Normal Bone Research Articles

Case report– Periapical cemento-osseous dysplasia–CBCT findings

Case report– Periapical cemento-osseous dysplasia–CBCT findings

Osteosarcopenia and Mortality in Older Adults Undergoing Transcatheter Aortic Valve Replacement

Osteosarcopenia is an emerging geriatric syndrome characterized by age-related deterioration in muscle and bone. Despite the established relevance of frailty and sarcopenia among older adults undergoing transcatheter aortic valve replacement (TAVR), osteosarcopenia has yet to be investigated in this setting. To determine the association between osteosarcopenia and adverse outcomes following TAVR. This is a post hoc analysis of the Frailty in Aortic Valve Replacement (FRAILTY-AVR) prospective multicenter cohort study and McGill extension that enrolled patients aged 70 years or older undergoing TAVR from 2012 through 2022. FRAILTY-AVR was conducted at 14 centers in Canada, the United States, and France between 2012 and 2016, and patients at the McGill University-affiliated center in Montreal, Québec, Canada, were enrolled on an ongoing basis up to 2022. Osteosarcopenia as measured on computed tomography (CT) scans prior to TAVR. Clinically indicated CT scans acquired prior to TAVR were analyzed to quantify psoas muscle area (PMA) and vertebral bone density (VBD). Osteosarcopenia was defined as a combination of low PMA and low VBD according to published cutoffs. The primary outcome was 1-year all-cause mortality. Secondary outcomes were 30-day mortality, hospital length of stay, disposition, and worsening disability. Multivariable logistic regression was used to adjust for potential confounders. Of the 605 patients (271 [45%] female) in this study, 437 (72%) were octogenarian; the mean (SD) age was 82.6 (6.2) years. Mean (SD) PMA was 22.1 (4.5) cm2 in men and 15.4 (3.5) cm2 in women. Mean (SD) VBD was 104.8 (35.5) Hounsfield units (HU) in men and 98.8 (34.1) HU in women. Ninety-one patients (15%) met the criteria for osteosarcopenia and had higher rates of frailty, fractures, and malnutrition at baseline. One-year mortality was highest in patients with osteosarcopenia (29 patients [32%]) followed by those with low PMA alone (18 patients [14%]), low VBD alone (16 patients [11%]), and normal bone and muscle status (21 patients [9%]) (P < .001). Osteosarcopenia, but not low VBD or PMA alone, was independently associated with 1-year mortality (odds ratio [OR], 3.18; 95% CI, 1.54-6.57) and 1-year worsening disability (OR, 2.11; 95% CI, 1.19-3.74). The association persisted in sensitivity analyses adjusting for the Essential Frailty Toolset, Clinical Frailty Scale, and geriatric conditions such as malnutrition and disability. The findings suggest that osteosarcopenia detected using clinical CT scans could be used to identify frail patients with a 3-fold increase in 1-year mortality following TAVR. This opportunistic method for osteosarcopenia assessment could be used to improve risk prediction, support decision-making, and trigger rehabilitation interventions in older adults.

Opportunistic prediction of osteoporosis in patients with degenerative lumbar diseases: a simplified T12 vertebral bone quality approach

BackgroundOsteoporosis is one of the risk factors for screw loosening after lumbar fusion. However, the probability of preoperative osteoporosis screening in patients with lumbar degenerative disease is low. Therefore, the aim of this study was to investigate whether a simplified vertebral bone quality (VBQ) score based on T12 T1-MRI could opportunistically predict osteoporosis in patients with degenerative lumbar spine diseases.MethodsWe retrospectively analyzed cases treated for lumbar degenerative diseases at a single institution between August 2021 and June 2022. The patients were divided into three groups by the lowest T-score: osteoporosis group, osteopenia group, and normal bone mineral density (BMD) group. The signal intensity based on the T12 vertebral body divided by the signal intensity of the cerebrospinal fluid was calculated to obtain the simplified VBQ score, as well as the CT-based T12HU value and the traditional L1-4VBQ score. Various statistical analyses were used to compare VBQ, HU and DEXA, and the optimal T12VBQ threshold for predicting osteoporosis was obtained by plotting the receiver operating curve (ROC) analysis.ResultsTotal of 166 patients were included in this study. There was a statistically significant difference in T12VBQ scores between the three groups (p < 0.001). Pearson correlation showed that there was a moderate correlation between T12VBQ and T-score (r=-0.406, p < 0.001). The AUC value of T12VBQ, which distinguishes between normal and low BMD, was 0.756, and the optimal diagnostic threshold was 2.94. The AUC value of T12VBQ, which distinguishes osteoporosis from non-osteoporosis, was 0.634, and the optimal diagnostic threshold was 3.18.ConclusionT12VBQ can be used as an effective opportunistic screening method for osteoporosis in patients with lumbar degenerative diseases. It can be used as a supplement to the evaluation of DEXA and preoperative evaluation.Trial registrationretrospectively registered number:1502-009-644; retrospectively registered number date:27 oct 2022.

Outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning.

To report the outcomes of 15 dogs and two cats with metabone fractures treated with fluoroscopically guided normograde metabone pinning (FGNMP). Retrospective case series. A total of 15 client owned dogs and two cats with 57 metabone fractures. Description of FGNMP and reporting of the following data: signalment, pre- and postoperative radiographs, intramedullary pin diameter used, anesthesia, surgery and coaptation times, duration to normal weightbearing and bone union, postoperative care and complications. Median surgery time was 54 min (range: 26-99), median duration of coaptation was 14 days (range: 1-5 weeks), median time to normal weightbearing was 16 days (range: 2-45) and median time to bone union was 6 weeks (range: 4-12). All cases had at least 12 months of post-surgical follow-up with a median follow-up of 18 months (range: 12-70). No major complications occurred. Mild radiographic changes associated with subchondral bone sclerosis were noted on follow-up radiographs in 13/57 fractures. All cases returned to normal gait and full (15) or acceptable (2) function. In this study, FGNMP was an effective and safe technique for metabone fracture repair, requiring only short-term external coaptation in most patients. Time to bone union and return to normal function compared favorably to previously reported techniques. Fluoroscopically guided normograde metabone pinning provides an alternative technique for treatment of metabone fractures.

Osteoporosis Prediction Using VGG16 and ResNet50

Low bone mass and structural degradation are the hallmarks of osteoporosis, a disorder that increases the risk of fractures, especially in the elderly. For prompt intervention and fracture prevention, early identification is essential. However, osteoporosis is frequently not detected until advanced stages by existing diagnostic techniques. In order to overcome this difficulty, scientists suggest using machine learning to automatically identify osteoporosis early in X-ray pictures. Utilizing two cutting- edge convolutional neural network architectures, ResNet50 and VGG16, their system was pretrained on extensive datasets and refined on a carefully selected dataset of X-ray pictures. When identifying images as suggestive of osteoporosis or normal bone density, the ResNet50 model showed an accuracy of 98%, whereas the VGG16 model achieved 78% accuracy. By combining these models and using sophisticated image segmentation methods, the system detects early osteoporosis indications with an overall accuracy of 96%. This automated method has the potential to decrease the incidence of fractures linked to osteoporosis, enable early treatment initiation, and increase the rate of early diagnosis.

IRE1α pathway: A potential bone metabolism mediator.

Osteoblasts and osteoclasts collaborate in bone metabolism, facilitating bone development, maintaining normal bone density and strength, and aiding in the repair of pathological damage. Endoplasmic reticulum stress (ERS) can disrupt the intracellular equilibrium between osteoclast and osteoblast, resulting in dysfunctional bone metabolism. The inositol-requiring enzyme-1α (IRE1α) pathway-the most conservative unfolded protein response pathway activated by ERS-is crucial in regulating cell metabolism. This involvement encompasses functions such as inflammation, autophagy, and apoptosis. Many studies have highlighted the potential roles of the IRE1α pathway in osteoblasts, chondrocytes, and osteoclasts and its implication in certain bone-related diseases. These findings suggest that it may serve as a mediator for bone metabolism. However, relevant reviews on the role of the IRE1α pathway in bone metabolism remain unavailable. Therefore, this review aims to explore recent research that elucidated the intricate roles of the IRE1α pathway in bone metabolism, specifically in osteogenesis, chondrogenesis, osteoclastogenesis, and osteo-immunology. The findings may provide novel insights into regulating bone metabolism and treating bone-related diseases.

Study on liver tissue derived-extracellular vesicles regulating the osteogenic differentiation ability of mesenchymal stem cells and promoting the healing of jaw bone defects

Objective: To explore the biological process of liver tissue-derived extracellular vesicle (LT-EV) in promoting osteogenic differentiation of mesenchymal stem cells and healing of jaw defects to provide a feasible treatment method for the clinical treatment of jaw bone defects. Methods: Enzymatic hydrolysis and differential centrifugation were used to extract LT-EV, scanning electron microscopy, Western blotting, and nanoparticle tracking analyzers were used to identify and characterize LT-EV, and further to explore the biological functions of LT-EV through proteomics and Kyoto Encyclopedia of Genes and Genomes. Flow cytometry was used to detect LT-EV plasma concentration and to calculate the plasma half-life of LT-EV. Small animal in vivo imaging system was used to detect the biological distribution of LT-EV 24 hours after injection. Six C57BL/6 mice were divided into control group and LT-EV group (3 mice in each group) by simple random sampling method. All mice underwent jaw bone defect surgery and tail vein injection every 7 days (the control group was injected with phosphoric buffer saline, LT-EV group was injected with LT-EV), micro-CT was used to evaluate the degree of mouse jaw bone healing 28 days after surgery, HE staining was used to analyze the multi-organ biosafety of LT-EV, and immunofluorescence staining was used to detect the jaw bone expression of osteogenic marker proteins in the defect area. Human jaw bone mesenchymal stem cells (hJBMSC) induced by osteogenic differentiation were treated with LT-EV (obtained from orthognathic surgery patients provided by the Department of Traumatology and Orthognathic Surgery of School of Stomatology of The Fourth Military Medical University resected normal jaw bone fragments), and the difference in osteogenic differentiation ability between the hJBMSC group and the control group (phosphate buffer saline treatment) was compared, and the in vitro bone differentiation promoting effect of LT-EV was verified through alkaline phosphatase (ALP) staining and real-time fluorescence quantitative PCR. Results: The yield of LT-EV was high, and proteomics and Kyoto Encyclopedia of Genes and Genomes showed that LT-EV contained a series of proteins that regulated cell biological functions. LT-EV injected into the tail vein could reach the mouse jaw bone defect area and promote the regeneration and repair of the jaw bone defect [the bone volume fractions of the LT-EV group and the control group were (36.06±4.20)% and (18.58±5.61)%, respectively; t=4.32, P=0.013], and had good biosafety. LT-EV could promote osteogenic differentiation of hJBMSC in vitro. Compared to the control group, ALP staining and osteogenic gene expression levels were significantly enhanced after osteogenic differentiation of hJBMSC (P<0.05). Conclusions: LT-EV exhibits a high yield, ease of acquisition, high biological safety, and excellent bone-promoting effects. It holds promise as a novel cell-free therapy strategy for regenerating craniofacial bone defects.

Anatomical variations of Koerner's septum: a computed tomography-based, single-centered study.

Koerner's septum (KS) is a bony plate located at the junction of the petrous and squamous parts of the temporal bone. The reported prevalence of KS varied between studies. KS variations are associated with various pathologies and pose difficulties during surgeries. The study aims to determine the KS frequency in Omani patients and analyze its association with sex and side. The present study investigated the KS topography in 344 computed tomography (CT) scans of normal temporal bones of adult Omani patients at Sultan Qaboos University Hospital. The presence of KS and its parts (complete or incomplete), as well as its thickness at three anatomical landmarks were recorded. Additionally, sex and laterality differences in KS parameters were analyzed using a Chi-square test. The overall frequency of KS among Omani subjects was 39.5%. The complete KS was observed only in 14% of cases. The thickness of KS was 0.78 ± 0.21 mm, 0.93 ± 0.28 mm and 0.78 ± 0.21 mm at the head of the malleus (HM), the superior semicircular canal (SSC) and the tympanic sinus (TS), respectively (p<0.01). KS was present most constantly at the level of HM (64.7%), followed by SSC (57.4%), and less constantly at the level of TS (49.3%). KS frequency was similar in both males than females (41.9% vs 37.3%), with statistically insignificant difference (p = 0.38). No side differences were observed concerning KS frequency (p = 0.955). The KS frequency in Omani subjects within the range of previously reported studies. It is incomplete in most of the cases and constantly present at the level of HM. Its thickness is more at the level of SSC.

Relationship between paraspinal muscle properties and bone mineral density based on QCT in patients with lumbar disc herniation

ObjectiveIncreasing research suggests that paraspinal muscle fat infiltration may be a potential biological marker for the assessment of osteoporosis. Our aim was to investigate the relationship between lumbar paraspinal muscle properties on MRI and volumetric bone mineral density (vBMD) based on QCT in patients with lumbar disc herniation (LDH).MethodsA total of 383 patients (aged 24–76 years, 193 females) with clinically and radiologically diagnosed LDH were enrolled in this retrospective study. The muscle cross-sectional area (CSA) and the proton density fat fraction (PDFF) were measured for the multifidus (MF), erector spinae (ES) and psoas major (PS) at the central level of L3/4, L4/5 and L5/S1 on lumbar MRI. QCT was used to measure the vBMD of two vertebral bodies at L1 and L2 levels. Patients were divided into three groups based on their vBMD values: normal bone density group (> 120 mg/cm3), osteopenia group (80 to 120 mg/cm3) and osteoporosis group (< 80 mg/cm3). The differences in paraspinal muscle properties among three vBMD groups were tested by one-way ANOVA with post hoc analysis. The relationships between paraspinal muscle properties and vBMD were analyzed using Pearson correlation coefficients. Furthermore, the association between vBMD and paraspinal muscle properties was further evaluated using multiple linear regression analysis, with age and sex also included as predictors.ResultsAmong the 383 LDH patients, 191 had normal bone density, 129 had osteopenia and 63 had osteoporosis. In LDH patients, compared to normal and osteopenia group, paraspinal muscle PDFF was significantly greater in osteoporosis group, while paraspinal muscle CSA was lower (p < 0.001). After adjusting for age and sex, it was found that MF PDFF and PS CSA were found to be independent factors influencing vBMD (p < 0.05).ConclusionIn patients with LDH, paraspinal muscle properties measured by IDEAL-IQ sequence and lumbar MR scan were found to be related to vBMD. There was a correlation between the degree of paraspinal muscle PDFF and decreasing vBMD, as well as a decrease paraspinal muscle CSA with decreasing vBMD. These findings suggest that clinical management should consider offering tailored treatment options for patients with LDH based on these associations.

The Long-Term Natural History of Fibrous Dysplasia.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.

127 Utilizing predictive models for bone mineral content and bone mineral density as a tool to assess dietary phosphorous

Abstract Dietary phosphorous is a necessary nutrient for bone development in pigs at all stages of its growing. Deficiencies in phosphorous decrease bone mineral content (BMC) and bone mineral density (BMD) and may be a causative of lameness. However, the normal range expected in whole body (WB) and individual bones for BMC and BMD in commercial pigs has been poorly defined. Therefore, our objectives were to 1) model normal WB bone density at multiple timepoints in wean to finish pigs, and 2) determine the extent to which individual bone (femur and 3rd metatarsal) BMC and BMD could predict WB BMC and BMD. Mixed sex pigs [Camborough (1050) x 337, PIC] were utilized and included freshly weaned ~21 d (n = 8), ~44 d of age (n = 24), ~84 d of age (n = 24) and ~154 d of age (n = 24). Pigs were individually penned. Excluding weaning age, at each age group pigs were randomly assigned to diets adequate, marginally deficient, or deficient in available phosphorus (avP) and fed for 3, 4, and 6 wk (age group 44, 84, 154, respectively). Within each age group, diets were formulated to meet nutrient and energy requirements except for avP and pigs fed ad libitum. On-test and off-test body weight (BW) and feed intake and gain to feed ratio were assessed for each age group. At the end of each feeding period, all pigs were euthanized and WB, femur (F) and 3rd metatarsal (M) BMC and BMD determined by dual X-ray absorptiometry (DXA). Data were analyzed using linear and generalized additive models that predicted response variables (BMC or BMD) as a function of BW or age. Only pigs fed adequate avP diets were used in the model fit. Pigs fed adequate avP diets increased BMD with age (0.22, 0.42, 0.84 and 1.10 g/cm2, days of age 21, 44, 84 and 154 respectively, P &amp;lt; 0.001). Within day of age 84, marginally and deficient avP diets reduced BMC and BMD by 21 to 41% (P = 0.002) and 12 to 25% (P = 0.006), respectively. Within day of age 154, marginally and deficient avP diets reduced BMC and BMD by 9% (P = 0.05) and 6 to 8% (P = 0.06), respectively. Body weight record and individual bone (F and M) BMC and BMD from pigs fed deficient avP diets were used to predict WB BMC and BMD and the mean square error of prediction was selected as a criterion to evaluate the ability of the models to detect these inadequately fed pigs. Using the selected models, pigs fed nutritionally deficient diets were detected due to 2- to 7-fold increase in MSE of predicted WBMD or WBMC compared with pigs fed adequate diets. These models can be used to assess bone development and strength in growing pigs and to infer the adequacy of avP level supplied in their diets.

Evaluating osteoporosis and bone quality in the aging spine: modern considerations for surgical management in the geriatric population.

Surgical management paradigms of spinal pathologies in the aging population carry inherent substantial risks, with surgical complications being more prevalent among patients with osteoporosis compared to those with normal bone mineral density. In this narrative review, we aim to highlight important clinical understanding and considerations in perioperative evaluation and management of patients elected to undergo spinal surgery. Osteoporosis is a well-defined risk factor for mechanical complications following spinal surgery, and as such, perioperative optimization of bone health in the setting of surgery for geriatric patients remains a critical research area alongside intraoperative surgical augmentation techniques. Surgical techniques to circumvent challenges with instrumentation of poor bone mineral density have included augmentation of pedicle screw fixation, including segmental bicortical screw fixation techniques, cement augmentation with fenestrated screws, or use of expandable pedicle screws to improve bone-implant interface. Judicious selection of treatment modalities and subsequent perioperative optimization is paramount to minimize surgical complications. Contemporary guidelines and evolving paradigms in perioperative evaluation, optimization, and management of the aging spine include the advent of quantitatively evaluating computed tomography (CT) via assessment of the magnitude of Hounsfield units. Prescribing pharmacotherapeutic agents and monitoring bone health requires a multidisciplinary team approach, including endocrinologists and geriatricians to coordinate high-quality care for advanced-age patients who require surgical management of their spinal disorders.

Value of third-generation of VNCa dual-energy CT for differentiating diffuse marrow infiltration of multiple myeloma from red bone marrow.

This study aims to investigate the ability of bone marrow imaging using third-generation dual-energy computed tomography (CT) virtual noncalcium (VNCa) to differentiate between multiple myeloma (MM) with diffuse bone marrow infiltration and red bone marrow (RBM). Bone marrow aspiration or follow-up results were used as reference. We retrospectively reviewed 188 regions of interests (ROIs) from 21 patients with confirmed MM and diffuse bone marrow infiltrations who underwent VNCa bone marrow imaging between May 2019 and September 2022. At the same time, we obtained 98 ROIs from 11 subjects with RBM for comparative study, and 189 ROIs from 20 subjects with normal yellow bone marrow for the control group. The ROIs were delineated by 2 radiologists independently, the interobservers reproducibility was evaluated by interclass correlation coefficients. The correlation with MRI grade results was analyzed by Spearman correlation coefficient. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal threshold for differentiating between these groups and to assess diagnostic performance. There were statistically significant differences in VNCa CT values of bone marrow among the MM, RBM, and control groups (all P < .001), with values decreasing sequentially. A strong positive rank correlation was observed between normal bone marrow, subgroup MM with moderately and severe bone marrow infiltration divided by MRI and their corresponding CT values (ρ = 0.897, 95%CI: 0.822 to 0.942, P < .001). When the CT value of VNCa bone marrow was 7.15 HU, the area under the curve (AUC) value for differentiating RBM and MM was 0.723, with a sensitivity of 50.5% and a specificity of 89.8%. When distinguishing severe bone marrow infiltration of MM from RBM, the AUC value was 0.80 with a sensitivity 70.9% and a specificity 78.9%. The AUC values for MM, RBM, and the combined group compared to the control group were all >0.99, with all diagnostic sensitivity and specificity exceeding 95%. VNCa bone marrow imaging using third-generation dual-energy CT accurately differentiates MM lesions from normal bone marrow or RBM. It demonstrates superior diagnostic performance in distinguishing RBM from MM with diffuse bone marrow infiltration.

Benign fibro-osseous lesions: A retrospective study of sixty-four cases from a single institute, Riyadh, Saudi Arabia

ObjectiveBenign fibroosseous lesions (BFOLs) encompass a heterogenous collection of bone conditions characterized by replacing normal bone with fibro-collagenous tissue with osteoid or woven bone, and cementicles. Despite their clinical significance, the frequency of BFOLs in Saudi Arabia still needs to be assessed. MethodsThis retrospective study investigated the frequency and demographics of BFOLs in Riyadh, Saudi Arabia, by retrieving all cases recorded between January 1984 and January 2013 from a single Oral Pathology Laboratory archive. ResultsA total of 64 cases were classified as BFOLs, with a predominance in females (67.2 %) and a median age of 21.5 years. The most prevalent condition identified was fibrous dysplasia (45.31 %), followed by cemento-ossifying fibroma (26.56 %). There were significant sex differences between BFOLs, with a p-value of 0.03. FD was predominantly located in the maxilla (65.5 %), whereas COF was predominantly found in the mandible (82.3 %). Recurrence was observed in 17.2 % of patients with FD, in contrast to no reported recurrence in patients with COF. ConclusionThis study represents the first exploration of BFOL frequency and demographics in Riyadh, Saudi Arabia, highlighting the need for further investigations to comprehensively understand the nature of these lesions in our population.

Time to full weight-bearing with the use of a calcium sulfate-calcium phosphate bone substitute as a bone void filler following extended curettage in the treatment of primary benign bone tumours.

The primary objective of this study was to determine time to full weight-bearing after the use of a calcium-sulfate-calcium phosphate bone substitute (CaSO4/CaPO4) as a bone void filler in the treatment of primary benign bone tumours following intralesional curettage. The secondary objectives were to determine surgical complications and recurrence rates. Retrospective review of patients identified from a surgeon-specific orthopaedic oncology database, who underwent curettage of benign bone tumours and subsequent bone void filling with CaSO4/CaPO4. A total of 39 patients (20 males, 19 females) met inclusion criteria with an average age of 31years (range: 13 to 62years), a median follow-up of 3.7years, and a maximum follow-up of 11years. The most common tumour diagnosis was giant cell tumour of bone (GCT) (n = 19), and the most common location was the proximal tibia (n = 9). The mean volume of tumour excised was 74.1cm3 including extraosseous bone expansion due to tumour growth, with a mean of volume of 21.4mL of CaSO4/CaPO4 used to fill the intraosseous cavitary defects to restore normal bone anatomy. None of the lesions required additional internal fixation. The primary outcome measure, average time to full weight-bearing/full range of motion, was 11weeks and 6weeks for upper and lower extremity lesions, respectively. Secondary outcomes included tumour recurrence requiring reoperation in five patients and infection requiring reoperation in two patients. This study demonstrates that CaSO4/CaPO4 is a viable option as a bone void filler in the reconstruction of cavitary defects following removal of primary benign bone tumours. CaSO4/CaPO4 provides sufficient bone regeneration early in the post-operative period to allow progression to full weight-bearing within weeks without the need for internal fixation. There were no graft-specific complications noted.

Flow cytometric immunophenotypic differentiation patterns of bone marrow eosinophilopoiesis.

Flow cytometry has been widely used to study immunophenotypic patterns of maturation of most hematopoietic lineages in normal human bone marrow aspirates, thus allowing identification of changes in patterns in many myeloid malignancies. Eosinophils play an important role in a wide variety of disorders, including some myeloid neoplasms. However, changes in flow cytometric immunophenotypic patterns during normal and abnormal bone marrow eosinophilopoiesis have not been well studied. Fresh bone marrow aspirates from 15 healthy donors, 19 patients with hypereosinophilic syndromes (HES), and 11 patients with systemic mastocytosis (SM) were analyzed for candidate markers that included EMR-1, Siglec-8, CCR3, CD9, CD11a, CD11b, CD11c, CD13, CD16, CD29, CD34, CD38, CD45, CD44, CD49d, CD49f, CD54, CD62L, CD69, CD117, CD125 (IL-5Rα), HLA-DR, using 10 parameter flow cytometry. Putative CD34-negative immature and mature normal eosinophil populations were first identified based on changes in expression of the above markers in healthy donors, then confirmed using fluorescence-based cell sorting and morphological evaluation of cytospin preparations. The normal immunophenotypic patterns were then compared to immunophenotypic patterns of eosinophilopoiesis in patients with HES and SM. The eosinophilic lineage was first verified using the human eosinophil-specific antibody EMR-1 in combination with anti-IL-5Rα antibody. Then, a combination of Siglec-8, CD9, CD11b, CCR3, CD49d, and CD49f antibodies was used to delineate normal eosinophilic maturational patterns. Early stages (eosinophilic promyelocytes/myelocytes) were identified as Siglec-8 dim/CD11b dim to moderate/CD9 dim/CCR3 dim/CD49d bright/CD49f dim, intermediate stages (eosinophilic myelocytes/metamyelocytes) as Siglec-8 moderate/CD11b moderate to bright/CD9 moderate/CCR3 moderate/CD49d moderate/CD49f moderate and mature bands/segmented eosinophils as Siglec-8 bright/CD11b bright/CD9 bright/CCR3 bright/CD49d dim/CD49f bright. Overall maturational patterns were also similar in patients with HES and SM; however, the expression levels of several surface markers were altered compared to normal eosinophils. A novel flow cytometric antibody panel was devised to detect alterations in immunophenotypic patterns of bone marrow eosinophil maturation and evaluated in normal, HES and SM samples. This approach will allow us to elucidate changes in immunophenotypic patterns of bone marrow eosinophilopoiesis in other hematological diseases.

Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

Application of machine learning algorithms to identify people with low bone density.

Osteoporosis is becoming more common worldwide, imposing a substantial burden on individuals and society. The onset of osteoporosis is subtle, early detection is challenging, and population-wide screening is infeasible. Thus, there is a need to develop a method to identify those at high risk for osteoporosis. This study aimed to develop a machine learning algorithm to effectively identify people with low bone density, using readily available demographic and blood biochemical data. Using NHANES 2017-2020 data, participants over 50 years old with complete femoral neck BMD data were selected. This cohort was randomly divided into training (70%) and test (30%) sets. Lasso regression selected variables for inclusion in six machine learning models built on the training data: logistic regression (LR), support vector machine (SVM), gradient boosting machine (GBM), naive Bayes (NB), artificial neural network (ANN) and random forest (RF). NHANES data from the 2013-2014 cycle was used as an external validation set input into the models to verify their generalizability. Model discrimination was assessed via AUC, accuracy, sensitivity, specificity, precision and F1 score. Calibration curves evaluated goodness-of-fit. Decision curves determined clinical utility. The SHAP framework analyzed variable importance. A total of 3,545 participants were included in the internal validation set of this study, of whom 1870 had normal bone density and 1,675 had low bone density Lasso regression selected 19 variables. In the test set, AUC was 0.785 (LR), 0.780 (SVM), 0.775 (GBM), 0.729 (NB), 0.771 (ANN), and 0.768 (RF). The LR model has the best discrimination and a better calibration curve fit, the best clinical net benefit for the decision curve, and it also reflects good predictive power in the external validation dataset The top variables in the LR model were: age, BMI, gender, creatine phosphokinase, total cholesterol and alkaline phosphatase. The machine learning model demonstrated effective classification of low BMD using blood biomarkers. This could aid clinical decision making for osteoporosis prevention and management.

Efficacy of fat quantification methods used in MRI to distinguish between normal, benign, and malignant bone marrow pathologies in children.

Fat quantification methods in magnetic resonance imaging (MRI) have been studied to differentiate bone marrow pathologies in adult patients; however, scarce literature is available in pediatric patients. To evaluate the efficacy of the T1 signal intensity value (T1-SIV), out-of-phase/in-phase signal ratio (OP/IP SR), and fat fraction (FF) to differentiate between normal, benign, and malignant pathological processes. A total of 48 pediatric patients with lumbar and pelvic MRI were classified into three groups according to bone marrow pathology (group 1, normal; group 2, benign pathology/reconversion; group 3, malignant). The efficacy of T1-SIV, OP/IP SR, and FF values in differentiating these pathologies was evaluated using Kruskal-Wallis or analysis of variance and followed by Bonferroni or Dunn-Bonferroni tests. Cutoff values for malignant infiltration were defined using ROC analysis. Although these values were significantly different in all three groups (P = 0.001-0.008), this difference was not sufficient to discriminate between all groups. Subgroup analyses showed significant differences in T1-SIV between groups 1-3, in OP/IP SR between groups 1-3, 2-3, and 1-2, in FF between groups 1-2 and 1-3 in various regions (P = 0.001-0.049). Cutoff values had a sensitivity and specificity of 90%-100% for OP/IP SR and FF. T1-SIV, OP/IP SR, and FF may potentially distinguish normal from pathological bone marrow. OP/IP SR and FF values detected malignant infiltration with high sensitivity and specificity in this study. However, only OP/IP SR may significantly differentiate benign and malignant bone marrow pathologies which needs to be confirmed in the future study with a larger patient population.

Long-duration leptin transgene expression in dorsal vagal complex does not alter bone parameters in female Sprague Dawley rats

The hypothalamus and dorsal vagal complex (DVC) are both important for integration of signals that regulate energy balance. Increased leptin transgene expression in either the hypothalamus or DVC of female rats was shown to decrease white adipose tissue and circulating levels of leptin and adiponectin. However, in contrast to hypothalamus, leptin transgene expression in the DVC had no effect on food intake, circulating insulin, ghrelin and glucose, nor on thermogenic energy expenditure. These findings imply different roles for hypothalamus and DVC in leptin signaling. Leptin signaling is required for normal bone accrual and turnover. Leptin transgene expression in the hypothalamus normalized the skeletal phenotype of leptin-deficient ob/ob mice but had no long-duration (≥10 weeks) effects on the skeleton of leptin-replete rats. The goal of this investigation was to determine the long-duration effects of leptin transgene expression in the DVC on the skeleton of leptin-replete rats. To accomplish this goal, we analyzed bone from three-month-old female rats that were microinjected with recombinant adeno-associated virus encoding either rat leptin (rAAV-Leptin, n = 6) or green fluorescent protein (rAAV-GFP, control, n = 5) gene. Representative bones from the appendicular (femur) and axial (3rd lumbar vertebra) skeleton were evaluated following 10 weeks of treatment. Selectively increasing leptin transgene expression in the DVC had no effect on femur cortical or cancellous bone microarchitecture. Additionally, increasing leptin transgene expression had no effect on vertebral osteoblast-lined or osteoclast-lined bone perimeter or marrow adiposity. Taken together, the findings suggest that activation of leptin receptors in the DVC has minimal specific effects on the skeleton of leptin-replete female rats.