Loss Of Bone Volume Research Articles

Bio-materials Used to Enhance Bone Healing in Implant Dentistry – A Review from the Past to Current

Abstract An alternating way of replacing the missing teeth involves the use of implants. In implant dentistry, an adequate amount of bone is crucial for the long-term prognosis. Bone volume loss can be caused by congenital, post-traumatic or post-surgical abnormalities, as well as disease processes. In scenarios with a bone defect at a site, where the primary stability of an implant cannot be established or where implant placement is not achievable in the best possible position for subsequent prosthetic therapy, guided bone regeneration before implantation represents the method of choice. During implant placement, a partial discrepancy between the implant’s surface and the socket’s osseous walls frequently leaves the peri-implant region with insufficient bone. It has been shown that barrier membranes can be successfully placed to allow the peri-implant space to be filled with new bone rather than lowering the height of the alveolar ridge to produce a sufficient breadth for implantation.

Use of autologous tooth-derived material as a graft in the post-extraction socket. Split-mouth study with radiological and histological analysis

BackgroundThe healing process after tooth removal involves bone remodelling which implies some loss of alveolar bone volume. Among materials proposed for minimising this remodelling and preserving the bone, autologous dental tissue is a promising option, but more data are needed. In this context, we evaluated size and density changes using cone beam computed tomography in autologous dental material (ADM)-preserved sockets compared to controls, and assessed biological responses by histological analysis.MethodsA split-mouth study was conducted including 22 patients, who underwent removal of ≥ 2 single-rooted teeth with intact sockets, assigning one socket to the experimental group which received ADM for alveolar preservation and another to the control group, which only underwent blood clot stabilisation. Cone beam computed tomography was performed postoperatively (week 0) and at weeks 8 and 16 to assess socket size and bone density. Histological analysis was carried out on trephine biopsies taken (Ø4 × 4.5 mm) from the experimental group.ResultsLess horizontal shrinkage was observed in the ADM group, especially at week 16 considering the group-by-time interaction for the following variables: difference in height between the lingual and buccal alveolar crests (-1.00; p < .01; 95% CI: -0.28 – -1.73), and half-widths, measured as the distance from the long axis of the missing tooth to the buccal alveolar crest at 1 mm (-0.61; p < .01; 95% CI: -0.18 – -1.04) and at 3 mm (-0.56; p < .01; 95% CI: -0.15 – -0.97) below the crest, with mean decreases of 1.07 and 2.14 mm in height difference, 0.66 and 1.32 mm in half-width at 1 mm and 0.43 and 1.02 mm in half-width at 3 mm in ADM and control groups respectively. Densitometry analysis showed higher bone densities in Hounsfield units in the ADM group considering all factors analysed regardless of time point and socket third (coronal, middle, or apical). Histologically, there were no signs of inflammation or foreign body reaction, and dentin particles were surrounded by and in close contact with bone tissue.ConclusionThese results add to the evidence that dentin can be used successfully as a material for alveolar socket preservation, given its desirable mechanical and biological properties, and warrant larger studies.

Healing of Extraction Sites after Alveolar Ridge Preservation Using Advanced Platelet-Rich Fibrin: A Retrospective Study.

Over time, numerous surgical procedures and biomaterials have been proposed for the reconstruction of post-extraction bone defects, each with their advantages and disadvantages. The main objective of this study was to evaluate dimensional changes in the alveolar bone 3 months after tooth extraction, before implant planning, comparing alveolar ridge preservation (ARP) with spontaneous healing. A total of 84 patients with non-restorable molars were included in the study. Forty-two patients received ARP with advanced platelet-rich fibrin (A-PRF) and spontaneous healing was evaluated in these patients. Cone beam computed tomography (CBCT) analysis performed before and after surgical intervention was used to determine the changes in vertical and horizontal bone dimensions produced after tooth extraction. CBCT measurements showed reduction in both vertical and horizontal alveolar bone size in both groups. For the study group, the alveolar parameters (height, width) were higher compared to the control group. The percentage variations between dimensional differences from the two groups were 38.58% for height, and for width were 36.88% at 0 mm, 35.56% at 3 mm, 36.61% at 5 mm, and 38.73% at 7 mm. The differences were statistically significant (p ˂ 0.0005). The results obtained after ARP with A-PRF showed a reduced loss of bone volume compared to spontaneous healing.

Histological Evaluation of Alveolar Ridge Preservation Using Different Bone Grafts: Clinical Study Analysis Part II.

To compare histologically the percentage of bone formation 12-20 weeks after ridge augmentation using 2 different techniques. Tooth loss is associated with 3-dimensional bone remodeling and ridge atrophy. Ridge preservation procedures can prevent alveolar bone volume loss. Different techniques and materials are used to preserve the alveolar ridge. Computer-generated randomization software was used to assign 2 ridge preservation techniques for 11 extraction sites. In group I, type I bovine Achilles tendon collagen plugs with bioactive resorbable calcium apatite crystals (CPCAC) were placed, and in group II, cortico-cancellous bone chips (CCBC) mix and an expanded polytetrafluoroethylene (ePTFE) barrier membrane were placed. The histomorphometric studies were performed using a computer-based image analysis system (ImageJ 1.4, National Institute of Health, Bethesda, Md) to calculate the pixel area of bone tissue and the remaining bone graft material. The histomorphometric data were analyzed using a Student t test to compare the measurements between the 2 experimental groups. This parametric statistical test was employed to determine if there were any statistically significant differences in the quantitative histological parameters between the groups. The sockets that received CPCAC showed a lower (31.89%) percentage of native bone surface area compared with the CCBC group (43.87%). However, the difference was not statistically significant (P < .05). In addition, the CPCAC group showed evidence of foreign-body reaction. The CCBC graft covered with an ePTFE barrier may induce more bone formation with minimal inflammation in an extraction socket compared with a collagen plug with calcium apatite crystals. In addition, histological analysis of the CPCAC graft showed evidence of foreign-body reaction, which indicates a negative clinical impact.

Temporal Trends in Body Composition and Metabolic Markers Prior to Diagnosis of Pancreatic Ductal Adenocarcinoma

Changes in body composition and metabolic factors may serve as biomarkers for the early detection of pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to capture the longitudinal changes in body composition and metabolic factors before diagnosis of PDAC. We performed a retrospective cohort study in which all patients (≥18 years) diagnosed with PDAC from 2002 to 2021 were identified. We collected all abdominal computed tomography scans and 10 different blood-based biomarkers up to 36 months before diagnosis. We applied a fully automated abdominal segmentation algorithm previously developed by our group for 3-dimensional quantification of body composition on computed tomography scans. Longitudinal trends of body composition and blood-based biomarkers before PDAC diagnosis were estimated using linear mixed models, compared across different time windows, and visualized using spline regression. We included 1690 patients in body composition analysis, of whom 516 (30.5%) had ≥2 prediagnostic computed tomography scans. For analysis of longitudinal trends of blood-based biomarkers, 3332 individuals were included. As an early manifestation of PDAC, we observed a significant decrease in visceral and subcutaneous adipose tissue (β= -1.94 [95% confidence interval (CI), -2.39 to -1.48] and β= -2.59 [95% CI, -3.17 to -2.02]) in area (cm2)/height (m2) per 6 months closer to diagnosis, accompanied by a decrease in serum lipids (eg, low-density lipoprotein [β= -2.83; 95% CI, -3.31 to -2.34], total cholesterol [β= -2.69; 95% CI, -3.18 to -2.20], and triglycerides [β= -1.86; 95% CI, -2.61 to -1.11]), and an increase in blood glucose levels. Loss of muscle tissue and bone volume was predominantly observed in the last 6 months before diagnosis. This study identified significant alterations in a variety of soft tissue and metabolic markers that occur in the development of PDAC. Early recognition of these metabolic changes may provide an opportunity for early detection.

Nasal septum-derived chondroprogenitor cells control mandibular condylar resorption consequent to orthognathic surgery: a clinical trial.

Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.

Phosphonated Heptamethine Dye Alleviates Radiation‐Induced Bone Loss

AbstractHigh levels of reactive oxygen species (ROS) are closely associated with osteoclast formation and function, resulting in bone loss. Herein, a novel ROS scavenger, named IR‐ALN, based on the heptamethine cyanine (Cy7) dyes is reported. IR‐ALN not only retains the inherent near‐infrared (NIR) fluorescence imaging and ROS scavenging activity of Cy7 dyes, but is also selectively absorbed by the osteoclast precursor cells, inhibiting osteoclast differentiation and bone resorption activity. Moreover, IR‐ALN exhibits bone‐targeted accumulation in a dose‐dependent manner and effectively alleviates bone and trabecular volume loss caused by X‐ray. The results suggest that IR‐ALN is a potential radioprotective agent that prevents radiation‐induced bone loss. Furthermore, the design strategy for IR‐ALN can be used as a reference for the development of new radioprotective agents.

Stimulation of Osteogenic Activity of Autologous Teeth Hard Tissues as Bone Augmentation Material.

The issue of bone volume loss is playing an increasing role in bone tissue engineering. Research has focused on studying the preparation and use of different types of human or xenogenic materials and their osteogenic properties. An alternative source for this purpose could be autologous extracted teeth. The simple preparation protocol, minimal immune response, and rapid organizing of the newly formed bone with optimal mechanical properties predispose autologous hard teeth tissues (HTTs) as a promising material suitable in the indication of augmentation of maxillary and mandible defects, comparable to other high-end augmentation materials. The aim of this study was to experimentally evaluate the osteogenic potential of ground native autologous HTTs prepared by different demineralization procedures, aimed at potentiating the osteoinductive and osteoconductive properties of their organic components. The results indicate that the most effective preparation process for HTT stimulation is the application of Cleanser for 10 min followed by exposure to 0.6 N HCl for 5 min with a wash in phosphate-buffered saline solution.

STEM CELLS IN BONE REGENERATION; THE FUTURE IS NOW

The aim of the ongoing projects was to demonstrate the efficacy of autologous bone marrow derived stem cells (MSC) combined with biomaterial to induced new bone formation in a randomized multicenter controlled clinical trial.Patients with a need for bone reconstruction of residual edentulous ridges in both the mandible and maxilla due to bone defects with a vertical loss of alveolar bone volume and/or knife edge ridges (≤ than 4,5 mm) unable to provide adequate primary stabilization for dental implants were included in the clinical study. Autologous bone marrow MSC were expanded, loaded on BCP and used to augment the alveolar ridges. After five months bone biopsies were harvested at the implant position site and implants were installed in the regenerated bone. The implants were loaded after 8–12 weeks. Safety, efficacy, quality of life and success/survival were assessed. Five clinical centers, 4 different countries participated. Bone grafts harvested from the ramus of the mandibles were used as control in the projects.

Результати модифікації аутотрансплантата після вторинної кісткової пластики альвеолярного відростка у пацієнтів з вродженим незрощенням верхньої губи та піднебіння.

Purpose. This study aimed to evaluate changes in structural parameters of neoformed osseous tissue after the bone grafting alveolar process with different types of autografts. Methods. The analysis of the anthropometric indices of neoformed bone tissue was conducted by multispiral computed tomography scanning. 29 children with congenital clefts of the alveolar process aged from 8-17 years were involved in the survey. The autotransplant was used from the mandibular symphysis (I group) and tibia (²² group). Results. The overall success rate of the formed bone bridge in the I group was 66,6% and 57,9% in ²² group (p = 0,632) according to the Bergland scale of complete regeneration. The average volume of the neoformed osseous tissue constituted in children of the I group stood at 71,0% ± 10,8, in the children of the ²² group the defect filling appeared to be 68,9% ± 3,7 after 1 year. There was a statistically significant loss of bone volume in percentage equivalent between the I (1%) and II (9,9%) groups over the last 6 months (p = 0,008). During a year the density of the neoformed bone of the I group tended to get 526,1 ± 90,4 HU, in the ²² group the average density was 288,0 ± 46,3 HU, this is 1,8 times less than in the I group (p = 0,054). Conclusions. It has been determined that the reparative processes and bone bridge formation of the mandibular symphysis autotransplant occur more rapidly during the first six months following grafting. At the end of the first year, the bone bridge’s volume and height parameters were similar, but the I group’s density remained higher than that of the II group. Key words: Congenital cleft lip and palate; autograft; bone grafting of the alveolar process; bone bridge height; bone bridge density.

Chronological analysis of periodontal bone loss in experimental periodontitis in mice.

Periodontal disease is understood to be a result of dysbiotic interactions between the host and the biofilm, causing a unique reaction for each individual, which in turn characterizes their susceptibility. The objective of this study was to chronologically evaluate periodontal tissue destruction induced by systemic bacterial challenge in known susceptible (BALB/c) and resistant (C57BL/6) mouse lineages. Animals, 6-8 weeks old, were allocated into three experimental groups: Negative control (C), Gavage with sterile carboxymethyl cellulose 2%-without bacteria (Sham), and Gavage with carboxymethyl cellulose 2% + Porphyromonas gingivalis (Pg-W83). Before infection, all animals received antibiotic treatment (sulfamethoxazole/trimethoprim, 400/80 mg/5 mL) for 7 days, followed by 3 days of rest. Microbial challenge was performed 3 times per week for 1, 2, or 3 weeks. After that, the animals were kept until the completion of 42 days of experiments, when they were euthanized. The alveolar bone microarchitecture was assessed bycomputed microtomography. Both C57BL/6 and BALB/c mice exhibited significant bone volume loss and lower trabecular thickness as well as greater bone porosity compared to the (C) and (Sham) groups after 1 week of microbial challenge (p < .001). When comparing only the gavage groups regarding disease implantation, time and lineage, it was possible to observe that within 1 week of induction the disease was more established in BALB/c than in C57BL/6 (p < .05). Our results reflected that after 1 week of microbial challenge, there was evidence of alveolar bone loss for both lineages, with the loss observed in BALB/c mice being more pronounced.

Effect of Recombinant Human Platelet-Derived Growth Factor on Healing of Chronic Periapical Tissue Pathosis Following Apical Surgery in a Canine Model: A Histomorphometric and Microcomputed Tomography Analysis.

This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and μCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery.

Clinical case of treatment of complications of the use of plate dental implants on the maxilla

Relevance. According to the conclusion of the European Federation of Periodontology, late complications of dental implantation include inflammation of the tissues in the reimplantation zone after the completion of osseointegration in the form of periimplantation mucositis and reimplantitis. According to many authors, in the first two months after dental implantation, in the case of initial insufficiency of soft tissue thickness in the operation area, when a minimum volume of biological width (3 mm on average) is formed, bone tissue loss is provoked, this property is especially pronounced when using lamellar dental implants. In the maxilla, overimplantation of a massive plate implant can lead to the development of inflammation of the paranasal sinuses. The most traditional options for mucosal augmentation in the area of implantation in the maxilla are grafting with local tissues or autotransplantation of a free flap from a donor site. Also used are resorbable collagen matrices (Resorbable Collagen Matrix – RCM) or membranes that protect the underlying tissues from external influences, completely close the surgical wound, prevent pathological scarring and allow you to control the epithelialization process.The purpose of the study. To increase the effectiveness of complex treatment of complicated reimplantitis in the maxilla, sinusoethmoiditis, by sanitation and the use of a collagen membrane for the combined closure of the oro-antral fistula.Material and methods. The article is devoted to the clinical case of complications of the use of a lamellar dental implant in the maxilla, diagnosis and treatment by an interdisciplinary surgical team of the City Clinical Hospital N.I. Pirogov of the Department of Healthcare of Moscow. A staged surgical intervention for the removal of a detailed laminar implant, unilateral ethmoidotomy and maxillary sinusectomy, and combined closure of the oro-antral communication with the use of local tissue plasty with a flap from the cheek and the installation of a collagen membrane are described.Results. To close a large bone defect in the area of the alveolar part of the maxilla, the bioPLATE Contur membrane was used, which is characterized by increased extensibility up to 50% of the original dimensions and elasticity. The mucoperiosteal flap was laid without tension over the collagen membrane and fixed with two-row interrupted sutures. The sutures were removed on the 14th postoperative day, the wound was epithelialized throughout, without signs of inflammation.Conclusions. Complications of dental implantation in the maxilla are manifested in the form of a loss of bone volume and a defect in the alveolar margin of the maxilla, the development of inflammatory complications of adjacent tissues and anatomical structures. This requires a multidisciplinary approach in diagnosis and surgical treatment with a comprehensive planning of patient rehabilitation. The use of a combined method of closing a bone defect with a collagen resorbable membrane and a buccal mucoperiosteal flap with suturing with a double-row suture makes it possible to achieve a satisfactory course of the postoperative period, avoid recurrence of the oro-antral fistula, and prepare the patient for further dental rehabilitation.

Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly understood. Here, we used mouse genetics, mechanical loading, and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in osteoblasts. We created and compared the skeletal phenotypes of control Pkd1flox/+;Wwtr1flox/+, Pkd1Oc-cKO, Wwtr1Oc-cKO, and Pkd1/Wwtr1Oc-cKO mice to investigate genetic interactions. Consistent with an interaction between polycystins and Wwtr1 in bone in vivo, Pkd1/Wwtr1Oc-cKO mice exhibited greater reductions of BMD and periosteal MAR than either Wwtr1Oc-cKO or Pkd1Oc-cKO mice. Micro-CT 3D image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKO or Wwtr1Oc-cKO mice. Pkd1/Wwtr1Oc-cKO mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKO or Wwtr1Oc-cKO mice. Moreover, we found that Pkd1/Wwtr1Oc-cKO mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of load-induced mechanosensing gene expression compared to control mice. Finally, control mice treated with a small molecule mechanomimetic, MS2 that activates the polycystin complex resulted in marked increases in femoral BMD and periosteal MAR compared to vehicle control. In contrast, Pkd1/Wwtr1Oc-cKO mice were resistant to the anabolic effects of MS2. These findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

Osteocyte RANKL Drives Bone Resorption in Mouse Ligature-Induced Periodontitis.

Mouse ligature-induced periodontitis (LIP) has been used to study bone loss in periodontitis. However, the role of osteocytes in LIP remains unclear. Furthermore, there is no consensus on the choice of alveolar bone parameters and time points to evaluate LIP. Here, we investigated the dynamics of changes in osteoclastogenesis and bone volume (BV) loss in LIP over 14 days. Time-course analysis revealed that osteoclast induction peaked on days 3 and 5, followed by the peak of BV loss on day 7. Notably, BV was restored by day 14. The bone formation phase after the bone resorption phase was suggested to be responsible for the recovery of bone loss. Electron microscopy identified bacteria in the osteocyte lacunar space beyond the periodontal ligament (PDL) tissue. We investigated how osteocytes affect bone resorption of LIP and found that mice lacking receptor activator of NF-κB ligand (RANKL), predominantly in osteocytes, protected against bone loss in LIP, whereas recombination activating 1 (RAG1)-deficient mice failed to resist it. These results indicate that T/B cells are dispensable for osteoclast induction in LIP and that RANKL from osteocytes and mature osteoblasts regulates bone resorption by LIP. Remarkably, mice lacking the myeloid differentiation primary response gene 88 (MYD88) did not show protection against LIP-induced bone loss. Instead, osteocytic cells expressed nucleotide-binding oligomerization domain containing 1 (NOD1), and primary osteocytes induced significantly higher Rankl than primary osteoblasts when stimulated with a NOD1 agonist. Taken together, LIP induced both bone resorption and bone formation in a stage-dependent manner, suggesting that the selection of time points is critical for quantifying bone loss in mouse LIP. Pathogenetically, the current study suggests that bacterial activation of osteocytes via NOD1 is involved in the mechanism of osteoclastogenesis in LIP. The NOD1-RANKL axis in osteocytes may be a therapeutic target for bone resorption in periodontitis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Anti-Siglec-15 Antibody Prevents Marked Bone Loss after Acute Spinal Cord Injury-Induced Immobilization in Rats.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts. Anti-Siglec-15 antibody (Ab) has been shown to inhibit osteoclast maturation and bone resorption while maintaining osteoblast activity, which is distinct from current antiresorptive agents that inhibit the activity of both osteoclasts and osteoblasts. The goal of the present study is to test a Siglec-15 Ab (NP159) as a new treatment option to prevent bone loss in an acute SCI model. To this end, 4-month-old male Wistar rats underwent complete spinal cord transection and were treated with either vehicle or NP159 at 20 mg/kg once every 2 weeks for 8 weeks. SCI results in significant decreases in bone mineral density (BMD, -18.7%), trabecular bone volume (-43.1%), trabecular connectivity (-59.7%), and bone stiffness (-76.3%) at the distal femur. Treatment with NP159 almost completely prevents the aforementioned deterioration of bone after SCI. Blood and histomorphometric analyses revealed that NP159 is able to greatly inhibit bone resorption while maintaining bone formation after acute SCI. In ex vivo cultures of bone marrow cells, NP159 reduces osteoclastogenesis while increasing osteoblastogenesis. In summary, treatment with NP159 almost fully prevents sublesional loss of BMD and metaphysis trabecular bone volume and preserves bone strength in a rat model of acute SCI. Because of its unique ability to reduce osteoclastogenesis and bone resorption while promoting osteoblastogenesis to maintain bone formation, Siglec-15 Ab may hold greater promise as a therapeutic agent, compared with the exclusively antiresorptive or anabolic agents that are currently used, in mitigating the striking bone loss that occurs after SCI or other conditions associated with severe immobilization. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Structural examination of experimental femoral head avascular necrosis

Aim. To conduct histological analysis of femoral head avascular necrosis in Wistar rats.Materials and Methods. Femoral head avascular necrosis was artificially induced in 12 Wistar rats which have been euthanised at 2, 4, 6, and 8 weeks postoperation (n = 3 per time point). Affected and intact femoral heads were examined by X-ray examination, haematoxylin and eosin staining, and scanning electron microscopy.Results. X-ray examination and haematoxylin and eosin staining showed the progressive development of osteonecrosis from 2 to 6 weeks and initiation of bone repair at 8 weeks postoperation. X-ray examination had less informative value as compared to routine histological examination. Progressive loss of bone volume was accompanied by osteolysis, resorption of hyaline cartilage, and replacement of bone and cartilage tissues with collagen fibers. Scanning electron microscopy provided an opportunity to assess cellular composition and showed that the maximum activity of osteoclasts and osteoblasts occurs at 6 and 8 weeks postoperation, respectively.Conclusion. X-ray examination was dispensable when investigating features of femoral head avascular necrosis. Histological examination using haematoxylin and eosin staining permitted detection of bone resorption, while scanning electron microscopy contributed to high-resolution visualisation of the bone cellular composition.

2349. Elucidating the Pathogenesis of Staphylococcus aureus During Hyperglycemic Osteomyelitis

Abstract Background Staphylococcus aureus is a leading cause of antibiotic-resistant bacterial infections and can infect nearly every organ of the human body. One common manifestation of S. aureus disease is invasive bone infection, or osteomyelitis. Osteomyelitis is one of the most difficult to treat infections, often necessitating prolonged antibiotic treatment and surgical interventions. Hyperglycemia, or elevated blood glucose concentration, increases the risk for developing osteomyelitis. We hypothesized that S. aureus adapts specifically to the altered host environment during hyperglycemic osteomyelitis, thereby contributing to the increased infection severity. Methods To model hyperglycemic osteomyelitis, we treated mice with streptozotocin prior to infection with S. aureus in a post-traumatic osteomyelitis model. We analyzed bacterial burdens in homogenized tissues and bone parameters with microcomputed tomography. To identify changes in the spatial molecular architecture of infected, hyperglycemic femurs, we utilized imaging mass spectrometry. Finally, to obtain a comprehensive understanding of S. aureus metabolic and virulence changes and identify genes essential for staphylococcal growth in vivo in hyperglycemic mice, we performed a transposon sequencing experiment. Results We discovered that hyperglycemic mice sustained increased bacterial burdens within infected femurs and greater dissemination to other organs. We also found that hyperglycemic infected mice experienced increased rates of bone destruction and loss of trabecular bone volume, suggesting that hyperglycemia exacerbates infection-associated bone loss. Finally, we identified 71 genes as uniquely essential for S. aureus growth during hyperglycemic infection compared to euglycemic infection. Conclusion Hyperglycemia results in increased osteomyelitis infection severity. Multiple S. aureus genes involved in metabolism with roles in bacterial fitness in acidic environments were uniquely essential for bacterial fitness during comorbid infection. By identifying genes contributing to S. aureus survival during hyperglycemic osteomyelitis, we have the potential to inform targeted therapeutic development for treatment of exacerbated infections in patients with comorbid hyperglycemia. Disclosures All Authors: No reported disclosures.

Inflammaging and Bone Loss in a Rat Model of Spinal Cord Injury.

Spinal cord injury (SCI) results in significant loss of sublesional bone, adding to the comorbidity of SCI with an increased risk of fracture and post-fracture complications. Unfortunately, the effect of SCI on skeletal health is also likely to rise, as the average age of SCI has increased and there are well-known negative effects of age on bone. To date, however, the impact of age and age-associated inflammation (inflammaging) on skeletal health after SCI remains largely unknown. To address this, we compared bone parameters in young (3 month) and middle-aged (9 month) male and female rats with a moderate thoracic contusion injury, to age- and sex-matched sham-operated controls. Skeletal parameters, locomotor function, and serum cytokine levels were assessed at both subchronic (30 days) and chronic (180 days) time points post-injury. We hypothesized that SCI would lead to a dramatic loss of bone immediately after injury in all SCI groups, with inflammaging leading to greater loss in middle-aged SCI rats. We also predicted that whereas younger rats might re-establish bone properties in more chronic phases of SCI, middle-aged rats would not. Supporting these hypothesis, trabecular bone volume was significantly lower in male and young female SCI rats early after injury. Contrary to our hypothesis, however, there was greater loss of trabecular bone volume, relative to age-matched shams, in young compared with middle-aged SCI rats, with no effects of SCI on trabecular bone volume in middle-aged female rats. Moreover, despite recovery of weight-supported locomotor activity, bone loss persisted into the chronic phase of injury for the young rats. Bone formation rates were lower in young male SCI rats, regardless of the time since injury, whereas both young and middle-aged female SCI rats had lower bone formation in the subchronic but not the chronic phase of SCI. In middle-aged rats, SCI-induced higher osteoclast surfaces, which also persisted into the chronic phase of SCI in middle-aged females. Neither age nor SCI-induced increases in inflammation seemed to be associated with bone loss. In fact, SCI had more dramatic and persistent effects on bone in male rats, whereas aging and SCI elevated serum cytokines only in female rats. Overall, this study demonstrates SCI-induced loss of bone and altered bone turnover in male and female rats that persists into the chronic phase post-injury. The sex- and age-dependent variations in bone turnover and serum cytokines, however, underscore the need to further explore both mechanisms and potential therapeutics in multiple demographics.

Lateral Displacement of Maxillary Sinus Palatal Wall: A 1-Year Retrospective Computerized Tomography Study.

To examine the short-term outcomes of maxillary sinus augmentations consisting of laterally and apically displacing the palatal wall through a transcrestal approach. The maxillary sinus floor was fractured in its palatal aspect by allowing a displacement in the buccal and apical direction with a magnetoelectric system. A medial displacement of the alveolar crest in its palatal bony plate was performed at the same time. Crestal bone change was investigated using superimposed preoperative and postsurgical computed tomography scans. Clinical and radiologic outcomes over 1 year were evaluated. A total of 18 implants were selected for retrospective volumetric and linear analyses. Sinus floor and alveolar bone augmentation surgery led to a significant increase in the bone volume (P = .0002) from 0.134 ± 0.060 cm3 to 0.639 ± 0.166 cm3, with an overall gain of +0.504 ± 0.139 cm3. No part of the implant apices appeared to protrude into the maxillary sinus at the 1-year follow-up. The width of the alveolar crest changed from 5.1 ± 0.5 mm to 6.5 ± 0.7 mm, with a significant increase of +1.4 ± 0.6 mm registered at 1 year. However, a marginal bone loss of 1.0 ± 0.8 mm was observed. When tooth positions were investigated, no significant differences between the two groups (premolars versus molars) were found. Significant and effective bone gains allowed proper placement of the dental implants but with a minimal loss of peri-implant bone volume.