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PURPOSE OF REVIEW: The impact of nephrolithiasis on skeletal growth and bone health across the life span of kidney stone formers is reviewed. MAIN FINDINGS: Bone disease is an early event among kidney stone formers (SF), with distinct phenotypes according to each age, sex, menopausal status, dietary, hormonal and genetic factors. Nephrolithiasis-associated bone disorder is characterized by reduced bone mineral density (BMD) and histologically discloses low bone formation, high bone resorption and abnormal mineralization. Although hypercalciuria has been presumed to be pathogenic for bone loss in SF, the association of BMD with urinary calcium is not uniform in all studies. Hypocitraturia, metabolic disturbances, cytokines and receptors, growth factors and acid-base status may all influence skeletal outcomes. The potential link of bone disease with vascular calcification and cardiovascular disease among SF is discussed. The unique vulnerability of the younger skeleton to the effects of nephrolithiasis on attainment of peak bone mass and strength is highlighted and the association of bone loss with kidney stone formation early in life indicate the opportunity for intervention to reduce the risk of future bone fractures.

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BACKGROUND: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. METHODS: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. RESULTS: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. CONCLUSION: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.

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Condylar resorption is an aggressive and disability form of temporomandibular joint (TMJ) degenerative disease, usually non-respondent to conservative or minimally invasive therapies and often leading to surgical intervention and prostheses implantation. This condition is also one of the most dreaded postoperative complications of orthognathic surgery, with severe cartilage erosion and loss of subchondral bone volume and mineral density, associated with a painful or not inflammatory processes. Because regenerative medicine has emerged as an alternative for orthopedic cases with advanced degenerative joint disease, we conducted a phase I/IIa clinical trial (U1111-1194-6997) to evaluate the safety and efficacy of autologous nasal septal chondroprogenitor cells. Ten participants underwent biopsy of the nasal septum cartilage during their orthognathic surgery. The harvested cells were cultured in vitro and analyzed for viability, presence of phenotype markers for mesenchymal stem and/or chondroprogenitor cells, and the potential to differentiate into chondrocytes, adipocytes, and osteoblasts. After the intra-articular injection of the cell therapy, clinical follow-up was performed using the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and computed tomography (CT) images. No serious adverse events related to the cell therapy injection were observed during the 12-month follow-up period. It was found that autologous chondroprogenitors reduced arthralgia, promoted stabilization of mandibular function and condylar volume, and regeneration of condylar tissues. This study demonstrates that chondroprogenitor cells from the nasal septum may be a promise strategy for the treatment of temporomandibular degenerative joint disease that do not respond to other conservative therapies.

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Esta tese foi dividida em três partes, sendo que cada uma consistiu estudo independente, com objetivos próprios. Na parte 1, o objetivo foi avaliar a influência do modo de representar a interface osso-OMI (osseointegrada ou não osseointegrada) sobre a previsão do risco de reabsorção óssea peri-implantar. Foram construídos quatro modelos tridimensionais que representaram o OMI inserido em quatro cilindros de osso de densidades crescentes, diferenciados pela espessura do osso cortical (Ct = 0,5; 1,2; 2,0 e 3,0 mm) e pelo módulo de elasticidade do osso trabecular (TE = 0,2; 1,4; 3,0 e 5,5 GPa). Para cada modelo, foram simuladas duas condições de interface osso-OMI: uma que considerava união perfeita entre osso e OMI (osseointegrado) e outra que considerava a possibilidade de movimentos relativos entre eles (não osseointegrado). Uma força horizontal de 2 N foi aplicada na cabeça do OMI, para simular a retração de dentes anteriores. A avaliação do risco de reabsorção óssea peri-implantar foi baseada no critério de falha da deformação principal maior, assumindo um valor crítico de 3.000 strain, tanto para tração quanto para compressão. Os resultados mostraram que, ao simular a interface osso-OMI como perfeitamente unida, o risco de perda de estabilidade do OMI por reabsorção óssea peri-implantar no osso menos denso fica subestimado. Na parte 2, foram novamente representadas as quatro condições de qualidade óssea, mas com modelos que representavam o contorno anatômico dos ossos correspondentes: maxila pouco densa, maxila controle, mandíbula controle e mandíbula muito densa. A AEF foi conduzida para tentar explicar por que os OMIs colocados na maxila apresentam maior taxa de sucesso em relação aos OMI colocados na mandíbula, apesar da melhor qualidade do osso mandibular. Além da força horizontal de 2 N (cenário clínico), foi simulada uma força horizontal de 10 N (condição de sobrecarga) e a interface osso OMI foi simulada como não-osseointegrada em todos os modelos. A avaliação do risco de reabsorção óssea peri-implantar seguiu o mesmo critério da parte 1 e foi também avaliado o risco de falta de estabilidade imediata, baseado no deslocamento intra-ósseo do OMI. Em todos os casos, o pico de deslocamento do OMI ficou muito abaixo do limiar de 50-100 m, o que sugere que a estabilidade primária seria suficiente mesmo no cenário de maxila de baixa densidade sobrecarregada. De acordo com os dados da deformação principal maior, a maxila está mais sujeita a perder sua estabilidade inicial devido à sobrecarga ortodôntica, especialmente na condição de baixa densidade, em que tanto a deformação de tração quanto a de compressão ultrapassaram o limiar de reabsorção óssea patológica. É provável que essa AEF não conseguiu prever o maior risco de falha de OMI em mandíbula de alta densidade porque não simulou as tensões residuais geradas pela inserção do OMI. Portanto, a simulação da inserção do OMI parece essencial para explicar a contradição que motivou esse estudo. Na parte 3, o objetivo foi comparar, através da AEF, o risco de reabsorção radicular inflamatória induzida ortodonticamente (RRIIO) entre duas mecânicas ortodônticas de intrusão (convencional e com mini-implantes), em situações de diferentes níveis de suporte periodontal. Foram construídos quatro modelos de um pré-molar superior inserido na maxila: controle (CTL) e 2, 4 ou 6 mm de perda óssea horizontal (R2, R4 e R6, respectivamente). Uma força de intrusão de 25 cN foi utilizada para as duas mecânicas em estudo. Nos modelos com mini-implante ortodôntico, a força foi dividida entre as faces vestibular e palatina. Nos modelos sem mini-implantes, a força foi aplicada apenas na vestibular. O índice de risco de reabsorção radicular (iRRR) foi calculado dividindo o pico de tensão hidrostática compressiva no ligamento periodontal pela tensão hidrostática dos capilares (4,7 kPa). A mecânica com mini-implante, além de apresentar iRRR sempre menores (CTL 1,2 e 1,4; R2: 1,4 e 1,7; R4: 1,7 e 2,2; R6: 2,4 e 3,2 - para mecânicas com e sem OMI, respectivamente), gerou apenas uma região com tensão hidrostática acima do valor crítico, próxima ao ápice do dente, para todos os modelos. Na mecânica convencional, houve também uma região com tensão hidrostática compressiva acima de 4,7 kPa na região cervical vestibular do modelo com 6 mm de perda óssea horizontal. O uso de mini-implante na intrusão ortodôntica diminuiu o risco de RRIIO em todos os casos simulados e o risco de reabsorção óssea adicional no modelo em que o dente apresentava uma perda óssea horizontal prévia de 6 mm.

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INTRODUCTION: This study evaluated the effects of cigarette smoke inhalation (CSI) on apical periodontitis (AP) induced in rats by histometric, immunohistochemical, and microtomographic analysis. METHODS: A total of 32 male Wistar rats were divided into 4 experimental groups (n = 8): control, CSI, AP, and CSI + AP. Rats in the CSI and CSI + AP groups inhaled cigarette smoke by remaining inside a smoking chamber for 8 minutes 3 times a day for 50 days. After 20 days of smoke inhalation, rats in the AP and CSI + AP groups had the pulp of their first right lower molar exposed to induce AP. Blood was collected on day 50 to evaluate nicotine and serum cotinine levels. The animals' mandibles were removed for histologic processing to evaluate bone resorption by histometric, immunohistochemical (receptor activator of nuclear factor kappa B ligand/osteoprotegerin), and microtomographic analysis. The Student t test was applied. RESULTS: Histometric analysis showed a larger area of bone resorption (P < .05) and microtomographic analysis found greater resorption volume (P < .001) for the CSI + AP group compared with the AP group. The CSI + AP group presented a high RANKL immunostaining pattern compared with the AP group (P < .001). CONCLUSIONS: CSI increased bone resorption caused by AP.

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INTRODUCTION: Bisphosphonates have an inhibitory impact on osteoclastic activity, reducing bone resorption. However, the influence of risedronate on tooth movement is not well-defined. OBJECTIVE: This systematic review assessed the effect of risedronate intake on orthodontic tooth movement. A case report was also provided. METHODS: Two independent reviewers searched six databases (PubMed, Web of Science, Ovid, Lilacs, Scopus, and Open Grey). The searches were carried out in April/2020, and an update was set in place in June/2023. Therefore, the searches considered a timeline from the databases' inception date until June/2023, with no publication date and/or language restrictions. The clinical question focused on evaluating the orthodontic tooth movement and relapse movement (Outcome) in animals (Population) exposed to risedronate (Exposure), compared to control groups (Comparison). The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were applied, and the protocol was registered in PROSPERO (CRD42020168581). The risk of bias was determined using the Systematic Review Centre for Laboratory Animal Experimentation protocol (SYRCLE). RESULTS: Two studies in rats and one in guinea pigs were included in the systematic review. The studies reported a decrease in orthodontic tooth movement, a reduction in the relapse movement, and a reduced number of positive tartrate-resistant acid phosphatase (TRAP) cells, with a significantly reduced number of bone gaps after the administration of risedronate in rats. A case report illustrated the effects of risedronate administration in one patient. CONCLUSION: Based on the systematic review, risedronate seems to impair orthodontic tooth movement and relapse due to a decrease in bone resorption cells.

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Because the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal and senescence pathology has been considered since long. One relevant melatonin target site in aging individuals is bone where melatonin chronobiotic effects mediated by MT1 and MT2 receptors are demonstrable. Precursors of bone cells located in bone marrow are exposed to high quantities of melatonin and the possibility arises that melatonin acts a cytoprotective compound via an autacoid effect. Proteins that are incorporated into the bone matrix, like procollagen type I c-peptide, augment after melatonin exposure. Melatonin augments osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts. Osteoclasts are target cells for melatonin as they degrade bone partly by generating free radicals. Osteoclast activity and bone resorption are impaired via the free radical scavenger properties of melatonin. The administration of melatonin in chronobiotic doses (less than 10 mg daily) is commonly used in clinical studies on melatonin effect on bone. However, human equivalent doses allometrically derived from animal studies are in the 1-1.5 mg/kg/day range for a 75 kg human adult, a dose rarely used clinically. In view of the absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers, further investigation is needed to determine whether high melatonin doses have higher therapeutic efficacy in preventing bone loss.

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Objective: This clinical study was conducted to evaluate the effect of loading protocol using hybrid ceramic resinous material on marginal bone loss. Material and Methods: This study was conducted in the fixed prosthodontics department, at Ain Shams University on 30 titanium endosseous tapered threaded implants which were placed in 30 patients in the upper premolar area. Patients were divided randomly according to the loading protocol into 3 groups (10 patients each): Group I (IFLV): patients received CAD/CAM polymer infiltrated ceramic (VITA-ENAMIC) crowns (immediate functional loading), Group II (IFLP): patients received CAD/CAM PMMA crowns (in occlusion for 3 months) followed by CAD/CAM polymer infiltrated ceramic (VITA-ENAMIC) crowns (functional loading), and Group III (INFLP): patients received CAD/CAM PMMA crowns (out of occlusion for 3 months) followed by CAD/CAM VITA-ENAMIC crowns (functional loading). Results: After three months; the highest value of marginal bone loss (mm) was found in IFLV, followed by IFLP, while the lowest value was found in INFLP. After six months, the highest value was found in IFLP, followed by IFLV, while the lowest value was found in INFLP. Also, after twelve months, the highest value was found in IFLV, followed by IFLP, while the lowest value was found in INFLP. Marginal bone loss values were within the accepted values for clinical success for all the tested groups. Conclusion: Immediate non-functional loading provided more acceptable outcomes than immediate functional loading. Also, immediately functional and non-functional implant loading using hybrid ceramic as permanent material has shown promising results with proper patient selection (AU)

Objetivo: Este estudo clínico foi realizado para avaliar o efeito do protocolo de carregamento utilizando material resinoso cerâmico híbrido na perda óssea marginal. Material e Métodos: Este estudo foi realizado no departamento de prótese fixa da Universidade Ain Shams em 30 implantes endósseos cônicos de titânio que foram instalados em 30 pacientes na região de pré-molares superiores. Os pacientes foram divididos aleatoriamente de acordo com o protocolo de carregamento em 3 grupos (10 pacientes cada): Grupo I (IFLV): os pacientes receberam coroas usinadas em CAD/CAM de cerâmica infiltrada com polímero (VITA-ENAMIC) (carga imediata), Grupo II (IFLP): os pacientes receberam coroas usinadas em CAD/CAM de PMMA (em oclusão por 3 meses) seguidas por coroas de cerâmica infiltrada com polímero (VITA-ENAMIC) (carga funcional), e Grupo III (INFLP): os pacientes receberam coroas usinadas em CAD/CAM de PMMA (infraoclusão por 3 meses) seguido de coroas de VITA-ENAMIC (carga funcional). Resultados: Após três meses; o maior valor de perda óssea marginal (mm) foi encontrado no IFLV, seguido pelo IFLP, enquanto o menor valor foi encontrado no INFLP. Após seis meses, o maior valor foi encontrado no IFLP, seguido do IFLV, enquanto o menor valor foi encontrado no INFLP. Além disso, após doze meses, o maior valor foi encontrado no IFLV, seguido pelo IFLP, enquanto o menor valor foi encontrado no INFLP. Os valores de perda óssea marginal estavam todos dentro de valores aceitáveis para sucesso clínico para todos os grupos testados. Conclusão: A carga funcional não imediata proporcionou resultados mais aceitáveis do que a carga imediata. Além disso, o carregamento funcional imediato e não imediato de implantes utilizando coroas finais de cerâmica híbrida mostrou resultados promissores com a seleção adequada dos pacientes.(AU)

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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.

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Osteoclasts are specialized cells responsible for bone resorption, a highly energy-demanding process. Focus on osteoclast metabolism could be a key for the treatment of osteolytic diseases including osteoporosis. In this context, AMP-activated protein kinase α1 (AMPKα1), an energy sensor highly expressed in osteoclasts, participates in the metabolic reconfiguration during osteoclast differentiation and activation. This study aimed to elucidate the role of AMPKα1 during osteoclastogenesis in vitro and its impact in bone loss in vivo. Using LysMcre/0AMPK⍺1f/f animals and LysMcre/0 as control, we evaluated how AMPKα1 interferes with osteoclastogenesis and bone resorption activity in vitro. We found that AMPKα1 is highly expressed in the early stages of osteoclastogenesis. Genetic deletion of AMPKα1 leads to increased gene expression of osteoclast differentiation and fusion markers. In addition, LysMcre/0AMPK⍺1f/f mice had an increased number and size of differentiated osteoclast. Accordingly, AMPKα1 negatively regulates bone resorption in vitro, as evidenced by the area of bone resorption in LysMcre/0AMPK⍺1f/f osteoclasts. Our data further demonstrated that AMPKα1 regulates mitochondrial fusion and fission markers upregulating Mfn2 and downregulating DRP1 (dynamics-related protein 1) and that Ctskcre/0AMPK⍺1f/f osteoclasts lead to an increase in the number of mitochondria in AMPK⍺1-deficient osteoclast. In our in vivo study, femurs from Ctskcre/0AMPK⍺1f/f animals exhibited bone loss associated with the increased number of osteoclasts, and there was no difference between Sham and ovariectomized group. Our data suggest that AMPKα1 acts as a negative regulator of osteoclastogenesis, and the depletion of AMPKα1 in osteoclast leads to a bone loss state similar to that observed after ovariectomy.

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Lipoproteins are immunostimulatory bacterial components suggested to participate in inflammation-induced bone loss in periodontal disease through stimulation of osteoclast differentiation. Toll-like receptor 2 activation by Pam2CSK4 (PAM2), known to mimic bacterial lipoproteins, was previously shown to enhance periodontal bone resorption in mice. The anti-inflammatory cytokine interleukin-4 (IL-4) is a known inhibitor of RANKL-induced bone resorption in vitro. Here, we have investigated whether IL-4 could decrease PAM2-induced periodontal bone loss and osteoclastogenesis in vivo. In a model of periodontitis induced by gingival injections of PAM2 in mice, concomitant injections of IL-4 reduced bone loss. Histologically, IL-4 reduced the recruitment of inflammatory cells and the formation of TRAP+ osteoclasts stimulated by PAM2. Mouse bone marrow macrophages (BMMs) and neonatal calvarial osteoblasts were used to assess the effect of IL-4 on PAM2-induced osteoclastogenesis in vitro. In RANKL-primed BMMs stimulated by PAM2 Nfatc1, Ctsk, and Acp5 gene expression was up-regulated and resulted in robust formation of TRAP+ multinucleated osteoclasts, effects which were impaired by IL-4. These effects were mediated by impairment in PAM2-induced c-fos expression. In primary calvarial osteoblast cultures, IL-4 decreased PAM2-induced Tnfsf11 (encoding RANKL) mRNA and enhanced Tnfrsf11b (encoding OPG) expression. Our data demonstrate that the osteoprotective effect by IL-4 on lipoprotein-induced periodontal disease occurs through the inhibition of osteoclastogenesis by three mechanisms, one by acting directly on osteoclast progenitors, another by acting indirectly through decreasing the expression of osteoclast-regulating cytokines in osteoblasts and a third by decreasing inflammation.

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El granuloma piogénico es una lesión vascular reactiva benigna del tejido blando que surge en respuesta a irritantes crónicos de bajo grado. Rara vez crece más de 2 cm de diámetro y por lo general, no provoca cambios en el hueso alveolar. Presentamos un caso inusual de granuloma piógeno en una mujer de 19 años, de extenso tamaño y comportamiento agresivo, asociado a resorción ósea severa, movilidad dentaria, hemorragia, anemia ferropénica y recurrencias.

Pyogenic granuloma is a benign reactive vascular lesion of the soft tissue that arises in response to chronic low-grade irritants. It rarely grows more than 2 cm in diameter and usually does not cause changes in the alveolar bone. We present the case of a 19-year-old woman with an unusual pyogenic granuloma of extensive size and aggressive behavior, associated with severe bone resorption, tooth mobility, hemorrhage, iron deficiency anemia and recurrences.

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INTRODUCTION: The aim of this study was to investigate the role of the proinflammatory axis TNF-α-TNFR1 in experimentally induced periapical inflammation and bone resorption in mice. METHODS: After receiving Ethics Committee Approval (2019.1.139.58.0), experimental apical periodontitis was induced by means of inoculating oral microorganisms into the root canals of molars of mice. Genetically deficient tumor necrosis factor-α receptor-1 mice (TNFR1-/-; n = 50) response was compared with that of C57Bl6 wild-type mice (wild-type; n = 50) after 7, 14, 28, and 42 days. The analyses performed were micro-computed tomographic, histopathologic, histomicrobiological, and histometric evaluation, tartrate-resistant acid phosphatase staining, immunohistochemistry, and quantitative reverse transcriptase polymerase chain reaction. Data were analyzed by using one-way analysis of variance, followed by Tukey or Bonferroni tests (α = 5%). RESULTS: TNFR1-/- mice exhibited lower recruitment of neutrophils at 14, 28, and 42 days (P < .05), which resulted in reduced area and volume of apical periodontitis at 42 days (P < .05). The number of osteoclasts was also lower in TNFR1-/- animals at 14 and 42 days (P < .01), along with reduced synthesis of CTSK, MMP-9, and COX-2. Expression of RANKL, but not OPG, was reduced at 14 and 42 days (P < .001). The highest RANKL expression over OPG (ratio > 1) was found in wild-type animals at 7 (P < .0001) and 42 days (P < .001). CONCLUSIONS: Periapical inflammation and bone resorption were exacerbated in wild-type animals compared with TNFR1-/- mice, demonstrating that the TNF-α-TNFR1 signaling pathway mediated catabolic events in bone after root canal contamination.

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Leukotrienes (LTs) are derived from arachidonic acid metabolism by the 5-lipoxygenase (5-LO) enzyme. The production of LTs is stimulated in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis, and periodontitis, with a relevant contribution to bone resorption. However, its role in bone turnover, particularly the suppression of bone formation by modulating the function of osteoclasts and osteoblasts, remains unclear. We investigated the effects of LTs on bone metabolism and their impact on osteogenic differentiation and osteoclastogenesis using a 5-LO knockout (KO) mouse model. Results from micro-computed tomography (µCT) analysis of femur from 8-week-old 5-LO-deficient mice showed increased cortical bone and medullary region in females and males and decreased trabecular bone in females. In the vertebra, we observed increased marrow area in both females and males 5-LO KO and decreased trabecular bone only in females 5-LO KO. Immunohistochemistry (IHC) analysis showed higher levels of osteogenic markers tissue-nonspecific alkaline phosphatase (TNAP) and osteopontin (OPN) and lower expression of osteoclastogenic marker tartrate-resistant acid phosphatase (TRAP) in the femurs of 5-LO KO mice versus wild-type (WT). Alkaline phosphatase activity and mineralization assay results showed that the 5-LO absence enhances osteoblasts differentiation and mineralization but decreases the proliferation. Alkaline phosphatase (ALP), Bglap, and Sp7 gene expression were higher in 5-LO KO osteoblasts compared to WT cells. Eicosanoids production was higher in 5-LO KO osteoblasts except for thromboxane 2, which was lower in 5-LO-deficient mice. Proteomic analysis identified the downregulation of proteins related to adenosine triphosphate (ATP) metabolism in 5-LO KO osteoblasts, and the upregulation of transcription factors such as the adaptor-related protein complex 1 (AP-1 complex) in long bones from 5-LO KO mice leading to an increased bone formation pattern in 5-LO-deficient mice. We observed enormous differences in the morphology and function of osteoclasts with reduced bone resorption markers and impaired osteoclasts in 5-LO KO compared to WT osteoclasts. Altogether, these results demonstrate that the absence of 5-LO is related to the greater osteogenic profile. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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SUMMARY: To evaluate the histological adverse effects of alendronate administered systemically and topically in combination with orthodontic movement by intense force. Thirty-six 24-week-old female Wistar rats, ovariectomized, were used and divided into three groups (n = 12/group): control, locally treated with saline (0.07 ml/kg/week) (group 1) and experimental, treated with alendronic acid systemically (0.07 mg/kg/week) (group 2) and locally (7 mg/kg/week) (group 3). At 14 days, an orthodontic anchor was installed in the right first molar, and a force of 144 cN was applied for 28 days. The samples were processed for histological evaluation. Descriptive statistics, Shapiro-Wilk tests, one-way ANOVA with Bonferroni correction, one-way repeated measures ANOVA and chi-square tests were performed. All tests were statistically significant at p <0.05. The adverse events found in all groups were inflammation and osteoclastic activity. In the bisphosphonate-treated groups, there were statistically significant differences (p = 0.005) in the osteoclastic activity between the two hemiarcates. All rats in group 2 presented paralytic ileus. Compared to local administration, systemic treatment with alendronic acid produces more adverse effects, such as inflammation, fibrinoid necrosis, and osteoclastic activity. During the application of intense forces, it was not possible to show that there is necrosis associated with bisphosphonates.

Evaluar los efectos adversos histológicos del alendronato administrado sistémica y tópicamente en combinación con movimientos ortodóncicos de fuerza intensa. Treinta y seis ratas Wistar hembras de 24 semanas de edad, ovariectomizadas, fueron utilizadas y divididas en tres grupos (n = 12/grupo): control, tratado localmente con solución salina (0,07 ml/kg/semana) (grupo 1) y experimental, tratados con ácido alendrónico por vía sistémica (0,07 mg/kg/semana) (grupo 2) y local (7 mg/kg/semana) (grupo 3). A los 14 días se instaló un anclaje de ortodoncia en el primer molar derecho y se aplicó una fuerza de 144 cN durante 28 días. Las muestras fueron procesadas para evaluación histológica. Se realizó estadística descriptiva, pruebas de Shapiro-Wilk, ANOVA de una vía con corrección de Bonferroni, ANOVA de medidas repetidas de una vía y pruebas de chi-cuadrado. Todas las pruebas fueron estadísticamente significativas con un p <0,05. Los eventos adversos encontrados en todos los grupos fueron inflamación y actividad osteoclástica. En los grupos tratados con bisfosfonatos hubo diferencias estadísticamente significativas (p = 0,005) en la actividad osteoclástica entre los dos hemiarcados. Todas las ratas del grupo 2 presentaron íleo paralítico. En comparación con la administración local, el tratamiento sistémico con ácido alendrónico produce más efectos adversos, como inflamación, necrosis fibrinoide y actividad osteoclástica. Durante la aplicación de fuerzas intensas, no fue posible demostrar que existe necrosis asociada con los bisfosfonatos.

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Normal bone remodeling depends of a balance between bone forming cells, osteoblasts and bone resorbing cells, the osteoclasts. In chronic arthritides and some inflammatory and autoimmune diseases such as rheumatoid arthritis, there is a great constellation of cytokines produced by pannus that impair bone formation and stimulate bone resorption by inducing osteoclast differentiation and inhibiting osteoblast maturation. Patients with chronic inflammation have multiple causes that lead to low bone mineral density, osteoporosis and a high risk of fracture including circulating cytokines, impaired mobility, chronic administration of glucocorticoids, low vitamin D levels and post-menopausal status in women, among others. Biologic agents and other therapeutic measures to reach prompt remission might ameliorate these deleterious effects. In many cases, bone acting agents need to be added to conventional treatment to reduce the risk of fractures and to preserve articular integrity and independency for daily living activities. A limited number of studies related to fractures in chronic arthritides were published, and future investigation is needed to determine the risk of fractures and the protective effects of different treatments to reduce this risk.

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BACKGROUND: Horizontal atrophic ridges need a regenerative procedure for implant positioning and fixed rehabilitation. Cone Morse taper implants are characterized by the intimate fitting of the prosthetic interface with the absence of microgaps and micromovements of the interfaces. The aim of this case report was to evaluate the clinical outcome of Cone Morse implant design in split crest augmentation treatment. CASE REPORT: A female patient with partial edentulism of atrophic posterior maxilla was treated for split crest procedure and implant-supported rehabilitation. A full-thickness flap was elevated, and horizontal and vertical osteotomic lines were produced with piezoelectric device. A total of 4 Cone Morse Taper implants (Universal III, Implacil de Bortoli, Brasil) were positioned and the site was grafted with bone substitute and covered by a heterologous membrane. CONCLUSIONS: A complete healing of the surgical site was evident at the follow-up with no evidence of bone resorption. No radiolucency or inflammatory aspects of the treated site were evident in the radiographic control. Simultaneous Cone Morse implants positioning with split crest technique seems to be a promising treatment for posterior maxillary rehabilitation of atrophic edentulous ridges.

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Chalcones are phenolic compounds produced during the biosynthesis of flavonoids that have numerous biological activities, including anti-inflammatory, antioxidant and anticancer. In this in vitro study, we investigate a newly synthesized chalcone (Chalcone T4) in the context of bone turnover, specifically on the modulation of osteoclast differentiation and activity and osteoblast differentiation. Murine macrophages (RAW 264.7) and pre-osteoblasts (MC3T3-E1) were used as models of osteoclasts and osteoblasts, respectively. Differentiation and activity osteoclasts were induced by RANKL in the presence and absence of non-cytotoxic concentrations of Chalcone T4, added in different periods during osteoclastogenesis. Osteoclast differentiation and activity were assessed by actin ring formation and resorption pit assay, respectively. Expression of osteoclast-specific markers (Nfatc1, Oscar, Acp5, Mmp-9 and Ctsk) was determined by RT-qPCR, and the activation status of relevant intracellular signaling pathways (MAPK, AKT and NF-kB) by Western blot. Osteoblast differentiation and activity was induced by osteogenic culture medium in the presence and absence of the same concentrations of Chalcone T4. Outcomes assessed were the formation of mineralization nodules via alizarin red staining and the expression of osteoblast-related genes (Alp e Runx2) by RT-qPCR. Chalcone T4 reduced RANKL-induced osteoclast differentiation and activity, suppressed Oscar, Acp5 and Mmp-9 expression, and decreased ERK and AKT activation in a dose-dependent manner. Nfact1 expression and NF-kB phosphorylation were not modulated by the compound. Mineralized matrix formation and the expression of Alp and Runx2 by MC3T3-E1 cells were markedly stimulated by Chalcone T4. Collectively, these results demonstrate that Chalcone T4 inhibits in osteoclast differentiation and activity and stimulates osteogenesis, which indicates a promising therapeutic potential in osteolytic diseases.

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Clinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses "in situ" using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1ß, IL-6 and TNF-α in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.

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Bisphosphonates are a group of drugs that can reduce bone resorption by incorporating into the crystal structure of exposed hydroxyapatite where they are taken up by osteoclasts. Bisphosphonates have several other mechanisms of action including reducing pain and inflammation and altering macrophage function. There are two types of bisphosphonates-nitrogenous and non-nitrogenous, the latter of which is used in horses. This article provides a literature-based review of the proposed mechanisms of action and therapeutic uses of bisphosphonates including a brief review of bone response to disease. A review of the literature available in horses including safety data and current rules and regulations is also provided.

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