Age-related hearing loss accelerates the decline in fast speech comprehension and the decompensation of cortical network connections

Patients with age-related hearing loss face hearing difficulties in daily life.The causes of age-related hearing loss are complex and include changes in peripheral hearing,central processing,and cognitive-related abilities.Furthermore,the factors by which aging relates to hearing loss via changes in audito ry processing ability are still unclear.In this cross-sectional study,we evaluated 27 older adults(over 60 years old) with age-related hearing loss,21 older adults(over 60years old) with normal hearing,and 30 younger subjects(18-30 years old) with normal hearing.We used the outcome of the uppe r-threshold test,including the time-compressed thres h old and the speech recognition threshold in noisy conditions,as a behavioral indicator of auditory processing ability.We also used electroencephalogra p hy to identify presbycusis-related abnormalities in the brain while the participants were in a spontaneous resting state.The timecompressed threshold and speech recognition threshold data indicated significant diffe rences among the groups.In patients with age-related hearing loss,information masking(babble noise) had a greater effect than energy masking(speech-shaped noise) on processing difficulties.In terms of resting-state electroencephalography signals,we observed enhanced fro ntal lobe(Brodmann’s area,BA11) activation in the older adults with normal hearing compared with the younger participants with normal hearing,and greater activation in the parietal(BA7) and occipital(BA19) lobes in the individuals with age-related hearing loss compared with the younger adults.Our functional connection analysis suggested that compared with younger people,the older adults with normal hearing exhibited enhanced connections among networks,including the default mode network,sensorimotor network,cingulo-opercular network,occipital network,and frontoparietal network.These results suggest that both normal aging and the development of age-related hearing loss have a negative effect on advanced audito ry processing capabilities and that hearing loss accele rates the decline in speech comprehension,especially in speech competition situations.Older adults with normal hearing may have increased compensatory attentional resource recruitment represented by the to p-down active listening mechanism,while those with age-related hearing loss exhibit decompensation of network connections involving multisensory integration.

Cinobufotalin prevents bone loss induced by ovariectomy in mice through the BMPs/SMAD and Wnt/β-catenin signaling pathways

Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.

Clinical Efficacy of GBR Technique Combined with Temporary Bridgework-Guided Gingival Contouring in Treating Upper Anterior Tooth Loss with Labial Bone Defects

Objective:To investigate the clinical effect of the guided bone regeneration(GBR)technique combined with temporary bridgework-guided gingival contouring in treating upper anterior tooth loss with labial bone defects.Methods:From July 2023 to April 2024,80 patients with upper anterior tooth loss and labial bone defects were admitted to the hospital and selected as evaluation samples.They were divided into an observation group(n=40)and a control group(n=40)using a numerical table lottery scheme.The control group received treatment with the GBR technique,while the observation group received treatment with the GBR technique combined with temporary bridges to guide gingival contouring.The two groups were compared in terms of clinical red aesthetic scores(PES),labial alveolar bone density,labial bone wall thickness,gingival papillae,gingival margin levels,and patient satisfaction.Results:The PES scores of patients in the observation group were higher than those in the control group after surgery(P<0.05).The bone density of the labial alveolar bone and the thickness of the labial bone wall in the observation group were higher than those in the control group.The levels of gingival papillae and gingival margins were lower in the observation group after surgery(P<0.05).Additionally,patient satisfaction in the observation group was higher than in the control group(P<0.05).Conclusion:The GBR technique combined with temporary bridge-guided gingival contouring for treating upper anterior tooth loss with labial bone defects can improve the aesthetic effect of gingival soft tissue,increase alveolar bone density and the thickness of the labial bone wall,and enhance patient satisfaction.This approach is suitable for widespread application in healthcare institutions.

Platelet factor 4 induces bone loss by inhibiting the integrinα5-FAK-ERK pathway

Background:The effect of platelet factor 4(PF4)on bone marrow mesenchymal stem cells(BMMSCs)and osteoporosis is poorly understood.Therefore,this study aimed to evaluate the effects of PF4-triggered bone destruction in mice and determine the underlying mechanism.Methods:First,in vitro cell proliferation and cell cycle of BMMSCs were assessed using a CCK8 assay and flow cytometry,respectively.Osteogenic differentiation was confirmed using staining and quantification of alkaline phosphatase and Alizarin Red S.Next,an osteoporotic mouse model was established by performing bilateral ovariectomy(OVX).Furthermore,the PF4 concentrations were obtained using enzymelinked immunosorbent assay.The bone microarchitecture of the femur was evaluated using microCT and histological analyses.Finally,the key regulators of osteogenesis and pathways were investigated using quantitative real-time polymerase chain reaction and Western blotting.Results:Human PF4 widely and moderately decreased the cell proliferation and osteogenic differentiation ability of BMMSCs.Furthermore,the levels of PF4 in the serum and bone marrow were generally increased,whereas bone microarchitecture deteriorated due to OVX.Moreover,in vivo mouse PF4 supplementation triggered bone deterioration of the femur.In addition,several key regulators of osteogenesis were downregulated,and the integrinα5-focal adhesion kinase-extracellular signalregulated kinase(ITGA5-FAK-ERK)pathway was inhibited due to PF4 supplementation.Conclusions:PF4 may be attributed to OVX-i nduced bone loss triggered by the suppression of bone formation in vivo and alleviate BMMSC osteogenic differentiation by inhibiting the ITGA5-FAK-ERK pathway.

Anti-apoptotic treatment in mouse models of age-related hearing loss

Age-related hearing loss (AHL), or presbycusis, is the most common neurodegenerative disorder and top communication deficit of the aged population. Genetic predisposition is one of the major factors in the development of AHL. Generally, AHL is associated with an age-dependent loss of sensory hair cells, spiral ganglion neurons and stria vascularis cells in the inner ear. Although the mechanisms leading to genetic hearing loss are not completely understood, caspase-family proteases function as important signals in the inner ear pathology. It is now accepted that mouse models are the best tools to study the mechanism of genetic hearing loss or AHL. Here, we provide a brief review of recent studies on hearing improvement in mouse models of AHL by anti-apoptotic treatment.

Peripheral vestibular system: Age-related vestibular loss and associated deficits

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.

Dietary resistant starch alleviates Escherichia coli-induced bone loss in meat ducks by promoting short-chain fatty acid production and inhibiting Malt1/NF-κB inflammasome activation

Background:Escherichia coli(E.coli)infection in humans and animals usually comes with gut dysbiosis,which is potential culprit to skeletal health,it is still unclear to whether diet interfered gut microbiome changes can be a protective strategy to bone loss development.Here,the effects of resistant starch from raw potato starch(RPS),a type of prebiotic,on E.coli-induced bone loss and gut microbial composition in meat ducks were evaluated.Results:The results showed that dietary 12%RPS treatment improved bone quality,depressed bone resorption,and attenuated the pro-inflammatory reaction in both ileum and bone marrow.Meanwhile,the 12%RPS diet also increased the abundance of Firmicutes in E.coli-treated birds,along with higher production of short-chain fatty acids(SCFAs)especially propionate and butyrate.Whereas addition ofβ-acid,an inhibitor of bacterial SCFAs production,to the drinking water of ducks fed 12%RPS diet significantly decreased SCFAs level in cecum content and eliminated RPS-induced tibial mass improvement.Further,treatment with MI-2 to abrogate mucosa-associated lymphoid tissue lymphoma translocation protein 1(Malt1)activity replicated the protective role of dietary 12%RPS in E.coli-induced bone loss including reduced the inhibition on nuclear factorκB(NF-κB)inflammasome activation,decreased bone resorption,and improved bone quality,which were correlated with comparable and higher regulatory T cells(Treg)frequency in MI-2 and 12%RPS group,respectively.Conclusions:These findings suggested that the diet with 12%RPS could alleviate E.coli-induced bone loss in meat ducks by changing the gut microbial composition and promoting concomitant SCFAs production,and consequently inhibiting Malt1/NF-κB inflammasome activation and Treg cells expansion.

Unusual clinical presentation of oral pyogenic granuloma with severe alveolar bone loss:A case report and review of literature

BACKGROUND Pyogenic granuloma(PG)is a localized,reddish and vascularized hyperplastic lesion of the connective tissue which occurs in the oral cavity.In most cases,the presence of this lesion does not show alveolar bone resorption.The pathology is diagnosed clinically with some caution.However,the diagnosis and treatment are usually corroborated with histopathological evidence.CASE SUMMARY Three clinical cases of PG associated with bone loss were described in this study.The three patients presented tumor-like growth which bled on touch,and were associated with local irritant factors.Radiographs showed bone loss.All cases were treated with conservative surgical excision.The scarring was satisfactory,and there was no case of recurrence.The diagnoses were based on clinical findings,and were confirmed histopathologically.CONCLUSION The occurrence of oral PG with bone loss is unusual.Therefore,clinical and radiographic evaluations are important for the diagnosis.

Expression ofα2-Na/K-ATPase in C57BL/6J Mice Inner Ear and Its Relationship with Age-related Hearing Loss

K^(+)cycling in the cochlea is critical to maintain hearing.Many sodium-potassium pumps are proved to participate in K^(+)cycling,such as Na/K-ATPase.Theα2-Na/K-ATPase is an important isoform of Na/K-ATPase.The expression ofα2-Na/K-ATPase in the cochlea is not clear.In this study,we used C57BL/6 mice as a model of presbycusis and implemented immunohistochemistry staining and quantitative real time-PCR,and theα2-Na/K-ATPase expression pattern was confirmed in the inner ear.It was foundα2-Na/K-ATPase was expressed widely in cochlea and its mRNA and protein expression was gradually reduced with aging(4-,14-,26-and 48-weeks old mice).We suspected that,the down-regulation ofα2-Na/K-ATPase expression might be associated with the remodeling of K^(+)cycling,degeneration of morphological structure and decrease of hearing function in aging C57 mice.In conclusion,we speculated that the reduction ofα2-Na/K-ATPase might play an important role in the pathogenesis of age-related hearing loss.

Effects of Wumen Gumi Bao Decoction on Ameliorating Bone Loss in Experimentally Induced Osteoporosis in Rats by Regulating Wnt3a/β-Catenin Pathway

[Objectives]To investigate the preventive effects of Wumen Gumi Bao Decoction(WMGBD)on estrogen deficiency-induced bone loss.[Methods]Three-month-old Sprague-Dawley rats were ovariectomized(OVX)and then treated with WMGBD,and their admixtures for six weeks.The bone trabecular microstructure,bone histopathological examination were determined in the rat femur tissue,and serum biomarkers of bone formation and resorption were analyzed by ELISA,and the protein expressions of Wnt3a,β-catenin,and phosphorylatedβ-catenin(p-β-catenin)were analyzed by Western blot.Statistical analysis was conducted by using one-way analysis of variance(ANOVA)followed by LSD post hoc analysis or independent samples t test using the scientific statistic software SPSS version 20.0.[Results]WMGBD could promote osteosis and ameliorate bone loss to improve the repair of cracked bone trabeculae of OVX rats.Furthermore,WMGBD also could prevent OVX-induced decrease in collagen fibers in the femoral tissue of ovariectomized rats and promote the regeneration of new bone or cartilage tissue,while WMGBD could activate the Wnt3a/β-catenin pathway.[Conclusions]WMGBD could ameliorate estrogen deficiency-induced bone loss via the regulation of Wnt3a/β-catenin pathway.

Factors influencing further vertebral height loss following percutaneous vertebroplasty in osteoporotic vertebral compression fractures:A 1-year follow-up study

BACKGROUND Osteoporotic vertebral compression fractures(OVCFs)contribute to back pain and functional limitations in older individuals,with percutaneous vertebroplasty(PVP)emerging as a minimally invasive treatment.However,further height loss post-PVP prompts investigation into contributing factors.AIM To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients.METHODS A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study.“Further height loss”during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of≥4 mm.The study population was divided into two groups for analysis:The“No Further Height Loss group(n=179)”and the“Further Height Loss group(n=21).”RESULTS In comparing two distinct groups of patients,significant differences existed in bone mineral density(BMD),vertebral compression degree,prevalence of intravertebral cleft(IVF),type of bone cement used,and cement distribution patterns.Results from binary univariate regression analysis revealed that lower BMD,the presence of IVF,cleft distribution of bone cement,and higher vertebral compression degree were all significantly associated with further height loss.Notably,the use of mineralized collagen modified-poly(methyl methacrylate)bone cement was associated with a significant reduction in the risk of further height loss.In multivariate regression analysis,lower BMD and the presence of IVF remained significantly associated with further height loss.CONCLUSION Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors,especially lower BMD and the presence of IVF.These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.

Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss

Hypoxia（low oxygen level） is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1（HIF-1）.Hypoxia interferes degradation of HIF-1 alpha subunit（HIF-1α）, leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit（HIF-1β） and subsequent activation of HIF-1 pathway. Apical periodontitis（periapical lesion） is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a wellcharacterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine（DMOG） and adenovirusinduced constitutively active HIF-1α（CA-HIF1 A）. Both DMOG and CA-HIF1 A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B（NF-κB） and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.

Current concepts in the management of recurrent anterior gleno-humeral joint instability with bone loss

The management of recurrent anterior gleno-humeral joint instability is challenging in the presence of boneloss.It is often seen in young athletic patients and dislocations related to epileptic seizures and may involve glenoid bone deficiency,humeral bone deficiency or combined bipolar lesions.It is critical to accurately identify and assess the amount and position of bone loss in order to select the most appropriate treatment and reduce the risk of recurrent instability after surgery.The current literature suggests that coracoid and iliac crest bone block transfers are reliable for treating glenoid defects.The treatment of humeral defects is more controversial,however,although good early results have been reported after arthroscopic Remplissage for small defects.Larger humeral defects may require complex reconstruction or partial resurfacing.There is currently very limited evidence to support treatment strategies when dealing with bipolar lesions.The aim of this review is to summarise the current evidence regarding the best imaging modalities and treatment strategies in managing this complex problem relating particularly to contact athletes and dislocations related to epileptic seizures.

Management bone loss of the proximal femur in revision hip arthroplasty: Update on reconstructive options

The number of revision total hip arthroplasties is expected to rise as the indications for arthroplasty will expand due to the aging population. The prevalence of extensive proximal femoral bone loss is expected to increase subsequently. The etiology of bone loss from the proximal femur after total hip arthroplasty is multifactorial. Stress shielding, massive osteolysis, extensive loosening and history of multiple surgeries consist the most common etiologies. Reconstruction of extensive bone loss of the proximal femur during a revision hip arthroplasty is a major challenge for even the most experienced orthopaedic surgeon. The amount of femoral bone loss and the bone quality of the remaining metaphyseal and diaphyseal bone dictate the selection of appropriate reconstructive option. These include the use of impaction allografting, distal press-fit fixation, allograft-prosthesis composites and tumor megaprostheses. This review article is a concise review of the current literature and provides an algorithmic approachfor reconstruction of different types of proximal femoral bone defects.

Bone Loss Induced by Simulated Microgravity,Ionizing Radiation and/or Ultradian Rhythms in the Hindlimbs of Rats

Objective To better understand the pathological causes of bone loss in a space environment, including microgravity, ionizing radiation, and ultradian rhythms.Methods Sprague Dawley （SD） rats were randomly divided into a baseline group, a control group, a hindlimb suspension group, a radiation group, a ultradian rhythms group and a combined-three-factor group. After four weeks of hindlimb suspension followed by X-ray exposure and/or ultradian rhythms, biomechanical properties, bone mineral density, histological analysis, microstructure parameters, and bone turnover markers were detected to evaluate bone loss in hindlimbs of rats.Results Simulated microgravity or combined-three factors treatment led to a significant decrease in the biomechanical properties of bones, reduction in bone mineral density, and deterioration of trabecular parameters. Ionizing radiation exposure also showed adverse impact while ultradian rhythms had no significant effect on these outcomes. Decrease in the concentration of the turnover markers bone alkaline phosphatase （bALP）, osteocalcin （OCN）, and tartrate-resistant acid phosphatase-5b （TRAP-Sb） in serum was in line with the changes in trabecular parameters.Conclusion Simulated microgravity is the main contributor of bone loss. Radiation also results in deleterious effects but ultradian rhythms has no significant effect. Combined-three factors treatment do not exacerbate bone loss when compared to simulated microgravity treatment alone.

Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss

Osteoclasts are bone-specific multinucleated cells generated by the differentiation of monocyte/macrophage lineage precursors. Regulation of osteoclast differentiation is considered an effective therapeutic approach to the treatment of bone-lytic diseases. Periodontitis is an inflammatory disease characterized by extensive bone resorption. In this study, we investigated the effects of sodium fluoride （NaF） on osteoclastogenesis induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of cathepsin K, interleukin （IL）-1β, matrix metalloproteinase 9 （MMP9）, and tartrate-resistant acid phosphatase, which were up-regulated during P. gingivalis-induced osteoclastogenesis. Consistent with the in vivo anti-osteoclastogenic effect, NaF inhibited osteoclast formation caused by the differentiation factor RANKL （receptor activator of nuclear factor KB ligand） and macrophage colony-stimulating factor （M-CSF）. The RANKL-stimulated induction of the transcription factor nuclear factor of activated T cells （NFAT） cl was also abrogated by NaF. Taken together, our data demonstrate that NaF inhibits RANKL-induced osteoclastogenesis by reducing the induction of NFATcl, ultimately leading to the suppressed expression of cathepsin K and MMP9. The in vivo effect of NaF on the inhibition of P. gingivalis-induced osteoclastogenesis strengthens the potential usefulness of NaF for treating periodontal diseases.

Auditory characteristics of noise-exposed memberscrossing age-related groups

Objective： To report audiological characteristics in a group of noise-exposed crew members on board ships. Methods and materials： Clinical and audiological measurements including pure-tone thresholds, acoustic immittance results and tinnitus questionnaires were collected from both the ship crew members （study subjects） and their land based colleagues （controls）. Results： 1） Noise exposed crew members showed not only high frequency, but also low frequency hearing loss; 2） Hearing impairment increased with age, with 65.5% of crew members younger than 50 years showing normal hearing while only 14.9% of those older than 50 years had normal hearing; 3） hearing loss gradually increased with the extension of on board career time; and 4） Most study subjects reported high pitch tinnitus, significantly more than the control group although not significantly different among different age groups. Conclusion： Noise induced hearing impairment from working on board ships shows specific frequency and age characteristics. Understanding these characteristics is important for advancing relevant studies and for effective prevention of noise-induced hearing loss in ship crew members.

Marginal bone loss around non-submerged implants is associated with salivary microbiome during bone healing

Marginal bone loss during bone healing exists around non-submerged dental implants. The aim of this study was to identify the relationship between different degrees of marginal bone loss during bone healing and the salivary microbiome. One hundred patients were recruited, and marginal bone loss around their implants was measured using cone beam computed tomography during a 3-month healing period. The patients were divided into three groups according to the severity of marginal bone loss.Saliva samples were collected from all subjected and were analysed using 16 SMiSeq sequencing. Although the overall structure of the microbial community was not dramatically altered, the relative abundance of several taxonomic groups noticeably changed. The abundance of species in the phyla Spirochaeta and Synergistetes increased significantly as the bone loss became more severe. Species within the genus Treponema also exhibited increased abundance, whereas Veillonella, Haemophilus and Leptotrichia exhibited reduced abundances, in groups with more bone loss. Porphyromonasgingivalis, Treponemadenticola and Streptococcus intermedius were significantly more abundant in the moderate group and/or severe group. The severity of marginal bone loss around the non-submerged implant was associated with dissimilar taxonomic compositions. An increased severity of marginal bone loss was related to increased proportions of periodontal pathogenic species. These data suggest a potential role of microbes in the progression of marginal bone loss during bone healing.

Anterior bone loss after cervical disc replacement: A systematic review

BACKGROUND Anterior bone loss(ABL)is a relatively easily neglected condition after cervical disc replacement(CDR).Whether this phenomenon is a radiological anomaly or a complication remains controversial.Several studies have reported the clinical characteristics of ABL and speculated on the pathogenic mechanism based on a certain type of artificial disc,while the overall understanding of ABL is lacking.AIM To describe the prevalence,impacts,and risk factors of ABL after CDR.METHODS We searched the PubMed,Cochrane Library,and Excerpta Medica databases using the terms“bone loss”or“bone remodeling”or“bone absorption”or“osteolysis”or“implant loosening”or“implant migration”or“hypersensitivity”or“hyperreactivity”,“cervical disc replacement”or“cervical disc arthroplasty”or“total disc replacement”.Eligible manuscripts on the prevalence and impacts of ABL were reviewed by the authors.Data extraction was performed using an established extraction form.The results of the included studies were described narratively.RESULTS Six studies met the inclusion and exclusion criteria.One was a prospective study and the others were retrospective studies.A total of 440 patients with 536 segments were included.The artificial cervical discs included Bryan,Baguera-C,Discocerv,and Mobi-C.The prevalence of ABL ranged from 3.13%to 91.89%,with a combined overall prevalence of 41.84%.ABL occurred within 6 mo and stopped 12 mo after surgery.Several cases were noted to have a self-healing process.Severe ABL resulted in segmental kyphosis,implant subsidence,and persistent neck pain.ABL may be related to heterotopic ossification.Multilevel surgery may be one of the risk factors for ABL.CONCLUSION ABL is a common condition after CDR.The underlying mechanisms of ABL may include stress concentration and injury to nutrient vessels.ABL should be considered a complication after CDR as it was associated with neck pain,implant subsidence,and heterotopic ossification.

Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine（PORCN） that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159（ETC-159） had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.