Bone Area Research Articles

The Emerging Role and Clinical Applications of Morphomics in Diagnostic Imaging.

Analytic morphomics refers to the accurate measurement of specific biological markers of human body composition in diagnostic medical imaging. The increasing prevalence of disease processes that alter body composition including obesity, cachexia, and sarcopenia has generated interest in specific targeted measurement of these metrics to possibly prevent or reduce negative health outcomes. Typical morphomic measurements include the area and density of muscle, bone, vascular calcification, visceral fat, and subcutaneous fat on a specific validated axial level in the patient's cross-sectional diagnostic imaging. A distinct advantage of these measurements is that they can be made retrospectively and opportunistically with pre-existing datasets. We provide a narrative review of the current state of art in morphomics, but also consider some potential future directions for this exciting field. Imaging based quantitative assessment of body composition has enormous potential across the breadth and scope of modern clinical practice. From risk stratification to treatment planning, and outcome assessment, all can be enhanced with the use of analytic morphomics. Moreover, it is likely that many new opportunities for personalized medicine will emerge as the field evolves. As radiologists, embracing analytic morphomics will enable us to contribute added value in the care of every patient.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (β-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/β-TCP scaffold, a stem cell-loaded 3D-printed nHA/β-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/β-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/β-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/β-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

SUCCINATE-RECEPTOR SYSTEM OF BONE AND CARTILAGE TISSUE IN PATIENTS WITH METABOLIC PHENOTYPE OF OSTEOARTHRITIS

Introduction. Currently, osteoarthritis (OA) has been identified as a polyetiological disease, where several phenotypes have been identified based on the leading frequency. Obviously, each clinical phenotype corresponds only to its fundamental changes on the part of various organs and systems. Un-til recently, special attention was paid to the study of metabolic processes in osteoarthritis (OA) and was paid to the state of the cartilage, but more and more interest was focused on the biochemistry of the subchondral bone, its microarchitectonics and signal function. Aid. To study the features of the manifestation of the succinate-receptor system of bone and cartilage tissue in patients with the metabolic phenotype of osteoarthritis. Material and methods. 42 patients took part in the study and were divided into 2 groups: 1 group – patients without articular disease, normal body mass index; 2 group – patients with metabolic phenotype of OA. The subjects were collected complaints, anamnesis, as well as general clinical and orthopedic examination. The levels of succinate, succinate receptor (SUCNR1) and succinate dehydrogenase (SDH) are measured in bone and cartilage tissue homogenates. Results. In the 2 group, an increase in SUCNR1 expression was detected in all studied areas of the joint in comparison with the 1 group. In the 2 group, the differences were tissue-specific in the distribution of SUCNR1 with a predominant increase in the amount of the receptor in the subchondral bone compared to the loaded (p=0.031) and non-loaded zone of cartilage (p=0.001). In the 1 group, the studied areas of cartilage and bone did not dif-fer in the amount of SUCNR1 from each other. In the group of patients with the metabolic phenotype of OA, an increase in mitochondrial succinate was found both in the subchondral bone tissue and in different zones of cartilage compared to the 1 group. The final indicators of SDH activity in the mito-chondria of the studied joint zones that we obtained turned out to be low in both groups, however, relatively high enzyme activity was observed in the subchondral zone of the bone of the group of metabolic phenotype of OA. Conclusion. In patients with the metabolic phenotype of OA, high expression of SUCNR1 in joint tissues is observed, which is tissue-specific with a predominant increase in the amount of SUCNR1 in the subchondral bone. We found higher levels of succinate in the subchondral bone and cartilaginous areas of joints in patients with the metabolic phenotype of OA and suggest that the succinate-SUCNR1 interaction in affected joints in OA is adaptive in nature.

Age-related changes in densitometry and histomorphometry of long bone during the pubertal growth spurt in male rats.

Because experimental studies to determine the developmental toxicity of exposure to various substances in children are impossible, many studies use immature male rats. This study aimed to provide normative data for longitudinal bone growth with age during the puberty in male rats. In order to evaluate long bone growth and mineralization we examined bone size and bone density by dual-energy X-ray absorptiometry, analyzed histomorphometry of the growth plate, and serum hormone levels relevant to bone growth from postnatal day (PD)20 to PD60. The length and weight of long bones increased strongly by PD40, and no further increase was observed after PD50. On the other hand, tibial growth plate height decreased sharply after PD50 along with a reduction in the number of cells and columns, which was probably responsible for the absence of further lengthening of long bones. Parameters related to bone formation such as bone area ratio, and the thickness and number of trabeculae, also increased significantly between PD40 and PD50. Furthermore, serum levels of IGF-1 peaked at PD30 and testosterone increased rapidly on and after PD40, when IGF-1 levels were going down. These changes may participate in the parallel increase in mineral acquisition, as well as lengthening of long bones. Our findings provide comprehensive data for changes in bone density, histomorphometry of long bones, and hormone levels relevant to bone growth during the growth spurt. This will be useful for planning animal toxicological studies, particularly for deciding on the appropriate age of animals to use in given experiments.

Evaluation of skull bone viability and effect of early surgical intervention in electrical contact burns using 18 F-Sodium Fluoride PET-CT imaging.

Electrical contact burns of the scalp cause serious morbidity and mortality. Early necrotic bone debridement and flap cover are crucial for successful wound closure. 18 F Sodium Fluoride (NaF), with high bone-to-soft tissue activity ratio, is useful for bone viability assessment. This study evaluated the role of 18 F NaF PET-computed tomography (CT) in objectively defining the extent and depth of nonviable calvarial bone, to guide adequate bone debridement. Of 20 patients referred to our institute with electrical contact burns of the scalp during a 2-year period, 15 were enrolled in the study. Two weeks after the initial management, tracer uptake pattern was noted on 18 F NaF PET-CT of the head and exposed bone measured. Surgical bone debridement was based on scan findings, followed by wound closure. All patients underwent clinical evaluation and follow-up scan 3 months after surgery. Eight patients showed a central photopenic area in the exposed bone (maximum standardized uptake value [SUVmax] of 0.76 ± 0.14 with mean maximum dimensions 4.10 ± 1.76/2.67 ± 1.54 cm). High tracer uptake (SUVmax, 9.66 ± 6.03) was seen peripheral to the exposed bone (mean maximum dimensions, 8.14 ± 3.03/4.75 ± 1.61 cm). Postoperatively, there was no significant change in tracer uptake in the central debrided region or peri-debridement bone area under the flap. Clinically all patients showed a well-healed flap. 18 F NaF PET-CT appears useful for objective evaluation of skull bone viability and planning necrotic bone debridement in patients with electrical contact burns. However, additional studies with longer patient follow-up are required to validate these results.

Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

ObjectiveLow vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. MethodsKnee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. ResultsAt week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​< ​0.001; spatial symmetry ​= ​48.4 ​± ​0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 ​± ​7.70 compared to the non-VGX animal sensitivity of 29.74 ​± ​9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p ​= ​0.076; VGX: 0.80 ​± ​0.036 ​mm2; non-VGX: 0.736 ​± ​0.066 ​mm2). No group differences in systemic inflammation were observed at endpoint. ConclusionsVGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.

Vitronectin regulates osteoclastogenesis and bone remodeling in a mouse model of osteoporosis.

Vitronectin (VN) is an extracellular matrix protein with a crucial role in regulating bone remodeling. In this study, we aimed to investigate the effect of VN deficiency in a mouse model of osteoporosis induced by ovariectomy (OVX). The findings revealed that the absence of VN led to an increase in the activity of tartrate-resistant acid phosphatase (TRAP), a marker for osteoclasts, in the plasma of OVX-operated mice. TRAP staining further demonstrated that VN deficiency resulted in a higher number of osteoclasts within the femurs of OVX-operated mice. X-ray micro-computed tomography analysis of the femurs in OVX-operated mice indicated that VN deficiency significantly suppressed the OVX-induced increase of marrow area and total volume of bone. Additionally, we assessed structural model index (SMI) and degree of anisotropy (DA) as indices of osteoporosis. The results showed that VN deficiency effectively attenuated the OVX-induced increase in SMI and DA among OVX-operated mice. In summary, our study demonstrates the vital role of VN in regulating osteoclastogenesis and bone remodeling in the mouse model of osteoporosis.

Sclerotic bone: a sign of bone reaction in patients with medication related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction associated with antiresorptive drugs such as bisphosphonates and denosumab. When dealing with advanced and/or multiple MRONJ lesions undergoing surgical therapy, the extent of surgery is often a topic of discussion. The aim of this study was to identify the differences in bone density in and around the MRONJ lesion before and after surgical treatment to evaluate the needed surgical extend of the modelling osteotomy. In this retrospective study 26 patients with MRONJ lesions that were surgically treated in our department were observed. Length, width and bone density were measured in panoramic radiograph pre and postoperatively with the Imaging processing software Sidexis and ImageJ (Fiji). The necrotic area, the surrounding sclerotic area as well as the healthy contralateral side were observed. Measurements were performed by two independent observers. Pearson correlation was calculated to determine the interobserver variability. Bone density was significantly reduced in the necrotic bone area compared to the healthy unaffected contralateral reference side. The sclerotic bone area surrounding the necrosis showed increased bone density compared to the contralateral unaffected reference side. The density of the sclerotic bone area was increased in the previously affected MRONJ area in the postoperative panoramic radiograph. The pre and postoperative density showed no significant correlation to healing behaviour. The focus of the modelling osteotomy in surgical treatment of mature MRONJ lesions should be predominantly on the parts that appear necrotic and less dense in the panoramic radiograph as sclerotic areas might be an expression of bone reaction.

Bone union-promoting effect of romosozumab in an ovariectomized rat posterolateral lumbar fusion model.

Spinal fixation surgery has been increasingly performed in patients with osteoporosis. Romosozumab, a drug that was introduced in Japan recently, is known to possibly promote bone healing. However, few studies have reported the therapeutic effects of romosozumab in clinical practice in Japan. Therefore, here, we investigated the effects of romosozumab dosage on bone fusion promotion using an ovariectomized rat spinal fusion model. Eight-week-old female Sprague-Dawley rats were matched by body weight and divided into three groups: 1.0 romosozumab (R) group (Evenity®, 25 mg/kg), 1/10R group (Evenity®, 2.5 mg/kg), and control (C) group (saline). Subcutaneous injections were administered twice a week for 8 weeks postoperatively. Computed tomography scans were performed every 2 weeks from the time of surgery till 8 weeks postoperatively. The mean fusion rates in terms of volume were significantly higher in the R groups [1/10R, 1.0R] than in the C group from 4 weeks postoperatively. The rate of increase was significantly higher in the 1.0R group from 4 weeks postoperatively and in the 1/10R group from 6 weeks postoperatively, than in the C group. The proportion of trabecular bone area was approximately 1.5 times higher in the R groups than in the C group. No significant differences were observed between the R groups. Our results suggest that romosozumab stimulates bone growth at the graft site, and similar effects were achieved at 1/10 of the standard dosage.

A Case Report and Functional Outcome in Bilateral Osteochondritis Dissecans in the Knee which was Operated Arthroscopically

Definition  Osteochondritis Dissecans (OCD) is a disorder of subchondral bone, which secondarily affects the overlying articular cartilage.  In OCD, an area of subchondral bone becomes necrotic, resulting in a loss of structural support for the overlying articular cartilage. This process leads to degeneration and fragmentation of the articular cartilage and underlying bone.  In the absence of treatment or spontaneous regression, the osteochondral fragment gradually separates from its bony bed, eventually forming a loose body.

Clinical evaluation of bone quality of particulate cancellous bone and marrow, and implant prosthetic rehabilitation

This study aimed to subjectively evaluate bone quality in the particulate cancellous bone and marrow (PCBM) graft area and to assess the survival rates of implants.A retrospective review was conducted based on patient age, sex, diagnosis, reconstructed site, number of implants, prosthetic type, and duration of follow-up. Images from computed tomography (CT) before implant insertion were obtained and used in this study. We selected a 4.0-mm diameter × 8.0-mm length region of interest in the implant placement area, and measured the CT attenuation value.No significant correlations were seen between CT attenuation values and implant survival rates in the maxilla and mandible. On the other hand, CT attenuation values and implant survival rates were significantly lower in patients with malignancy than in non-malignant cases.Placing implants in PCBM grafted bone requires a full understanding of bone quality before surgery and drilling to ensure primary stability, along with consideration of soft tissue management and maintenance programs.

The Preventive Effect of Preoperative and Postoperative Selenium on the Medication-Related Osteonecrosis of the Jaw: An Animal Study in Rats

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE). PurposeThis study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model. Study design, setting, and sampleThis study was a longitudinal, in vivo animal study using a TE model in a sample of 48 Wistar rats. Predictor variableThe predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to four treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SELpreop+ZOL, and 4) ZOL+SELpostop. The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the 5th week. Selenium (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SELpreop+ZOL group before TE and to the ZOL+SELpostop group after TE. All animals were sacrificed at the end of the 9th week. Main outcome variablesThe primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis. CovariatesThere was none. AnalysesStatistical analysis was conducted using the Kruskal–Wallis test, followed by post-hoc Bonferroni-corrected Mann–Whitney U tests, with a significance level of p ≤ 0.05. ResultsThe new bone area was higher in the ZOL+SELpostop group (3.00 score) than in the saline group (0.58 ± 1.08 score, p < 0.001) and the ZOL group (0.82 ± 1.40 score, p = 0.001), while the necrotic bone area was lower in the ZOL+SELpostop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, p < 0.001) and the SELpreop+ZOL group (1.67 ± 0.89 score, p = 0.007). The percentage of osteoblasts was higher in the ZOL+SELpostop group (18.73%) than in the saline group (8.63%, p < 0.001) and the ZOL group (0.07%, p < 0.001), and it was also higher in the SELpreop+ZOL group (18.49%) than in the ZOL group (0.07%, p < 0.001). ConclusionIn conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ.

Biomechanical and histomorphometric analysis of osseodensification drilling versus conventional technique: a systematic review and meta-analysis.

This systematic review aimed to search the literature for the answer to the following questions. In human studies: Does the osseodensification technique increase the resonance frequency analysis given in implant stability quotient value and the insertion torque value compared to the conventional technique? In animal studies: Does the osseodensification technique increase implant stability quotient, bone-to-implant contact, and bone area fraction occupancy values over the conventional technique? A search for studies was carried out in eight databases until August 2021. Out of the 447 publications found, 11 were included. In human studies, osseodensification technique showed better results for implant stability quotient values with a summarized median difference of 8.57. As for secondary stability, there was no significant difference, with summarized median difference of 4.49 in favor of the osseodensification technique. In animal studies, all results were favorable to the osseodensification technique. Regarding insertion torque, bone-to-implant contact, and bone area fraction occupancy between counterclockwise osseodensification technique vs conventional, the mean difference was 46.79 for insertion torque, 2.17 for bone-to-implant contact, and 2.11 for bone area fraction occupancy. High heterogeneity was observed between the studies. The risk of bias in humans was moderate in three studies and low in one; and in animal studies, four presented moderate risk, two low risk, and one high risk. The certainty of evidence ranged from low to moderate. The osseodensification technique showed improvement concerning the resonance frequency and the insertion torque value of implants in human studies. In addition, it increased the values of bone-to-implant contact, bone area fraction occupancy, and implant stability quotient in animal studies, when compared to the conventional technique.

Abstract 688: Radium-223 in combination with darolutamide exhibits synergistic antitumor efficacy in LNCaP prostate cancer models

Abstract Radium-223 dichloride (radium-223) is a targeted alpha therapy that binds to newly formed abnormal bone in bone metastases and induces DNA double-strand breaks (DSBs) in cancer cells, osteoblasts and osteoclasts. Radium-223 is used for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Darolutamide is an androgen receptor inhibitor indicated for patients with metastatic hormone-sensitive prostate cancer or non-metastatic CRPC. We studied the antitumor effects of radium-223 in combination with darolutamide using LNCaP human prostate cancer cells in vitro and an intratibial LNCaP model mimicking prostate cancer metastasized to bone. The in vitro antiproliferative effects of radium-223 and darolutamide were determined using LNCaP cells. Gene set enrichment analysis (GSEA) was conducted on RNA sequencing data from LNCaP cells treated with the synthetic androgen R1881 alone or in combination with darolutamide. LNCaP cells were inoculated into the right tibia of male NOD.scid mice. The mice (n=7-9/group) were randomized based on serum prostate-specific antigen (PSA) and treated with vehicle, radium-223 (330 kBq/kg, Q4Wx2, i.v.), darolutamide (100 mg/kg, BID, p.o.), or with a combination of radium-223 and darolutamide, for 41 days. PSA and the bone turnover markers PINP and CTX-I were measured every second week in serum. Tumor-induced abnormal bone area, bone formation rate and radium-223 uptake in tumor-bearing tibiae were determined by X-ray, histomorphometry and gamma counter, respectively. The combination of radium-223 and darolutamide showed synergistic antiproliferative effects with combination indexes between 0.69-0.75 in vitro. GSEA demonstrated a prominent darolutamide-induced downregulation of DNA damage response (DDR) signaling pathways. In vivo, the combination treatment showed synergistic antitumor efficacy (p=0.04) as demonstrated by lower PSA concentrations when compared with the vehicle, radium-223 or darolutamide monotherapies (p=0.004, p=0.011 and p=0.002, respectively). In the vehicle and combination treatment groups, the mean serum PSA was 541% and 95.9% of the pre-treatment level, respectively. Furthermore, radium-223 alone or in combination with darolutamide inhibited increased bone turnover, tumor-induced abnormal bone growth and trabecular bone formation when compared to vehicle. Concurrent administration of darolutamide did not affect radium-223 uptake in tibiae. Radium-223 in combination with darolutamide exhibited synergistic antitumor efficacy both in vitro and in vivo. The synergistic effects could be due to the radiosensitization of cancer cells by darolutamide-induced downregulation of DDR pathways. Our results suggest that the combination of targeted alpha therapy with an androgen receptor inhibitor is a promising treatment strategy for mCRPC. Citation Format: Christoph A. Schatz, Mari I. Suominen, Andreas Schlicker, Matias Knuuttila, Esa Alhoniemi, Sanna-Maria Käkönen, Bernard Haendler, Urs B. Hagemann, Arne Scholz. Radium-223 in combination with darolutamide exhibits synergistic antitumor efficacy in LNCaP prostate cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 688.

A radiographic and histological study to compare red (650 nm) versus near infrared (810 nm) diode lasers photobiomodulation for alveolar socket preservation

Previous findings indicated that the laser photobiomodulation is more effective than the control or placebo in preserving the alveolar socket. This study aimed to compare two different lasers regarding their effectiveness in aiding alveolar socket preservation. Twenty extraction sockets were selected then divided into two equal groups. Group A was exposed to 650 nm Diode laser, and Group B to 810 nm Diode laser following the same protocol and parameters after a standard alveolar socket preservation procedure with collagen plug. Radiographic analysis with cone beam computed tomography was done to compare the alveolar bone surface area immediately after extraction and three months post-operatively, while bone samples collected before implant drilling were histologically examined for newly formed bone evaluation and histomorphometric analysis in terms of percentage of new bone surface area, percentage of unmineralized bone and finally, immunohistochemical analysis of Osteocalcin reaction surface area as well as optical density. Radiographically, infrared (810 nm) Diode effect on alveolar bone surface area has significantly exceeded the red laser, while histologically, red (650 nm) Diode has demonstrated statistical significance regarding all parameters; newly formed bone surface area percentage, unmineralized bone area percentage and finally Osteocalcin bone marker reaction surface area percentage and optical density. Under the specified conditions and laser parameters, photobiomodulation using the 810 nm Diode got the upper hand radiographically, yet histologically, the red 650 nm Diode managed to dominate all histological parameters when both employed as an adjunct to alveolar socket preservation procedures.

Influence of anti-sclerostin monoclonal antibody in the repair of post-extraction sockets of ovariectomized rats

ObjectiveThis study assessed the impact of an anti-sclerostin monoclonal antibody (Scl-Ab)-based osteoporosis drug on the post-extraction alveolar repair of ovariectomized rats. DesignFifteen female rats were randomly distributed into three groups: CTR (healthy animals), OST (osteoporosis induced by ovariectomy), and OST+Scl-Ab (osteoporosis induction followed by Scl-Ab treatment). Ovariectomy or sham surgery was performed 30 days before baseline, and Scl-Ab or a vehicle was administered accordingly in the groups. After seven days, all rats underwent the first lower molar extraction and were euthanized 15 days later. Computed microtomography, histological analysis, and collagen content measurement were performed on post-extraction sockets and intact mandibular and maxillary bone areas. ResultsMicrotomographic analyses of the sockets and mandibles did not reveal significant differences between groups on bone morphometric parameters (p > 0.05), while maxillary bone analyses resulted in better maintenance of bone architecture in OST+Scl-Ab, compared to OST (p < 0.05). Descriptive histological analysis and polarization microscopy indicated better post-extraction socket repair characteristics and collagen content in OST+Scl-Ab compared to OST (p < 0.05). ConclusionsScl-Ab-based medication did not accelerate alveolar bone formation but exhibited better post-extraction repair characteristics, and collagen content compared to ovariectomized animals only.

Case report of a primary ectopic extradural and extraspinal meningioma of the brachial plexus

Primary ectopic extradural and extraspinal meningiomas are rare. We present a unique case of this type of meningioma in the brachial plexus.A 25-year-old man consulted us because of neuropathic supraclavicular pain and the appearance of a supraclavicular mass whose volume had increased. Clinical examination found paresis of the deltoid, biceps brachii and brachialis muscles rated as M4 (MRC) and a strong Tinel sign at the supraclavicular fossa, over the palpable mass. There was no sign pointing towards central nervous system involvement or altered general condition. MRI revealed a mass measuring 53 × 24 mm invading the C5-C6 plexus roots and the primary upper trunk, but not the bone or spinal area. This lesion was hyperintense on DWI/ADC, hyperintense on T2 with hypointense spots, and hypointense on T1 with intense heterogeneous gadolinium enhancement.Excisional biopsy was done 6 months after symptoms started. The tumor had developed at the C5 root, which was fibrous and at the C6 root, which was grossly normal.Anatomical pathology confirmed the WHO grade 1 meningioma, meningothelial and psammomatous histological subtypes.At 6 months, a follow-up MRI found no postoperative tumor remnants or recurrence. During the postoperative course, persistent paralysis of the deltoid muscle at 5 months justified a nerve transfer.This is a rare case of ectopic extraspinal and extradural meningioma of the brachial plexus. The diagnosis of an ectopic meningioma must be considered when a patient presents with a brachial plexus tumor causing neurological deficits. The extradural nature is not sufficient to rule out this diagnosis.

Subchondral bone expansion in advanced knee osteoarthritis: Relation with radiographic severity and role in surgical decision-making

BackgroundJoint space width (JSW) is a traditional imaging marker for knee osteoarthritis (OA) severity, but it lacks sensitivity in advanced cases. We propose tibial subchondral bone area (TSBA), a new CT imaging marker to explore its relationship with OA radiographic severity, and to test its performance for classifying surgical decisions between unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) compared to JSW. MethodsWe collected clinical, radiograph, and CT data from 182 patients who underwent primary knee arthroplasty (73 UKA, 109 TKA). The radiographic severity was scored using Kellgren-Lawrence (KL) grading system. TSBA and JSW were extracted from 3D CT-reconstruction model. We used independent t-test to investigate the relationship between TSBA and KL grade, and binary logistic regression to identify factors associated with TKA risk. The accuracy of TSBA, JSW and established classification model in differentiating between UKA and TKA was assessed using AUC. ResultsAll parameters exhibited inter- and intra-class coefficients greater than 0.966. Patients with KL grade 4 had significantly larger TSBA than those with KL grade 3. TSBA (0.708 of AUC) was superior to minimal/average JSW (0.547/0.554 of AUC) associated with the risk of receiving TKA. Medial TSBA, together with gender and Knee Society Knee Score, emerged as independent classification factors in multivariate analysis. The overall AUC of composite model for surgical decision-making was 0.822. ConclusionTibial subchondral bone area is an independent imaging marker for radiographic severity, and is superior to JSW for surgical decision-making between UKA and TKA in advanced OA patients.

Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect.

The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3-wall intra-bony defects. Brain-derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non-neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)-related proteins and proliferation of human periodontal ligament cells. Six weeks after extraction of mandibular first and third premolars, 3-wall intra-bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 μg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA-positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN-positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose-dependently increased. These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3-wall intra-bony defects.

Efficacy of bone ring grafts for the reconstruction of alveolar ridge deficiencies: a systematic review. Part II: animal trials.

Bone ring (BR) grafts have been introduced to reconstruct alveolar ridge defects with simultaneous implant placement, but their clinical effectiveness remains undetermined. The aim of the current systematic review was to critically appraise evidence from animal studies regarding the effectiveness of BR grafts in alveolar ridge reconstruction and their variations under different surgical protocols. Electronic retrieval of six databases (MEDLINE, Embase, Cochrane Library, ScienceDirect, Web of Science, and Scopus) and citation search until 11 October 2023, for animal studies on bone augmentation employing BR grafts. The outcome variables were total bone area (BA), bone volume (BV), bone-implant contact (BIC), and histology. The protocol was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and prospectively registered with PROSPERO (CRD42023453949). Ten studies were included in the qualitative analysis according to the screening criteria. Two studies demonstrated favorable bone remodeling and osseointegration of the BR with both the implant and pristine bone. A comparative study between autogenous BRs and allogenic BRs reported a higher percentage of BA and BIC at 4 months of healing, but conflicting data were observed at 8 months. Another study indicated a significant advantage of autogenous BRs over bovine and biphasic ceramic BRs in terms of BA and BIC after 5 weeks. Three studies found that using collagen membranes did not significantly affect BA, BV, or BIC when used simultaneously with autogenous BRs during implant placement. Two studies evaluated one-stage and two-stage implant placement in conjunction with BR grafts, revealing similar levels of BA, BV, and BIC except for differences in total treatment time. Furthermore, one study found that the use of mucogingival junction incision and split-thickness flap significantly reduced the incidence of wound dehiscence compared with conventional incision and flap. Vertical bone augmentation surgery utilizing BR grafts with one-stage implant placement yielded histological and histomorphometric outcomes comparable to those achieved with two-stage implant placement or the additional application of collagen membrane.