Mesenchymal stem cell-derived exosomes: a potential cell-free therapy for orthodontic tooth stability management.

Orthodontic relapse (OR) occurs at a rate of over 70%. Retention is the current attempt at prevention, but it requires a considerable amount of time and cannot fully block OR. It's imperative to find a safe and effective method for managing post-orthodontic tooth stability. Periodontal bone remodeling is one crucial biological foundation of OR. Mesenchymal stem cell-derived exosomes (MSC-Exo) show promise in relapse management by regulating periodontal bone remodeling. MSC-Exo can prevent relapse by regulating periodontal ligament function, osteoclast activity, osteoblast differentiation, macrophage polarization, and periodontal microcirculation. In recent years, exosome-loaded hydrogels, which achieve controlled exosome release, have demonstrated efficacy in promoting bone regeneration and remodeling, offering promising prospects for OR management. This review aims to highlight the use of MSC-Exo-based therapy for preventing OR, offering new insights for future research focused on improving tooth stability and enhancing orthodontic anchorage.

Potential of combined red and near-infrared photobiomodulation to mitigate pro-osteoclastic and inflammatory gene expression in human mandibular osteogenic cells.

Appropriate regeneration of jawbone after dental or surgical procedures relies on the recruitment of osteoprogenitor cells able to differentiate into matrix-producing osteoblasts. In this context, photobiomodulation (PBM) has emerged as promising therapy to improve tissue regeneration and to facilitate wound healing processes. The aim of this study was to determine the effect of PBM on human osteoprogenitor cells isolated from mandibular trabecular bone.Bone marrow stromal cell cultures were established from 4 donors and induced toward osteogenic differentiation for 14 days in a standard osteogenic assay. Cells were irradiated with a combined red/near-infrared (NIR) laser following different schedules and expression of osteogenic, matrix-related, osteoclastogenic and inflammatory genes was analyzed by quantitative PCR.Gene expression analysis revealed no overall effects of PBM on osteogenic differentiation. However, a statistically significant reduction was observed in the transcripts of COL1A1 and MMP13, two important genes involved in the bone matrix homeostasis. Most important, PBM significantly downregulated the expression of RANKL, IL6 and IL1B, three genes that are involved in both osteoclastogenesis and inflammation.In conclusion, PBM with a red/NIR laser did not modulate the osteogenic phenotype of mandibular osteoprogenitors but markedly reduced their expression of matrix-related genes and their pro-osteoclastogenic and pro-inflammatory profile.

Dual role of Sfrp4 in bone remodelling during orthodontic tooth movement.

OBJECTIVES: The objective of this study was to determine changes in gene expression by establishing an orthodontic tooth movement (OTM) rat model with appropriate and excessive orthodontic force. MATERIALS AND METHODS: Using a closed coil nickel-titanium spring, the OTM was carried out to apply a mesial force of 50 or 100 g to the maxillary first molars. Micro-CT, histological and immunohistochemical staining were used to evaluate the bone formation at the tension site and the bone resorption and bone formation at pressure site. Then RNA sequencing and bioinformatic analysis were performed. RESULTS: According to the results of the Mirco-CT scan of OTM rat models, both the 50 g group and the 100 g group showed variable degrees of reduction in alveolar bone density on the tension and pressure sides. The results of histological and immunohistochemical staining demonstrated that the periodontal tissue and osteogenic ability of the 50 g group were restored at the 14 days, while the 100 g group caused severe periodontal tissue damage. The GO and KEGG analysis results, as well as the number of differentially expressed genes (DEGs), varied depending on the loading time and value of appliance, according to the results of the RNA sequencing. And the immunohistochemical staining results showed that Sfrp4 functioned by efficiently influencing both bone formation and bone absorption. CONCLUSIONS: Appropriate orthodontic force value could cause appropriate movement of teeth in rats without adverse periodontal damage. Simultaneously, distinct gene expression patterns were observed at various force levels and time intervals.

In vitro Assessment of the Effects of Host Modulatory Agents on Osteoclastogenesis.

Background: Osteoclastogenesis, the formation of osteoclasts from precursor cells, plays a pivotal role in bone remodeling and associated pathologies like osteoporosis and rheumatoid arthritis. Host modulatory agents (HMAs) have emerged as potential therapeutic candidates for modulating osteoclastogenesis. However, their effects need comprehensive evaluation through in vitro studies. Materials and Methods: In this study, we conducted an in vitro assessment of the effects of a novel HMA on osteoclastogenesis. Primary murine bone marrow-derived macrophages were cultured with the receptor activator of nuclear factor kappa-B ligand to induce osteoclast differentiation. The HMA was administered at various concentrations, and osteoclastogenesis was evaluated through tartrate-resistant acid phosphatase (TRAP) staining, osteoclast size measurement, and gene expression analysis of osteoclast markers. Results: Treatment with the HMA resulted in a dose-dependent inhibition of osteoclast formation. At the highest concentration (100 µM), osteoclastogenesis was significantly suppressed, with a reduction in the number of TRAP-positive multinucleated cells from 50 ± 5 to 10 ± 2 per field (P < 0.001). Moreover, the osteoclast size was markedly reduced, with an average diameter of 20 ± 3 µm compared to 35 ± 4 µm in the control group (P < 0.05). Gene expression analysis revealed downregulation of osteoclast-specific markers, including TRAP, Cathepsin K, and NFATc1, confirming the inhibitory effect of the HMA on osteoclastogenesis. Conclusion: Our findings demonstrate the potential of the investigated HMA as a modulator of osteoclastogenesis. By suppressing osteoclast formation and activity, this agent holds promise for the development of novel therapeutic strategies targeting bone resorption-associated disorders.

Natural Compounds for Bone Remodeling: Targeting osteoblasts and relevant signaling pathways.

In the process of bone metabolism and bone remodeling, bone marrow mesenchymal stem cells (BM-MSCs) differentiate into osteoblasts (OBs) under certain conditions to enable the formation of new bone, and normal bone reconstruction and pathological bone alteration are closely related to the differentiation and proliferation functions of OBs. Osteogenic differentiation of BM-MSCs involves multiple signaling pathways, which function individually but interconnect intricately to form a complex signaling regulatory network. Natural compounds have fewer adverse effects than chemically synthesized drugs, optimize bone health, and are more suitable for long-term use. In this paper, we focus on OBs, summarize the current research progress of signaling pathways related to OBs differentiation, and review the molecular mechanisms by which chemically synthesized drugs with potential anti-osteoporosis properties regulate OBs-mediated bone formation.

Rapid correction of chronic hyperglycemia and bone remodeling, warning against overdoing.

It is widely recognized that chronic hyperglycemia decreases bone quality, although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling. This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.

Erythropoietin regulates osteoclast formation via up-regulating PPARγ expression.

Erythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPARγ expression through activating the Jak2/ERK signaling pathway. Consistently, PPARγ antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPARγ agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPARγ signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient's recovery and quality of life.

Effects of Cannabidiol on Bone Quality in Ovariectomized Rats.

The incidence of osteoporosis and related fractures increases significantly with age, impacting public health and associated costs. Postmenopausal osteoporosis results from increased bone resorption due to decreased estrogen levels. The endocannabinoid system, especially cannabidiol (CBD), has shown therapeutic potential in modulating bone formation. This study investigated the effects of administration of CBD in rats after the onset of with ovariectomy-induced osteopenia (OVX). Forty-eight female Sprague‒Dawley rats were divided into four groups (n = 12): OVX + CBD, SHAM + CBD, OVX + vehicle, and SHAM + vehicle. CBD was administered intraperitoneally for 3 weeks. After euthanasia, the bone quality, mechanical properties, and bone microarchitecture of the femurs and lumbar vertebrae were assessed by microcomputed tomography (micro-CT), bone densitometry, mechanical tests, and histological and immunohistochemical analyses. CBD treatment improved the bone mineral density (BMD) of the lumbar vertebrae and increased the BV/TV% and Tb.N in the femoral neck. There were also improvements in the mechanical properties, such as the maximum force and stiffness of the femurs and vertebrae. CBD significantly increased the bone matrix in osteopenic femurs and vertebrae, Although did not significantly influence the expression of RANKL and OPG, in ovariectomized animals, there was an increase in osteoblasts and a decrease in osteoclasts. Determining the optimal timing for CBD use in relation to postovariectomy bone loss remains a crucial issue. Understanding when and how CBD can be most effective in preventing or treating bone loss is essential to emphasize the importance of early diagnosis and treatment of osteoporosis. However, further studies are needed to explore in more detail the efficacy and safety of CBD in the treatment of postmenopausal osteoporosis.

Prediction of micro-scale bone adaptation of human trabecular bone under different implanted conditions.

BACKGROUND AND OBJECTIVE: Different bone remodeling algorithms are used to predict bone adaptation and to understand how bones respond to the mechanical stimuli altered by implants. This paper introduces a novel micro-scale bone remodeling algorithm, which deviates from conventional methods by focusing on structure-based bone adaptation instead of density-based approaches. METHODS: The proposed model simulated cellular activities such as bone resorption, new bone formation, and maturation of newly formed bone. These activities were assumed to be triggered by mechanical stimuli. Model parameters were evaluated for the 3D geometries of trabecular bone from intact femur developed from micro computed tomography (CT) scan data. Two different hip implants, solid and porous were used, and two different bone remodeling methods were performed using the proposed and conventional methods. RESULTS: Results showed that micro CT scan-based finite element (FE) models accurately captured the microarchitecture and anisotropy of trabecular bone. The predicted bone resorption rate at the peri-prosthetic regions for the solid and porous implants was in the range of 17-27% and 4.5-7.3%, respectively, for a simulated period of four years. CONCLUSIONS: The results obtained from FE analysis strongly align with clinical findings, confirming the effectiveness of the proposed algorithm. By emphasizing the structural aspect of bone adaptation, the proposed algorithm brings a fresh perspective on bone adaptation at the peri-prosthetic bone. This method can help researchers and clinicians to improve implant designs for better clinical outcomes.

Dietary supplementation with calcitriol or quercetin improved eggshell and bone quality by modulating calcium metabolism.

This study was aimed to investigate the effects of dietary calcitriol or quercetin supplementation on eggshell and bone quality of laying hens. In trial 1, 72 Hy-Line Brown layers (80-week-old) with weak-shelled strength (25 to 30 N) were assigned into 4 dietary treatments with 6 replicates of 3 birds and fed a basal diet (4% calcium level) or basal diets supplemented with 0.5% calcium, 5 µg/kg calcitriol or 500 mg/kg quercetin for 4 weeks. In trial 2, 360 Hy-Line Brown layers (60-week-old) were divided into 3 groups with 8 replicates of 15 birds: control group (basal diet), calcitriol group (basal diet + 5 µg/kg calcitriol), and quercetin group (basal diet + 500 mg/kg quercetin). This trial lasted for 12 weeks. The results showed that dietary calcitriol or quercetin improved eggshell quality in both trials (P < 0.05). In trial 2, compared with the control group, both calcitriol and quercetin supplementations improved femoral bone quality, calcium retention of hens and calcium content in uterine fluid at 18.5 h post-oviposition (PO) (P < 0.05), along with enhancing uterine morphology. Compared to the control group, supplemental calcitriol or quercetin up-regulated the relative mRNA expression levels of uterine transient receptor potential cation channel, subfamily V, member 6 (TRPV6) at 8.5 h PO and plasma membrane calcium-ATPase (PMCA), vitamin D receptor (VDR), estrogen receptor alpha (ERα) at 18.5 h PO (P < 0.05), but down-regulated the uterine caspase 3 (CASP3) relative mRNA expression level at 8.5 h PO (P < 0.05). Meanwhile, the femoral relative mRNA expression levels of tartrate-resistant acid phosphatase (TRAP) (up-regulated at 8.5 and 18.5 h PO) and alkaline phosphatase (ALP) (up-regulated at 8.5 h PO but down-regulated at 18.5 h PO) were also affected by calcitriol or quercetin supplementation (P < 0.05). Compared to the calcitriol, quercetin increased hen-day egg production and femoral medullary bone volume/bone tissue volume but reduced femoral stiffness (P < 0.05), which were accompanied by increased relative mRNA expression levels of uterine TRPV6, estrogen receptor beta (ERß) at 18.5 h PO (P < 0.05). Overall, both dietary calcitriol and quercetin could improve eggshell and bone quality by modulating calcium metabolism of aged layers. Compared to calcitriol, dietary quercetin up-regulated the expression of uterine calcium transporters, without affecting eggshell quality.

Culture system for longitudinal monitoring of bone dynamics ex vivo.

To quantify and visualize both bone formation and resorption within osteochondral explants cultured ex vivo is challenging with the current analysis techniques. An approach that enables monitoring of bone remodeling dynamics is longitudinal microcomputed tomography (µCT), a non-destructive technique that relies on repeated µCT scanning and subsequent registration of consecutive scans. In this study, a two-compartment culture system suitable for osteochondral explants that allowed for µCT scanning during ex vivo culture was established. Explants were scanned repeatedly in a fixed orientation, which allowed assessment of bone remodeling due to adequate image registration. Using this method, bone formation was found to be restricted to the outer surfaces when cultured statically. To demonstrate that the culture system could capture differences in bone remodeling, explants were cultured statically and under dynamic compression as loading promotes osteogenesis. No quantitative differences between static and dynamic culture were revealed. Still, only in dynamic conditions, bone formation was visualized on trabecular surfaces located within the inner cores, suggesting enhanced bone formation towards the center of the explants upon mechanical loading. Taken together, the ex vivo culture system in combination with longitudinal µCT scanning and subsequent registration of images demonstrated potential for evaluating bone remodeling within explants.

The cross-sectional morphology of the proximal femoral diaphysis is defined by the anteversion angle.

Osteoporosis in postmenopausal women is one of the causes of femoral fractures and is prevented by the administration of bisphosphonates. Individual morphologies are considered to increase the risk of atypical fractures associated with long-term administration. To evaluate cortical bone morphology quantitatively, we established a method to measure the distance from the center point of a cross-section to the external and internal borders based on CT images. Using this method, 44 sides of a female femoral skeleton specimen were examined and areas of protrusion and thickening in the medial anterior and lateral posterior regions just below the lesser trochanter were identified. These positions strongly correlated with the anteversion angle, suggesting the involvement of the distribution of the load received from body weight defined by the angle. The finite element method was used to examine the relationships between the positions of these areas with compressive and tensile stress distribution areas in the one-legged standing condition. The medial anterior region and lateral posterior region protruded and thickened in response to compressive and tensile stress, respectively. In addition, a hierarchical relationship was observed between the anteversion angle, tensile stress distribution, protrusion, and thickening in femurs with thinning of cortical bone, indicating that morphogenesis occurs adaptively to loading. The present results demonstrate the usefulness of this method in considering the formation mechanism and function of the femoral diaphysis and suggest that bone remodeling is necessary to maintain adaptability.

Genetic Variants in RANK and OPG Could Influence Disease Severity and Bone Remodeling in Patients with Early Arthritis.

The aim of this study was to identify single-nucleotide polymorphisms (SNPs) in bone remodeling-related genes associated with disease severity and bone mineral density (BMD) in early arthritis (EA) patients. For this purpose, the genotyping of 552 SNPs located in gene regions of semaphorins 4b, 4d, 4f, DKK1, 2 and 3, sclerostin, OPG, RANK and RANKL was performed using Immunochip from Illumina Inc. in 268 patients from the Princesa Early Arthritis Register Longitudinal (PEARL) study. Measurements of BMD and disease activity were chosen as outcome variables to select SNPs of interest. The relationships of SNPs with the BMD of the forearm, lumbar spine and hip (Hologic-4500 QDR) were analyzed by linear regression adjusted for age, sex, body mass index and presence of anti-citrullinated peptide antibodies (ACPAs). The association of each SNP with activity variables was analyzed by linear regression, logistic regression or ordered logistic regression according to the variable, and multivariate models were adjusted for potentially confounding variables, such as age, sex and presence of ACPAs. These analyses showed that four SNPs located in the genes coding for RANK (TNFRSF11A) and OPG (TNFRSF11B) were significantly associated with clinical variables of severity. SNP rs1805034 located in exon 6 of TNFRSF11A, which causes a non-synonymous (A/V) mutation, showed significant association with BMD and therefore may be considered as a possible biomarker of severity in RA patients. SNPs in the OPG gene showed an association with serum OPG levels and predicted disease activity after two years of follow-up.

Exploring vertebral bone density changes in a trunk with adolescent idiopathic scoliosis: a mechanobiological modeling investigation of intact and unilaterally paralyzed muscles.

This study aimed to elucidate the vertebral bone density variations associated with adolescent idiopathic scoliosis (AIS), specifically examining the impact of unilateral muscle paralysis using an integrated approach combining Frost's Mechanostat theory, a three-dimensional subject-specific finite element model and a musculoskeletal model of the L2 vertebra. The findings revealed a spectrum of bone density values ranging from 0.29 to 0.31 g/cm3, along with vertebral micro-strain levels spanning from 300 to 2200, consistent with existing literature. Furthermore, the ratio of maximum von Mises stress between the concave and convex side in the AIS model with intact muscles was approximately 1.08, which decreased by 4% due following unilateral paralysis of longissimus thoracis pars thoracic muscle. Overall, this investigation contributes to a deeper understanding of AIS biomechanics and lays the groundwork for future research endeavors aimed at optimizing clinical management approaches for individuals with this condition.

Influence of interstitial fluid pressure, porosity, loading magnitude, and anisotropy in cortical bone adaptation.

Adaptive elasticity in cortical bone has traditionally been modeled using Strain Energy Density (SED). Recent studies have highlighted the importance of interstitial fluid in bone adaptation, yet no research has quantified the role of interstitial fluid pressure and its effects, specifically incorporating both SED and interstitial fluid pressure in the adaptation process. This study introduces a novel formulation combining theory of porous media and theory of adaptive elasticity that considers both SED and interstitial fluid's pressure in cortical bone adaptation. The formulation is solved using ANSYS Fluent and a MATLAB script, and sensitivity analyses were conducted, analyzing various porosities, loading magnitudes, anisotropic properties of cortical bone, and involvement coefficients of interstitial fluid's pressure. This study reveals that bones with different vascular porosities (PV) tend to achieve similar density distributions under uniform loading over time. This highlights the significant role of interstitial fluid pressure in accelerating the convergence to optimal bone properties, especially in specimens with larger PV porosities. The findings emphasize the importance of fluid pressure in bone remodeling, aligning with previous studies. Furthermore, this study demonstrates that considering transversely isotropic material properties can significantly alter the remodeling configuration compared to isotropic material properties. This highlights the importance of accurately representing the anisotropic nature of cortical bone in models to better predict its adaptive responses. However, aspects such as fluid density variations and bone geometry changes remain unexplored, suggesting directions for future research. Overall, this research enhances the understanding of cortical bone adaptation and its mechanical interactions.

Mitigating aging and doxorubicin induced bone loss in mature mice via mechanobiology based treatments.

Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles for 5 days/week), individually and combined, on mature mice (∼50 weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by -4.3 % over four weeks and the bone deterioration occurred in the majority (64 %) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3 %, +9.5 %, +12.0 % and increased the % of samples with positive Ct.pMOI changes by +32 %, +26 %, and +43 %, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5 mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0 %, +15 %, and +29 % relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.

The role of Clec11a in bone construction and remodeling.

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.

Comparison of bone turnover suppression in atypical femoral fractures and osteoporotic hip fractures.

We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and -3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P < 0.001) and calcium levels (8.8 vs 8.3 ng/dL, P = 0.009) and lower serum CTX levels (0.33 vs 0.54 ng/mL, P = 0.010) in the AFF group than in the TFF group, suggesting a more suppressed bone remodeling. No differences in the other BTM levels were found. Despite identical histories and durations of BP use, the AFF group exhibited lower CTX levels, suggesting more suppressed bone remodeling. This observation leads us to infer that more suppressed bone remodeling, indicated by lower CTX levels, could be linked to the occurrence of AFFs.

Research progress on labial protuberances of anterior teeth in orthodontic treatment. / æ­£ç•¸æ²»ç–—ä¸­å‰ç‰™ç‰™æ§½éª¨å”‡ä¾§éª¨æ€§å‡¸èµ·ç ”ç©¶è¿›å±•.

Orthodontic treatment is a commonly utilized method for improving both facial aesthetics and occlusal function. During orthodontic treatment irregular, nodular labial protuberances on the labial side of the anterior teeth may occasionally occur, varying in number and size, which is closely connected to the differential bone remodeling patterns on the internal and external surfaces of the labial alveolar bone. Labial protuberances can not only affect the aesthetic results of orthodontic treatment, but also pose potential risks to periodontal health. Currently, it is believed that the influencing factors of the formation of the labial protuberances may be related to the patient's gender and age, tooth movement speed, and extent of anterior teeth retraction. Labial protuberances typically resolve spontaneously, however, if it is persistent, alveoloplasty may be necessary for treatment. This review provides a summary on the occurrence hypothesis, influencing factors of formation, potential biological mechanisms, and corresponding treatment methods of labial protuberances during orthodontic treatment.

Osteoporosis treatment: current drugs and future developments.

Osteoporosis is a common systemic metabolic disease characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility. Pharmacological treatment of osteoporosis is the focus of current research, and anti-osteoporosis drugs usually play a role in inhibiting bone resorption, promoting bone formation, and having a dual role. However, most of the drugs have the disadvantages of single target and high toxic and side effects. There are many types of traditional Chinese medicines (TCM), from a wide range of sources and mostly plants. Herbal plants have unique advantages in regulating the relationship between osteoporosis and the immune system, acupuncture therapy has significant therapeutic effects in combination with medicine for osteoporosis. The target cells and specific molecular mechanisms of TCM in preventing and treating osteoporosis have not been fully elucidated. At present, there is a lack of comprehensive understanding of the pathological mechanism of the disease. Therefore, a better understanding of the pathological signaling pathways and key molecules involved in the pathogenesis of osteoporosis is crucial for the design of therapeutic targets and drug development. In this paper, we review the development and current status of anti-osteoporosis drugs currently in clinical application and under development to provide relevant basis and reference for drug prevention and treatment of osteoporosis, with the aim of promoting pharmacological research and new drug development.