MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.

PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle. RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3ß activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.

Bone Remodeling and Bone Structural Genes in Legg-Calvé-Perthes Disease: The OPG rs2073618 and IL-6 rs1800795 Are Associated with High Risk in Mexican Patients.

Legg-Calve-Perthes disease (LCPD) is an idiopathic avascular necrosis of the pediatric femoral head. Bone remodeling and bone structural genes have the potential to contribute to the progression of LCPD when there is disequilibrium between bone resorption and bone formation. A case-control study was performed to search for associations of several common polymorphisms in the genes Receptor Activator for Nuclear Factor κappa B (RANK), Receptor Activator for Nuclear Factor κappa B Ligand (RANKL), osteoprotegerin (OPG), interleukin (IL)-6, and type 1 collagen (COL1A1) with LCPD susceptibility in Mexican children. A total of 23 children with LCPD and 46 healthy controls were genotyped for seven polymorphisms (rs3018362, rs12585014, rs2073618, rs1800795, rs1800796, rs1800012, and rs2586498) in the RANK, RANKL, OPG, IL-6, and COL1A1 genes by real-time polymerase chain reaction with TaqMan probes. The variant allele (C) of IL-6 rs1800795 was associated with increased risk of LCPD (odds ratio [OR]: 3.8, 95% confidence interval [CI]: [1.08-13.54], p = 0.033), adjusting data by body mass index (BMI) and coagulation factor V (FV), the association with increased risk remained (OR: 4.9, 95% CI: [1.14-21.04], p = 0.025). The OPG polymorphism rs2073618, specifically GC-GG carriers, was associated with a more than fourfold increased risk of developing LCPD (OR: 4.34, 95% CI: [1.04-18.12], p = 0.033) when data were adjusted by BMI-FV. There was no significant association between RANK rs3018362, RANKL rs12585014, IL-6 rs1800796, COL1A1 rs1800012, and rs2586498 polymorphisms and LCPD in a sample of Mexican children. The rs1800975 and rs2037618 polymorphisms in the IL-6 and OPG genes, respectively, are informative markers of increased risk of LCPD in Mexican children.

Analysis of inflammation and bone remodeling of atmospheric plasma therapy in experimental periodontitis.

BACKGROUND AND OBJECTIVE: The biological effects of atmospheric plasma (cold plasma) show its applicability for controlling the etiological factors that involve tissue repair. Thus, the study evaluated the effect of atmospheric plasma therapy in the control of tissue inflammation and bone remodeling in experimental periodontitis. METHODS: Fifty-six rats were subjected to ligation in the cervical region of the first maxillary molars (8 weeks). The animals were divided into two groups (n = 28): periodontitis without treatment group (P group), and periodontitis with atmospheric plasma treatment group (P + AP group). Tissue samples were collected at 2 and 4 weeks after treatment to analyze the inflammation and bone remodeling by biochemical, histomorphometric, and immunohistochemical analyses. RESULTS: Inflammatory infiltration in the gingival and periodontal ligament was lower in the P + AP group than in the P group (p < .05). The MPO and NAG levels were higher in the P + AP group compared to P group (p < .05). At 4 weeks, the TNF-α level was lower and the IL-10 level was higher in the P + AP group compared to P group (p < .05). In the P + AP group, the IL-1ß level increased in the second week and decreased in the fourth week (p < .05), the number of blood vessels was high in the gingival and periodontal ligament in the second and fourth week (p < .05); and the number of fibroblasts in the gingival tissue was low in the fourth week, and higher in the periodontal tissue in both period (p < .05). Regarding bone remodeling, the RANK and RANKL levels decreased in the P + AP group (p < .05). The OPG level did not differ between the P and P + AP groups (p > .05), but decreased from the second to the fourth experimental week in P + AP group (p < .05). CONCLUSIONS: The treatment of experimental periodontitis with atmospheric plasma for 4 weeks modulated the inflammatory response to favor the repair process and decreased the bone resorption biomarkers, indicating a better control of bone remodeling in periodontal disease.

Aumento de coroa clínica: reparação do desequilíbrio dentogengival com finalidade estética / Clinical crow augmentum: repair of the dentogengival imbalance with aesthetic purpose

O anseio por um sorriso harmônico tem se tornado cada vez maior, uma vez que muitos pacientes relatam desconforto ao sorrir, pois correlacionam a estética do sorriso a problemas de baixa autoestima e em alguns casos suscetibilidade a alterações psicossociais decorrente aos padrões estéticos impostos pela sociedade. O sorriso gengival é uma das grandes queixas relatadas por pacientes. A exposição excessiva de gengiva maxilar pode ser decorrente a fatores gengivais, ósseos, dentários e musculares. Dentre os tratamentos disponíveis para diminuir essa exposição, contamos com cirurgias periodontais, aplicação de toxina botulínica, tratamentos ortodônticos, cirurgia ortognática e reposicionamento labial. O tratamento adequado será definido de acordo com o fator etiológico de cada caso. Diante disso o objetivo do trabalho é realizar um relato de caso sobre aumento de coroa clínica estética. A paciente estava descontente com a exibição de uma grande quantidade gengival ao sorrir. Após estudos clínicos e de imagem o diagnóstico foi de erupção passiva alterada, tipo IB. O tratamento de escolha foi a gengivoplastia associada a remodelação óssea osteotomia e osteoplastia. O tratamento estético vai além de uma boa aparência, através deste trabalho, foi possível evidenciar impactos benéficos que o sorriso harmônico pode acarretar na vida do indivíduo, atendendo suas expectativas e a do cirurgião-dentista(AU)

The desire for a harmonic smile has become increasing, since many patients report discomfort when smiling, as they correlate smile aesthetics to problems of low self-esteem and in some cases susceptibility to psychosocial changes due to aesthetic standards imposed by society. Gummy smile is one of the major complaints reported by patients. Excessive exposure of the maxillary gingiva may be due to gingival, bone, dental and muscular factors. Among the treatments available to reduce this exposure, we have periodontal surgeries, botulinum toxin application, orthodontic treatments, orthognathic surgery and lip repositioning. The appropriate treatment will be defined according to the etiological factor of each case. Therefore, the objective of this work is to carry out a case report on aesthetic clinical crown augmentation. Patient discount with the display of a large amount of gingival when smiling. After clinical and imaging studies, the diagnosis was an altered passive eruption, type IB. The treatment of choice was gingivoplasty associated with bone remodeling, osteotomy and osteoplasty. Final comments and conclusions: The aesthetic treatment goes beyond a good appearance, through this work, it was possible to evidence beneficial impacts that the harmonic smile can have on the individual's life, meeting their expectations and that of the dentist(AU)

Protective Effect of Bovine Milk Extracellular Vesicles on Alveolar Bone Loss.

SCOPE: Bovine milk extracellular vesicles (MEVs) have demonstrated therapeutic potential in regulating bone cell activity. However, the outcome of their use on alveolar bone loss has not yet been demonstrated. METHODS AND RESULTS: This study evaluates the effect of oral administration of MEVs on ovariectomized (OVX) mice. There is a reduced height of the alveolar bone crest in OVX mice by MEVs treatment, but the alveolar bone parameters are not altered. OVX mice are then submitted to a force-induced bone remodeling model by orthodontic tooth movement (OTM). MEVs-treated mice have markedly less bone remodeling movement, unlike the untreated OVX mice. Also, OVX mice treated with MEVs show an increased number of osteoblasts and osteocytes associated with higher sclerostin expression and reduce osteoclasts in the alveolar bone. Although the treatment with MEVs in OVX mice does not show differences in root structure in OTM, few odontoclasts are observed in the dental roots of OVX-treated mice. Compared to untreated mice, maxillary and systemic RANKL/OPG ratios are reduced in OVX mice treated with MEVs. CONCLUSION: Treatment with MEVs results in positive bone cell balance in the alveolar bone and dental roots, indicating its beneficial potential in treating alveolar bone loss in the nutritional context.

Targeting phosphatidylinositol-3-kinase for inhibiting maxillary bone resorption.

Previous studies have suggested a role of phosphatidylinositol-3-kinase gamma (PI3Kγ) in bone remodeling, but the mechanism remains undefined. Here, we explored the contribution of PI3Kγ in the resorption of maxillary bone and dental roots using models of orthodontic tooth movement (OTM), orthodontic-induced inflammatory root resorption, and rapid maxillary expansion (RME). PI3Kγ-deficient mice (PI3Kγ-/- ), mice with loss of PI3Kγ kinase activity (PI3KγKD/KD ) and C57BL/6 mice treated with a PI3Kγ inhibitor (AS605240) and respective controls were used. The maxillary bones of PI3Kγ-/- , PI3KγKD/KD , and C57BL/6 mice treated with AS605240 showed an improvement of bone quality compared to their controls, resulting in reduction of the OTM and RME in all experimental groups. PI3Kγ-/- mice exhibited increased root volume and decreased odontoclasts counts. Consistently, the pharmacological blockade or genetic deletion of PI3K resulted in increased numbers of osteoblasts and reduction in osteoclasts during OTM. There was an augmented expression of Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (Alp), a reduction of interleukin-6 (Il-6), as well as a lack of responsiveness of receptor activator of nuclear factor kappa-Β (Rank) in PI3Kγ-/- and PI3KγKD/KD mice compared to control mice. The maxillary bones of PI3Kγ-/- animals showed reduced p-Akt expression. In vitro, bone marrow cells treated with AS605240 and cells from PI3Kγ-/- mice exhibited significant augment of osteoblast mineralization and less osteoclast differentiation. The PI3Kγ/Akt axis is pivotal for bone remodeling by providing negative and positive signals for the differentiation of osteoclasts and osteoblasts, respectively.

Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials.

Menopause and vitamin D deficiency increase bone reabsorption and bone fracture risk in women in postmenopause, and vitamin D supplementation may improve bone health and decrease bone fracture risk. This study aims to discuss the effect of vitamin D supplementation, isolated or calcium-associated, on remodeling and fracture risk bone in women in postmenopause without osteoporosis. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO database registration: CRD42022359796). A search was conducted in four databases and gray literature using MeSH and similar terms related to supplements, vitamin D, calcium, remodeling, and fracture bone, without the restriction of language and year of publication. A total of 3460 studies were identified, and nine were selected. Vitamin D supplementation increased 25-hydroxyvitamin D levels ≥10 ng/mL and decreased parathyroid hormone secretion dependent on baseline levels. The doses of 400 IU of vitamin D improved the percentage of carboxylated osteocalcin, whereas 800 to 1000 IU combined with calcium resulted in reduced, improved, or maintained bone mineral density and reduced alkaline phosphatase levels. However, 4000 IU alone or combined with calcium for 6 mo did not improve C-telopeptide and procollagen type 1 peptide levels. Additionally, 15 000 IU/wk increased the cortical area of metacarpal bone, whereas 500 000 IU of vitamin D annually for 5 y did not contribute to reducing the fracture risk and falls. Only one study found a reduction in fracture risk (dose of 800 IU of vitamin D plus 1200 mg of calcium). Thus, the vitamin D supplementation, alone or calcium-associated, improved the status of 25-hydroxyvitamin D and bone remodeling, but it was not possible to assert that it reduced fracture bone risk in postmenopausal women.

Extracellular Vesicles in Bone Remodeling and Osteoporosis.

Osteoporosis is a systemic disorder characterized by bone mass loss, leading to fractures due to weak and brittle bones. The bone tissue deterioration process is related to an impairment of bone remodeling orchestrated mainly by resident bone cells, including osteoblasts, osteoclasts, osteocytes, and their progenitors. Extracellular vesicles (EVs) are nanoparticles emerging as regulatory molecules and potential biomarkers for bone loss. Although the progress in studies relating to EVs and bone loss has increased in the last years, research on bone cells, animal models, and mainly patients is still limited. Here, we aim to review the recent advances in this field, summarizing the effect of EV components such as proteins and miRNAs in regulating bone remodeling and, consequently, osteoporosis progress and treatment. Also, we discuss the potential application of EVs in clinical practice as a biomarker and bone loss therapy, demonstrating that this rising field still needs to be further explored.

O papel da infecção e inflamação na etiopatogênese da osteonecrose dos maxilares induzida por medicamentos / The role of infection and inflammation in the etiopathogenesis of medication-related osteonecrosis of the jaw

Objetivo: O objetivo desta revisão de literatura é evidenciar o papel da infecção e inflamação na etiopatogenia da osteonecrose dos maxilares induzida por medicamentos (MRONJ). Revisão da literatura: A MRONJ é uma condição rara e grave que impacta negativamente a vida dos pacientes afetados. Sua etiopatogenia é multifatorial e ainda não foi totalmente compreendida. Uma das hipóteses propostas para explicá-la sugere que, além da inibição do turnover ósseo pelos medicamentos antirreabsortivos, a infecção associada à exodontia e a inflamação local desempenham papel decisivo no desencadeamento da condição. O entendimento da etiopatogenia da MRONJ permite ao cirurgião-dentista a identificação dos pacientes com risco maior para a doença, assim como o auxilia no monitoramento e escolha do manejo mais adequado. No campo da pesquisa, ele pode aprimorar estudos pré-clínicos e aprofundar a investigação de biomarcadores para diagnóstico precoce de MRONJ. Considerações finais: Conhecer a contribuição da infecção e inflamação na etiopatogênese da MRONJ é fundamental para orientar a pesquisa e a adoção de estratégias preventivas para os pacientes em risco, e de manejo e monitoramento adequado para aqueles já acometidos. (AU)

Aim: The aim of this literature review is to highlight the role of infection and inflammation in the etiopathogenesis of drug-induced osteonecrosis of the jaw (MRONJ). Literature review: MRONJ is a rare and serious condition that negatively impacts the lives of affected patients. Its etiopathogenesis is multifactorial and has not yet been fully understood. One of the hypotheses proposed to explain it suggests that, in addition to the inhibition of bone turnover by antiresorptive drugs, the infection associated with tooth extraction and local inflammation play a decisive role in triggering the condition. Understanding the etiopathogenesis of MRONJ allows the dentist to identify patients at higher risk for the disease, as well as assisting in monitoring and choosing the most appropriate management. In research, it can improve preclinical studies and deepen the investigation of biomarkers for early diagnosis of MRONJ. Conclusion: Knowing the contribution of infection and inflammation in the etiopathogenesis of MRONJ is essential to guide research and the adoption of preventive strategies for patients at risk, and adequate management and monitoring for those already affected.(AU)

Uso de microvibración e inhibidores de la catepsina K en tratamientos de regeneración ósea dental / Use of micro-vibration and cathepsin K inhibitors in dental bone regeneration treatments

Introducción: el hueso está en remodelación constante para mantener la estructura del esqueleto, tener un ciclo de resorción por los osteoclastos y formación de hueso nuevo a cargo de los osteoblastos; el hueso también es susceptible a enfermedades sistémicas, traumas, edad y trastornos genéticos que afectarán el remodelado óseo, produciendo una pérdida masiva de masa ósea regulado por hormonas, citocinas, enzimas, etcétera. El objetivo es realizar una revisión sistemática de artículos que muestren cambio o alteración al utilizar tratamientos con microvibraciones y farmacológicos sobre la catepsina K en el hueso alveolar. Material y métodos: para realizar una comparación entre la efectividad del tratamiento a base de microvibraciones y con inhibidores de la catepsina K, se realizó una revisión sistemática en nueve bases de datos (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO y Springer Link). La población de estudio fueron ratas y ratones. Resultados: en este estudio se incluyeron 20 artículos cuya investigación se realizó en estudios clínicos. En los resultados podemos observar cómo todos los tratamientos de alguna forma mejoran el proceso de remodelado óseo. Es difícil comparar cuál de los tratamientos dentro de cada grupo es mejor que otro, debido a que los resultados expresados son cualitativos. Conclusión: acorde a los resultados expresados se opta por realizar un tratamiento con microvibraciones debido a que el uso de inhibidores de la catepsina K aún no se encuentra completamente desarrollado y no se comprenden sus consecuencias debido a su manera sistémica de actuar (AU)

Introduction: the bone is in constant remodeling to maintain the skeletal structure, having a cycle of resorption by osteoclasts and formation of new bone by osteoblasts, the bone is also susceptible to systemic diseases, trauma, age and genetic disorders that affect bone remodeling, producing a massive loss of bone mass regulated by hormones, cytokines, enzymes, etcetera. The objective is to perform a systematic review of articles that show a change or alteration when using micro-vibration and pharmacological treatments on cathepsin K in the alveolar bone. Material and methods: in order to make a comparison between the effectiveness of micro-vibration and cathepsin K inhibitor treatments, a systemic review was carried out in nine databases (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO and Springer Link). The study population was rats and mice. Results: this study included 20 articles whose research was carried out in clinical studies. In the results we can see how all the treatments in some way improve the bone remodeling process, it is difficult to compare which treatment within each group is better than the other, because the results expressed are qualitative. Conclusion: according to the results expressed, it is decided that it is better to perform a treatment with micro vibrations because the use of cathepsin K inhibitors are not yet fully developed and their consequences are not understood due to their systemic way of acting (AU)

Photobiomodulation increases uprighting tooth movement and modulates IL-1ß expression during orthodontically bone remodeling.

This study investigated the effects of photobiomodulation (PBM) in acceleration of orthodontic movement of inferior molar uprighting movement. Thirty-four individuals, with indication of molar uprighting movement for oral rehabilitation, were randomly divided in two groups: verticalization + PBM (808 nm, 100 mW, 1 J per point, 10 points and 25 J/cm2 ) or verticalization + PBM simulation. Elastomeric chain ligatures were changed every 30 days for 3 months. FBM was performed immediately, 24 h, 72 h, 1 and 2 months after activation. The primary outcome was the amount of uprighting movement. Secondary outcomes were pain, amount of medication, OHIP-14 questionnaire, and cytokine IL-1ß. PBM group increase uprighting movement when compared to control after 3 months and modulate IL-1ß expression. For pain control, the amount of medication and OHIP-14 no difference were found. This study suggests that PBM accelerates tooth movement during molar uprighting, due to modulation of IL-1ß during bone remodeling.

Viable cryopreserved human bone graft exhibit superior osteogenic properties in mandibular lateral augmentation.

Lack of bone volume to place dental implants is frequently a problem in the reconstruction of edentulous patients. Even though autografts are the gold standard for jaw regeneration, morbidity associated with the harvesting site stimulates the demand for other substitutes. The aim of this study is to characterize the incorporation and the osteogenic ability of a viable cryopreserved human bone graft (VC-HBG) in the mandibular augmentation in rats. Bone chips from fresh human vertebrae cadaveric donors were processed, cryoprotected and deep-frozen at - 80 °C maintaining its cell viability. A jaw augmentation model was used in 20 athymic nude rats allocated into 2 groups to either receive the VC-HBG or an acellular graft as control (A-HBG). The assessment of the grafts' incorporation was performed at 4 and 8 weeks by micro-CT, histomorphometry and immunohistochemistry. Bone volume gain was significantly higher for the VC-HBG group at both time points. At 4 weeks, the A-HBG group presented significantly higher mineral density, but at 8 weeks, the VC-HBG group showed significantly higher values than the A-HBG. There was no statistical difference between VC-HBG and A-HBG groups at 4-weeks for remaining graft particles, while at 8 weeks, the VC-HBG group showed significantly less graft remnants. Collagen I, osteopontin and tartrate-resistant acid phosphatase expression were significantly higher in the VC-HBG group at both time points, while osteocalcin expression was significantly higher in the VC-HBG group at 8-weeks compared to the A-HBG group. This experimental research demonstrated that the VC-HBG shows positive osteogenic properties, greater bone formation, higher rate of bone remodeling and a better overall incorporation in rats' mandibles compared to the A-HBG.

[Determination of reference values of CTx and NMID-Osteocalcin and their association with osteoporosis in postmenopausal chilean women]. / Determinación de rangos de BCTx y N-MID Osteocalcina y asociación con Osteoporosis en mujeres chilenas posmenopáusicas.

INTRODUCTION: Bone densitometry (BD) has high specificity in the osteoporosis diagnosis but suboptimal sensitivity to estimate fracture risk. It was proposed that bone turnover markers (BTM) could be included in the osteoporosis risk algorithm, although the extent of its association is unknown. One recommended BTM to assess bone resorption is Beta-Cross Laps (B-CTx), while a BTM to assess bone formation is osteocalcin. AIMS: To establish BCTx and N-MID osteocalcin (N-MID) ranges in postmenopausal women (PM) and compare BTM levels in two groups: control and with abnormal BD. METHODS: PM with BD within the last year were recruited. A questionnaire of risk factors for fractures was applied, and BTM was measured. Volunteers with diseases that would affect bone remodeling were excluded. RESULTS: 117 PM (57 control and 60 with abnormal BD) were recruited. 18% had osteoporosis, and the groups were comparable. The ranges for B-CTx and N-MID were 0.41 ± 0.18 [IC95% 0.37-0.45] and 22.76 ± 7.73 [IC95% 21.29-24.24] ng/mL. The mean levels of B-CTx and N-MID were higher in the group with abnormal BD (0.46 ± 0.19 and 24.29 ± 8.04 ng/mL). A moderate correlation between both BTM was found, but it was weak with abnormal BD. CONCLUSIONS: B-CTx and N-MID ranges were assessed for the first time in Chilean PM, similar to values found in other countries. Slightly higher values of BTM were found in the group with abnormal BD, which the presence of omitted secondary causes could explain. These BTM could be a complementary tool to BD and FRAX in bone evaluation.

Acompanhamento clínico e dados moleculares de pacientes submetidos à cirurgia de implante: estudo de casos / Clinical follow-up and molecular data of patients undergoing implant surgery: case stud / Clinical follow-up and molecular data of patients undergoing implant surgery: case stud

A prática clínica dos implantodontistas mostra uma importante taxa de insucesso pós reabilitações com implantes, cujas causas variam e muitas vezes não são identificadas. Este estudo de caso avaliou a presença de doenças peri-implantares em pacientes fumantes, pacientes fumantes em terapia anti-hipertensiva, pacientes em terapia anti-hipertensiva e pacientes controle, levando em consideração os seguintes dados: avaliação da expressão gênica por reação em cadeia da polimerase, por tempo real e transcrição reversa, do osso do leito receptor do implante; profundidade de sondagem (PS) das próteses implantadas; sangramento a sondagem; índice de biofilme dental; análise radiográfica da perda óssea e avaliação de citocinas inflamatórias do fluido gengival desses pacientes, por ELISA (Enzyme-linked immunosorbent assay). O presente estudo objetivou avaliar marcadores moleculares relacionados ao remodelamento ósseo e ao processo inflamatório expressos pelo osso no momento de inserção do implante, traçando correlações clínicas de 16 pacientes, que foram avaliados 3 anos após terem sido reabilitados com implantes dentais osseointegrados, na busca de fatores preditivos de sucesso do tratamento. Os dados foram avaliados por estatística descritiva (média, mediana, desvio padrão), pelos testes paramétricos (ANOVA) e não paramétricos (Kruskall Wallis) e por análises de correlação de Pearson. Não houveram correlações significativas entre os marcadores moleculares do metabolismo ósseo e citocinas inflamatórias do fluido gengival com as condições clínicas avaliadas após a reabilitação com próteses. A profundidade de sondagem foi maior nos pacientes fumantes e correlacionou-se significativamente à perda óssea. Concluiu-se os fatores moleculares não tiveram significância preditiva de sucesso dos tratamentos com implantes dentais osseointegrados e que pacientes com um ou mais fatores de risco apresentam um pior prognóstico cuja manifestação inicial ocorre com uma maior profundidade de sondagem correlacionada com maior perda óssea (AU).

The clinical practice of implant dentists shows an important failure rate after implant rehabilitations, whose causes vary and are often not identified. This present case study evaluated the presence of peri-implant diseases in smokers, smokers on antihypertensive therapy, patients on antihypertensive therapy and control patients, taking into account the following data: evaluation of gene expression by chain reaction of polymerase, by real time and reverse transcription, of the bone of the implant recipient bed; probing depth (PS) of implanted prostheses; bleeding on probing; dental biofilm index; radiographic analysis of bone loss and evaluation of inflammatory cytokines in the gingival fluid of these patients, by ELISA (Enzymelinked immunosorbent assay). The present study aimed to evaluate molecular markers related to bone remodeling and the inflammatory process expressed by the bone at the time of implant insertion, tracing clinical correlations of 16 patients, who were evaluated 3 years after being rehabilitated with osseointegrated dental implants, in the search for predictive factors of treatment success. The data were evaluated by descriptive statistics (mean, median, standard deviation), by parametric (ANOVA) and non-parametric (Kruskall Wallis) tests and by Pearson transfer analysis. There was no correlation between molecular markers of bone metabolism and cytokines, inflammation of the gingival fluid with clinical conditions after rehabilitation with prostheses. Probing depth was greater in smokers and was significantly correlated with bone loss. It was concluded that molecular factors had no predictive significance for the success of treatments with osseointegrated dental implants and that patients with one or more risk factors had a worse prognosis whose initial manifestation occurs with a greater depth of probing correlated with greater bone loss (AU)

Histological and Immunohistochemical Analysis of the Effects of Topical Melatonin Treatment Associated with Collagen Sponge and rhBMP-2 Protein on Bone Remodeling.

Extensive bone defect healing is an important health issue not yet completely resolved. Different alternative treatments have been proposed but, in face of a critical bone defect, it is still very difficult to reach a complete regeneration, with the new-formed bone presenting all morphological and physiological characteristics of a normal, preinjury bone. Topical melatonin use has shown as a promising adjuvant for bone regeneration due to its positive effects on bone metabolism. Thus, to search for new, safe, biological techniques that promote bone repair and favor defect healing, we hypothesized that there is a synergistic effect of melatonin treatment associated with rhBMP-2 to guide bone regeneration. This study aimed to investigate bone repair effects of topical melatonin administration in different concentrations (1, 10, and 100 µg), associated or not with rhBMP-2. Surgical-induced bone defect healing was qualitatively evaluated through histopathological analysis by light microscopy. Additionally, quantitative stereology was performed in immunohistochemistry-prepared tissue to identify angiogenic, osteogenic, and osteoclastogenic factors. Quantification data were compared between groups by the ANOVA/Tukey test and differences were considered significant when p < 0.05. Our results showed that the presence of the scaffold in the bone defect hindered the process of bone repair because in the group treated with "blood clot + scaffold" the results of bone formation and immunolabeling were reduced in comparison with all other groups (treated with melatonin alone or in association with rhBMP-2). Statistical analysis revealed a significant difference between the control group (bone defect + blood clot), and groups treated with different concentrations of melatonin in association with rhBMP-2, indicating a positive effect of the association for bone repair. This treatment is promising once it becomes a new safe alternative technique for the clinical treatment of fractures, bone defects, and bone grafts. Our results support the hypothesis of the safe use of the association of melatonin and rhBMP-2 and have established a safe and effective dose for this experimental treatment.

Bone, fat, and muscle interactions in health and disease.

Energy metabolism is a point of integration among the various organs and tissues of the human body, not only in terms of consumption of energy substrates but also because it concentrates a wide interconnected network controlled by endocrine factors. Thus, not only do tissues consume substrates, but they also participate in modulating energy metabolism. Soft mesenchymal tissues, in particular, play a key role in this process. The recognition that high energy consumption is involved in bone remodeling has been accompanied by evidence showing that osteoblasts and osteocytes produce factors that influence, for example, insulin sensitivity and appetite. Additionally, there are significant interactions between muscle, adipose, and bone tissues to control mutual tissue trophism. Not by chance, trophic and functional changes in these tissues go hand in hand from the beginning of an individual's development until aging. Likewise, metabolic and nutritional diseases deeply affect the musculoskeletal system and adipose tissue. The present narrative review highlights the importance of the interaction of the mesenchymal tissues for bone development and maintenance and the impact on bone from diseases marked by functional and trophic disorders of adipose and muscle tissues.

Effects of ultra-low dose hormone therapy on biochemical bone turnover markers in postmenopausal women: A randomized, placebo-controlled, double-blind trial.

OBJECTIVE: Evaluate the effects of ultra-low-dose hormone therapy (Ultra-LD HT) with 17ß-estradiol 0.5 mg and norethisterone acetate 0.1 mg (E2 0.5/NETA 0.1) versus placebo on bone turnover markers (BTM) in postmenopausal women. STUDY DESIGN: A multicenter, double-blind, randomized, placebo-controlled study was performed with 107 participants who received one tablet daily of E2 0.5/NETA 0.1 or placebo for 24-weeks. Bone formation markers-N-terminal propeptide of type I procollagen (PINP) and Bone-specific alkaline phosphatase (BSAP), and bone resorption markers-C-telopeptide of type I collagen (CTX-I) and N-telopeptide crosslinked of type I collagen (NTX) were assessed before and at 12 and 24-weeks of treatment. RESULTS: Women treated with E2 0.5/NETA 0.1 had a significant reduction in the PINP marker from baseline (58.49 ± 21.12 µg/L) to week 12 (48.31 ± 20.99 µg/L) and week 24 (39.16 ± 16.50 µg/L). Placebo group, the PINP marker did not differ significantly. The analysis of the BSAP indicated a significant increase in the placebo group (13.8 ± 5.09 µg/L and 16.29 ± 4.3 µg/L, at baseline and week 24, respectively), whereas in the treatment group the values did not change. The analysis of the NTX marker showed a significant reduction only in the treatment group (43.21 ± 15.26 nM/mM and 33.89 ± 14.9 nM/mM, at baseline and week 24, respectively). CTX-I had a significant decrease in the treatment group from baseline (0.3 ± 0.16 ng/L) to week 12 (0.21 ± 0.14 ng/L) and week 24 (0.21 ± 0.12 ng/L). CONCLUSION: Women receiving E2 0.5/NETA 0.1 experienced reductions in bone resorption and formation markers, an expected effect during the anti-resorptive therapy, suggesting a protective bone effect with the Ultra-LD HT.

Prospective Evaluation of Bone Remodeling in Full-Arch Rehabilitations with Morse Taper Implants: A Case Series Study with One-Year Follow-Up.

This case series study evaluated the survival, success rate and marginal bone remodeling of Morse taper hydrophilic implants placed for full-arch rehabilitations over a 1-year follow-up period. Ten patients in need of maxillary and/or mandibular full-arch rehabilitation were selected. Sixty-six Morse taper implants and sixty-six abutments were inserted. All implants were placed using a surgical flap approach without bone regeneration and were immediately loaded with definitive prostheses according to the passive fitting technique. The patients underwent clinical and radiographic follow-up at different postoperative periods: T0 = immediate (up to 1 month after surgery); T1 = 3-4 months after surgery; T2 = 6-8 months after surgery; and T3 = 1 year after surgery. The survival and success rate of the implants and the marginal bone remodeling were evaluated. Normal distribution of the outcomes was verified by Kolmogorov-Smirnov tests. Therefore, changes in vertical and horizontal marginal bone levels were assessed with paired t-tests. Results were considered significant for P < 0.05. Survival and success rates of 100% and 92.4%, respectively, were observed. Statistically significant vertical bone level changes were shown for all periods. From T0 to T3, there was a mean difference in vertical bone loss of -1.02 mm on the mesial surface and of -0.93 mm on the distal surface, for horizontal bone loss in the same period, it was observed mean changes of -0.14 mm on the mesial surface and -0.09 mm on the distal surface. This 1-year case series follow-up of immediate full-arch rehabilitation, using one-step hybrid passive fitting supported by four to six hydrophilic tapered implants, suggests predictability with high survival and success rates in edentulous patients.