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BACKGROUND: The application of orthodontic force triggers autophagy in the periodontal tissue via diverse signaling pathways, augmenting or attenuating the activity of relevant cell types such as periodontal ligament cells, osteocytes, osteoclasts, and osteoblasts, thus facilitating the process of periodontal remodeling. OBJECTIVE: To review the research progress in orthodontic force mediated autophagy in periodontal tissue and its impact on orthodontic tooth movement. METHODS: The PubMed, Web of Science, China Biology Medicine disc and CNKI were searched for literature published from 2010 to 2023 to summarize the progress in orthodontics-related autophagy. And 76 papers were finally included in the analysis and discussion. RESULTS AND CONCLUSION: Orthodontic force can trigger a series of biochemical signal changes through periodontal mechanical receptors and aseptic inflammation they cause, leading to autophagy in periodontal tissue. Subsequently, autophagy generates corresponding feedback through cascaded amplified signaling pathways such as Phosphoinositide 3-kinase/protein kinase B, Hippo, and mitogen-activated protein kinase pathways, promoting periodontal tissue remodeling and ultimately achieving tooth movement and stability. Orthodontic force-induced autophagy can differentially regulate bone resorption on the tooth pressure side and bone formation on the tension side. Related targets have good prospects in the clinical application of orthodontic treatment. Orthodontics and autophagy have complex mechanisms. However, existing research has only focused on exploring the role of autophagy in orthodontic tooth movement. Further exploration is needed to investigate the mutual regulatory effects between autophagy and orthodontic tooth movement, as well as the interactions between upstream mechanical receptors and signaling pathways involved in related pathways. [ABSTRACT FROM AUTHOR]

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Secreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild‐type (WT) and SPARC null (SPARC(−/−)) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC(−/−) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three‐point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC(−/−) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC(−/−) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC(−/−) on bone mineral density was only detected in female SPARC(−/−) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC(−/−) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs. [ABSTRACT FROM AUTHOR]

Progressive osteolysis can occur at the cement–bone interface of joint replacements and the associated loss of fixation can lead to clinical loosening. We previously developed a rat hemiarthroplasty model that exhibited progressive loss of fixation with the development of cement–bone gaps under the tibial tray that mimicked patterns found in human arthroplasty retrievals. Here we explored the ability of a bisphosphonate (zoledronic acid, ZA) to attenuate cement–bone osteolysis and maintain implant stability. Sprague‐Dawley rats (n = 59) received a poly(methylmethacrylate) cemented tibial component and were followed for up to 12 weeks. Treatment groups included peri‐operative administration of ZA (ZA group), administration of ZA at 6 weeks postop (late ZA group), or vehicle (Veh group). There was a 60% reduction in the rate of cement–bone gap formation for the ZA group (0.15 mm3/week) compared to Veh group (0.38 mm3/week, p = 0.016). Late ZA prevented further progression of gap formation but did not reverse bone loss to the level achieved in the ZA group. Micromotion from five times body weight toggle loading was positively correlated with cement–bone gap volume (p = 0.009) and negatively correlated with the amount of cement in the metaphysis (p = 0.005). Reduced new bone formation and enduring nonviable bone in the epiphysis for the ZA group were found. This suggests that low bone turnover in the epiphysis may suppress the early catabolic response due to implantation, thereby maintaining better fixation in the epiphysis. This preclinical model presents compelling supporting data documenting improved maintenance of the cement–bone fixation with the use of peri‐operative bisphosphonates. [ABSTRACT FROM AUTHOR]

Large acetabular bone defects are challenging in hip revision surgery. Clinical assessment is crucial to evaluate modern technologies in surgical reconstruction. We aimed to better understand the bone remodeling that occurs following acetabular reconstruction. Our objectives were: (1) To characterize changes in the shape of the pelvis by studying sequential computed tomography (CT) scans collected immediately and 1‐year postoperatively and (2) to identify which part of the pelvis is most susceptible to remodeling. We used the CT scans taken at two timepoints, of 24 patients with acetabular bone defects classified as Paprosky IIIB, treated with three‐dimensional (3D)‐printed custom‐made acetabular implants. Segmented 3D models of the bony pelvis were co‐registered using three different techniques. A global co‐registration of the full pelvis was conducted, followed by the co‐registration of the innominate bone and then ilium only, on the ipsilateral reconstructed side. The relative movements of the ilium, ischium, and pubis were analyzed from visual inspection and using co‐registration metrics (root mean square error and intersection over union). No bone remodeling was found in 14/24 patients (58%). The co‐registration of the innominate bone indicated bone remodeling in five cases (21%), while the remaining five cases (21%) presented remodeling in the global co‐registration but not the innominate bone co‐registration, suggestive of changes occurring at the sacroiliac joint. Changes in the pelvic shape were greatest at the pubis and ischium. Bone remodeling may occur in complex cases of Paprosky type IIIB defects, after acetabular reconstruction (occurrence of 21%, 5/24 cases). Surgeons and engineers should consider this when monitoring implant migration. [ABSTRACT FROM AUTHOR]

The current study aims to prepare and compare three injectable hydrogels consisting of chitosan, hyaluronic acid, and hydroxyapatite in different combinations using two solvents and homoginizer that can be employed in bone tissue engineering (BTE) for remodelling and healing bones. The hydrogel structures were well characterized by FT-IR, XRD and SEM analyses. Surface study, porosity, percolation capacity, bone cell adhesion and proliferation, and swelling properties were tested and was found that these hydrogels are better candidates for BTE. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) analysis showed better compatibility with mononuclear cells derived from human peripherals. Our findings suggest that these hydrogels can be efficiently used as injectable hydrogels in BTE applications. [ABSTRACT FROM AUTHOR]

Objective: Patients with type IIA craniofacial microsomia (CFM) may benefit from mandibular distraction osteogenesis (MDO) treatment during childhood; however, remodelling of the mandible during the consolidation phase, which may affect the short‐term outcomes of MDO, has not yet been quantitatively analysed using computed tomography. Therefore, we aimed to investigate bone remodelling of the mandible in children with type IIA CFM treated with MDO before distractor removal and the factors that influence ramus vertical elongation efficiency. Materials and Methods: Twenty‐three children with unilateral CFM were studied between 2020 and 2024. Longitudinal computed tomography data (preoperative, end of active phase and at pre‐distractor removal) were analysed. Condyle positions and the mandibular cant were analysed using a paired‐sample t test. The relapse rates of vertical lengthening and mandibular cant were calculated. The correlation between distraction efficiency and preoperative craniofacial morphology was analysed. Results: The condyle on the affected side moved upwards and backwards by 28.84 ± 4.08 and 2.85 ± 4.33 mm, respectively during the active phase but lost 7.66 ± 2.64 mm of vertical extension during the consolidation phase. The relapse rates for vertical extension of the condyle and occlusal plane were 27% and 35%, respectively. The ratio of mandibular ramus height was positively related to EV. Conclusions: In children with CFM, attention should be paid to vertical elongation instability and relapse of mandibular inclination during consolidation. Severe mandibular ramus hypoplasia is a preoperative risk factor for vertical skeletal relapse during consolidation. Further efforts are required to reduce the stress that leads to relapse. [ABSTRACT FROM AUTHOR]

Current evidence suggests that proper implant transmucosal contouring can significantly impact supracrestal soft tissue development and crestal bone response both in early and late stages of treatment. The macrodesign and composition of the anatomical healing abutment or temporary prosthesis used during transmucosal contouring are crucial elements for establishing biologic and prosthetic conditions that minimize early bone remodeling, improve esthetic outcomes, and reduce the possibility for future peri-implant inflammation. This article presents clinical directions on the design and fabrication processes of anatomical healing abutments or temporary prostheses for single implant sites under the interpretation of currently available scientific data. [ABSTRACT FROM AUTHOR]

This study evaluated how implant design features influence osseointegration. Two implant macrogeometries and surface treatments were evaluated: (1) progressive buttress threads with an SLActive surface (SLActive/BL), and (2) inner and outer trapezoidal threads with a nanohydroxyapatite coating over a dual acid-etched surface (Nano/U). Implants were placed in the right ilium of 12 sheep, and histologic and -metric analyses were conducted after 12 weeks. Percentages of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within the threads were quantified. Histologically, the SLActive/BL group showed greater and more intimate BIC than the Nano/U group. In contrast, Nano/U group depicted woven bone formation within the healing chambers, between the osteotomy wall and implant threads, and bone remodeling was evident at the outer thread tip. Significantly higher BAFO was seen in the Nano/U group than the SLActive/BL group at 12 weeks (P < .042). Different implant design features influenced the osseointegration pathway, supporting further investigations to describe the differences and clinical performance. [ABSTRACT FROM AUTHOR]

The histologic findings and histomorphometric analysis of peri-implant tissues from nine functionally loaded implants from an adult cadaver were analyzed. Despite the presence of peri-implant bone loss, all implants were found to have a high degree of osseointegration, with the bone-implant contact (BIC) ranging from 69% to 88%. The mean BIC was 83.2% ± 4.3% (range: 76.5% to 87.7%) for maxillary implants and was 74.4% ± 7.1% (range: 69.4% to 84.9%) for mandibular implants, which were comparable. Relatively prominent bone remodeling and resorption with soft tissue ingrowth were observed in the vertical bony defects compared to the areas without intrabony components, which might represent the sequence of bone loss around the implants. [ABSTRACT FROM AUTHOR]

The temporomandibular joint is the only joint structure within the craniofacial skeletal system, responsible for performing functions related to opening and closing mouth movements, such as chewing, speaking, and facial expression in daily life. The condyle of the mandible, as a vital component of the temporomandibular joint, originates from the mandibular process formed by the first gill arch and is the key growth center at the end of the mandibular ramus. Condyle is composed of a layer of cartilage as its surface and subchondral bone below, exhibiting unique biological processes during its growth and development. In the articular fossa, the functional movement of the condyle depends on its normal physiological and anatomical structure, which plays a crucial role in establishing occlusion and shaping facial features. Abnormal growth and development can lead to the occurrence of condylar deformities, which affect the vertical height of the patient's maxillofacial region and ultimately lead to secondary skeletal class Ⅱ or Ⅲ craniofacial deformities. During the process of growth and development, the condyle is subject to complex signal regulation. In recent years, with in-depth research on the temporomandibular joint, researchers have begun to discuss the regulatory mechanisms of condyle growth and development from the perspectives of gene expression and molecular level, in order to explain the causes of temporomandibular joint diseases and condylar deformities. This article provides a review on the growth process and structure of condyle, classification and pathological manifestations of condylar deformities, and related regulatory mechanisms of the growth and development of condyle, as well as pathogenesis of condylar deformities. The aim of this article is to provide research ideas for temporomandibular joint diseases and craniofacial malformations caused by abnormal development of the mandibular condyle in clinical practice.

Abstract Hormonal changes in pregnant and lactating women significantly affect bone metabolism and overall stress levels, positioning them as a unique group within the orthodontic population. Fluctuations in estrogen, progesterone, prolactin, and other hormones are closely linked to bone remodeling and the periodontal tissue’s response to inflammation caused by dental plaque. Hormones such as thyrotropin, leptin, and melatonin also play crucial roles in pregnancy and bone remodeling, with potential implications for orthodontic tooth movement. Additionally, adverse personal behaviors and changes in dietary habits worsen periodontal conditions and complicate periodontal maintenance during orthodontic treatment. Notably, applying orthodontic force during pregnancy and lactation may trigger stress responses in the endocrine system, altering hormone levels. However, these changes do not appear to adversely affect the mother or fetus. This review comprehensively examines the interaction between hormone levels and orthodontic tooth movement in pregnant and lactating women, offering insights to guide clinical practice.

Abstract Background Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling. Methods Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro. Results The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio. Conclusions Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.

Sclerostin is a glycoprotein predominantly released by specialized bone-forming cells (osteocytes). It serves as a principal inhibitor of osteogenesis and plays a key act in modulating the metabolism of alveolar bone. Sclerostin is shown to contribute to the occurrence of periodontitis by regulating the remodeling of the alveolar bone. A monoclonal antibody which antagonizes sclerostin has become extremely useful for osteoanabolic therapies. Romosozumab is an Food and Drug Administration-approved anti-sclerostin antibody that has shown promising results in the treatment of osteoporosis. Research is being conducted on the effect of anti-sclerostin antibody (Scl-Ab) as a therapeutic option in the management of periodontitis, and up till now, the results are promising. A comprehensive review of the literature was done using the PubMed database and Google Scholar. Research articles published before April 2023 with the search terms “sclerostin,” “periodontitis,” and “anti-sclerostin antibody” (Scl-Ab) were included. Most of the studies point toward a definitive association between chronic periodontitis and the levels of sclerostin. Numerous investigations underscore the significance of evaluating sclerostin levels as a diagnostic marker for periodontitis, and the application of anti-sclerostin antibodies as a potential therapeutic option for managing periodontitis and peri-implant diseases. However, further researches are required to delve into the therapeutic effects and possible side effects of Scl-Ab. Sclerostin antibodies show promise as an anabolic drug that enhances bone mass and could potentially become a viable therapeutic alternative for addressing periodontal conditions in future.

Abstract Background There is a lack of knowledge about the biological process of intercorporal bone graft remodeling after posterior lumbar interbody fusion surgery and whether this process is associated with changes in back pain and intercorporal fusion status. As an alternative to the commonly used but unreliable fusion criteria, Hounsfield units can be used to quantify biological activity and changes in bone mineral content. However, studies assessing Hounsfield units conducted to date do not provide sufficient details about how the bone grafts were segmented to measure the Hounsfield units to allow for replication, and did not assess individual patient trends in graft changes over time. Using the data of nine patients after posterior lumbar interbody fusion, a novel Hounsfield units measurement procedure was developed and used to explore its usability to quantify the bone graft remodeling process. Case details We report a case series of nine patients (six male, three female, mean age 64 years, all Caucasian) who all had computed tomography scans performed at 1 and 2 years after posterior lumbar interbody fusion surgery. Overall, seven out of the nine (78%) cases had a 3–41% increase in their bone grafts’ Hounsfield units between 1 and 2 years after surgery. The cases showed large interindividual variability in their Hounsfield units values over time, which coincided with varying levels of back pain and intercorporal fusion status. Conclusion The Hounsfield units measurement procedure used for this case series may be useful to quantify intercorporal bone graft remodeling in patients after posterior lumbar interbody fusion, and may be used as an adjunct diagnostic measure to monitor bone graft remodeling over time. Future research is warranted to explore how to interpret bone graft Hounsfield units-values and Hounsfield units trajectories in light of clinical variables or intercorporal fusion status.

Abstract The optimal configuration of a customized implant abutment is crucial for bone remodeling and is influenced by various design parameters. This study introduces an optimization process for designing two-piece zirconia dental implant abutments. The aim is to enhance bone remodeling, increase bone density in the peri-implant region, and reduce the risk of late implant failure. A 12-month bone remodeling algorithm subroutine in finite element analysis to optimize three parameters: implant placement depth, abutment taper degree, and gingival height of the titanium base abutment. The response surface analysis shows that implant placement depth and gingival height significantly impact bone density and uniformity. The taper degree has a smaller effect on bone remodeling. The optimization identified optimal values of 1.5 mm for depth, 35° for taper, and 0.5 mm for gingival height. The optimum model significantly increased cortical bone density from 1.2 to 1.937 g/cm3 in 2 months, while the original model reached 1.91 g/cm3 in 11 months. The standard deviation of density showed more uniform bone apposition, with the optimum model showing values 2 to 6 times lower than the original over 12 months. The cancellous bone showed a similar trend. In conclusion, the depth and taper have a significant effect on bone remodeling. This optimized model significantly improves bone density uniformity.

Abstract O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling. Graphical Abstract

Abstract Background The number of adult orthodontic patients is increasing, and studies have shown that autophagy is involved in regulating orthodontic tooth movement and plays an important role in aging-related changes. Therefore, we aimed to explore the role of autophagy in aging-related changes during orthodontic tooth movement by establishing a rat orthodontic tooth movement model. Methods Forty-five 6-week-old and sixty-five 8-month-old male Sprague–Dawley rats were selected to represent adolescents and adults and establish orthodontic tooth movement model. They were sacrificed on days 0,1,3,7 and 14. Immunohistochemistry, immunofluorescence and tartrate resistant acid phosphatase (TRAP) staining were applied to measure the expression level of osteogenesis, autophagy, aging factors and osteoclast number in periodontal membrane of left upper first molar during orthodontic tooth movement. Then, we regulated the autophagy level by injecting autophagy activator rapamycin during orthodontic tooth movement and measured these factors and tooth movement distance by micro-computed tomography. Results Aging factor levels in the periodontal membrane were higher in adult rats than in adolescent rats and the autophagy factor levels were lower. The levels of osteogenic factors were lower on the tension side in adult rats than in adolescent rats. The peak osteoclast number on the pressure side occurred later in adult rats than in adolescent rats. The injection of rapamycin increased autophagy, accelerated orthodontic tooth movement in adult rats, and reduced the levels of aging factors. The levels of osteogenic factors were higher and reached those in adolescent rats at some time points. The number of osteoclasts increased significantly in the early stage. Conclusions Autophagy may play a substantial role in regulating aging-related changes in orthodontic tooth movement.

With the aging population, intertrochanteric femur fracture in the elderly has become one of the most serious public health issues and a hot topic of research in trauma orthopedics. Due to the limitations of internal fixation techniques and the insufficient mechanical design of nails, the occurrence of complications delays patient recovery after surgical treatment. Design of a proximal femur bionic nail (PFBN) based on Zhang’s N triangle theory provides triangular supporting fixation, which dramatically decreases the occurrence of complications and has been widely used for clinical treatment of unstable intertrochanteric femur fracture worldwide. In this work, we developed an equivalent biomechanical model to analyze improvement in bone remodeling of unstable intertrochanteric femur fracture through PFBN use. The results show that compared with proximal femoral nail antirotation (PFNA) and InterTan, PFBN can dramatically decrease the maximum strain in the proximal femur. Based on Frost’s mechanostat theory, the local mechanical environment in the proximal femur can be regulated into the medium overload region by using a PFBN, which may render the proximal femur in a state of physiological overload, favoring post-operative recovery of intertrochanteric femur fracture in the elderly. This work shows that PFBN may constitute a panacea for unstable intertrochanteric femur fracture and provides insights into improving methods of internal fixation.

Abstract Objective To construct the deep learning convolution neural network (CNN) model and machine learning support vector machine (SVM) model of bone remodeling of chronic maxillary sinusitis (CMS) based on CT image data to improve the accuracy of image diagnosis. Methods Maxillary sinus CT data of 1000 samples in 500 patients from January 2018 to December 2021 in our hospital was collected. The first part is the establishment and testing of chronic maxillary sinusitis detection model by 461 images. The second part is the establishment and testing of the detection model of chronic maxillary sinusitis with bone remodeling by 802 images. The sensitivity, specificity and accuracy and area under the curve (AUC) value of the test set were recorded, respectively. Results Preliminary application results of CT based AI in the diagnosis of chronic maxillary sinusitis and bone remodeling. The sensitivity, specificity and accuracy of the test set of 93 samples of CMS, were 0.9796, 0.8636 and 0.9247, respectively. Simultaneously, the value of AUC was 0.94. And the sensitivity, specificity and accuracy of the test set of 161 samples of CMS with bone remodeling were 0.7353, 0.9685 and 0.9193, respectively. Simultaneously, the value of AUC was 0.89. Conclusion It is feasible to use artificial intelligence research methods such as deep learning and machine learning to automatically identify CMS and bone remodeling in MSCT images of paranasal sinuses, which is helpful to standardize imaging diagnosis and meet the needs of clinical application.

Objectives Materials and Methods Results Conclusions To investigate whether a labially inclined implant axis compromises the clinical outcomes of immediate implant placement and provisionalization (IIPP) in the anterior maxilla.Patients with unsalvageable central or lateral maxillary incisors were enrolled. IIPP with simultaneous connective tissue graft (CTG) was performed in all participants. In the control group, the alveolar ridge had a long axis aligned with the tooth, which ensured that the immediate implant was aimed at the incisor edge or the cingulum of future restoration. The test group had a large angle between the axes of the ridge and tooth. To avoid bone fenestration, the implants were placed labially inclined and emerged from the labial side of future restoration. Intra‐oral scanning and cone‐beam computed tomography were performed to record soft and hard tissue profiles at baseline and 1 year later. Soft tissue stability, bone remodeling, and pink esthetic score (PES) were evaluated and compared between two groups.Thirty‐nine participants (19 tests and 20 controls) completed the study. At 1‐year post‐surgery, the mid‐facial gingival margin migrations were 0.85 ± 0.37 mm (test) and 0.81 ± 0.33 mm (control), without significant differences. No differences were identified in buccal profile alteration, linear ridge reduction, buccal bone thickness, or PES scores. The test group demonstrated thinner buccal soft tissue at the crestal level than the control group.When large tooth‐ridge angulation presented, labially inclined implant, avoiding buccal ridge fenestration in IIPP with CTG, did not compromise the clinical outcome in short term. [ABSTRACT FROM AUTHOR]

AbstractEmerging evidence suggests that bone turnover is influenced by the gut microbiome through critical bone signaling pathways. The purpose of this scoping review is to examine prebiotic, probiotic, and synbiotic interventions on bone outcomes in humans across the lifespan. PubMed, Scopus, and EBSCOhost were searched until January 2023 to identify clinical trials examining bone mineral density (BMD) or bone mineral content (BMC) with gut microbiome interventions. Of three prebiotic interventions, one reported higher areal BMD (aBMD) in adolescents. In two studies in postmenopausal women, no changes in aBMD were observed despite decreased biomarkers of bone resorption. Probiotic interventions in perimenopausal or postmenopausal women demonstrated increased aBMD or attenuated bone loss in various bone regions. All studies observed attenuated bone loss (n = 4) or increased aBMD (n = 1). One study assessed a synbiotic intervention on aBMD and observed decreased biomarkers of bone resorption but no changes in aBMD. Results suggest potential for microbiome-targeted therapies (prebiotics, probiotics and synbiotics) to attenuate bone loss. However, changes in biomarkers of bone turnover were not always accompanied by changes in bone mineralization. Future studies should utilize longer duration interventions to investigate the influence of prebiotic, probiotic, and synbiotic interventions across diverse age, sex, and ethnic cohorts. [ABSTRACT FROM AUTHOR]

Background: Serum bone turnover markers offer limited insight into metabolic activity at the individual vertebra level in osteoporosis. This study introduces a novel image-derived bone turnover marker for individual vertebrae to address this limitation, utilizing volumetric density-adjusted quantitative bone single-photon emission computed tomography/computed tomography (SPECT/CT) with [99mTc]Tc-DPD. This retrospective study included 177 lumbar vertebrae from 55 postmenopausal South Korean women. The mean standardized uptake value (SUVmean, g/cm3) and volumetric bone mineral density (vBMD, mg/cm3) were determined within a 2-cm³ volume of interest in the trabecular portion of each vertebra using quantitative SPECT and CT. The density-adjusted mean standardized uptake value (dSUVmean) was calculated by dividing the SUVmean by the vBMD and multiplying by 1,000. Results: SUVmean correlated positively with vBMD (r = 0.60, p < 0.001). Conversely, dSUVmean correlated negatively with vBMD (ρ = −0.66, p < 0.001), highlighting the inverse relationship between bone mass and turnover after density adjustment of SUVmean. Patients with major osteoporotic fractures had lower vBMD (62.5 ± 29.4 vs. 92.3 ± 27.4 mg/cm³, p = 0.001) but higher dSUVmean (100.8 ± 60.7 vs. 62.6 ± 17.5, p = 0.001) compared to those without fractures, reinforcing the association between fracture prevalence, low bone mass, and high bone turnover. Conclusion: Volumetric density-adjusted quantitative bone SPECT/CT offers a novel image-derived bone turnover marker for assessing bone turnover in osteoporosis. This method provides a precise assessment of fragility at the individual vertebra level, which may enhance personalized osteoporosis management. [ABSTRACT FROM AUTHOR]

Bone is a dynamically active tissue whose health status is closely related to its construction and remodeling, and imbalances in bone homeostasis lead to a wide range of bone diseases. The sulfated glycoprotein C-type lectin structural domain family 11 member A (Clec11a) is a key factor in bone mass regulation that significantly promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts and stimulates chondrocyte proliferation, thereby promoting longitudinal bone growth. More importantly, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis. Clec11a is also involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1. Clec11a plays an important role in promoting bone health and preventing bone disease and may represent a new target and novel drug for bone disease treatment. Therefore, this review aims to explore the role and possible mechanisms of Clec11a in the skeletal system, evaluate its value as a potential therapeutic target against bone diseases, and provide new ideas and strategies for basic research on Clec11a and preventing and treating bone disease. [ABSTRACT FROM AUTHOR]

Hormonal changes in pregnant and lactating women significantly affect bone metabolism and overall stress levels, positioning them as a unique group within the orthodontic population. Fluctuations in estrogen, progesterone, prolactin, and other hormones are closely linked to bone remodeling and the periodontal tissue's response to inflammation caused by dental plaque. Hormones such as thyrotropin, leptin, and melatonin also play crucial roles in pregnancy and bone remodeling, with potential implications for orthodontic tooth movement. Additionally, adverse personal behaviors and changes in dietary habits worsen periodontal conditions and complicate periodontal maintenance during orthodontic treatment. Notably, applying orthodontic force during pregnancy and lactation may trigger stress responses in the endocrine system, altering hormone levels. However, these changes do not appear to adversely affect the mother or fetus. This review comprehensively examines the interaction between hormone levels and orthodontic tooth movement in pregnant and lactating women, offering insights to guide clinical practice. [ABSTRACT FROM AUTHOR]

The complex relationship between trace elements and skeletal health has received increasing attention in the scientific community. Among these minerals, manganese (Mn) has emerged as a key element affecting bone metabolism and integrity. This review examines the multifaceted role of Mn in bone health, including its effects on bone regeneration, mineralization, and overall skeletal strength. This review article is based on a synthesis of experimental models, epidemiologic studies, and clinical trials of the mechanisms of the effect of Mn on bone metabolism. Current research data show that Mn is actively involved in the processes of bone remodeling by modulating the activity of osteoblasts and osteoclasts, as well as the main cells that regulate bone formation and resorption. Mn ions have a profound effect on bone mineralization and density by intricately regulating signaling pathways and enzymatic reactions in these cells. Additionally, Mn superoxide dismutase (MnSOD), located in bone mitochondria, plays a crucial role in osteoclast differentiation and function, protecting osteoclasts from oxidative damage. Understanding the nuances of Mn's interaction with bone is essential for optimizing bone strategies, potentially preventing and managing skeletal diseases. Key findings include the stimulation of osteoblast proliferation and differentiation, the inhibition of osteoclastogenesis, and the preservation of bone mass through the RANK/RANKL/OPG pathway. These results underscore the importance of Mn in maintaining bone health and highlight the need for further research into its therapeutic potential. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in the treatment of acute lymphoblastic leukemia (ALL) have led to a marked improvement in the survival rate of patients. Nevertheless, these patients may develop adverse effects during and after treatment, such as bone abnormalities and vitamin D deficiency. Bone remodeling allows for bone volume and structure to be maintained, which is controlled by the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system-determining pathway in the balance between bone formation and resorption. Some reports have explored the role of corticosteroids in modulating the RANKL and OPG levels and RANKL/OPG ratio in pediatric patients. Nevertheless, studies evaluating the role of RANKL and OPG in the bone health of pediatric ALL patients during treatment are limited. During remission, we observed an increase in the RANKL/OPG ratio, increased RANKL levels, and decreased OPG levels in ALL patients. These changes may predispose such patients to the development of bone health disorders in their adult lives. Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. Methods: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4–17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = −0.454, p = 0.008) was observed. Conclusions: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients. [ABSTRACT FROM AUTHOR]

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology. [ABSTRACT FROM AUTHOR]

Introduction: Changes to bone physiology play a central role in the development of osteoarthritis with the mechanosensing osteocyte releasing factors that drive disease progression. This study developed a humanised in vitro model to detect osteocyte responses to either interleukin-6, a driver of degeneration and bone remodelling in animal and human joint injury, or mechanical loading, to mimic osteoarthritis stimuli in joints. Methods: Human MSC cells (Y201) were differentiated in 3-dimensional type I collagen gels in osteogenic media and osteocyte phenotype assessed by RTqPCR and immunostaining. Gels were subjected to a single pathophysiological load or stimulated with interleukin-6 with unloaded or unstimulated cells as controls. RNA was extracted 1-hour post-load and assessed by RNAseq. Markers of pain, bone remodelling, and inflammation were quantified by RT-qPCR and ELISA. Results: Y201 cells embedded within 3D collagen gels assumed dendritic morphology and expressed mature osteocytes markers. Mechanical loading of the osteocyte model regulated 7564 genes (Padj p<0.05, 3026 down, 4538 up). 93% of the osteocyte transcriptome signature was expressed in the model with 38% of these genes mechanically regulated. Mechanically loaded osteocytes regulated 26% of gene ontology pathways linked to OA pain, 40% reflecting bone remodelling and 27% representing inflammation. Load regulated genes associated with osteopetrosis, osteoporosis and osteoarthritis. 42% of effector genes in a genome-wide association study meta-analysis were mechanically regulated by osteocytes with 10 genes representing potential druggable targets. Interleukin-6 stimulation of osteocytes at concentrations reported in human synovial fluids from patients with OA or following knee injury, regulated similar readouts to mechanical loading including markers of pain, bone remodelling, and inflammation. Discussion: We have developed a reproducible model of human osteocyte like cells that express >90% of the genes in the osteocyte transcriptome signature. Mechanical loading and inflammatory stimulation regulated genes and proteins implicated in osteoarthritis symptoms of pain as well as inflammation and degeneration underlying disease progression. Nearly half of the genes classified as 'effectors' in GWAS were mechanically regulated in this model. This model will be useful in identifying new mechanisms underlying bone and joint pathologies and testing drugs targeting those mechanisms. [ABSTRACT FROM AUTHOR]

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long‐term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti‐inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)‐stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX‐induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro‐CT and histological data, which also showed that CN attenuated MPS‐induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs‐induced ONFH. [ABSTRACT FROM AUTHOR]

Background: Orthodontic tooth movement (OTM) is a dynamic equilibrium of bone remodeling, involving the osteogenesis of new bone and the osteoclastogenesis of old bone, which is mediated by mechanical force. Periodontal ligament stem cells (PDLCSs) in the periodontal ligament (PDL) space can transmit mechanical signals and regulate osteoclastogenesis during OTM. KAT6A is a histone acetyltransferase that plays a part in the differentiation of stem cells. However, whether KAT6A is involved in the regulation of osteoclastogenesis by PDLSCs remains unclear. Results: In this study, we used the force-induced OTM model and observed that KAT6A was increased on the compression side of PDL during OTM, and also increased in PDLSCs under compression force in vitro. Repression of KAT6A by WM1119, a KAT6A inhibitor, markedly decreased the distance of OTM. Knockdown of KAT6A in PDLSCs decreased the RANKL/OPG ratio and osteoclastogenesis of THP-1. Mechanistically, KAT6A promoted osteoclastogenesis by binding and acetylating YAP, simultaneously regulating the YAP/TEAD axis and increasing the RANKL/OPG ratio in PDLSCs. TED-347, a YAP-TEAD4 interaction inhibitor, partly attenuated the elevation of the RANKL/OPG ratio induced by mechanical force. Conclusion: Our study showed that the PDLSCs modulated osteoclastogenesis and increased the RANKL/OPG ratio under mechanical force through the KAT6A/YAP/TEAD4 pathway. KAT6A might be a novel target to accelerate OTM. [ABSTRACT FROM AUTHOR]

Preparative regimens before Hematopoietic Cell Transplantation (HCT) damage the bone marrow (BM) microenvironment, potentially leading to secondary morbidity and even mortality. The precise effects of cytotoxic preconditioning on bone and BM remodeling, regeneration, and subsequent hematopoietic recovery over time remain unclear. Moreover, the influence of recipient age and cytotoxic dose have not been fully described. In this study, we longitudinally investigated bone and BM remodeling after busulfan treatment with low intensity (LI) and high intensity (HI) regimens as a function of animal age. As expected, higher donor chimerism was observed in young mice in both LI and HI regimens compared to adult mice. Noticeably in adult mice, significant engraftment was only observed in the HI group. The integrity of the blood-bone marrow barrier in calvarial BM blood vessels was lost after busulfan treatment in the young mice and remained altered even 6 weeks after HCT. In adult mice, the severity of vascular leakage appeared to be dose-dependent, being more pronounced in HI compared to LI recipients. Interestingly, no noticeable change in blood flow velocity was observed following busulfan treatment. Ex vivo imaging of the long bones revealed a reduction in the frequency and an increase in the diameter and density of the blood vessels shortly after treatment, a phenomenon that largely recovered in young mice but persisted in older mice after 6 weeks. Furthermore, analysis of bone remodeling indicated a significant alteration in bone turnover at 6 weeks compared to earlier timepoints in both young and adult mice. Overall, our results reveal new aspects of bone and BM remodeling, as well as hematopoietic recovery, which is dependent on the cytotoxic dose and recipient age. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion This study aimed to compare the efficacy of two techniques—acellular dermal matrix (ADM) grafting and tenting technique (TT)—for soft tissue height (STH) augmentation simultaneous to implant placement to minimize peri‐implant crestal bone level (CBL) changes.Forty patients with a healed single mandibular posterior edentulous site with a thin soft tissue phenotype were enrolled. Twenty patients received simultaneously to implant placement ADM grafting, while the others received submerged healing abutment (TT). Clinical peri‐implant soft tissue height and radiographic CBL changes were measured at restoration delivery and 1‐year follow‐up.Both techniques effectively increased soft tissue thickness, resulting in a final average STH of 3.4 ± 0.5 mm after augmentation. On average, soft tissue increased by 1.6 ± 0.5 mm in group ADM and by 1.8 ± 0.4 mm in group TT after augmentation. In Group ADM, mesial CBL decreased from 0.4 ± 0.3 mm to 0.1 ± 0.2 mm, and distal CBL decreased from 0.5 ± 0.3 mm to 0.2 ± 0.3 mm over 1 year. In Group TT, mesial CBL remained stable at 0.3 ± 0.2 mm, while distal CBL reduced slightly from 0.5 ± 0.5 mm to 0.3 ± 0.2 mm. Both groups showed minimal changes in CBL, indicating great stability (pmesial = 0.003, pdistal = 0.004). TT was particularly effective in preventing mesial bone loss (pmesial = 0.019). The mesial CBL changes significantly differed between groups (p = 0.019), and not significantly at distal sites (p = 0.944). Neither treatment exhibited significant bone remodeling below the implant shoulder.This study suggests that both techniques were successful in STH augmentation, and they may effectively reduce peri‐implant crestal bone level changes, with TT being slightly superior. TT was more prone to post‐surgical complications. This RCT was not registered before participant recruitment and randomization. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to compare periprosthetic femoral bone remodeling after cementless total hip arthroplasty (THA) using a short-tapered wedge stem and a fully hydroxyapatite (HA)-coated stem. Materials and methods: In this retrospective study, 24 primary cementless THA procedures with short-tapered wedge stem and 24 using a fully HA-coated stem were performed. The follow-up duration was 2 years for both groups. Clinical evaluation was performed using the Merle d'Aubigné and Postel scoring systems. Standardized anteroposterior radiographs of the pelvis and femur were obtained. Dual-energy X-ray absorptiometry was performed, and the bone mineral density (BMD) around the stem was assessed in each Gruen zone at the first postoperative week as a baseline value and at 6 weeks, 3 and 6 months, and 1 and 2 years postoperatively. Results: The mean Merle d'Aubigné and Postel scores improved significantly postoperatively in both groups. None of the hips showed loosening in either group. Spot welds occurred in zones 1, 2, 6, and 7 in the short-tapered wedge group, and in all zones in the fully HA-coated group. Significant BMD loss occurred only in zone 4 in the short-tapered wedge group, and no significant bone loss occurred in any zone in the fully HA-coated stem group; a significant difference between the two groups was observed only in zone 4 at 2 years after THA. Conclusions: Clinical and radiographical outcomes in both groups were good, and both stems suppressed postoperative BMD loss at 2 years. [ABSTRACT FROM AUTHOR]

Introduction: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure. Materials and methods: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs. Results: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m2) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031). Conclusion: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery. [ABSTRACT FROM AUTHOR]

We developed a model of inflammation and airway remodeling in C57 mice provoked by exosomes derived from bone marrow mesenchymal stem cells infected by respiratory syncytial virus (RSV). The mean size of control and infected exosomes in vitro were 167.9 and 118.5 nm, respectively. After induction of modeled pathology, the severity of airway inflammation and its remodeling were analyzed by histopathological methods. In addition, the blood levels of inflammatory factors IL-10, IL-17, transforming growth factor-β (TGF-β), and TNFα were assayed; in the lung tissues, the expression levels of MMP-2, MMP-9, α-smooth muscle actin (α-SMA), and TGF-β were measured. In the developed model, the effects of RSV-induced and non-induced exosomes were compared with those of inactivated and non-inactivated RSV. Intranasal administration of RSV-induced exosomes decreased the levels of serum inflammatory factors IL-10 and IL-17 and increased the expression of serum proinflammatory cytokine TNFα. Increased levels of MMP-2, MMP-9, and α-SMA, enhanced expression of TGF-β in the lung tissue, and pathological staining of the lung tissues indicated infiltration with inflammatory cells and luminal constriction. Thus, RSV-induced exosomes can provoke airway inflammation and remodeling in mice similar to RSV, while non-induced exosomes cannot produce such alterations. [ABSTRACT FROM AUTHOR]

Background: As bone mass decreases due to osteoporosis, bone fragility increases. Research in the literature indicates that beta blocker users had a higher bone mineral density and a lower risk of fracture. Few research, meanwhile, have shown that either selective or non-selective beta blockers had no influence on the risk of fracture in individuals with osteoporosis. Aim: The purpose of this study was to evaluate the impact of selective and non-selective betablockers on the risk of fracture in individuals with osteoporosis who were Indian. Methods: Using cardio-selective beta-blockers (CSBB), non-selective beta-blockers (NSBB), and a control group, 120 osteoporosis patients of both genders were split into 3 groups. Bone turnover markers, BMD (bone mineral density), FR (fracture risk), and T-scores were evaluated in each individual, and conclusions were drawn. Results: It was observed that there was a significant difference in mean T-scores between the three groups after six months of testing. When comparing the receiving group with non-selective beta-blockers (NSBBs) to the control group, there was a substantial increase in bone mineral density. The CSBB and NSBB groups had a statistically lower fracture risk. Additionally, both the NSBB and CSBB groups showed lower levels of bone turnover indicators as compared to the control group. Conclusion, CSBB and NSBB can assist in lowering bone turnover markers and fracture risk in individuals with osteoporosis while also increasing bone mineral density. At all three of the locations under study, the impact of NSBB on lowering fracture risk is more noticeable. Additionally, s-CTX showed a significantly lower level of bone turnover indicators than the CSBB group did. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass, decreased bone mineral density, and degradation of bone tissue microarchitecture. However, our understanding of the mechanisms of bone remodeling and factors affecting bone mass remains incomplete. Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase that regulates a variety of cellular metabolisms, including inflammation, tumorigenesis, and bone metabolism. Recent studies have emphasized the important role of SIRT1 in bone homeostasis. This article reviews the role of SIRT1 in bone metabolism and OP and also discusses therapeutic strategies and future research directions for targeting SIRT1. [ABSTRACT FROM AUTHOR]

Alkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion. Lumbar spinal fusion procedures from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44–147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications. A total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83–11.97), pneumonia (OR 2.89, 95% CI 1.59–5.25), requiring a transfusion (OR 2.09, 95% CI 1.68–2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12–2.52), readmission within 30 days (OR 1.60, 95% CI 1.16–2.21), increased length of stay (OR 1.87, 95% CI 1.49–2.36), and nonhome discharge (OR 2.18, 95% CI 1.80–2.66). Elevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether a progressive marginal bone loss (PMBL) occurring beyond the initial bone remodeling (IBR) is linked with bleeding on probing. Materials and Methods: A total of 70 partially edentulous patients exhibiting 112 two‐piece bone‐level implants were included in this retrospective study. Panoramic radiographs were obtained after implant insertion (T0), after delivery of a final prosthetic restoration (T1) and subsequently during the 1‐(T2), 5‐(T3), 10‐(T4), and 15‐years (T5) follow‐up visits. At each time point, radiographic marginal bone levels were assessed from the implant shoulder to the first bone‐to‐implant contact at mesial and distal aspects. The IBR was defined as a bone loss occurring up to prosthesis delivery, that is, from T0 to T1. The PMBL was defined as bone loss occurring after T1. At T2, T3, T4, and T5, the presence or absence of bleeding on probing (BOP) was recorded at four sites. A median regression with mixed models was performed to assess the difference of PMBL in PMBL + BOP+ and PBML + BOP− groups. Results: Over the mean implant functioning time of 4.44 ± 4.91 years, 38 (34%) implants showed no PBML, whereas 74 (66%) implants featured PMBL. Of these, 35 (47%) and 39 (53%) implants were assigned to the PMBL + BOP− and PMBL + BOP+ groups, respectively. The mean PMBL after 1, 5, 10, and 15 years were comparable between implants featuring PMBL with or without BOP. At 1 year, BOP intensity significantly correlated PMBL, with each increase in one BOP‐positive site being associated with increase in PMBL by 0.55 mm (p = 0.038), whereas this association was not found at 5, 10, and 15 years. The IBR values in the no PBML, PMBL + BOP+, and PBML + BOP− groups were −0.24 ± 0.31, −0.41 ± 0.59, and −0.24 ± 0.33 mm, respectively, with no significant differences found among the groups. Conclusion: Progressive bone loss at implant sites is not always linked with bleeding on probing. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of a two‐piece abutment workflow on enhancing the stability of the alveolar bone and gingiva surrounding the dental implant, and to determine the level of patient satisfaction. Materials and Methods: A total of 48 patients with dentition defect in the posterior region were included and divided into two groups: the two‐piece abutment workflow (TAW) and the sealing screw with submerged healing workflow (SHW). Marginal bone level (MBL), soft tissue indicators, oral hygiene indicators, and patient satisfaction were assessed and recorded partially at 0, 3, 6, and 12 months after surgery. The primary outcome was the change of MBL in different time periods. A generalized linear mixed model (GLMM) was used to take into account the correlated nature of the data, and adjust for potential confounding factors within inter‐group differences. Results: The survival rate of implants and prosthesis reached 100% at 12‐month follow‐up, with an average decrease of 0.25 mm (SD 0.23 mm) of MBL in the TAW group and 0.48 mm (SD 0.45 mm) in the SHW group. The change of MBL in the TAW group (0.15 ± 0.31 mm) was significantly lower than the SHW group (0.41 ± 0.41 mm) through the analysis of GLMM within 6 months, while no significance was found in 12 months. Moreover, less gingival pain and oppression during prosthesis loading, and less time consumption overall duration were showed in the TAW group through Visual Analogue Scale (VAS, p < 0.05). Conclusions: Within a 6‐month period, the two‐piece abutment workflow showed superior efficacy in preserving the integrity of the marginal bone level. Furthermore, it streamlined treatment procedures and mitigated discomfort, hence increasing patient satisfaction. [ABSTRACT FROM AUTHOR]

Background: Nutritional strategies to maintain bone health in aging individuals are of great interest. Given the beneficial nutrient composition of walnuts, rich in alpha‐linolenic (the vegetable n‐3 fatty acid) and polyphenols, their regular consumption might be a dietary option to reduce age‐related bone loss. We determined whether daily walnut consumption improves bone mineral density (BMD) and circulating biomarkers of bone turnover. Methods: The Walnuts and Healthy Aging study (WAHA) is a two‐center, parallel, randomized controlled trial evaluating the effect of a diet enriched with walnuts at ≈15% energy compared with a control diet for 2 years on age‐related health outcomes in healthy men and women aged 63–79 years. Changes in BMD were a prespecified secondary outcome only at the Barcelona node of the trial, where 352 participants were randomized. Retention rate was 92.6%. Primary endpoints were 2‐year changes in BMD at the spine and the nondominant femoral neck, determined by dual‐energy X‐ray absorptiometry (DXA). Secondary endpoints were 2‐year changes in bone turnover biomarkers (adrenocorticotropic hormone, Dickkopf WNT signaling pathway inhibitor‐1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, parathyroid hormone, and fibroblast growth factor‐23), which were quantified in 211 randomly selected participants. Results: The walnut diet versus the control diet had no effect on 2‐year changes in BMD at the spine (0.15% vs. 0.35%, p = 0.632) and femoral neck (−0.90% vs. −0.70%, p = 0.653), or on bone turnover biomarkers. Results were similar in participants treated or not with bone resorption inhibitors or those with or without osteoporosis/osteopenia at inclusion. Conclusions: Compared with the usual diet, a diet enriched with walnuts at 15% of energy for 2 years failed to improve BMD or circulating markers of bone metabolism in healthy older people. [ABSTRACT FROM AUTHOR]

Bone health is a critical aspect of overall well-being, and disorders such as osteoporosis pose significant challenges worldwide. East Asian Herbal Medicine (EAHM), with its rich history and holistic approach, offers promising avenues for enhancing bone regeneration. In this critical review article, we analyze the intricate mechanisms through which EAHM compounds modulate bone health. We explore the interplay between osteogenesis and osteoclastogenesis, dissect signaling pathways crucial for bone remodeling and highlight EAHM anti-inflammatory effects within the bone microenvironment. Additionally, we emphasize the promotion of osteoblast viability and regulation of bone turnover markers by EAHM compounds. Epigenetic modifications emerge as a fascinating frontier where EAHM influences DNA methylation and histone modifications to orchestrate bone regeneration. Furthermore, we highlight EAHM effects on osteocytes, mesenchymal stem cells and immune cells, unraveling the holistic impact in bone tissue. Finally, we discuss future directions, including personalized medicine, combinatorial approaches with modern therapies and the integration of EAHM into evidence-based practice. [ABSTRACT FROM AUTHOR]

In revision total hip arthroplasty, achieving robust fixation is difficult and implant movement may occur over time. Bone may also rearrange around the implant as a result of mechanical loading, making the measurement of migration challenging. The study aimed to quantify changes in bone shape and implant position 1 year following acetabular reconstruction using custom three‐dimensional‐printed cups. This observational retrospective cohort study involved 23 patients with Paprosky type IIIB defects. Postop computed tomography scans taken within 1 week of surgery and at 1‐year postsurgery were co‐registered and analyzed. Three co‐registration strategies were implemented including bone‐to‐bone and implant‐to‐implant. (1) Co‐registration of the ipsilateral innominate bone (diseased anatomy) was used to measure changes in implant position. (2) Co‐registration of the implant was carried out to quantify changes in the ipsilateral innominate bone shape. (3) Co‐registration of the contralateral innominate bone (nondiseased anatomy) was performed to measure changes in the ipsilateral innominate bone shape and implant position. The median centroid distances (interquartile range [IQR]) were 2.3 mm (IQR: 3.7–1.7 mm) for changes in implant position, 2.4 mm (IQR: 3.6–1.6 mm) for changes in ipsilateral innominate bone shape, and 3.7 mm (IQR: 4.6–3.5 mm) for changes in ipsilateral innominate bone shape and implant position. Following acetabular reconstruction, implant movements and periprosthetic bone remodeling are physiological and of a similar extent. Surgeons and engineers should consider this when performing implant monitoring in these patients. [ABSTRACT FROM AUTHOR]

Positron Emission Tomography (PET) is an important part of the medical imaging field which is continually exploring novel biological targets as exemplified by PET imaging of neuroinflammation. Due to limitations stemming from either sub‐optimal biological targets or a lack of available selective radiotracers, alternative biomarkers and PET imaging agent candidates are considered. One such possible target is microRNA (miRNA) and herein, we discuss the potential of miRNA for PET imaging. With the aim of addressing key strategies for imaging miRNA with PET, we identify three distinct approaches as follows: small molecules directly targeting miRNA, small molecules indirectly targeting Argonaute 2 (AGO2)‐protein complexes, and direct chemical modification of antisense oligonucleotides. The radiosynthetic approaches are based on the methods of direct radiolabelling of respective antisense oligonucleotides and several examples are described herein, showcasing the potential of miRNA in PET imaging. Whilst these approaches offer different radiolabelling strategies, application of these radiolabelled molecules towards PET imaging of miRNA are scarce with only one, limited example applied to bone remodeling reported in the literature. [ABSTRACT FROM AUTHOR]

Purpose: In craniofacial surgery, the stable fixation of transposed bone segments is crucial in order to ensure good long-term results. The use of absorbable material in fixation avoids the need for a second surgery, which would otherwise be required to remove osteosynthesis material. The authors of the present manuscript have already demonstrated that absorbable sutures ensure the stable fixation of bone segments in patients up to 24 months of age. However, it has thus far remained unclear whether stable fixation is possible in older patients by using only absorbable sutures due to the slower bone remodelling and prolonged healing time in this cohort. Method: For the present study, osteosynthesis was performed in 50 patients ranging from 25.7 to 192.1 months of age (mean, 61.4 ± 21.7 months) using solely absorbable sutures (PDS II®, Ethicon, Germany). Post-operative stability and possible restrictions—such as foreign body reactions—were evaluated within clinical and radiological routine follow-ups. Results: All children demonstrated clinically and radiologically stable osteosynthesis both directly post-operatively and in follow-ups. No significant foreign body reaction could be seen. Conclusion: The present study demonstrates—for the first time—that absorbable sutures with a longer absorption period are also very well suited for the fixation of bone segments in patients over 24 months of age. The sole use of absorbable sutures in children over 24 months of age is a safe procedure with nearly no foreign body reactions. The procedure enables stable and highly cost-effective osteosynthesis without altering the osteotomy design. [ABSTRACT FROM AUTHOR]

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. In addition to improvements in bone delivery, potential regulation of bone development mechanisms involving receptor-regulated pathways has also been utilized. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems. [ABSTRACT FROM AUTHOR]

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) represents a serious health condition, impacting the lives of many patients worldwide. The condition challenges clinical care due to its complex etiology and limited therapeutic options. A thorough understanding of the pathophysiological and patient-related factors that promote disease development is essential. Recently, the oral microbiome has been implicated as a potential driver and modulating factor of BRONJ by several studies. Modern genomic sequencing methods have provided a wealth of data on the microbial composition of BRONJ lesions; however, the role of individual species in the process of disease development remains elusive. A comprehensive PubMed search was conducted to identify relevant studies on the microbiome of BRONJ patients using the terms "microbiome", "osteonecrosis of the jaws", and "bisphosphonates". Studies focusing on symptoms, epidemiology, pathophysiology, risk factors, and treatment options were included. The principal risk factors for BRONJ are tooth extraction, surgical procedures, and the administration of high doses of bisphosphonates. Importantly, the oral microbiome plays a significant role in the progression of the disease. Several studies have identified alterations of microbial composition in BRONJ lesions. However, there is no consensus regarding bacterial species that are associated with BRONJ across studies. The bacterial genera typically found include Actinomyces, Fusobacterium, and Streptococcus. It is postulated that these microbes contribute to the pathogenesis of BRONJ by promoting inflammation and disrupting normal bone remodeling processes. Current therapeutic approaches are disease-stage-specific and the necessity for more effective treatment strategies remains. This review examines the potential causes of and therapeutic approaches to BRONJ, highlighting the link between microbial colonization and BRONJ development. Future research should seek to more thoroughly investigate the interactions between bisphosphonates, the oral microbiome, and the immune system in order to develop targeted therapies. [ABSTRACT FROM AUTHOR]

RANKL (Receptor Activator of Nuclear Factor Kappa-B Ligand) is a cytokine that plays a crucial role in bone remodeling by regulating differentiation and activation of osteoclast, which breaks down old bone tissue. In this study, we attempted to produce human-derived RANKL using plant expression systems. The RANKL expressed in Nicotiana benthamiana leaves was designed to accumulate within the endoplasmic reticulum lumen. The purified RANKL from N. benthamiana induced the differentiation of bone marrow-derived macrophages to mature osteoclast, albeit modestly. In conclusion, human-derived RANKL could be produced using a plant expression system, but it requires further improvement. [ABSTRACT FROM AUTHOR]

Background Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third-trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. The potential mechanisms underlying this observation are unknown. Methods The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in the third trimester vs none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4 to 30 days, to compare slopes by TDF exposure. Results Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of −0.58 vs −0.08/day (difference −0.50/day [95% CI −0.88, −0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels were lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] vs 26 [22, 37] ng/mL). No differences were observed for other biomarkers. Conclusions Third-trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates. [ABSTRACT FROM AUTHOR]