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Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Materials and Methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CDIIb, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress. [ABSTRACT FROM AUTHOR]

Surface contaminants on customized implant abutments could trigger an inflammatory response in the peri-implant tissues. The aim of this randomized controlled study was to assess the radiographic bone changes around implants restored with customized, platform-switched abutments, with and without autoclave treatment, 12 months after definitive restoration. Dental implants were placed 1 mm subcrestally in 64 systemically healthy patients (mean age: 63.3 ± 10.0 years; 31 patients had a history of periodontitis) to replace single or multiple missing teeth. According to a randomization list, abutments were subjected to steam and autoclave sterilization (43 implants, test group) or steam cleaning alone (44 implants, control group). Periapical standardized radiographs were taken at implant placement, prosthetic abutment connection, and 12 months after definitive cement-retained restoration. All implants were clinically stable without any sign of infection at the 12-month follow-up. An average marginal bone loss of 0.25 ± 0.19 mm was found in the test group compared to 0.35 ± 0.23 mm in the control group (no statistically significant difference), while the percentage of bleeding sites was significantly higher in the control group (8.7% ± 13.1% vs 19.1% ± 19.8%; P = .035). Autoclave treatment of customized abutments seems to reduce the inflammatory response around subcrestally placed implants. [ABSTRACT FROM AUTHOR]

Purpose: To determine the characteristics of dental implant transmucosal surfaces that influence soft tissue attachment and marginal bone loss (MBL). Materials and Methods: The PubMed, Embase, and Cochrane Library electronic databases were searched based on predefined PICO eligibility criteria. Data from animal studies that compared junctional epithelium and connective tissue attachment and MBL from 4 days to 72 weeks were analyzed. The risk of bias was performed with the Systematic Review Centre for Laboratory Animal Experimentation tool. A rank analysis evaluation of data was performed, and the most frequently appearing materials/surfaces for each tissue compartment were identified. Results: The search identified 3,549 studies, 28 of which were eligible for analysis, with an average risk of bias of 28% ± 10%. Machined, polished, etched, sandblasted, or coated titanium and zirconia materials/surfaces were most frequently examined. Several studies investigated lithium disilicate, polyether ether ketone (PEEK) or polyether ketone ketone (PEKK), aluminum oxide, and gold. Based on ranking and frequency of use at different time points, titanium grade IV (Ti-4) microthreads with a polished neck area most frequently supported natural tooth-like junctional epithelial attachment (= 1.5 mm), while machined Ti-4 and machined titanium grade V (Ti-5) most frequently supported connective tissue attachment (= 1.25 mm) and led to the least MBL (= 0.75 mm). Conclusions: Analyzed data suggest that Ti-4 microthreads with a polished neck area and machined Ti-4 and Ti-5 were the materials/surfaces of choice for the transmucosal part of implants. However, the extensive heterogeneity in reported studies precludes solid identification of the best materials/surfaces. [ABSTRACT FROM AUTHOR]

Purpose: To review experimental peri-implantitis studies using rat models and summarize different peri-implantitis induction techniques and evaluate their effectiveness. Materials and Methods: Electronic searches were conducted by two independent examiners to address the following issues. Meta-analyses explored the marginal bone loss (MBL) of four types of peri-implantitis induction methods in rats. The detailed induction tactics--such as the implant design, implant size, surgical process, time cost, induction methods, and endpoint measurements--were summarized. Results: Of the 18 included studies, 38.9% of the studies placed implants at the maxillary first molar, and 44.4% placed them at the alveolar ridge region anterior to the maxillary first molar. As for the induction method, the numbers of published studies on ligature methods, bacterial inoculation, and bacterial lipopolysaccharide inoculation were equally high among all selected studies. The total implant survival rate at the end was 160 out of 213 implants (75.11%). Eight studies with high pooled heterogeneity (I2 = 98, P < .01) in the meta-analysis reported an overall MBL (µ-CT) of 0.47 mm (95% CI = 0.14 to 0.81). A subgroup analysis estimated an MBL of 0.31 mm (95% CI = 0.12 to 0.50) for bacterial inoculation and 0.66 mm (95% CI = 0.07 to 1.26) for the ligature method. Histopathologic analysis revealed that peri-implantitis in rats was similar to peri-implantitis lesions in humans. Conclusions: Implant placement at the maxillary first molar with bacterial inoculation and the silk ligature method to build peri-implantitis rat models is reliable to use for research on peri-implantitis. [ABSTRACT FROM AUTHOR]

Post-traumatic critical-sized bone defects pose a reconstructive challenge for reconstructive surgeons. The vascularized fibula graft is a well-described treatment for osseous defects of the femur and tibia. This study aimed to assess long-term patient-reported quality of life, the success-, and complication rates in lower extremity reconstruction with vascularized fibula grafts. A retrospective cohort of 29 patients who underwent fibula graft reconstruction for critical-sized bone defects after post-traumatic tibial and femoral bone loss between 1990 and 2021 was included. To assess the health-related quality of life and return to work and satisfaction, a cross-sectional survey was performed using the short-form-36, lower extremity functional scale, and a self-made questionnaire including the DN4, satisfaction, and subjective ankle function. The median bone defect size was 8 cm (IQR 9–7 cm). The mental component scores were comparable to the Dutch population norm, whereas the impaired physical function scores were associated with pain (r 0.849, p < 0.001). Neuropathic symptoms were reported in 7 out of 19 patients, and 11 out of 19 patients returned to normal daily activity. All respondents reported positive or neutral scores on overall satisfaction with the recovery. Bone healing was uneventful in 19 out of 29 patients. Union was achieved in 25 out of 29 patients. Persistent nonunion was observed in 4 patients, leading to amputation in 2 patients. Vascularized fibula graft use led to high union rates and limb salvage in patients with post-traumatic segmental bone loss of the tibia and femur. Patient satisfaction with the overall recovery was positive; however, functional outcomes remained impaired. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Materials and Methods Results Conclusion To evaluate long‐term survival and success of dental implants and evaluate indicators affecting the long‐term outcome.Implant survival, success and crestal bone loss (BL) over time were evaluated. For covariates at patient level, Kaplan–Meier estimates of implant survival were compared between groups with the log‐rank test. Observed mean bone loss (MBL) was plotted as a function of time. Cumulative frequencies of BL were plotted for different post‐op times. Uni‐ and multivariate analysis was performed. Simple linear mixed and multiple linear mixed models for BL at 1, 5 and 10 years were fitted.407 patients (221 women, 186 men; mean age 64.86 years (range 28–92, SD 10.11)), with 1482 implants, responded. Absolute implant survival was 94.74%; MBL was 0.81 mm (SD 1.58, range 0.00–17.00) after an average follow‐up of 10.66 years (range 10–14, SD 0.87). Implant survival was influenced on implant level by smoking, implant width and early bone loss (EBL) > 0.5 mm; on patient level by a history of periodontitis. Indicators influencing MBL after the 1st year were abutment height, type of surgery and implant width, while after 5 and 10 years of function were abutment height, EBL > 0.5 mm and smoking.Implant survival was significantly affected by a history of periodontitis on patient level and by smoking, implant width and EBL > 0.5 mm on implant level. Late bone loss was significantly affected by abutment height, EBL > 0.5 mm and smoking.Trial Registration: B670201524796 [ABSTRACT FROM AUTHOR]

Alzheimer's diseases (AD) patients suffer from more serious bone loss than cognitively normal subjects at the same age. Type H blood vessels were tightly associated with bone homeostasis. However, few studies have concentrated on bone vascular alteration and its role in AD‐related bone loss. In this study, APP/PS1 mice (4‐ and 8‐month‐old) and age‐matched wild‐type mice were used to assess the bone vascular alteration and its role in AD‐related bone loss. Transmission electron microscopy, immunofluorescence staining and iGPS 1.0 software database were utilized to investigate the molecular mechanism. Mitochondrial division inhibitor (Mdivi‐1) and GSK‐3β inhibitor (LiCl) were used to rescue type H blood vessels injury and verify the molecular mechanism. Our results revealed that APP/PS1 mice exhibited more serious bone blood vessels injury and bone loss during ageing. The bone blood vessel injury, especially in type H blood vessels, was accompanied by impaired vascularized osteogenesis in APP/PS1 mice. Further exploration indicated that beta‐amyloid (Aβ) promoted the apoptosis of vascular endothelial cells (ECs) and resulted in type H blood vessels injury. Mechanistically, Aβ‐induced excessive mitochondrial fission was found to be essential for the apoptosis of ECs. GSK‐3β was identified as a key regulatory target of Aβ‐induced excessive mitochondrial fission and bone loss. The findings delineated that Aβ‐induced excessive mitochondrial fission drives type H blood vessels injury, leading to aggravate bone loss in APP/PS1 mice and GSK‐3β inhibitor emerges as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR]

The gut microbiota may help mitigate bone loss linked to postmenopausal osteoporosis by affecting the immune and inflammatory responses and the gut-bone axis. Dihydromyricetin (DMY), a natural flavonoid, has some antiinflammatory and antioxidant properties. This study aimed to investigate the mechanisms underlying the amelioration of bone loss in ovariectomized (OVX) mice treatedwith various doses of DMY. Eight-week-old C57/BL6mice underwent ovariectomy and received varying DMY doses over 8 weeks. Thereafter, femoral bone microarchitecture, serumbiomarker levels, and colon samples were analyzed to assess bone metabolism and inflammatory and hormonal responses. Fecal samples were subjected to 16S rDNA sequencing, and short-chain fatty acids were quantified. An untargetedmetabolomics approachwas applied to both serum and fecal samples to investigate alterations in the intestinal microbiota and metabolic profiles following DMY treatment in the OVX mice. The results show high-dose DMY has anti-osteoporotic effects. Compared to the OVX group, the DMY-treated group showed enhanced bone mineral density and reduced inflammation and colonic damage levels. The DMY treatment altered the gut microbiota composition, including the relative abundances at both the phylum and genus levels. In addition, DMY treatment increased the production of acetate and propionate. Metabolomic analysis revealed differential regulation of 37 and 70 metabolites in the serum and feces samples, respectively, in the DMY-treated group compared to those in the OVX group, affecting the serotonergic signaling, arachidonic acid metabolism, and unsaturated fatty acid biosynthesis pathways. In conclusion, these findings indicate thatDMY can ameliorate bone loss in OVXmice via the gut-bone axis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to describe outcomes of patients undergoing reverse total shoulder arthroplasty (rTSA) using a patient-specific, custom glenoid component to address severe glenoid deficiency. Methods: Retrospective chart review identified patients at a single institution undergoing rTSA using the glenoid vault reconstruction system (VRS) between 2017 and 2022. Radiographic evaluation, range of motion and patient-reported outcome (PRO) measures, complications, and re-operations were assessed. Results: Fourteen shoulders were included. There was 100% implant survivorship of the glenoid baseplate at mean follow-up of 26.6 months. Mean range of motion improved in forward elevation (62–106 degrees), abduction (41–100 degrees), and external rotation (11–36 degrees). In 7 of 13 patients available for PRO collection, the mean final Visual Analog Pain Scale (VAS) score was 1.29, Single Assessment Numeric Evaluation (SANE) score was 72.14, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score was 77.14, and Penn Shoulder score was 72.26. Conclusions: Use of this custom glenoid resulted in encouraging clinical and radiographic outcomes, with no failures in implant survivorship seen at early follow-up. Larger prospective studies with longer-term follow-up should be undertaken in order to better determine the efficacy and longevity of this implant. Study Design: Retrospective case series; Level of evidence, 4. [ABSTRACT FROM AUTHOR]

Purpose: Cervical disc arthroplasty (CDA) is widely employed for patients diagnosed with cervical degenerative disc disease (CDDD). Postoperative bone loss (BL) represents a radiological alteration that is a relatively novel consideration in the realm of CDA. This study endeavors to examine the risk factors associated with BL following CDA, aiming to elucidate the underlying mechanisms and the impact of BL on surgical outcomes. Methods: A retrospective study was undertaken, encompassing consecutive patients subjected to one-level CDA, two-level CDA, or two-level hybrid surgery (HS) for the treatment of CDDD at our institution. Patient demographic and perioperative data were systematically recorded. Radiological images obtained preoperatively, at 1-week post-operation, and during the last follow-up were collected and evaluated, following with statistical analyses. Results: A total of 295 patients and 351 arthroplasty segments were involved in this study. Univariate logistic regressions indicated that age ≥ 45 years and two-level HS was associated with lower risk of BL; and a greater ΔDA (change of disc angle before and after surgery) was correlated with an increased risk of BL. Multivariate logistic regression determined that two-level HS and greater ΔDA were independent preventative and risk factors for BL, respectively. Further analysis revealed that severe BL significantly elevated the risk of implant subsidence compared to non-BL and mild BL. Conclusions: This study posited bone remodeling and micromotion as potential underlying mechanisms of BL. Subsequent research endeavors should delve into the divergent mechanisms and progression observed between lower- and higher-grade BL, aiming to prevent potential adverse outcomes associated with severe BL. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic bone loss is a well‐known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. Methods: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta‐analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. Results: Twenty‐nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). Conclusion: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy. [ABSTRACT FROM AUTHOR]

This study aimed to develop an algorithm for modelling bone loss defects in a given mandibular geometry, with a user-defined depth, width, place, and defect type. The algorithm was implemented using Grasshopper and models with different bone loss types and depths around a dental implant were built. The models were used in a finite element analysis (FEA) to predict the stresses in peri-implant bone. The FEA showed that the stresses in peri-implant bone depend primarily on the depth of bone loss, whereas the type of bone loss showed no major influence. [ABSTRACT FROM AUTHOR]

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post‐menopausal women. Bone loss has also been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms are well documented but the causal connectivity of events to bone loss development remains incompletely understood. Herein, the adverse outcome pathway (AOP) framework was used to organize data and develop a qualitative AOP beginning from deposition of energy (the molecular initiating event) to bone loss (the adverse outcome). This qualitative AOP was developed in collaboration with bone loss research experts to aggregate relevant findings, supporting ongoing efforts to understand and mitigate human system risks associated with radiation exposures. A literature review was conducted to compile and evaluate the state of knowledge based on the modified Bradford Hill criteria. Following review of 2029 studies, an empirically supported AOP was developed, showing the progression to bone loss through many factors affecting the activities of bone‐forming osteoblasts and bone‐resorbing osteoclasts. The structural, functional, and quantitative basis of each proposed relationship was defined, for inference of causal changes between key events. Current knowledge and its gaps relating to dose‐, time‐ and incidence‐concordance across the key events were identified, as well as modulating factors that influence linkages. The new priorities for research informed by the AOP highlight areas for improvement to enable development of a quantitative AOP used to support risk assessment strategies for space travel or cancer radiotherapy. [ABSTRACT FROM AUTHOR]

This study aimed to assess clinical and radiographic outcomes, including implant survival, marginal bone loss, and patient satisfaction, in individuals with severe bone atrophy treated using a newly developed system of short and extra-short implants. A total of 44 implants (37 short and 7 extra-short) were placed with immediate loading in 11 patients. The patients were followed up at between 6 and 24 months. Bone changes, keratinized mucosa, bleeding on probing, probing depth, crown-to-implant ratio, and patient satisfaction were evaluated. An implant survival and success rate of 100% was observed. The peri-implant bone condition showed no significant associations between marginal bone loss (MBL) and gingival recession. In extra-short implants, the crown-to-implant ratio did not affect MBL in the evaluated times. However, short implants showed a statistically significant inverse correlation between mesial measurement and crown-to-implant ratio (p = 0.006) and between distal measurement and crown-to-implant ratio (p = 0.004) over six months. Plaque was present in the mesiobuccal regions in 38.64% of the implants, with extra-short implants having the highest relative frequency (71.4%). Bleeding was observed in 18.9% of the short implants in the mesiolingual region and 14.3% of the extra-short implants. There was a statistically significant association between bleeding on probing in the mesiobuccal region and the type of implant (p = 0.026). The analysis of probing depth showed no difference between the types of implants. Within the limits of this study, short and extra-short implants presented similar clinical and radiographic behavior of soft and hard tissues in the evaluated times. [ABSTRACT FROM AUTHOR]

Bio-calcium derived from fish frames may offer several advantages for osteoporosis prevention. This study aimed to evaluate the effects of bio-calcium derived from skipjack tuna frames on bone loss in ovariectomized rats. Tuna bio-calcium was prepared through enzymatic hydrolysis, defatting, bleaching, and grinding processes. The bioavailability of calcium was tested using the Caco-2 cell monolayer model, showing that 13% of tuna bio-calcium was absorbed, compared to 10% for calcium carbonate. Rats were divided into the five following groups: (1) OVX, (2) sham-operated, (3), OVX + estrogen-treated (4) OVX + calcium carbonate-treated, and (5) OVX + tuna bio-calcium-treated. All groups were raised for eight weeks. Tuna bio-calcium was able to increase BV/TV by 26% in the femur and 29% in the tibia, compared to 13% and 17% in the OVX group, respectively. Trabecular thickness in the femur upsurged to 360 µm in the tuna group, while a thickness of 290 µm was observed in the control. Additionally, osteoclast numbers were reduced to 5 N.Oc/mm in the femur and 6 N.Oc/mm in the tibia in the tuna group, compared to 35 and 45 N.Oc/mm in the control. Overall, tuna bio-calcium effectively prevented bone loss and can serve as a promising natural alternative for managing osteoporosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the responses of periodontal environment to hormone replacement therapy (HRT) in postmenopausal women with or without periodontitis. Background: HRT is a common and effective strategy for controlling menopausal symptoms, while the changes of periodontal environment under it, particularly in postmenopausal women with periodontitis, remain unclear. Methods: As a prospective cohort study, a total of 97 postmenopausal women receiving HRT were screened, including 47 with and 50 without periodontitis. Correspondingly, 97 women did not receiving HRT were screened as controls during the same period. The full‐mouth sulcus bleeding index (SBI), bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were measured using periodontal probes. The levels of interleukin‐6 (IL‐6) and tumor necrosis factor α (TNF‐α) in the gingival crevicular fluid were measured using enzyme‐linked immunosorbent assay. In addition, cone beam computed tomography was performed to measure the alveolar bone height (ABH) and bone mineral density (BMD). Results: In postmenopausal women without periodontitis, no significantly changes on periodontal parameters were observed after HRT. In women with stage II periodontitis, SBI, BOP, IL‐6, and TNF‐α were significant decreased after one year and two years of HRT. Compared to the controls, women with stage II periodontitis who underwent HRT had significantly lower CAL and ABH and higher BMD in the second year. The incidence of at least one site with CAL increase ≥1 mm between baseline and 2 years was significantly lower in the HRT group than in the control group in women with stage II periodontitis. In addition, HRT was significantly associated with a decrease in SBI, BOP, IL‐6, and TNF‐α in the first year and with a decrease in CAL, SBI, BOP, IL‐6, and ABH and an increase in BMD in the second year. Conclusions: In postmenopausal women with stage II periodontitis, HRT is associated with the alleviation of inflammation within two years and the remission of alveolar bone loss in the second year. HRT appears to decrease the incidence of CAL increase ≥1 mm within 2 years in women with periodontitis by inhibiting inflammation and alveolar bone loss. [ABSTRACT FROM AUTHOR]

Objectives: Osteoporosis is widely regarded as a typical aged-related disease caused by impaired bone remodeling. This research was designed to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in a rat model and investigate the underlying mechanisms. Methods: Three-month-old rats were randomly selected as the youth group, and 24-month-old rats were randomly assigned to the elderly and EA groups. Rats in the EA group received 30 min of EA at bilateral SP10, ST36, K13 and GB34 daily, 5 days a week for 8 weeks. Bone mineral density (BMD), microstructure of the bone tissue, bone turnover biomarkers and expression level of autophagy-related proteins were detected. Results: Compared with the elderly group, EA treatment significantly increased BMD of the femur and ameliorated the microstructure. EA treatment increased trabecular bone volume ratio (= bone volume / total volume [BV/TV]) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) in senile osteoporosis rats. Compared with the elderly group, the serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment. Conclusions: EA can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms. [ABSTRACT FROM AUTHOR]

Reducing marginal bone resorption is a challenge in implant dentistry. Sub-gingival implant placement has been suggested as a suitable strategy to avoid long-term esthetic and biological complications. A total of 38 healthy patients received bone-level (BLG-Control) or 2 mm sub-crestal (SCG-Test) conical connection, platform-switched implants. The test group received an immediate tissue-level abutment, following the one-time abutment (OTA) concept. Marginal bone modification (MBM) was calculated on standardized radiographs at surgery (T0), loading (T1), and 6 (T2) and 12 (T3) months after loading and classified as bone loss (BL) if it occurred below the implant neck and bone remodeling (BR) if above. Pocket-probing depth (PPD), Bleeding on probing (BoP), and Plaque Index (PI) were collected. At 12 months, the mean MBM was 0.61 mm in the test group and 0.52 mm in the control group. In all the cases of the test group (SCG), MBM occurred only above the implant neck, therefore being classified as BR, and no BL was observed. In the control group (BLG), MBM occurred below the implant neck, thus corresponding entirely to BL. The test group had an average PPD of 2.38 mm compared to 3.04 mm in the control group, with BoP at 50% and 43%, and PI at 33% and 19.44%, respectively. At one year after loading, sub-crestal conical connection, platform-switched implants show comparable MBM to bone level implants; however, no bone loss was observed. [ABSTRACT FROM AUTHOR]

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model. Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy. Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals. Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival. Graphical Abstract Article highlights The treatment of breast cancer leads to an imbalance in bone metabolism, promoting the reabsorption of the mineral portion of the tissue. The use of doxorubicin is widespread in the clinic, but it intensifies bone loss, reducing survival. The use of solid lipid nanoparticles containing doxorubicin is promising as a treatment capable of mitigating adverse effects. SLNDox prevented bone loss in mice, preventing the reduction of mineralization and changes in the architecture of long bones. When the treatment is administered to animals with tumors, SLNDox also prevents damage to the growth plate, in addition to calcium loss and reduction in cancellous bone volume. In addition to the benefits of using nanostructures to treat neoplasms, the potential for preventing long-term damage has been observed with the prevention of bone loss through: Reducing the concentration of doxorubicin in the kidneys and heart. Delaying tumor progression and the emergence of lung metastases. Preventing the destruction of cancellous bone. Preventing demineralization of bone tissue. [ABSTRACT FROM AUTHOR]

The search for medications that can effectively reduce alveolar bone loss following tooth extraction is of great interest. This study aimed to observe the roles of 4-octyl itaconate (4-OI) in RANKL-induced osteoclastogenesis of bone marrow macrophages (BMMs) in vitro. Mandibular second molars were extracted to evaluate whether 4-OI could alleviate alveolar bone loss. 4-OI inhibited RANKL-induced osteoclastogenesis and promoted Nrf2 expression in bone marrow macrophages in vitro. Positive Nrf2 expressions were observed in inflammatory cells and osteoclasts in vivo. Treatment with 4-octyl itaconate increased Nrf2 expression, resulting in reduced inflammatory infiltration and osteoclastic activity after tooth extraction. Furthermore, increased expression of OCN and enhanced-alveolar bone healing of extraction socket were observed in the 4-OI group compared to the control group. Our results suggested that 4-OI could serve as a promising pharmacologic candidate for alveolar ridge preservation by alleviating alveolar bone loss following tooth extraction in rats. [ABSTRACT FROM AUTHOR]

Objective: Although guidelines support the efficacy of Modified Qing' E Formula (MQEF) in treating postmenopausal osteoporosis (PMOP), its underlying mechanisms remain incompletely understood. This retrospective investigation aims to elucidate MQEF's impact on serum exosomal miRNA expression in postmenopausal osteoporosis patients and to explore potential therapeutic mechanisms. Methods: Following ethical approval and registration, postmenopausal osteoporosis patients aged 50-85 years, meeting the diagnostic criteria were randomly selected and received MQEF decoction supplementary therapy. Serum samples were collected pre- and post-treatment, followed by isolation and sequencing of exosomal miRNAs. Differential miRNAs in serum exosomes were identified, and bioinformatics analysis was conducted to discern the principal exosomal miRNAs involved in MQEF's effects on PMOP and the associated signaling pathways. Results: Eighteen clinical blood samples were collected. A total of 282,185 target genes were detected across the three groups. 306 miRNAs exhibited altered expression in serum exosomes of PMOP patients, while MQEF intervention resulted in changes in 328 miRNAs. GO enrichment analysis revealed the immune and endocrine systems was pertained. KEGG enrichment analysis indicated associations between PMOP occurrence and MQEF treatment with cytokine interactions, oxidative phosphorylation, and the renin-angiotensin system. Intersectional analysis identified 17 miRNAs, including 2 consistent trends. miR-3188 as a potentially pivotal miRNA implicated in both PMOP occurrence and MQEF treatment. Conclusion: This study constitutes the first randomized, retrospective clinical exploration confirming that MQEF demonstrates regulatory influence over exosomal miRNA expression in PMOP patients' serum, its impact likely involves modulation of the immune and endocrine systems, as well as the renin-angiotensin system. [ABSTRACT FROM AUTHOR]

Background: Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. Methods: We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. Results: Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. Conclusion: Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss. [ABSTRACT FROM AUTHOR]

Porous tantalum metaphyseal cones may facilitate reconstructions of severe bone defects during revision total knee arthroplasty (TKA), but there remains a paucity of data on their outcomes at mean 5 years of follow-up. This study reports the component survivorship, patient satisfaction, functional outcomes, radiographic osseointegration, and complications of revision TKA with porous tantalum metaphyseal cones at mid-term (mean 5-year) follow-up. This study included 152 patients who had a mean age of 66 years (range, 33 to 86 years) undergoing revision TKA with porous tantalum metaphyseal cones. Indications for surgery included aseptic loosening (n = 87, 57.3%), second-stage reimplantation for infection (n = 42, 27.6%), osteolysis with well-fixed components (n = 20, 13.2%), and periprosthetic fracture (n = 3, 2.0%). Component survivorship, clinical outcomes, radiographic outcomes, and any complications were recorded. The mean follow-up time was 5.6 years (range, 2.2 to 13.7). Survivorship was 100% when the end point was revision of the metaphyseal cone (no cones were revised) and 83.8% (95% confidence interval: 77.9 to 90.2%) when the end point was reoperation for any reason at 5-year follow-up. Reoperations were performed for infection (n = 10), instability (n = 4), periprosthetic fracture (n = 2), and quadriceps rupture/dehiscence (n = 3). The mean patient satisfaction score was 78.8 ± 11.3 and the mean Forgotten Joint Score was 62.2 ± 16.7 at the final follow-up. The preoperative median University of California at Los Angeles score improved from 2 (interquartile range 2 to 3) to 6 points (interquartile range 5 to 6) (P <.001), and the preoperative Oxford knee score improved from 15.2 ± 3.8 to 39.4 ± 5.1 points (P <.001) at the final follow-up. All metaphyseal cones showed radiographic evidence of osteointegration without any subsidence or loosening. Porous tantalum metaphyseal cones enabled robust reconstructions of severe femoral and tibial bone defects during revision TKA. These reconstructions were associated with excellent survivorship, improvements in functional outcomes, and reproducible radiographic osseointegration at mean 5-year follow-up. The most common reasons for reoperation were infection and instability. [ABSTRACT FROM AUTHOR]

Preclinical research on diabetes and obesity has been carried out in various animal models over the years. These animal models are developed from genetic manipulation that affects their body metabolism, chemical-induced procedures, diet alteration/modifications, or combinations of the aforementioned approaches. The diabetic and obesity animal models have allowed researchers to not only study the pathological aspect of the diseases but also enable them to screen and explore potential therapeutic compounds. Besides several widely known complications such as macrovascular diseases, diabetic neuropathy, nephropathy and retinopathy, type 2 diabetes mellitus is also known to affect bone health. There is also evidence to suggest obesity affects bone health. Therefore, continuous research needs to be conducted to find a remedy or solution to this matter. Previous literature reported evidence of bone loss in animal models of diabetes and obesity. These findings, as highlighted in this review, further augment the suggestion of an inter-relationship between diabetes, obesity and bone loss. [ABSTRACT FROM AUTHOR]

Aim: Autophagy is involved in human apical periodontitis (AP). However, it is not clear whether autophagy is protective or destructive in bone loss via the receptor activator of nuclear factor‐κB ligand (RANKL)/RANK/osteoprotegerin (OPG) axis. This study aimed to investigate the involvement of autophagy via the RANKL/RANK/OPG axis during the development of AP in an experimental rat model. Methodology: Twenty‐four female Sprague–Dawley rats were divided into control, experimental AP (EAP) + saline, and EAP + 3‐methyladenine (An autophagy inhibitor, 3‐MA) groups. The control group did not receive any treatment. The EAP + saline group and the EAP + 3‐MA group received intraperitoneal injections of saline and 3‐MA, respectively, starting 1 week after the pulp was exposed. Specimens were collected for microcomputed tomography (micro‐CT) scanning, histological processing, and immunostaining to examine the expression of light chain 3 beta (LC3B), RANK, RANKL, and OPG. Data were analysed using one‐way analysis of variance (p <.05). Results: Micro‐CT showed greater bone loss in the EAP + 3‐MA group than in the EAP + saline group, indicated by an elevated trabecular space (Tb.Sp) (p <.05). Inflammatory cell infiltration was observed in the EAP + saline and EAP + 3‐MA groups. Compared with EAP + saline group, the EAP + 3‐MA group showed weaker expression of LC3B (p <.01) and OPG (p <.05), more intense expression of RANK (p <.01) and RANKL (p <.01), and a higher RANKL/OPG ratio (p <.05). Conclusion: Autophagy may exert a protective effect against AP by regulating the RANKL/RANK/OPG axis, thereby inhibiting excessive bone loss. [ABSTRACT FROM AUTHOR]

The sequalae of periodontitis include irreversible degradation of tooth-supporting structures and circulatory spread of inflammatory mediators. However, the serum protein profile in periodontitis is not well described, which is partly attributable to the limited number of studies based on large and well-characterized periodontitis cohorts. This study aims to identify novel, circulating inflammation-related proteins associated with periodontitis within the PerioGene North case-control study, which includes 478 cases with severe periodontitis and 509 periodontally healthy controls. The serum concentrations of high-sensitivity C-reactive protein (hs-CRP) and a panel of 45 inflammation-related proteins were analyzed using targeted proteomics. A distinguishable serum protein profile was evident in periodontitis cases. The protein pattern could separate cases from controls with a sensitivity of 0.81 and specificity of 0.81 (area under the curve = 0.87). Adjusted levels for hs-CRP and 24 of the 45 proteins were different between cases and controls. High levels of hs-CRP and matrix metalloproteinase–12, and low levels of epidermal growth factor (EGF) and oxidized low-density lipoprotein receptor 1 (OLR-1) were detected among the cases. Furthermore, the levels of C-C motif chemokine–19, granulocyte colony-stimulating factor–3 (CSF-3), interleukin-7 (IL-7), and hs-CRP were significantly higher in cases with a high degree of gingival inflammation. The levels of CSF-3 and tumor necrosis factor ligand superfamily member–10 TNFSF-10 were higher in cases with many deep periodontal pockets. The PerioGene North study includes detailed clinical periodontal data and uncovers a distinct serum protein profile in periodontitis. The findings of lower EGF and OLR-1 among the cases are highlighted, as this has not been presented before. The role of EGF and OLR-1 in periodontitis pathogenesis and as possible future biomarkers should be further explored. [ABSTRACT FROM AUTHOR]

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Bioactive glass synthetic bone grafts are used to treat osseous defects in orthopaedic surgery. Characterization of the clinical scenarios associated with bioactive glass use in the context of orthopaedic trauma, are not well established. This study aims to characterize population demographics, operative variables, as well as postoperative variables, for patients who required bone grafting for treatment of traumatic orthopaedic injuries and received a bioactive glass bone substitute intraoperatively. The electronic medical record at a large Level I trauma center was queried for fracture patients between January 1st, 2019, and April 30th, 2022. Our retrospective cohort included fracture patients who received Fibergraft Matrix or Fibergraft Putty intraoperatively, and their respective control groups. This study ascertained patient demographic variables, operative variables, and postoperative variables. Differences in categorical variables were tested with Fischer's Exact Tests, while differences in continuous variables were tested with ANOVA. Statistical significance was determined as P < 0.05. If the overall Group model was significant for a given variable, post-hoc Fischer's Exact or Tukey HSD tests were used to assess pairwise significance between individual Group pairs. A total of four categories across our analysis of demographic, operative, and postoperative variables displayed significant differences amongst subject Groups (P ≤ 0.03). Individual groups were compared such that significant differences between subject groups could be appreciated for a specific variable. FM subjects had greater length of surgery, billable costs, and vitamin D supplementation at the time of surgery compared to FM controls. Similarly, FP subjects had greater length of surgery, billable cost, and implants used intraoperatively compared to FP controls. This analysis revealed Fibergraft patients to have greater length of surgery and billable cost, with respect to their matched controls. These data suggest that Fibergraft patients had more severe orthopaedic fractures compared to matched controls. [ABSTRACT FROM AUTHOR]

Introduction: Post-menopausal women living with Human Immunodeficiency Virus (WLHIV) face an increased risk of bone fractures due to the relationship between HIV-related factors and menopause. This narrative review aims to summarise the current knowledge about fracture risk among post-menopausal WLHIV in particular looking at hormonal changes, combined antiretroviral therapy (cART), lifestyle factors, and psychosocial implications. We also profiled a summary of the significant, recent studies of post-menopausal WLHIV residing in low-income countries (LIC). Methods: A thorough search of the literature was performed across PubMed, Medline, Scopus, and Google Scholar, focussing on studies published between 2000 and 2024. Inclusion criteria entailed original research, reviews, and meta-analyses addressing bone mineral density (BMD), fracture incidence, and related risk factors in post-menopausal WLHIV. Results: The review identified 223 relevant studies. Post-menopausal WLHIV exhibit significantly lower BMD and higher fracture rates compared to both HIV-negative post-menopausal women and pre-menopausal WLHIV. cART, particularly tenofovir disoproxil fumarate (TDF), contributes to reduced BMD. Menopausal status exacerbates this risk through decreased oestrogen levels, leading to increased bone resorption. Moreover, lifestyle choices such as smoking, alcohol consumption, and low physical activity are more prevalent in PWHIV, which further elevates fracture risk. Different psychosocial factors may make WLWHIV more vulnerable at this stage of their life, such as depression, isolation, stigma, and housing and nutritional issues. Women living in LICs face a variety of challenges in accessing HIV care. There are gaps in research related to the prevalence of osteoporosis and bone loss in post-menopausal WLHIV in LICs. Conclusion: Post-menopausal women living with HIV face a significantly higher risk of bone loss and fractures due to the combined effects of HIV and menopause. Antiretroviral therapy (particularly TDF), lifestyle factors, and psychosocial challenges exacerbate this risk. There is a need for careful selection of cART, hormone replacement therapy (HRT), and emerging treatments such as Abaloparatide. A holistic approach including lifestyle changes and psychosocial support is crucial to reduce fracture risk in WLHIV, especially in low-income countries. [ABSTRACT FROM AUTHOR]

Background Periprosthetic bone loss is a well‐known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. Methods A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta‐analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. Results Twenty‐nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). Conclusion Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy.

Abstract Background Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. Methods We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. Results Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. Conclusion Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

Glucocorticoid-induced bone loss is a severe and toxic effect of long-term therapy with glucocorticoids, which are currently prescribed for millions of people worldwide. Previous studies have uncovered that glucocorticoids reciprocally converted osteoblast lineage cells into endothelial-like cells to cause bone loss and showed that the modulations of Foxc2 and Osterix were the causative factors that drove this harmful transition of osteoblast lineage cells. Here, we find that the inhibition of aurora kinase A halts this transition and prevents glucocorticoid-induced bone loss. We find that aurora A interacts with the glucocorticoid receptor and show that this interaction is required for glucocorticoids to modulate Foxc2 and Osterix. Together, we identify a new potential approach to counteracting unwanted transitions of osteoblast lineage cells in glucocorticoid treatment and may provide a novel strategy for ameliorating glucocorticoid-induced bone loss.

BACKGROUND: Sepsis-induced systemic inflammation leads to rapid bone mass loss; however, there is a lack of effective treatments. Ulinastatin is an antiinflammatory drug, but its protective effect and mechanism on bone under sepsis-induced systemic inflammation are still unclear. OBJECTIVE: To explore whether ulinastatin can relieve acute bone loss caused by lipopolysaccharide. METHODS: (1) Animal experiment. Thirty male C57BL/6 mice were randomly divided into three groups (n=10 per group): control group, model group and experimental group. The control group was injected intraperitoneally with normal saline, the model group was injected intraperitoneally with lipopolysaccharide, and the experimental group was injected intraperitoneally with lipopolysaccharide and ulinastatin. In the experimental group, ulinastatin was injected continuously for 3 days. After intraperitoneal injection of ulinastatin for 14 days, femoral tissues were taken for CT scanning and pathological observation. (2) Cell experiment. C57BL/6 mouse primary osteoblasts were isolated and divided into three groups: the control group was routinely cultured, lipopolysaccharide was added to the model group, and lipopolysaccharide with ulinastatin was added to the experimental group. Cell proliferation and osteogenic differentiation were detected. C57BL/6 mouse bone marrow mononuclear cells were isolated and divided into three groups: the control group was routinely cultured, lipopolysaccharide was added to the model group, and lipopolysaccharide and ulinastatin were added to the experimental group. Osteoclast differentiation was detected. RESULTS AND CONCLUSION: (1) Animal experiment. CT scanning and hematoxylin-eosin staining showed that bone mass in lipopolysaccharide-treated mice was reduced but increased after treatment with ulinastatin. Tartrate resistant acid phosphatase staining showed that the number of osteoclasts in bone tissue increased in the model group, but significantly decreased in the experimental group compared with the model group. (2) Cell experiment. Cell counting kit-8 assay showed that lipopolysaccharide treatment inhibited the proliferation of osteoblasts, and ulinastatin elevated the proliferation of osteoblasts after lipopolysaccharide treatment. Alkaline phosphatase staining, alizarin red staining and osteogenesis-related gene (alkaline phosphatase, Runx2, osteocalcin, osteoblastin, nuclear factor κB receptor-activating factor ligand, osteoprotegerin) detection showed that lipopolysaccharide treatment inhibited osteogenic differentiation of osteoblasts and elevated the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio; ulinastatin did not have any significant effect on the reduction of osteoblast function induced by lipopolysaccharide but decreased the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio. Tartrate resistant acid phosphatase staining and osteoclast-related gene (tartrate resistant acid phosphatase and matrix metalloproteinase 9) detection showed that lipopolysaccharide treatment could promote osteoclast differentiation of bone marrow monocytes, while ulinastatin could inhibit lipopolysaccharide-induced osteoclast differentiation of bone marrow monocytes. (3) Overall, ulinastatin can significantly inhibit lipopolysaccharide-induced bone loss, mainly through promoting osteoblast proliferation and directly or indirectly inhibiting osteoclast differentiation to alleviate bone loss and achieve osteoprotective effects. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the cumulative oral implant survival rates and changes in radiographic bone levels based on the configuration of the implant-abutment connection type over time. Materials and Methods: An electronic literature search was conducted in four databases (PubMed/MEDLINE, Cochrane Library, Web of Science, and Embase), and records were refereed by two independent reviewers based on the inclusion criteria. Data from included articles were grouped by implant-abutment connection type into four categories ([1] external hex; [2] bone level, internal, narrow cone < 45 degrees; [3] bone level, internal wide cone ≥ 45 degrees or flat; and [4] tissue level) and duration of follow-up (short-term 1 to 2 years, mid-term 2 to 5 years, and long-term > 5 years). Meta-analyses were performed for cumulative survival rate (CSR) and changes in marginal bone level (ΔMBL) from baseline (loading) to last reported follow-up. Studies were split or merged as appropriate based on the implants and follow-up duration in the study and trial design. The study was compiled under PRISMA 2020 guidelines and registered in the PROSPERO database. Results: A total of 3,082 articles were screened. Fulltext review of 465 articles resulted in a total of 270 articles (representing 16,448 subjects with 45,347 implants) included for quantitative synthesis and analysis. Mean ΔMBL (95% CI) was as follows: short-term external hex = 0.68 mm (0.57, 0.79); short-term bone level, internal, narrow cone < 45 degrees = 0.34 mm (0.25, 0.43); short-term bone level, internal wide cone ≥ 45 degrees = 0.63 mm (0.52, 0.74); short-term tissue level = 0.42 mm (0.27, 0.56); mid-term external hex = 1.03 mm (0.72, 1.34); mid-term bone level, internal, narrow cone < 45 degrees = 0.45 mm (0.34, 0.56); mid-term bone level, internal wide cone ≥ 45 degrees = 0.73 mm (0.58, 0.88); mid-term tissue level = 0.4 mm (0.21, 0.61); long-term external hex = 0.98 mm, 0.70, 1.25); long-term bone level, internal, narrow cone < 45 degrees = 0.44 mm (0.31, 0.57); long-term bone level, internal wide cone ≥ 45 degrees = 0.95 mm (0.68, 1.22); and long-term tissue level = 0.43 mm (0.24, 0.61). CSRs (95% CI) were: short-term external hex = 97% (96%, 98%); short-term bone level, internal, narrow cone < 45 degrees = 99% (99%, 99%); short-term bone level, internal wide cone ≥ 45 degrees = 98% (98%, 99%); short-term tissue level = 99% (98%, 100%); mid-term external hex = 97% (96%, 98%); mid-term bone level, internal, narrow cone < 45 degrees = 98% (98%, 99%); midterm bone level, internal wide cone ≥ 45 degrees = 99% (98%, 99%); mid-term tissue level = 98% (97%, 99%); long-term external hex = 96% (95%, 98%); long-term bone level, internal, narrow cone < 45 degrees = 98% (98%, 99%); long-term bone level, internal wide cone ≥ 45 degrees = 99% (98%, 100%); and long-term tissue level = 99% (98%, 100%). Conclusion: The configuration of the implant-abutment interface has a measurable effect on the ΔMBL over time. These changes can be observed over a period of at least 3 to 5 years. At all measured time intervals, similar ΔMBL was noted for external hex and internal wide cone ≥ 45-degree connections, as were internal, narrow cone < 45-degree and tissue-level connections. [ABSTRACT FROM AUTHOR]

Home care therapy is indispensable to manage periodontal disease successfully. Often, during and following initial periodontal treatment, it is unclear how much of the clinical improvement was due to patients' home care or to professional intervention, as these two therapeutic components are often amalgamated in clinical practice as well as in studies. In this case series, four patients with periodontal disease received education on using oral hygiene devices and used them competently prior to initiation of professional periodontal treatment. The changes in their clinical presentations, solely attributed to their home care therapy, were documented. The rationale and suggested clinical guidelines are also presented. Conclusion: Home care therapy is an indispensable but often overlooked step in the successful management of periodontal diseases. Ideally, this step should be solidified prior to proceeding with any professional treatment. By motivating patients to participate in the treatment more actively, clinicians can significantly improve the outcome and longevity of their professional interventions. [ABSTRACT FROM AUTHOR]

Introduction: Saliva, a versatile biological fluid, has gained recognition as an invaluable medium for point-of-care diagnostics, offering insight into the complex dynamics of periodontal tissue inflammation. Aims: This study aimed to assess salivary lactoferrin (LF) concentration among individuals diagnosed with periodontitis (PDS) compared to a control group. Materials and Methods: A randomized, observational study enrolled 441 participants residing in Southern Sweden, aged 20 and 89 years and diagnosed with PDS. Clinical examination was performed following a standardized periodontal protocol, measuring key periodontal parameters such as plaque index (PI), bleeding index (BI), periodontal pocket depth (PPD), and marginal alveolar bone level/bone loss using posterior intraoral bitewing radiographs. Stimulated saliva samples were analyzed for LF concentration using enzyme e-linked immunosorbent assay. Statistical analysis included Pearson correlation and ANOVA variance with a 95% confidence interval. Results and Discussion: We found no significant difference among the studied groups in mean salivary LF concentration (P > 0.05), whereas we observed a negative association between PI and salivary LF concentration (Pearson correlation = 0.110, P = 0.024), suggesting that increased plaque scores were associated with decreased LF level. In addition, smokers exhibited lower LF levels (P = 0.001). Notably, salivary LF concentration did not correlate with selected clinical parameters of PDS, including BI and PPD. Conclusions: These results underscore the multifaceted nature of salivary components and emphasize the need to consider various factors when evaluating the impact of PDS on saliva. Further research is imperative to validate risk factors contributing to the development of PDS and the diagnostic potential of salivary biomarkers, considering the intricate interplay between saliva and periodontal status. This study contributes valuable insight into the potential utility of saliva as a diagnostic medium.

Abstract 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 (0.25 mg/kg in vivo, 0.05 μM 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.

Stage IV grade C localized periodontitis (pre-puberal localized aggressive periodontitis/LPP), an extremely rare form of periodontal disease, occurs in otherwise healthy individuals (no signs of dental plaque/calculus) due a hyper-aggressive auto-immune response to high periodontopathic bacteria levels. Methods: A 4-year-old Caucasian girl with unusually high mobility of the deciduous lower left canine and localized gingival inflammation was misrecognized by multiple clinicians (initially diagnosed with hypophosphatasia, genetic and metabolic disorders, all turning negative), over a period of 4–6 months, despite initial radiographs showing clear pathognomonic signs. The LPP diagnostic was made by the last clinician, but by then the tooth was lost. Similar inflammation signs appeared around the lower deciduous right canine. X-ray examination showed similar bone and periodontal loss as previously seen, while periodontopathic bacteria tested highly positive. The patient received both mechanical cleaning and ten days of systemic antibiotic treatment (Augmentin and Metronidazole). Results: Two months later, inflammation signs disappeared, with periodontal regeneration radiologically present, and only small periodontopathic bacteria precursor concentrations. Conclusions: Despite initial periodontal loss, an adequate treatment can keep under control an LPP disease. Moreover, bone and periodontal regeneration appears if periodontopathic bacteria scores are kept lower, showing the importance of fast adequate diagnostic and treatment. [ABSTRACT FROM AUTHOR]

Until recently, research on the pathogenesis and treatment of osteoporosis and sarcopenia has primarily focused on local and systemic humoral mechanisms, often overlooking neuronal mechanisms. However, there is a growing body of literature on the neuronal regulation of bone and skeletal muscle structure and function, which may provide insights into the pathogenesis of osteosarcopenia. This review aims to integrate these neuronal regulatory mechanisms to form a comprehensive understanding and inspire future research that could uncover novel strategies for preventing and treating osteosarcopenia. Specifically, the review explores the functional adaptation of weight‐bearing bone to mechanical loading throughout evolutionary development, from Wolff's law and Frost's mechanostat theory to the mosaic hypothesis, which emphasizes neuronal regulation. The recently introduced bone osteoregulation reflex points to the importance of the osteocytic mechanoreceptive network as a receptor in this neuronal regulation mechanism. Finally, the review focuses on the bone myoregulation reflex, which is known as a mechanism by which bone loading regulates muscle functions neuronally. Considering the ageing‐related regressive changes in the nerve fibres that provide both structural and functional regulation in bone and skeletal muscle tissue and the bone and muscle tissues they innervate, it is suggested that neuronal mechanisms might play a central role in explaining osteosarcopenia in older adults. [ABSTRACT FROM AUTHOR]

Objective To investigate the key targets and pathways for preventing bone loss caused by aromatase inhibitors (AIs) by tonifying the kidney and activating the blood. Methods Thirty mice were randomly divided into sham operation group, model group, and drug administration group. After castration, mice in the model group and drug administration group were subcutaneously injected with letrozole solution of 10 μg/d to establish an animal model of postmenopausal osteoporosis caused by AIs. Mice in the drug administration group was also given 19.24 g/(kg·d) of Huangqi Bushen Huoxue decoction (HQD) to prevent bone loss, while mice in the sham operation group and model group were given the same amount of normal saline. After three months of drug administration, the femurs of the mice were collected to test the bone mineral density and to verify the model. Results Compared to those in the blank group, the trabecular structure of the model group was loose and disordered, and the number was reduced, which proved that the model was successful. Compared to those in the model group, the trabecular bone in the drug group was thick and dense, and the number increased, which proved that the method of tonifying kidney and promoting blood circulation had a significant preventive effect. Compared to those in the blank group, 275 proteins were up-regulated and 189 proteins were down-regulated in the model group. Compared to those in the model group, 286 proteins were up-regulated and 898 proteins were down-regulated. There were 18 intersecting proteins among the three groups after comparison, including Ptbp1, Epx, Ear1, Ear2, Col6a5, Mta2, Alox15, Lztfl1, Ccl6, Diaph2, Wfdc21, Smarcb1, Strip1, C19orf12, Pex14, Akr1b7, Fahd1, and Nr1d2. Differential proteins were mainly involved in the regulation of cell development and differentiation, lipid metabolism, endonuclease activity, and other biological processes, and were significantly enriched in iron death, arachidonic acid metabolism pathway, troponin cytoskeleton regulation, and PI3K-AKT and other signal pathways. Conclusion Tonifying kidney and activating the blood effectively prevents bone loss caused by AIs. Its key target and mechanism may be related to Ptbp1, Alox15, iron death, and PI3K-AKT and other pathways. [ABSTRACT FROM AUTHOR]

Introduction: This research paper investigates whether robotic total knee replacement (TKR) reduces bone resection compared to conventional TKR. While TKR is a successful procedure, revision surgery remains a challenge with up to 8.3% of all knee replacement procedures requiring revisions. Materials and methods: The study retrospectively analyzed the tibial polyethylene inserts used and bone cuts made in 157 primary TKRs performed by a single surgeon. The results show that 93.3% of robotic TKRs used the base size tibial polyethylene of 9 mm, and the average distal femoral cut was 7.4 mm and the average tibial cut was 6.4 mm, with the minimum being 3 mm. Conclusion: The study suggests that robotic TKR reduces bone resection compared to conventional TKR. [ABSTRACT FROM AUTHOR]

Purpose: Cervical total disc replacement (cTDR) has been established as an alternative treatment for degenerative cervical radiculopathy and myelopathy. While the rate of complications for cTDR is reasonably low, recent studies have focused on bone loss after cTDR. The purpose of this work is to develop a clinical management plan for cTDR patients with evidence of bone loss. To guide our recommendations, we undertook a review of the literature and aimed to determine: (1) how bone loss was identified/imaged, (2) whether pre- or intraoperative assessments of infection or histology were performed, and (3) what decision-making and revision strategies were employed. Methods: We performed a search of the literature according to PRISMA guidelines. Included studies reported the clinical performance of cTDR and identified instances of cervical bone loss. Results: Eleven case studies and 20 cohort studies were reviewed, representing 2073 patients with 821 reported cases of bone loss. Bone loss was typically identified on radiographs during routine follow-up or by computed tomography (CT) for patients presenting with symptoms. Assessments of infection as well as histological and/or explant assessment were sporadically reported. Across all reviewed studies, multiple mechanisms of bone loss were suspected, and severity and progression varied greatly. Many patients were reportedly asymptomatic, but others experienced symptoms like progressive pain and paresthesia. Conclusion: Our findings demonstrate a critical gap in the literature regarding the optimal management of patients with bone loss following cTDR, and treatment recommendations based on our review are impractical given the limited amount and quality evidence available. However, based on the authors' extensive clinical experience, close follow-up of specific radiographic observations and serial radiographs to assess the progression/severity of bone loss and implant changes are recommended. CT findings can be used for clinical decision-making and further follow-up care. The pattern and rate of progression of bone loss, in concert with patient symptomatology, should determine whether non-operative or surgical intervention is indicated. Future studies involving implant retrieval, histopathological, and microbiological analysis for patients undergoing cTDR revision for bone loss are needed. [ABSTRACT FROM AUTHOR]

The periodontal ligament (PDL) is a fibrillar connective tissue that lies between the alveolar bone and the tooth and is composed of highly specialized extracellular matrix (ECM) molecules and a heterogeneous population of cells that are responsible for collagen formation, immune response, bone formation, and chewing force sensation. Type VI collagen (COL6), a widely distributed ECM molecule, plays a critical role in the structural integrity and mechanical properties of various tissues including muscle, tendon, bone, cartilage, and skin. However, its role in the PDL remains largely unknown. Our study shows that deficiency of COL6 impairs PDL fibrillogenesis and exacerbates tissue destruction in ligature-induced periodontitis (LIP). We found that COL6-deficient mice exhibited increased bone loss and degraded PDL in LIP and that fibroblasts expressing high levels of Col6α2 are pivotal in ECM organization and cell-ECM interactions. Moreover, COL6 deficiency in the PDL led to an increased number of fibroblasts geared toward the inflammatory response. We also observed that cultured COL6-deficient fibroblasts from the PDL exhibited decreased expression of genes related to collagen fiber turnover and ECM organization as well as migration and proliferation. Our findings suggest that COL6 plays a crucial role in the PDL, influencing fibroblast function in fibrillogenesis and affecting the immune response in periodontitis. These insights advance our understanding of the molecular mechanisms underlying PDL maturation and periodontal disease. [ABSTRACT FROM AUTHOR]

The aim of the present review is to discuss the roles of vitamin K (phylloquinone or menaquinones) and vitamin K-dependent proteins, and the combined action of the vitamins K and D, for the maintenance of bone health. The most relevant vitamin K-dependent proteins in this respect are osteocalcin and matrix Gla-protein (MGP). When carboxylated, these proteins appear to have the ability to chelate and import calcium from the blood to the bone, thereby reducing the risk of osteoporosis. Carboxylated osteocalcin appears to contribute directly to bone quality and strength. An adequate vitamin K status is required for the carboxylation of MGP and osteocalcin. In addition, vitamin K acts on bone metabolism by other mechanisms, such as menaquinone 4 acting as a ligand for the nuclear steroid and xenobiotic receptor (SXR). In this narrative review, we examine the evidence for increased bone mineralization through the dietary adequacy of vitamin K. Summarizing the evidence for a synergistic effect of vitamin K and vitamin D3, we find that an adequate supply of vitamin K, on top of an optimal vitamin D status, seems to add to the benefit of maintaining bone health. More research related to synergism and the possible mechanisms of vitamins D3 and K interaction in bone health is needed. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age–sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of S ubdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy. [ABSTRACT FROM AUTHOR]

This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT's metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways. [ABSTRACT FROM AUTHOR]

Objectives: Dental implant procedures are crucial for replacing missing teeth, with various surgical techniques impacting the outcome. This systematic review and meta- analysis aimed to evaluate the effects of flapped and flapless surgical techniques on implant survival and marginal bone loss (MBL). Methods: We included clinical studies with at least ten subjects, excluding review articles, editorials, and conference abstracts. Studies were sourced from PubMed, Medline, ERIC, and Wiley, published between 2000 and 2022. Data were analyzed using random-effects models to compare implant survival and MBL between flapped and flapless techniques. Results: The review identified 21 studies meeting the inclusion criteria. Flapless techniques showed a higher implant survival rate with an approximate survival rate of 98.6% in prospective cohort studies and 95.9% in retrospective studies. MBL was consistently lower in the flapless group, averaging 0.6–2.1 mm, compared to 1.5–3 mm in the flapped group. Low-risk studies demonstrated more consistent and reliable results, supporting the efficacy of flapless procedures. Conclusion: Flapless implant surgery offers a viable alternative to traditional flapped surgery, showing higher rates of implant survival and less MBL. However, successful outcomes depend on advanced imaging, precise surgical techniques, and adequate training. Further high-quality studies are needed to confirm these findings and refine clinical recommendations. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Jaboticaba is a small, round fruit with white pulp and purple peel that concentrates compounds that may have therapeutic applications. Since jaboticaba peel extract (JPE) enhances the activity of osteoblasts (the cells that form bone) under osteoporotic conditions, we hypothesized that JPE prevents the development of osteoporosis induced by the removal of the ovaries. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. JPE attenuated ovariectomy-induced bone loss due to its ability to prevent the imbalance between osteoblast and adipocyte (the cells that produce bone and fat, respectively) differentiation. These data indicate the potential therapeutic use of JPE to prevent osteoporosis. Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis. [ABSTRACT FROM AUTHOR]