Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Copper nanoparticles incorporated visible light-curing chitosan-based hydrogel membrane for enhancement of bone repair.

Alveolar bone defects caused by tumor, trauma and inflammation can lead to the loss of oral function and complicate denture restoration. Currently, guided bone regeneration (GBR) barrier membranes for repairing bone defect cannot effectively promote bone regeneration due to their unstable degradation rate and poor antibacterial properties. Furthermore, they require additional tailoring before implantation. Therefore, this study developed a visible light-curing hydrogel membrane (CF-Cu) comprising methacrylated carboxymethyl chitosan (CMCS-MA), silk fibroin (SF), and copper nanoparticles (Cu NPs) to address these shortcomings of commercial membranes. The CF-Cu hydrogel, characterized by scanning electron microscopy (SEM), a universal testing machine, and swelling and degradation tests, demonstrated a smooth porous network structure, suitable swelling ratio, biodegradability, and enhanced mechanical strength. Cytotoxicity and hemolysis tests in vitro demonstrated excellent cyto- and hemo-compatibility of the CF-Cu hydrogel extracts. Additionally, evaluation of antibacterial properties in vitro, including colony forming unit (CFU) counts, MTT assays, and live/dead fluorescence staining, showed that the CF-Cu hydrogel exhibited excellent antibacterial properties, inhibiting over 80% of S. aureus, S. mutans, and P. gingivalis with CF-1Cu hydrogel compared to the control group. Moreover, evaluation of osteogenic differentiation of rBMSCs in vitro suggested that the CF-1Cu hydrogel significantly improved alkaline phosphatase (ALP) activity and the mineralization of extracellular matrix, up-regulating the expressions of osteogenesis-related genes (Runx2, ALP, Col-1, OPN and BSP). In summary, these results indicated that CF-1Cu hydrogel exhibited excellent cytocompatibility, antibacterial and osteogenic properties in vitro. Therefore, the CF-1Cu hydrogel holds potential as a viable material for application in GBR procedures aimed at addressing bone defects.

Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus.

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow­derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. µCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.

Non-classical monocytes scavenge the growth factor CSF1 from endothelial cells in the peripheral vascular tree to ensure survival and homeostasis.

Unlike sessile macrophages that occupy specialized tissue niches, non-classical monocytes (NCMs)-circulating phagocytes that patrol and cleanse the luminal surface of the vascular tree-are characterized by constant movement. Here, we examined the nature of the NCM's nurturing niche. Expression of the growth factor CSF1 on endothelial cells was required for survival of NCMs in the bloodstream. Lack of endothelial-derived CSF1 did not affect blood CSF1 concentration, suggesting that NCMs rely on scavenging CSF1 present on endothelial cells. Deletion of the transmembrane chemokine and adhesion factor CX3CL1 on endothelial cells impaired NCM survival. Mechanistically, endothelial-derived CX3CL1 and integrin subunit alpha L (ITGAL) facilitated the uptake of CSF1 by NCMs. CSF1 was produced by all tissular endothelial cells, and deletion of Csf1 in all endothelial cells except bone marrow sinusoids impaired NCM survival, arguing for a model where the full vascular tree acts as a niche for NCMs and where survival and patrolling function are connected.

The cell membrane as biofunctional material for accelerated bone repair.

The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n=75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area=15.02), contrasting with the partial integration (% non-integrated bone area=56.10; p<0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10±1.75) exhibited hardness similar to native bone (31.07±2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE: : • For the first time, the cell (plasma) membrane of cells is used as a cell-free material for bone repair. • The plasma membrane from chondrocytes promoted rapid bone repair within 2 weeks, with complete integration of the newly formed bone with the surrounding native tissue. • The plasma membrane from chondrocytes presented multifaceted effects, strongly promoting the attraction of macrophages, endothelial cells and osteoblasts to the healing site.

Bioactive Polymer Composite Scaffolds Fabricated from 3D Printed Negative Molds Enable Bone Formation and Vascularization.

Scaffolds for bone defect treatment should ideally support vascularization and promote bone formation, to facilitate the translation into biomedical device applications. This study presents a novel approach utilizing 3D-printed water-dissolvable polyvinyl alcohol (PVA) sacrificial molds to engineer polymerized High Internal Phase Emulsion (polyHIPE) scaffolds with microchannels and distinct multiscale porosity. Two sacrificial mold variants (250 µm and 500 µm) were generated using fused deposition modeling, filled with HIPE, and subsequently dissolved to create polyHIPE scaffolds containing microchannels. In vitro assessments demonstrated significant enhancement in cell infiltration, proliferation, and osteogenic differentiation, underscoring the favorable impact of microchannels on cell behavior. High loading efficiency and controlled release of the osteogenic factor BMP-2 were achieved, with microchannels facilitating release of the growth factor. Evaluation in a mouse critical-size calvarial defect model revealed enhanced vascularization and bone formation in microchanneled scaffolds containing BMP-2. This study not only introduces an accessible method for creating multiscale porosity in polyHIPE scaffolds but also emphasizes its capability to enhance cellular infiltration, controlled growth factor release, and in vivo performance. The findings suggest promising applications in bone tissue engineering and regenerative medicine, and are expected to facilitate the translation of this type of biomaterial scaffold. STATEMENT OF SIGNIFICANCE: This study holds significance in the realm of biomaterial scaffold design for bone tissue engineering and regeneration. We demonstrate a novel method to introduce controlled multiscale porosity and microchannels into polyHIPE scaffolds, by utilizing 3D-printed water-dissolvable PVA molds. The strategy offers new possibilities for improving cellular infiltration, achieving controlled release of growth factors, and enhancing vascularization and bone formation outcomes. This microchannel approach not only marks a substantial stride in scaffold design but also demonstrates its tangible impact on enhancing osteogenic cell differentiation and fostering robust bone formation in vivo. The findings emphasize the potential of this methodology for bone regeneration applications, showcasing an interesting advancement in the quest for effective and innovative biomaterial scaffolds to regenerate bone defects.

Conversion Total Hip Arthroplasty After Failed Pedicled Peri-Hip Bone Flap Grafting: The Chinese Experience.

BACKGROUND: This study investigated the perioperative outcomes of patients undergoing conversion total hip arthroplasty (THA) after failed peri-hip bone flap grafting (PBFG) and compared them with those patients undergoing primary THA for osteonecrosis of the femoral head (ONFH). METHODS: From January 2010 to December 2021, 163 Chinese patients (163 hips) were treated by conversion THA after failed PBFG (containing 94 patients who had pedicled vascularized iliac bone flap grafting and 69 patients who had pedicled vascularized greater trochanter bone flap grafting), and 178 Chinese patients were treated by primary THA. The preoperative baseline data and perioperative indicators in both groups were compared. RESULTS: In the conversion group, patients had significantly greater blood loss, a longer length of stay, and greater changes in serum hemoglobin than those in the primary THA group (P < 0.05). The operative room time, transfusion volume, calculated blood loss, changes in serum hematocrit, and increased superficial infection (P > 0.05) in the conversion group were greater compared with the primary cohort; however, the difference was not statistically significant. The mean postoperative Harris Hip Scoring System (HHS) of the PBFG group at the one-month follow-up was 81, and the control group had an 82 score. Importantly, subgroup analysis of the PBFG group indicated that there was no significant difference between patients who had prior pedicled vascularized iliac bone flap grafting and pedicled vascularized greater trochanter bone flap grafting (P > 0.05), except for the operative room time (P = 0.032). CONCLUSION: Hip-sparing surgery of ONFH did not make THA more difficult or lead to more peri-operative complications, but increased blood loss and extended hospital stay from a prior PBFG are still notable problems in clinical practice. Thus, it is necessary for surgeons to focus attention on the improvement of the preoperative condition and prepare for any specific intraoperative challenges.

NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway.

INTRODUCTION: Excessive osteoclastogenesis is a key driver of inflammatory bone loss. Suppressing osteoclastogenesis has always been considered essential for the treatment of inflammatory bone loss. N-acetyltransferase 10 (NAT10) is the sole enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNA, and is involved in cell development. However, its role in osteoclastogenesis and inflammatory bone loss remained elusive. OBJECTIVES: We aimed to clarify the regulatory mechanism of NAT10 and ac4C modification in osteoclastogenesis and inflammatory bone loss. METHODS: NAT10 expression and ac4C modification during osteoclastogenesis were determined by quantitative real-time PCR (qPCR), western blotting, dot blot and immunofluorescent staining, and the effect of NAT10 inhibition on osteoclast differentiation in vitro was measured by the tartrate-resistant acid phosphatase staining, podosome belts staining assay and bone resorption pit assay. Then, acRIP-qPCR and NAT10RIP-qPCR, ac4C site prediction, mRNA decay assay and luciferase reporter assay were performed to further study the underlying mechanisms. At last, mice models of inflammatory bone loss were applied to verify the therapeutic effect of NAT10 inhibition in vivo. RESULTS: NAT10 expression was upregulated during osteoclast differentiation and highly expressed in alveolar bone osteoclasts from periodontitis mice. Inhibition of NAT10 notably reduced osteoclast differentiation in vitro, as indicated by great reduction of tartrated resistant acid phosphatse positive multinuclear cells, osteoclast-specific gene expression, F-actin ring formation and bone resorption capacity. Mechanistically, NAT10 catalyzed ac4C modification of Fos (encoding AP-1 component c-Fos) mRNA and maintained its stabilization. Besides, NAT10 promoted MAPK signaling pathway and thereby activated AP-1 (c-Fos/c-Jun) transcription for osteoclastogenesis. Therapeutically, administration of Remodelin, the specific inhibitor of NAT10, remarkably impeded the ligature-induced alveolar bone loss and lipopolysaccharide-induced inflammatory calvarial osteolysis. CONCLUSIONS: Our study demonstrated that NAT10-mediated ac4C modification is an important epigenetic regulation of osteoclast differentiation and proposed a promising therapeutic target for inflammatory bone loss.

Advances in Bone Marrow Evaluation.

Evaluation of bone marrow aspirate smear and trephine biopsy specimens is critical to the diagnosis of benign and malignant hematologic conditions. Digital pathology has the potential to revolutionize bone marrow assessment through implementation of artificial intelligence for assisted and automated evaluation, but there remain many barriers toward this implementation. This article reviews the current state of digital evaluation of bone marrow aspirate smears and trephine biopsies, recent research using machine learning models for automated specimen analysis, an outline of the advantages and barriers facing clinical implementation of artificial intelligence, and a potential vision of artificial intelligence-associated bone marrow evaluation.

Stem Cell Therapy for Wound Healing in Ischemic Limbs: Is It Effective?

Critical limb ischemia is an important clinical entity due to its association with increased morbidity and mortality. The mortality and amputation-free survival remains poor especially in those where revascularization is not an option. Recently, the role of cellular therapy has emerged as a promising therapeutic measure that may aid in wound healing and revascularization and improve functional outcomes.

RUNX2 regulation in osteoblast differentiation: A possible therapeutic function of the lncRNA and miRNA-mediated network.

Osteogenic differentiation is a crucial process in the formation of the skeleton and the remodeling of bones. It relies on a complex system of signaling pathways and transcription factors, including Runt-related transcription factor 2 (RUNX2). Non-coding RNAs (ncRNAs) control the bone-specific transcription factor RUNX2 through post-transcriptional mechanisms to regulate osteogenic differentiation. The most research has focused on microRNAs (miRNAs) and long ncRNAs (lncRNAs) in studying how they regulate RUNX2 for osteogenesis in both normal and pathological situations. This article provides a concise overview of the recent advancements in understanding the critical roles of lncRNA/miRNA/axes in controlling the expression of RUNX2 during bone formation. The possible application of miRNAs and lncRNAs as therapeutic agents for the treatment of disorders involving the bones and bones itself is also covered.

In situ metabolomic analysis of osteonecrosis of the femoral head (ONFH) using MALDI MSI.

Osteonecrosis of the femoral head (ONFH) is a common orthopedic disease characterized by disability and deformity. To better understand ONFH at molecular level and to explore the possibility of early diagnosis, instead of diagnosis based on macroscopic spatial characteristics, a matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) method was developed for ONFH disease for the first time. The most challenging step for ONFH MSI is to deal with human bone tissues which are much harder than the other biological samples studied by the reported MSI studies. In this work, the MSI sectioning method of hard bone tissues was established using tender acids and a series of test criteria. Small-molecule metabolites, such as lipids and amino acids, were detected in bone sections, realizing the in situ detection of spatial distribution of biometabolites. By comparing the distribution of metabolites from different regions of normal femoral head, ONFH bone tissue (ONBT), and adjacent ONFH bone tissue (ANBT), the whole process of femoral head from normal stage to necrosis was monitored and visualized at molecular level. Moreover, this developed MSI method was used for metabolomics study of ONFH. 72 differential metabolites were identified, suggesting that disturbances in energy metabolism and lipid metabolism affected the normal life activities of osteoblasts and osteoclasts. This study provides new perspectives for future pathological studies of ONFH.

Reproducibility of CT-based opportunistic vertebral volumetric bone mineral density measurements from an automated segmentation framework.

BACKGROUND: To investigate the reproducibility of automated volumetric bone mineral density (vBMD) measurements from routine thoracoabdominal computed tomography (CT) assessed with segmentations by a convolutional neural network and automated correction of contrast phases, on diverse scanners, with scanner-specific asynchronous or scanner-agnostic calibrations. METHODS: We obtained 679 observations from 278 CT scans in 121 patients (77 males, 63.6%) studied from 04/2019 to 06/2020. Observations consisted of two vBMD measurements from Δdifferent reconstruction kernels (n = 169), Δcontrast phases (n = 133), scan Δsessions (n = 123), Δscanners (n = 63), or Δall of the aforementioned (n = 20), and observations lacking scanner-specific calibration (n = 171). Precision was assessed using root-mean-square error (RMSE) and root-mean-square coefficient of variation (RMSCV). Cross-measurement agreement was assessed using Bland-Altman plots; outliers within 95% confidence interval of the limits of agreement were reviewed. RESULTS: Repeated measurements from Δdifferent reconstruction kernels were highly precise (RMSE 3.0 mg/cm3; RMSCV 1.3%), even for consecutive scans with different Δcontrast phases (RMSCV 2.9%). Measurements from different Δscan sessions or Δscanners showed decreased precision (RMSCV 4.7% and 4.9%, respectively). Plot-review identified 12 outliers from different scan Δsessions, with signs of hydropic decompensation. Observations with Δall differences showed decreased precision compared to those lacking scanner-specific calibration (RMSCV 5.9 and 3.7, respectively). CONCLUSION: Automatic vBMD assessment from routine CT is precise across varying setups, when calibrated appropriately. Low precision was found in patients with signs of new or worsening hydropic decompensation, what should be considered an exclusion criterion for both opportunistic and dedicated quantitative CT. RELEVANCE STATEMENT: Automated CT-based vBMD measurements are precise in various scenarios, including cross-session and cross-scanner settings, and may therefore facilitate opportunistic screening for osteoporosis and surveillance of BMD in patients undergoing routine clinical CT scans. KEY POINTS: Artificial intelligence-based tools facilitate BMD measurements in routine clinical CT datasets. Automated BMD measurements are highly reproducible in various settings. Reliable, automated opportunistic osteoporosis diagnostics allow for large-scale application.

From Modic to Disc Endplate Bone Marrow Complex - The Natural Course and Clinical Implication of Vertebral Endplate Changes.

STUDY DESIGN: Review article. OBJECTIVES: A review of literature on the epidemiology, natural course, pathobiology and clinical implications of vertebral endplate changes. METHODS: A literature search was performed using the Cochrane Database of Systematic Reviews, EMBASE, and PubMed. Studies published over the last 10 years were analysed. The searches were performed using Medical Subject Headings terms, and the subheadings used were "Vertebral endplate changes", "Modic changes", "Disc Endplate Bone Marrow complex". RESULTS: The disc, endplate (EP), and bone marrow region of the spine constitute a unified morphological and functional unit, with isolated degeneration of any one structure being uncommon. Disc degeneration causes endplate defects, which result in direct communication and a constant cross-talk between the disc and the vertebral body. This may result in a persistent inflammatory state of the vertebral bone marrow, serving as a major pain generator. This review article focuses on vertebral endplate changes and how the current understanding has progressed from the Modic classification to the Disc Endplate Bone Marrow complex classification. It provides a clear portrayal of the natural course of these alterations and their clinical implications in low back pain. CONCLUSIONS: In light of the heightened interest and current prominence of vertebral endplate changes within the spine community, we must progress beyond the Modic changes to achieve a comprehensive understanding. The DEBM complex classification will play a major part in disc degeneration research and clinical care, representing a considerable advancement in our understanding of the vertebral endplate changes over the classical Modic changes.

Deep learning-based automated bone age estimation for Saudi patients on hand radiograph images: a retrospective study.

PURPOSE: In pediatric medicine, precise estimation of bone age is essential for skeletal maturity evaluation, growth disorder diagnosis, and therapeutic intervention planning. Conventional techniques for determining bone age depend on radiologists' subjective judgments, which may lead to non-negligible differences in the estimated bone age. This study proposes a deep learning-based model utilizing a fully connected convolutional neural network(CNN) to predict bone age from left-hand radiographs. METHODS: The data set used in this study, consisting of 473 patients, was retrospectively retrieved from the PACS (Picture Achieving and Communication System) of a single institution. We developed a fully connected CNN consisting of four convolutional blocks, three fully connected layers, and a single neuron as output. The model was trained and validated on 80% of the data using the mean-squared error as a cost function to minimize the difference between the predicted and reference bone age values through the Adam optimization algorithm. Data augmentation was applied to the training and validation sets yielded in doubling the data samples. The performance of the trained model was evaluated on a test data set (20%) using various metrics including, the mean absolute error (MAE), median absolute error (MedAE), root-mean-squared error (RMSE), and mean absolute percentage error (MAPE). The code of the developed model for predicting the bone age in this study is available publicly on GitHub at https://github.com/afiosman/deep-learning-based-bone-age-estimation . RESULTS: Experimental results demonstrate the sound capabilities of our model in predicting the bone age on the left-hand radiographs as in the majority of the cases, the predicted bone ages and reference bone ages are nearly close to each other with a calculated MAE of 2.3 [1.9, 2.7; 0.95 confidence level] years, MedAE of 2.1 years, RMAE of 3.0 [1.5, 4.5; 0.95 confidence level] years, and MAPE of 0.29 (29%) on the test data set. CONCLUSION: These findings highlight the usability of estimating the bone age from left-hand radiographs, helping radiologists to verify their own results considering the margin of error on the model. The performance of our proposed model could be improved with additional refining and validation.

Arthroscopic assisted versus open non-vascularized bone grafting in delayed union and nonunion of the scaphoid: a systematic review and meta-analysis.

BACKGROUND: Delayed union and nonunion of the scaphoid is a common complication often requiring surgical reconstruction and bone grafting. Our goal was to systematically assess the healing time and clinical outcomes following arthroscopic-assisted versus open non-vascularized bone grafting of the scaphoid. METHODS: A comprehensive search of the MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases was completed from inception to September 2023. We included randomized trials and observational studies that reported outcomes following scaphoid delayed union/nonunion comparing arthroscopic-assisted vs. open non-vascularized bone grafting. Two reviewers independently extracted data and assessed the risk of bias. One investigator assessed certainty of evidence and a senior investigator confirmed the assessment. We pooled effects using random-effects models, when possible, for all outcomes reported by more than 1 study. RESULTS: Overall, 26 studies and 822 patients were included in the study. Very low certainty evidence demonstrated that arthroscopic-assisted surgery may decrease healing time compared to open surgery (weighted mean difference [WMD] -7.8 weeks; 95%CI -12.8 to -2.8). Arthroscopic bone grafting did not result in an improvement in union rate (relative risk 1.01; 95%CI 0.9 to 1.09). The pooled data in arthroscopic graft group showed mean time to union of 11.4 weeks (95%CI: 10.4 to 12.5) with union rate of 95% (95%CI 91-98%). A single comparative study reported very low certainty evidence that arthroscopy-assisted vs. open surgery may not have an effect on pain relief (MD 0 cm, 95%CI -0.4 to 0.5 on VAS 10 cm for pain) or improving function (MD -1.2, 95% CI -4.8 to 2.3 on 100 points DASH). CONCLUSION AND FUTURE DIRECTIONS: Our results suggest that arthroscopic-assisted non-vascularized bone grafting may be associated with improved average weeks to heal in comparison with open surgery for scaphoid delayed union/nonunion reconstruction with overall comparable union rates. There is insufficient evidence to assess the effects of arthroscopic-assisted reconstruction on union rate, time to union, and patient-reported outcomes in patients with other important nonunion characteristics such as established humpback deformity.

Variations in the alveolar bone morphology in maxillary molar area: a retrospective CBCT study.

BACKGROUND: This study quantitatively analyzed the anatomic structure of the alveolar bone in the maxillary molar region at three potential locations for Temporary Anchorage Device (TAD) placement. Additionally, the study compared the variability in this region across different age groups, sagittal skeletal patterns, vertical facial types, and sexes. METHODS: In this retrospective cone-beam computed tomography study, the buccal alveolar bone was analyzed in the posterior molar area of 200 patients, the measurement items include buccal alveolar bone height, alveolar bone thickness, interradicular distance, and maxillary retromolar space. RESULTS: Buccal alveolar height was greatest in the U56 region. The interradicular space was largest in the U56 region and increased from the alveolar crest to the sinus floor. Buccal alveolar bone thickness was highest in the U67 region and generally increased from the alveolar crest to the sinus floor. The maxillary retromolar space gradually increased from the alveolar crest to the root apex. CONCLUSIONS: TADs are safest when placed in the buccal area between the maxillary second premolar and the first molar, particularly at the 9 mm plane. The U67 region is the optimal safe zone for TAD placement for maxillary dentition distalization. TADs placement in adolescents can be challenging. Maxillary third molar extraction can be considered for maxillary dentition distalization.

Intermittent mechanical loading on mouse tibia accelerates longitudinal bone growth by inducing PTHrP expression in the female tibial growth plate.

It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4-week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones. Lastly, microCT analysis revealed no difference between loaded and unloaded tibiae with respect to the fraction of bone volume relative to the total volume of the region of interest or the tibial trabecular bone volume. Thus, our findings suggest that intermittent compressive forces applied on tibiae at mild-moderate strain magnitude induce a significant and persistent longitudinal bone growth. PTHrP expressed in the growth plate appears to be one growth factor responsible for stimulating endochondral ossification and bone growth in female mice.

Effect of Matrix Size and Acquisition Mode on Image Quality and Radiation Dose of Ultra-High-Resolution CT of the Temporal Bone: An Anatomical Study.

Purpose: To compare image quality and radiation exposure between super- and ultra-high-resolution helical and super-high-resolution volumetric CT of the temporal bone. Methods: Six cadaveric temporal bone specimens were used to evaluate key temporal bone structures using the following CT reconstruction and acquisition modes: helical and single-volume acquisition modes in super-high resolution (0.25-mm slice thickness, 10242 matrix), and helical mode in ultra-high resolution (0.25-mm slice thickness, 20482 matrix). Two observers performed 5 previously described preoperative measurements, measured noise and signal-to-noise ratios for air, and noise for bone, and rated the visualization of 5 anatomical structures on a 4-point scale, for each reconstruction mode. Radiation dose exposure was recorded for each examination. Results: There was no significant difference between any of the quantitative or qualitative measurements in any of the reconstruction and acquisition modes. There was a slight increase in noise and a decrease in signal-to-noise ratio in the air using the single-volume mode (115 ± 13.1 HU and 8.37 ± 0.91, respectively) compared to the helicoidal super-high-resolution (92.4 ± 11.8 HU and 10.8 ± 1.26, respectively) and helicoidal ultra-high-resolution (91.1 ± 10.7 HU and 10.9 ± 1.39, respectively) modes (P < .002). The volumic CT dose index was 50.9 mGy with helical acquisition and 29.8 mGy with single-volume acquisition mode (P < .0001). Conclusion: The single-volume super-high-resolution acquisition mode allows a reduction in radiation dose exposure without compromising image quality compared to helical scanning, but with a slightly lower signal-to-noise ratio in air with the single-volume mode, while there was no difference in image quality between the helical super- and ultra-high-resolution modes.