2-receptor blockers, bisphosphonates, minocycline, biologics, ACTH analogues, colchicine, calcium channel blockers, vitamins K2 and D, magnesium, zinc, curcumin, and phytates. Given that ectopic calcification is sometimes paradoxically associated with reduced bone mineralization, it appears particularly reasonable to employ strategies that can both inhibit ectopic calcification and promote bone mineralization, such as bisphosphonates and the combination of vitamin K2 and vitamin D, along with other supplements such as magnesium and zinc. Future studies need to test whether differential therapeutic approaches are needed in different phases of the disease and whether different mechanisms of ectopic calcification require different therapeutic strategies. A precondition for such approaches is further clinical and/or imaging delineation and differentiation of various types and phases of calcific diseases. Finally, it is essential to ensure that anti-calcification effects of new treatment strategies do not harm bone formation and skeletal mineralization. © The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR) 2025.

Background: Doctoral programmes are an important pillar of medical education, and although many universities award the best theses, the criteria for selection of awardees and the topics of their doctoral theses are seldom analysed. Objectives: To analyse the landscape of doctoral research through assessing the temporal trends in the criteria related to recognising the best theses. Methods: A total of 55 award-winning doctoral theses, from those submitted to the Faculty of Medicine, University of Belgrade, over 7 years (2016–2022), were examined, focusing on the number of awardees, publications based on the theses, research subfields, and keywords. Results: The awardees comprised 36 women (65%) and 19 men (35%). The number of award-winning theses per year in clinical medicine and public health increased over the years (P < .05 for both the fields). The awardees had published a total of 134 articles based on their theses before the thesis defence, and half of these were published in open-access journals. The journals that each published at least 4 of these articles were PLOS One, Experimental and Molecular Pathology, and Oxidative Medicine and Cellular Longevity. The cumulative impact factor of these publications showed no significant increase (P > .05). The subfields that accounted for at least 5 of the publications were molecular medicine (13 publications) among the basic or translational fields, cardiology (5) among clinical medicine, and epidemiology (7) among public health. Mapping the co-occurrence of keywords from all the dissertations identified some research hotspots, which included cancer, oxidative stress, Parkinsonism, risk factors, genetic polymorphisms, and biomarkers. Conclusion: The increasing number of award-winning theses reflects the rising quality of doctoral research and the growing motivation of candidates to choose indexed journals as outlets for papers based on the theses. This approach can serve as a basis for strategic evaluation of the practices for evaluating PhD theses and for identifying strong and weak spots in the research landscape of medical schools to guide future doctoral research and the competitiveness of doctoral programmes. © 2025 the authors.