Probiotics: a promising intervention for osteoporosis prevention and management.

Osteoporosis (OP) is a systemic skeletal disease that is characterized by low bone mass and increased fracture risk. This article explores the potential of probiotics as an adjunctive approach for the prevention and management of OP. It has been well established that the gut microbiota (GM), a complex community of microbes, plays an important role in bone health. The gut dysbiosis is linked with a higher risk of OP. However, the consumption of probiotics in adequate amounts restores gut health thus improving bone health. Probiotics may influence bone metabolism through enhanced calcium absorption, reduced inflammation, and increased bone formation. The animal and human studies demonstrate the positive effects of probiotics on bone health parameters like reduced osteoclastogenesis, bone resorption markers, osteoblast, osteocyte apoptosis, and increased bone mineral density and expression of osteoprotegerin. The current evidence suggests that probiotics can be used as an adjunctive approach along with the existing therapies for the prevention and management of OP.

Exogenous iron caused osteocyte apoptosis, increased RANKL production, and stimulated bone resorption through oxidative stress in a murine model.

Iron overload is a risk factor for osteoporosis due to its oxidative toxicity. Previous studies have demonstrated that an excessive amount of iron increases osteocyte apoptosis and receptor activator of nuclear factor κ-B ligand (RANKL) production, which stimulates osteoclast differentiation in vitro. However, the effects of exogenous iron supplementation-induced iron overload on osteocytes in vivo and its role in iron overload-induced bone loss are unknown. This work aimed to develop an iron overloaded murine model of C57BL/6 mice by intraperitoneal administration of iron dextran for two months. The iron levels in various organs, bone, and serum, as well as the microstructure and strength of bone, apoptosis of osteocytes, oxidative stress in bone tissue, and bone formation and resorption, were assessed. The results showed that 2 months of exogenous iron supplementation significantly increased iron levels in the liver, spleen, kidney, bone tissue, and serum. Iron overload negatively affected bone microstructure and strength. Osteocyte apoptosis and empty lacunae rate were elevated by exogenous iron. Iron overload upregulated RANKL expression but had no significant impact on osteoprotegerin (OPG) and sclerostin levels. Static and dynamic histologic analyses and serum biochemical assay showed that iron overload increased bone resorption without significantly affecting bone formation. Exogenous iron promoted oxidative stress in osteocytes in vivo and in vitro. Additional supplementation of iron chelator (deferoxamine) or N-acetyl-L-cysteine (NAC) partially alleviated bone loss, osteocyte apoptosis, osteoclast formation, and oxidative stress due to iron overload. These findings, in line with prior in vitro studies, suggest that exogenous iron supplementation induces osteoclastogenesis and osteoporosis by promoting osteocyte apoptosis and RANKL production via oxidative stress.

Influence of mucosal tissue height on implant crestal bone: A 10-year follow-up of a controlled clinical trial.

OBJECTIVE: To evaluate the 10-year influence of soft tissue height (STH) on crestal bone level changes (CBC) in bone-level implants with non-matching internal conical connections. MATERIAL & METHODS: From the initial 97 patients, 59 (19 men, 40 women, age 55.86 ± 9.5 years) returned for the recall visit. Based on baseline STH, they were categorized into T1 (thin STH ≤2 mm, n = 33), T2 (thin STH augmented with allogenic tissue matrix (ATM), n = 32), and C (thick STH >2 mm, n = 32). Implants were placed in the posterior mandible using a one-stage approach and received single screw-retained restorations. Clinical (PPD, BOP, PI) and radiographic examinations were conducted after 10 years, with CBC calculated mesial and distal to each implant. RESULTS: After 10 years, implants in surgically thickened (T2) or naturally thick STH (C) showed bone gains of 0.57 ± 0.55 mm and 0.56 ± 0.40 mm, respectively (p < 0.0001) shifting from an initial CBC of -0.21 ± 0.33 mm to 0.36 ± 0.29 mm in the thick STH group and -0.2 ± 0.35 mm to 0.37 ± 0.29 mm in the surgically thickened STH group. Implants in naturally thin STH yielded a non-significant trend of bone loss (-0.12 ± 0.41 mm; p > 0.05). CONCLUSIONS: Implants in thin STH (≤2 mm) exhibited greater CBC over the study period. Significant bone gains were observed in thick STH cases, indicating that naturally thick STH or STH augmentation with ATM may contribute to maintain CBC in long-term around implants. CLINICAL SIGNIFICANCE: This is the first long-term follow-up study suggesting that adequate soft tissue height around implants helps maintain stable peri­implant bone levels. While tissue thickness plays a key role, other factors also interact with peri­implant tissue height to sustain crestal bone stability over time.

The G9a histone methyltransferase represses osteoclastogenesis and bone resorption by regulating NFATc1 function.

Epigenetic modifications affect cell differentiation via transcriptional regulation. G9a/EHMT2 is an important epigenetic modifier that catalyzes the methylation of histone 3 lysine 9 (H3K9) and interacts with various nuclear proteins. In this study, we investigated the role of G9a in osteoclast differentiation. When we deleted G9a by infection of Cre-expressing adenovirus into bone marrow macrophages (BMMs) from G9afl/fl (Ehmt2fl/fl) and induced osteoclastic differentiation by the addition of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL), the number of TRAP-positive multinucleated osteoclasts significantly increased compared with control. Furthermore, the mRNA expression of osteoclast markers, TRAP, and cathepsin K, and to a lesser extent, NFATc1, a critical transcription factor, increased in G9a KO cells. Infection of wild-type (WT) G9a-expressing adenovirus in G9a KO cells restored the number of TRAP-positive multinucleated cells. In G9a KO cells, increased nuclear accumulation of NFATc1 protein and decreased H3K9me2 accumulation were observed. Furthermore, ChIP experiments revealed that NFATc1 binding to its target, Ctsk promoter, was enhanced by G9a deletion. For in vivo experiments, we created G9a conditional knock-out (cKO) mice by crossing G9afl/fl mice with Rank Cre/+ (Tnfrsf11aCre/+) mice, in which G9a is deleted in osteoclast lineage cells. The trabecular bone volume was significantly reduced in female G9a cKO mice. The serum concentration of the C-terminal telopeptide of type I collagen (CTX), a bone-resorbing indicator, was higher in G9a cKO mice. In addition, osteoclasts differentiated from G9a cKO BMMs exhibited greater bone-resorbing activity. Our findings suggest that G9a plays a repressive role in osteoclastogenesis by modulating NFATc1 function.

Biological alterations associated with the orthodontic treatment with conventional appliances and aligners: A systematic review of clinical and preclinical evidence.

Background&objectives: Mechanical forces applied during an orthodontic tooth movement (OTM) propel several biochemical and molecular responses in the periodontal ligament and alveolar bone. Here, we compile the existing clinical and preclinical evidence on these biological changes, aiming to provide a comprehensive discussion on the influence of the mechanical parameters of the OTM in the biological profile of the periodontium. Material and methods: This systematic integrative review was conducted according to PICOS strategy and PRISMA guidelines. A bibliographic search was performed in three electronic databases (PubMed, Scopus, and Web of Science) to find research articles published until 2023 and written in English. This search resulted in a total of 2279 publications, which were independently assessed by two evaluators using appropriate tools. Results: Forty-six studies were selected for this review. These revealed that compression, and stretching of the periodontal ligament fibers and cells are observed in the initial phase of the OTM. Specifically, on the tension side, high levels of IL-1ß, OPG, and TIMPs are identified. On the compression side, an increase of RANKL, RANK, and MMPs levels predominate. Conclusion: This paper describes the release profile of common biomarkers according to the orthodontic protocol, suggesting the most appropriate parameters to keep the teeth and their supporting structures healthy. Overall, this manuscript provides a better understanding of the OTM-associated biological phenomena, also highlighting the importance of early evaluation of oral health, and thus it contributes as a fundamental basis for the development of more effective and safe orthodontic treatments with conventional appliances and aligners.

A finite element study on the risk of bone loss around posterior short implants in an atrophic mandible.

PURPOSE: This study aimed to evaluate the risk of bone loss around single short molar crown-supporting implants in an atrophic mandible. METHODS: Implants of different lengths (L = 4 or 6 mm) and diameters (Ø = 4.1 or 4.8 mm) were placed in the molar area of an atrophic mandible. Additional control mandible models were simulated for 4.1 mm diameter implants (L = 4, 6, 8, and 10 mm). A vertical masticatory load of 200 N was applied to three or six occlusal contact areas (3ca or 6ca) of the prosthetic crown. The bone strain energy density (SED) of 109.6 µJ/mm3 was assumed to be the pathological threshold for cortical bone. The peri-implant bone resorption risk index (PIBRri) was calculated by dividing the maximum SED of the crestal cortical bone by the SED pathological threshold. RESULTS: Increasing the implant length from 4 to 6 mm, implant diameter from 4.1 to 4.8 mm, and number of contact areas from 3 to 6 reduced the SED and PIBRri values by approximately 20%, 35%, and 40%, respectively, when comparing pairs of models that isolated a specific variable. All models with 6ca had a low bone resorption risk (PIBRri<0.8), while the Ø4.1 short implant with 3ca had a medium (0.8≤PIBRri≤1.0) or high (PIBRri>1.0) resorption risk. CONCLUSIONS: Increasing the diameter or occlusal contact area of a 4 mm short implant in an atrophic mandible resulted in reduced bone resorption risks, similar to or lower than those observed in a regular mandible with standard-length implants.

Flavonoid gossypetin protects alveolar bone and limits inflammation in ligature-induced periodontitis in mice.

BACKGROUND: Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders. METHODS: In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice. RESULTS: Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca2+ oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6. CONCLUSION: Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.

Circadian clock disruption stimulates bone loss via regulatory T cell-Mediated regulation of IL-10 expression.

Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body's ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.

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.

Impdh2 deficiency suppresses osteoclastogenesis through mitochondrial oxidative phosphorylation and alleviates ovariectomy-induced osteoporosis.

Abnormalities in osteoclastic generation or activity disrupt bone homeostasis and are highly involved in many pathologic bone-related diseases, including rheumatoid arthritis, osteopetrosis, and osteoporosis. Control of osteoclast-mediated bone resorption is crucial for treating these bone diseases. However, the mechanisms of control of osteoclastogenesis are incompletely understood. In this study, we identified that inosine 5'-monophosphate dehydrogenase type II (Impdh2) positively regulates bone resorption. By histomorphometric analysis, Impdh2 deletion in mouse myeloid lineage cells (Impdh2LysM-/- mice) showed a high bone mass due to the reduced osteoclast number. qPCR and western blotting results demonstrated that the expression of osteoclast marker genes, including Nfatc1, Ctsk, Calcr, Acp5, Dcstamp, and Atp6v0d2, was significantly decreased in the Impdh2LysM-/- mice. Furthermore, the Impdh inhibitor MPA treatment inhibited osteoclast differentiation and induced Impdh2-cytoophidia formation. The ability of osteoclast differentiation was recovered after MPA deprivation. Interestingly, genome-wide analysis revealed that the osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation, were impaired in the Impdh2LysM-/- mice. Moreover, the deletion of Impdh2 alleviated ovariectomy-induced bone loss. In conclusion, our findings revealed a previously unrecognized function of Impdh2, suggesting that Impdh2-mediated mechanisms represent therapeutic targets for osteolytic diseases.

Evaluation of Different Subperiosteal Implant Thicknesses on Mechanical Strength and Stress on Bone by Finite Element Analysis.

Implants have always been within the interest of both clinicians and material scientists due to their places in reconstructive and prosthetics surgery. Excessive bone loss or resorption in some patients makes it difficult to design and manufacture the implants that bear the necessary loads to carry the final prosthetics. With this study; we tried to determine the minimum material thickness of the subperiosteal implants that can withstand the physiological forces. We have created a digital average bone structure based on actual patient data and designed different subperiosteal implants with 1, 1.5, and 2mm material thicknesses (M1, M2, M3) for this digital model. The designed implant models are subjected to 250 Newtons (N) of force, and the implant and bone are tested for the stress they are exposed to, the pressure they transmit to, and their mechanical strength with Finite Element Analysis with the physical parameters boot for the implant material and human bone. Results show us that under specific design parameters and thicknesses, the 1mm thickness design failed due to exceeding the yield stress limit of 415MPa with a 495,44MPa value. The thinnest implant showed plastic deformation and transmitted excessive forces, which may cause bone resorption due to residual stress. We determined that thinner subperiosteal implants down to 1.5mm that have the necessary material parameters for function and tissue support can be designed and manufactured with current technologies.

Prevalence and Risk Factors of Bone and Dental Lesions in Neotropical Deer.

Bone and dental lesions have been documented in various deer species globally, affecting the efficiency of ingestion and digestion, consequently influencing their general health and leading to a decline in survival and reproductive performance. The present study aimed to characterize bone and dental lesions in the dry skulls of individual deer, estimate the prevalence of these lesions, and assess potential risk factors associated with the development of bone and dental alterations. This study assessed bone and dental lesions in 180 dry skulls of eleven neotropical deer species, originating from both captivity and wildlife conditions, through direct visual inspection. A high prevalence of bone and dental lesions was observed in all analyzed species. Dental calculus was the most common alteration (96.7%), followed by dental wear (71.1%). Animal age positively correlated with most bone and dental alterations, indicating that older animals showed more lesions. Additionally, the prevalence of these alterations was similar between sexes. Moreover, all lesions were more common in captive-bred animals, likely attributed to their older age and a less diverse diet. Blastocerus dichotomus and Mazama americana were most affected by bone resorption and dental trauma and had the highest dental calculus prevalence, along with Subulo gouazoubira and Passalites nemorivagus. All eleven species evaluated in the present study were susceptible to the occurrence of bone and dental lesions. Therefore, monitoring oral health and diet in captivity are fundamental practices for the conservation of these species.

Association between dietary insulin index and postmenopausal osteoporosis in Iranian women: a case-control study.

BACKGROUND: The relationship between the dietary insulin index (DII) and the disease's risk is unknown, despite the fact that hyperinsulinemia is presumed to contribute to osteoporosis. The insulin response of various diets determines the DII. This study aimed to investigate the connection between postmenopausal Iranian women's adherence to a diet with a higher insulinemic potential and osteoporosis. METHODS: A total of 380 postmenopausal women were included in the current case-control study. A 168-item food frequency questionnaire (FFQ) with established validity and reliability was used to evaluate individuals' daily calorie intake. The standard formula was employed to determine the dietary insulin load of each product. Subsequently, the calculation of DII was performed by dividing the dietary insulin load by the total energy consumed for each individual. In order to investigate the relationship between osteoporosis and DII, logistic regression was implemented. RESULTS: The results of the current study demonstrated a substantial inverse relationship between osteoporosis and the DII, even after accounting for confounding variables (OR = 0.927; 95% CI = 0.888-0.967). The mean scores of DII (P < 0.001) was significantly higher in control group (36.82 ± 8.98) compared to the case group (33.53 ± 6.28). CONCLUSIONS: Our findings suggest that keeping a diet high in insulin index and low in foods that are insulinogenic may improve bone mass density. Consequently, it may be essential for postmenopausal women to consume nutrients that stimulate insulin production in order to prevent osteoporosis.

Evaluation of peri-implant bone defects on cone-beam computed tomography and the diagnostic accuracy of detecting these defects on panoramic images.

Purpose: This study was conducted to identify the typical sites and patterns of peri-implant bone defects on cone-beam computed tomography (CBCT) images, as well as to evaluate the detectability of the identified bone defects on panoramic images. Materials and Methods: The study population included 114 patients with a total of 367 implant fixtures. CBCT images were used to assess the presence or absence of bone defects around each implant fixture at the mesial, distal, buccal, and lingual sites. Based on the number of defect sites, the presentations of the peri-implant bone defects were categorized into 3 patterns: 1 site, 2 or 3 sites, and circumferential bone defects. Two observers independently evaluated the presence or absence of bone defects on panoramic images. The bone defect detection rate on these images was evaluated using receiver operating characteristic analysis. Results: Of the 367 implants studied, 167 (45.5%) had at least 1 site with a confirmed bone defect. The most common type of defect was circumferential, affecting 107 of the 167 implants (64.1%). Implants were most frequently placed in the mandibular molar region. The prevalence of bone defects was greatest in the maxillary premolar and mandibular molar regions. The highest kappa value was associated with the mandibular premolar region. Conclusion: The typical bone defect pattern observed was a circumferential defect surrounding the implant. The detection rate was generally higher in the molar region than in the anterior region. However, the capacity to detect partial bone defects using panoramic imaging was determined to be poor.

Lead Acetate-Injected Mice is an Animal Model for Extrapolation of Calcifying Response to Humans Due to Low Involvement of Bone Resorption.

Vascular calcification affects the prognosis of patients with renal failure. Bisphosphonates are regarded as candidate anti-calcifying drugs because of their inhibitory effects on both calcium-phosphate aggregation and bone resorption. However, calcification in well-known rodent models is dependent upon bone resorption accompanied by excessive bone turnover, making it difficult to estimate accurately the anti-calcifying potential of drugs. Therefore, models with low bone resorption are required to extrapolate anti-calcifying effects to humans. Three bisphosphonates (etidronate, alendronate, and FYB-931) were characterised for their inhibitory effects on bone resorption in vivo and calcium-phosphate aggregation estimated by calciprotein particle formation in vitro. Then, their effects were examined using two models inducing ectopic calcification: the site where lead acetate was subcutaneously injected into mice and the transplanted, aorta obtained from a donor rat. The inhibitory effects of bisphosphonates on bone resorption and calcium-phosphate aggregation were alendronate > FYB-931 > etidronate and FYB-931 > alendronate = etidronate, respectively. In the lead acetate-induced model, calcification was most potently suppressed by FYB-931, followed by alendronate and etidronate. In the aorta-transplanted model, only FYB-931 suppressed calcification at a high dose. In both the models, no correlation was observed between calcification and bone resorption marker, tartrate-resistant acid phosphatase (TRACP). Results from the lead acetate-induced model showed that inhibitory potency against calcium-phosphate aggregation contributed to calcification inhibition. The two calcification models, especially the lead acetate-induced model, may be ideal for the extrapolation of calcifying response to humans because of calcium-phosphate aggregation rather than bone resorption as its mechanism.

Factors affecting radiographic marginal bone resorption at dental implants in function for at least 5 years: A multicenter retrospective study.

OBJECTIVE: To evaluate the influence of patient and implant-related factors on the changes of marginal bone levels (MBL) at implants with a follow-up ≥5 years. MATERIALS AND METHODS: At baseline (within 6 months from prosthetic insertion) and long-term (≥5 years after implant placement) visits, interproximal (mesial and distal) MBL were radiographically evaluated. To analyze factors predicting MBL change, the site (either mesial or distal) showing the highest MBL change (hChMBL site) was identified for each implant. Multilevel regression models were built to explain MBL change as well as the probability for a bone loss ≥2 mm at long-term. RESULTS: 942 implants in 312 patients with a mean follow-up of 8.02 ± 2.5 years were analyzed. MBL change was significantly predicted by baseline MBL, oral bisphosphonate (BP) intake, history of periodontitis, diabetes, and super-hydrophilic implant surface. Higher risk for a bone loss ≥2 mm was observed in patients with history of periodontitis (OR = 9.52, 95% CI 0.72-3.79) and taking BP (OR = 6.84, 95% CI 0.21-3.63). Mandibular implants had higher odds for bone loss ≥2 mm compared to maxillary implants (OR = 3, 95% CI 0.39-1.87). CONCLUSIONS: The findings of the present study contribute to the identification of specific clinical scenarios at higher risk for implant-supporting bone loss that need to be strictly monitored during maintenance.

Maxillary and mandibular overdentures retained by two unsplinted narrow-diameter titanium-zirconium implants - A clinical pilot study.

OBJECTIVES: To evaluate the survival rates and marginal bone loss of narrow-diameter titanium-zirconium implants supporting complete maxillary and mandibular overdentures up to 3 years after loading. MATERIALS AND METHODS: Ten completely edentulous patients who were dissatisfied with their complete dentures were enrolled. Two narrow-diameter implants were placed in the canine region of the maxilla and mandible. After second-stage surgery, implant-supported overdentures (palatal-free) attached by parallel alignable stud-attachments were placed. Patients were followed periodically for up to 36 months. Standardized radiographs were taken at baseline, 12 and 36 months to analyze mean marginal bone level changes around the implants. RESULTS: The Kaplan-Meier survival rates were 100% for mandibular and 68.0% (SE ± 10.9%) for maxillary implants at 36 months (p = .008). Six maxillary implants failed after loading; no mandibular implants were lost. Five implants failed due to loss of osseointegration. One implant fractured. The mean marginal bone level changes around the analyzed implants (n = 28, 9 patients) were -0.71 ± 0.82 mm in the mandible and -2.08 ± 1.52 mm in the maxilla at the 36-month follow-up. The difference in marginal bone level changes between the maxilla and mandible was significant (p = .019) at the 12- and 36-month follow-ups. CONCLUSION: Two narrow-diameter titanium-zirconium implants with stud-attachments showed a highly satisfactory outcome in the mandible. The maxillary implants showed a high failure rate and significantly more bone loss over time than the mandibular implants. The minimal concept of two implants and an overdenture should be limited to the edentulous mandible.

A p38 MAP kinase inhibitor suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss through the inhibition of bone turnover.

Inhibition of excessive osteoclastic activity is an efficient therapeutic strategy for many bone diseases induced by increased bone resorption, such as osteoporosis. BMS-582949, a clinical p38α inhibitor, is a promising drug in Phase II studies for treating rheumatoid arthritis. However, its function on bone resorption is largely unknown. In this study, we find that BMS-582949 represses RANKL-induced osteoclast differentiation in a dose-dependent manner. Moreover, BMS-582949 inhibits osteoclastic F-actin ring formation and osteoclast-specific gene expression. Mechanically, BMS-582949 treatment attenuates RANKL-mediated osteoclastogenesis through mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) signaling pathways without disturbing nuclear factor-κB (NF-κB) signaling. Interestingly, BMS-582949 impairs osteoclastic mitochondrial biogenesis and functions, such as oxidative phosphorylation (OXPHOS). Furthermore, BMS-582949 administration prevents bone loss in ovariectomized mouse mode by inhibiting both bone resorption and bone formation in vivo. Taken together, these findings indicate that BMS-582949 may be a potential and effective drug for the therapy of osteolytic diseases.

TGF-ß Signaling in Cranial Neural Crest Affects Late-Stage Mandibular Bone Resorption and Length.

Malocclusions are common craniofacial malformations which cause quality of life and health problems if left untreated. Unfortunately, the current treatment for severe skeletal malocclusion is invasive surgery. Developing improved therapeutic options requires a deeper understanding of the cellular mechanisms responsible for determining jaw bone length. We have recently shown that neural crest mesenchyme (NCM) can alter jaw length by controlling recruitment and function of mesoderm-derived osteoclasts. Transforming growth factor beta (TGF-ß) signaling is critical to craniofacial development by directing bone resorption and formation, and heterozygous mutations in TGF-ß type I receptor (TGFBR1) are associated with micrognathia in humans. To identify what role TGF-ß signaling in NCM plays in controlling osteoclasts during mandibular development, mandibles of mouse embryos deficient in the gene encoding Tgfbr1 specifically in NCM were analyzed. Our lab and others have demonstrated that Tgfbr1fl/fl;Wnt1-Cre mice display significantly shorter mandibles with no condylar, coronoid, or angular processes. We hypothesize that TGF-ß signaling in NCM can also direct later bone remodeling and further regulate late embryonic jaw bone length. Interestingly, analysis of mandibular bone through micro-computed tomography and Masson's trichrome revealed no significant difference in bone quality between the Tgfbr1fl/fl;Wnt1-Cre mice and controls, as measured by bone perimeter/bone area, trabecular rod-like diameter, number and separation, and gene expression of Collagen type 1 alpha 1 (Col1α1) and Matrix metalloproteinase 13 (Mmp13). Though there was not a difference in localization of bone resorption within the mandible indicated by TRAP staining, Tgfbr1fl/fl;Wnt1-Cre mice had approximately three-fold less osteoclast number and perimeter than controls. Gene expression of receptor activator of nuclear factor kappa-ß (Rank) and Mmp9, markers of osteoclasts and their activity, also showed a three-fold decrease in Tgfbr1fl/fl;Wnt1-Cre mandibles. Evaluation of osteoblast-to-osteoclast signaling revealed no significant difference between Tgfbr1fl/fl;Wnt1-Cre mandibles and controls, leaving the specific mechanism unresolved. Finally, pharmacological inhibition of Tgfbr1 signaling during the initiation of bone mineralization and resorption significantly shortened jaw length in embryos. We conclude that TGF-ß signaling in NCM decreases mesoderm-derived osteoclast number, that TGF-ß signaling in NCM impacts jaw length late in development, and that this osteoblast-to-osteoclast communication may be occurring through an undescribed mechanism.

Standard Versus Step Burs for Implant Site Preparation: A Randomized Controlled Clinical Trial.

PURPOSE: There are several factors that may influence implant site preparation with implant design being a paramount factor; however, few studies investigate its impact. The purpose of the study was to explore the comparative efficacy of using two different drilling protocols using burs with different design for preparing implant sites, by evaluating radiographic and clinical outcomes. MATERIALS AND METHODS: The present randomized controlled clinical trial with an allocation ratio of 1:1 was carried on in two private practice offices by two experienced surgeons and researchers. In the control group the surgeons followed the protocol with standard straight burs while in the test group they used step burs. In both groups the patients received the same type of implants and prosthesis. The primary outcome was the marginal bone resorption one year after the prosthetic placement. RESULTS: In the study were included and treated a total of 60 subjects (86 implants). At the one-year follow-up were screened 54 subjects (74 implants), and 50 at the 2-year follow-up (69 implants). This study showed no evidence of a difference in bone resorption, which increased significantly over time, between the two groups. CONCLUSIONS: Both clinical parameters and patientcentered outcomes revealed no difference between the two protocols of implant site preparation with two different drill shape.