Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus.

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow­derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. µCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.

Does Robotic Assistance Help with Bone Preservation in Total Knee Replacement?

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.

Aromatase inhibitor-induced bone loss osteosarcopenia in older patients with breast cancer: effects of the RANK/RANKL system's inhibitor denosumab vs. bisphosphonates.

The raising number of older patients who are diagnosed with breast cancer represents a significant medical and societal challenge. Aromatase inhibitors (AI), which are commonly utilized to treat this condition in these patients have significant adverse events on bone and muscle health. Falling estrogen production leads to an increase in RANKL secretion by osteoblasts with accelerated bone remodeling due to osteoclast activity. Furthermore, estrogen deficiency reduces skeletal muscle strength and mass. The humanized monoclonal antibody, denosumab, neutralizes RANKL, thereby inhibiting osteoclast formation, function and survival and ultimately exerting powerful anti-resorptive effects.. In this study, we report on the efficacy of denosumab in mitigating aromatase inhibitor-induced bone loss (AIBL) and sarcopenia in older women with breast cancer. From January 2022 to January 2023, we enrolled 30 patients (female sex, ≥ 65 years) diagnosed with non-metastatic breast cancer undergoing adjuvant endocrine therapy; patients received, as per clinical practice, primary bone prophylaxis with denosumab (60 mg via subcutaneous injection every 6 months) according to oncologic guidelines. This group was matched with 30 patients with non-metastatic breast cancer, who were treated with biphosphonates (BF) therapy (oral alendronate 70 mg/week). For each patient bone mineral density (BMD) and bone quality in terms of trabecular bone score (TBS) in addition to body composition and Relative Skeletal Muscle Index (RSMI) was assessed by bone densitometry at baseline and after one year of treatment. Significant improvements in TBS at the lumbar spine, RSMI and whole-body composition (arms, legs, and trunk) were observed in the denosumab group compared with the BF group. These findings underscore the role of denosumab as an effective strategy in managing AIBL and osteosarcopenia in older women with breast cancer and undergoing adjuvant endocrine therapy, which is crucial for improving quality of life, preventing functional decline, and optimizing treatment outcomes.

NAT10 promotes osteoclastogenesis in inflammatory bone loss by catalyzing Fos mRNA ac4C modification and upregulating MAPK signaling pathway.

INTRODUCTION: Excessive osteoclastogenesis is a key driver of inflammatory bone loss. Suppressing osteoclastogenesis has always been considered essential for the treatment of inflammatory bone loss. N-acetyltransferase 10 (NAT10) is the sole enzyme responsible for N4-acetylcytidine (ac4C) modification of mRNA, and is involved in cell development. However, its role in osteoclastogenesis and inflammatory bone loss remained elusive. OBJECTIVES: We aimed to clarify the regulatory mechanism of NAT10 and ac4C modification in osteoclastogenesis and inflammatory bone loss. METHODS: NAT10 expression and ac4C modification during osteoclastogenesis were determined by quantitative real-time PCR (qPCR), western blotting, dot blot and immunofluorescent staining, and the effect of NAT10 inhibition on osteoclast differentiation in vitro was measured by the tartrate-resistant acid phosphatase staining, podosome belts staining assay and bone resorption pit assay. Then, acRIP-qPCR and NAT10RIP-qPCR, ac4C site prediction, mRNA decay assay and luciferase reporter assay were performed to further study the underlying mechanisms. At last, mice models of inflammatory bone loss were applied to verify the therapeutic effect of NAT10 inhibition in vivo. RESULTS: NAT10 expression was upregulated during osteoclast differentiation and highly expressed in alveolar bone osteoclasts from periodontitis mice. Inhibition of NAT10 notably reduced osteoclast differentiation in vitro, as indicated by great reduction of tartrated resistant acid phosphatse positive multinuclear cells, osteoclast-specific gene expression, F-actin ring formation and bone resorption capacity. Mechanistically, NAT10 catalyzed ac4C modification of Fos (encoding AP-1 component c-Fos) mRNA and maintained its stabilization. Besides, NAT10 promoted MAPK signaling pathway and thereby activated AP-1 (c-Fos/c-Jun) transcription for osteoclastogenesis. Therapeutically, administration of Remodelin, the specific inhibitor of NAT10, remarkably impeded the ligature-induced alveolar bone loss and lipopolysaccharide-induced inflammatory calvarial osteolysis. CONCLUSIONS: Our study demonstrated that NAT10-mediated ac4C modification is an important epigenetic regulation of osteoclast differentiation and proposed a promising therapeutic target for inflammatory bone loss.

Comparative efficacy of flapped versus flapless dental implant procedures: A meta-analysis.

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.

Acute Necrotizing Ulcerative Gingivitis: A Case Report.

Compared to other conditions found in the necrotizing periodontal diseases group, acute necrotizing ulcerative gingivitis (ANUG) is a definite and specific disease. This illness has a long history that originates from the time of Hippocrates and is also referred to by several synonyms. ANUG occurs less commonly than other oral disorders, even though it is typically not rare. It starts suddenly, advances quickly, and finally results in significant loss of alveolar bone and soft tissue. Viral microorganisms and weakened host defenses have been linked to the etiology and pathophysiology of ANUG. In situations where there is psychological and physiological stress, the incidence of ANUG rises. In developed nations, the incidence of ANUG has declined and, in some cases, gone extinct due to the development of antibiotics and improved nutritional status. However, due to the persistently low nutritional status, the illness continues to be a frequently diagnosed clinical lesion in developing nations. This case report presents the case of a 24-year-old ANUG patient and the sequential treatment of this patient.

Host-derived lactic acid bacteria alleviate short beak and dwarf syndrome by preventing bone loss, intestinal barrier disruption, and inflammation.

Short-beak and dwarf syndrome (SBDS) is caused by novel goose parvovirus (NGPV) infection, which leads to farm economic losses. Our research aimed to investigate the potential of administering isolated lactic acid bacteria (LAB) in alleviating SBDS in ducks. Eight wild LAB strains were isolated from duck feces and their biosecurity was investigated in both duck embryo fibroblast (DEF) and live ducks. Moreover, the LAB strains exhibited no detrimental effects on bone metabolism levels and facilitated the tight junction proteins (TJPs) mRNA expression, and contributing to the mitigation of inflammation in healthy ducks. Subsequently, we conducted in vitrol and in vivo experiments to assess the impact of LAB on NGPV infection. The LAB strains significantly reduced the viral load of NGPV and downregulated the mRNA levels of pro-inflammatory factors in DEF. Additionally, LAB treatment alleviated SBDS in NGPV-infected ducks. Furthermore, LAB treatment alleviated intestinal damage, and reduced the inflammatory response, while also mitigating bone resorption in NGPV-infected ducks. In conclusion, the LAB strains isolated from duck feces have favorable biosecurity and alleviate SBDS in ducks, and the mechanism related to LAB improves intestinal barrier integrity, alleviates inflammation, and reduces bone resorption. Our study presents a novel concept for the prevention and treatment of NGPV, thereby establishing a theoretical foundation for the future development of probiotics in the prevention and treatment of NGPV.

Do Intrabony Defects Have a Worse Clinical Response to Step 2 of Periodontal Therapy and Repeated Subgingival Instrumentation Compared with Suprabony Defects? A Systematic Review.

AIM: To assess the differential clinical response to step 2 of periodontal therapy and repeated subgingival instrumentation between teeth with suprabony and intrabony defects. METHODS: Electronic and manual search were performed to identify studies reporting the differential clinical outcomes of non-surgical periodontal therapy (NSPT) in presence or absence of intrabony defects. The Cochrane Risk of Bias 2 and the Newcastle Ottawa scale were used to assess the risk of bias. RESULTS: Two thousand three hundred forty-eight articles were initially screened, and a total of 5 articles were finally included. Regarding the primary outcome measure, two studies reported PPD reduction values at 6 months after step 2 of periodontal therapy, showing an opposite response of intrabony defects compared to suprabony defects (3.2 mm ± 1.9 versus 2.2 mm ± 1.7 and 0.48 mm ± 0.42 versus 0.72 mm ± 0.36, respectively), while one study reported no differences at 3 months. One study showed a negative association between the presence of intrabony defect and PPD reduction at 9 months after non-surgical step 3 (p < 0.05). CONCLUSION: Due to the limited number of studies and heterogeneity of the data, conflicting evidence emerged for the differential response to NSPT of intrabony and suprabony defects.

Comparing the Efficacy of Antiosteoporotic Drugs in Preventing Periprosthetic Bone Loss Following Total Hip Arthroplasty: A Systematic Review and Bayesian Network Meta-Analysis.

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.

Evaluation of Periodontal Clinicoradiographic Status and Whol Salivary Prostaglandin E2 Levels among Users of Water Pipe and Cigarettes.

PURPOSE: The objective was to evaluate the periodontal clinicoradiographic status and whole salivary prostaglandin E2 (PgE2) levels among users of water pipe and cigarettes. MATERIALS AND METHODS: Demographic data, duration of smoking (pack years), and familial history of smoking were recorded using a questionnaire. Participants were allocated into three groups based on their smoking status: group 1: self-reported cigarette smokers (CS); group 2: self-reported water-pipe-users; and group 3: non-smokers. The assessment included measurements of full-mouth plaque and gingival indices (PI and GI), as well as probing depth (PD), clinical attachment loss (CAL), and marginal bone loss (MBL). Unstimulated whole saliva samples were collected and PgE2 levels were measured. Group comparisons were done and p<0.05 was considered statistically significant. RESULTS: Thirty-three, 34 and 33 individuals were included in groups 1, 2 and 3, respectively. Full mouth PI (p<0.05), GI (p<0.05), PD (p<0.05) and mesial (p<0.05) and distal (p<0.05) MBL were statistically significantly higher among patients in groups 1 and 2 than group 3. The scores of CAL in groups 1 and 2 were 3.45 ± 0.97 and 3.62 ± 1.2 mm, respectively. None of the individuals in the control group displayed CAL. PgE2 levels were statistically significantly higher among patients in groups 1 (231.5 ± 66.3 pg/ml) (p<0.05) and 2 (231.5 ± 66.3 pg/ml) (p<0.05) compared with group 3 (76.6 ± 10.6 pg/ml). In groups 1 and 2, a statistically significant relationship was observed between pack-years, the duration of water-pipe smoking, and the levels of PgE2 and PD. CONCLUSION: There is no difference in periodontal clinicoradiographic status and whole salivary PgE2 levels between CS and waterpipe-users; however, these parameters are worse in CS and water-pipe users than in non-smokers.

Early wound healing at 1 week postoperatively in periodontal tissue regeneration therapy: enamel matrix derivative versus recombinant human fibroblast growth factor.

PURPOSE: Recombinant human fibroblast growth factor-2 (rhFGF-2) has demonstrated positive effects on wound healing at 2 weeks after periodontal surgery relative to enamel matrix derivative (EMD). However, the effects at earlier postoperative stages have not been reported. This retrospective study compared the early wound healing outcomes 1 week after surgery using the modified papilla preservation technique (mPPT) with either EMD or rhFGF-2 therapy. METHODS: We compiled a list of all mPPT sites treated with EMD or rhFGF-2 during the survey period (September 2011 to March 2022). Early wound healing was assessed using the early wound healing score (EHS) and the modified early wound healing index (mEHI). Inter-rater reliability for the EHS and mEHI was established using intraclass correlation coefficients. Factors influencing mPPT were identified by analyzing the correlation coefficients between the EHS items, mEHI items, and potential influencing factors. After adjusting for factors impacting EHS, mEHI, and mPPT, we compared the EHS and mEHI between EMD and rhFGF-2 groups. RESULTS: In total, 72 sites were evaluated. The scores for incision line, step, and dehiscence were significantly higher in those receiving rhFGF-2 (n=42) compared to those treated with EMD (n=30). The EHS item scores did not differ significantly between groups. Among patients aged ≥50 years, but not those <50 years, significantly higher step and dehiscence scores were found in the rhFGF-2 group than the EMD group (P<0.01). Additionally, for patients exhibiting a clinical attachment level (CAL) ≥8 mm, the step score was significantly higher in the rhFGF-2 group than in the EMD group (P<0.05), but this trend was not reflected in those with a CAL <8 mm. CONCLUSIONS: In this study, early wound closure at mPPT sites was more effectively achieved with rhFGF-2 than with EMD. Nevertheless, biochemical assessments are required to compare the re-epithelialization effects of these therapies.

The influence of implant depth, abutment height and mucosal phenotype on peri­implant bone levels: A 2-year clinical trial.

OBJECTIVES: To evaluate the bone changes around equicrestal and subcrestal implants, analyzing the effect of abutment height [short abutments (SA < 2 mm) and long abutments (LA > 2 mm)] and the three components of the peri­implant soft-tissue phenotype. METHODS: Twenty-six patients received 71 implants that were placed according to supracrestal tissue height (STH) in an equicrestal (n = 17), shallow subcrestal ≈1 mm (n = 33), or deep subcrestal ≈2 mm (n = 21) position. After 3 months of healing, rehabilitation was completed using metal-ceramic crowns on multi-unit abutments of 1.5 mm, 2.5 mm, or 3.5 mm in height, depending on the prosthetic space and STH. Longitudinal clinical parameters (STH, mucosal thickness, and keratinized mucosa width) and radiographic data [bone remodelling and marginal bone loss (MBL)] were collected at 3, 6, 12, and 24 months postsurgery. RESULTS: The gain in STH was significantly greater around the implants placed in a subcrestal ≈2 mm position. After 2 years, the mean change in bone remodelling in the SA group was significantly greater than in the LA group. According to the multiple linear regression, bone remodelling depends primarily on abutment height (ß = -0.43), followed by crestal position (ß = 0.34), and keratinized mucosa width (ß = -0.22), while MBL depends on abutment height (ß = -0.37), and the patient's age (ß = -0.36). CONCLUSIONS: Implants placed in an equicrestal or subcrestal ≈1 mm position with LA undergo less bone remodelling, while the lowest level of MBL occurs in subcrestal ≈2 mm implants with LA. Differing soft-tissue thicknesses combined with the use of either SA or LA produced significant intergroup differences in bone remodelling and MBL. CLINICAL SIGNIFICANCE: Abutment height is the most powerful predictor variable affecting bone remodelling and MBL. Depending on the dimensions of the peri­implant soft-tissue phenotype, placing the implants subcrestally may also be a viable option to decrease bone remodelling and, consequently, reduce MBL. CLINICAL TRIAL REGISTRATION: identification number: NCT05670340.

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

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.

Rehabilitation Using Implants with Sloped Platform Edge vs. Standard Platform with Guided Bone Regeneration: A Randomized Control Clinical Trial.

The purpose of this study was to evaluate the vertical bone loss after using different techniques: sloped implants or standard implants with guided bone regeneration. Patients with tooth gap and horizontal bone deficiency were randomly allocated to the test group (implants with sloped platform-SLP) and control group (standard design implants with guided bone regeneration-GBR). The primary outcome was bone loss (6 months after finishing the prosthetic treatment). Secondary outcomes included the following: patient-reported outcome measures (PROMs), post-operative edema, keratinized mucosa width, and pink aesthetic score (PES). The average bone loss at 6 months was 0.23 ± 0.15 mm and 1.03 ± 0.37 mm in the SLP and GBR groups, respectively. The SLP group was characterized by lower pain intensity the first 7 days (p < 0.001), lower post-operative edema (p < 0.001), lower consumption of NSAIDs on days 1, 3, 5, and 7 (p = 0.002, <0.001, <0.001, and 0.008), and lower total OHIP-14 (p = 0.047) on day 7. The keratinized mucosa width was 3.7 (3.4-4.0) mm and 2 (1.4-2.0) mm in the SLP and GBR groups, respectively. The preservation of the mesial, distal papillae, and the level of soft tissue correspondence were significantly higher in the SLP group (p = 0.003, 0.038, <0.001). In the SLP group, more natural color and better texture of soft tissues were found (p = 0.048, p = 0.041). The use of implants with a sloped platform resulted in superior outcomes compared to the standard-design implants with GBR.

Emerging Insights into the Endocrine Regulation of Bone Homeostasis by Gut Microbiome.

Gut microbiota plays an important role in the regulation of bone homeostasis and bone health. Recent studies showed that these effects could be mediated through microbial metabolites released by the microbiota like short-chain fatty acids, metabolism of endogenous molecules such as bile acids, or a complex interplay between microbiota, the endocrine system, and the immune system. Importantly, some studies showed a reciprocal relationship between the endocrine system and gut microbiota. For instance, postmenopausal estrogen deficiency could lead to dysbiosis of the gut microbiota, which could in turn affect various immune response and bone remodeling. In addition, evidence showed that shift in the indigenous gut microbiota caused by antibiotics treatment may also impact normal skeletal growth and maturation. In this mini-review, we describe recent findings on the role of microbiome in bone homeostasis, with a particular focus on molecular mechanisms and their interactions with the endocrine and immune system. We will also discuss the recent findings on estrogen deficiency and microbiota dysbiosis, and the clinical implications for the development of new therapeutic strategies for osteoporosis and other bone disorders.

Feasibility and Preliminary Efficacy of α-Calcium Sulfate Hemihydrate in Socket Preservation: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Tooth extraction procedures often lead to bone resorption, which can have adverse effects on the dimensions of the alveolar ridge. Research has shown that socket preservation techniques using bone graft substitutes can effectively minimize early bone loss in such cases. α-calcium sulfate hemihydrate (α-CSH) has garnered significant attention as a potential bone graft material due to its favorable properties, including osteoconductivity, angiogenic potential, and biocompatibility. Considering these facts, we developed a preliminary protocol for applying α-CSH in addressing alveolar bone loss following tooth extraction. OBJECTIVE: This research's general objective is to evaluate the feasibility and initial effectiveness of α-CSH as bone-inducing graft material for socket preservation after tooth extraction. METHODS: This preliminary clinical trial will involve 30 fresh extraction sockets from individuals aged 18-35 years. The participants will be divided into 2 groups: one group will receive α-CSH graft material after tooth extraction for socket preservation, while the other group will not receive any graft material. Throughout the study, the participants will be closely monitored for safety measures, which will include clinical examinations, radiographic imaging, and blood tests. Radiographic imaging will be used extensively to assist the progress of bone formation. RESULTS: The study commenced enrollment in August 2022 and is scheduled to conclude post assessments and analyses by the end of 2023. The results of the study are anticipated to be accessible in late 2024. CONCLUSIONS: This clinical study represents the initial investigation in humans to assess the feasibility and efficacy of α-CSH in alveolar bone regeneration. We hypothesize that the inclusion of α-CSH can greatly expedite the process of bone formation within fresh sockets, resulting in a swift restoration of bone height without the disadvantages associated with harvesting autogenous bone graft. TRIAL REGISTRATION: Indonesia Registry Center INA-D02FAHP; https://tinyurl.com/2jnf6n3s. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49922.

Deciphering the Biological Ageing Impact on Alveolar Bone Loss: Insights from α-Klotho and Renal Function Dynamics.

Alveolar bone loss is generally considered as a chronological age-related disease. As biological ageing process is not absolutely determined by increasing age, whether alveolar bone loss associated with increasing chronological age or biological ageing remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological ageing-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body ageing. 3635 participants from National Health and Nutrition Examination Survey and 71 living kidney transplant recipients from Gene Expression Omnibus Datasets were enrolled. Multivariate regression analysis, smooth curve fittings and generalized additive models were used to explore the association among alveolar bone loss, age, serum α-Klotho level, renal function markers, as well as between preoperative creatinine and renal cortex related α-Klotho gene expression level. Meanwhile, a two-sample Mendelian randomization study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4,376 individuals versus 361,194 individuals). As biological ageing related indicator, α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with down-regulated expression level of α-Klotho in renal cortex and aggravated alveolar bone loss. The MR analysis further identified the negative association between higher genetically predicted α-Klotho concentrations with alveolar bone loss susceptibility using the IVW (OR=0.999, P=0.005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which especially stable in men (the optimal cut-off values were both 62 years old). For male above 62 years old, increasing age converted to protective factor and accompanied by alleviated alveolar bone loss. Alveolar bone loss which directly associated to decreased renal function and α-Klotho level was related to biological ageing rather than chronological age. The renal-alveolar bone axis could provide new sight of clinical therapy in alveolar bone loss.

Custom fabricated three-dimensional printed surgical guide for trephine bur in autogenous bone graft: A technique report.

This technique presents a workflow that designs the custom surgical guide to cover a trephine bur using simple slicer software and three-dimensional (3D) printing to perform the semilunar technique. This method in autogenous bone grafting surgery harvests a thin layer of cortical bone in the donor site with a trephine bur. Its biologically favorable, round shape can be used as a shell to reconstruct the ridge with a 3D contour acceptable for future implant placement. A 78-year-old female patient required vertical and horizontal bone grafting for future implant placement due to the infection caused by the vertically fractured root of a premolar. The patient's cone beam computed tomography (CBCT) file was translated into a standard tessellation language (STL) file, and recipient and donor site models were created. Simulated surgery was done using the software first to detect any possible complications during surgery. The trephine bur planned for use in surgery was measured in necessary dimensions, and the values were added to create a guide for surgery in slicer software. Then, it was 3D-printed with a stereolithography (SLA) printer. After testing the fit of the guide, it was further tested on a fused filament fabrication (FFF) printed donor site model to check if the desired shape and size of the plate were acquired after harvest. Then, the plates were used for model surgery on the recipient site model. After no issues from the previous steps, the final patient surgery was approved and completed with success. This technique utilizes the SLA printing method to create the custom surgical guide for a trephine bur without using commercially available products. Moreover, it could be tested on FFF 3D-printed anatomical models to ensure its validity. With this innovative technique, clinicians can efficiently perform a semilunar technique, facilitating the surgery and improving patient care.

Neuroprotective macromolecular methylprednisolone prodrug nanomedicine prevents glucocorticoid-induced muscle atrophy and osteoporosis in a rat model of spinal cord injury.

To address the adverse side effects associated with systemic high-dose methylprednisolone (MP) therapy for acute spinal cord injury (SCI), we have developed a N-2-hydroxypropyl methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP). Intravenous Nano-MP selectively targeted to the inflamed SCI lesion and significantly improved neuroprotection and functional recovery after acute SCI. In the present study, we comprehensively assessed the potential adverse side effects associated with the treatment in the SCI rat models, including reduced body weight and food intake, impaired glucose metabolism, and reduced musculoskeletal mass and integrity. In contrast to free MP treatment, intravenous Nano-MP after acute SCI not only offered superior neuroprotection and functional recovery but also significantly mitigated or even eliminated the aforementioned adverse side effects. The superior safety features of Nano-MP observed in this study further confirmed the clinical translational potential of Nano-MP as a highly promising drug candidate for better clinical management of patients with acute SCI.

TRIM16 mitigates impaired osteogenic differentiation and antioxidant response in D-galactose-induced senescent osteoblasts.

Senile osteoporosis (SOP), characterized by significant bone loss, poses a substantial threat to elderly skeletal health, with oxidative stress playing a crucial role in its pathogenesis. Although Tripartite Motif 16 (TRIM16) has been identified as a promoter of antioxidant response and osteogenic differentiation, its regulatory role in SOP remains incompletely understood. This study aims to elucidate the underlying mechanism of TRIM16 in mitigating D-galactose (D-gal)-induced senescent osteoblasts. Initially, we observed diminished bone mineral density (BMD) and impaired bone microstructure in naturally aging (24 months) and D-gal-induced (18 months) aged mice through Dual-energy X-ray absorptiometry (DEXA), micro-CT, hematoxylin and eosin staining, and Masson staining. Immunohistochemistry analysis revealed downregulation of TRIM16 and osteogenic differentiation markers (Collagen-1, Runx-2, osteopontin) in femur samples of aged mice. Furthermore, in D-gal-induced senescent MC3T3-E1 osteoblasts, we observed the suppression of osteogenic differentiation and maturity, along with cytoskeleton impairment via Alkaline phosphatase (ALP), Alizarin Red S, and Rhodamine-phalloidin staining. The protein expression of TRIM16, osteogenic differentiation markers, and antioxidant indicators (Nrf-2, HO-1, SOD1) decreased, while the production of reactive oxygen species (ROS) significantly increased. Knockdown and overexpression of TRIM16 using lentivirus in osteoblasts revealed that the downregulation of TRIM16 inhibited osteogenic differentiation and induced oxidative stress. Notably, TRIM16 overexpression partially attenuated D-gal-induced inhibition of osteogenic differentiation and increased oxidative stress. These findings suggest TRIM16 may mitigate impaired osteogenic differentiation and antioxidant response in D-gal-induced senescent osteoblasts, suggesting its potential as a therapeutic target for SOP.