Rapid Bone Resorption Research Articles

Role of Piezo1 in modulating the RANKL/OPG ratio in mouse osteoblast cells exposed to Porphyromonas gingivalis lipopolysaccharide and mechanical stress.

Excessive occlusal force with periodontitis leads to rapid alveolar bone resorption. However, the molecular mechanism by which inflammation and mechanical stress cause bone resorption remains unclear. We examined the role of Piezo1, a mechanosensitive ion channel expressed on osteoblasts, in the changes in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio in mouse MC3T3-E1 osteoblast-like cells under Porphyromonas gingivalis lipopolysaccharide (P.g.-LPS) and mechanical stress. To investigate the effect of P.g.-LPS and mechanical stress on the RANKL/OPG ratio and Piezo1 expression, we stimulated MC3T3-E1 cells with P.g.-LPS. After 3 days in culture, shear stress, a form of mechanical stress, was applied to the cells using an orbital shaker. Subsequently, to investigate the role of Piezo1 in the change of RANKL/OPG ratio, we inhibited Piezo1 function by knockdown via Piezo1 siRNA transfection or by adding GsMTx4, a Piezo1 antagonist. The RANKL/OPG ratio significantly increased in MC3T3-E1 cells cultured in a medium containing P.g.-LPS and undergoing mechanical stress compared to cells treated with P.g.-LPS or mechanical stress alone. However, the expression of Piezo1 was not increased by P.g.-LPS and mechanical stress. In addition, phosphorylation of MEK/ERK was induced in the cells under P.g.-LPS and mechanical stress. MC3T3-E1 cells treated with P.g.-LPS and mechanical stress when cocultured with RAW264.7 cells induced their differentiation into osteoclast-like cells. The increased RANKL/OPG ratio was suppressed by either Piezo1 knockdown or the addition of GsMTx4. Furthermore, GsMTx4 inhibited the phosphorylation of MEK/ERK. These findings suggest that P.g.-LPS and Piezo1-mediated mechanical stress induce MEK/ERK phosphorylation and increase RANKL expression in osteoblasts. Consequently, this leads to the differentiation of osteoclast precursor cells into osteoclasts.

Reduced osteoprotegerin expression by osteocytes may contribute to rebound resorption after denosumab discontinuation.

Denosumab is an anti-RANKL Ab that potently suppresses bone resorption, increases bone mass, and reduces fracture risk. Discontinuation of denosumab causes rapid rebound bone resorption and bone loss, but the molecular mechanisms are unclear. We generated humanized RANKL mice and treated them with denosumab to examine the cellular and molecular conditions associated with rebound resorption. Denosumab potently suppressed both osteoclast and osteoblast numbers in cancellous bone in humanized RANKL mice. The decrease in osteoclast number was not associated with changes in osteoclast progenitors in bone marrow. Long-term, but not short-term, denosumab administration reduced osteoprotegerin (OPG) mRNA in bone. Localization of OPG expression revealed that OPG mRNA is produced by a subpopulation of osteocytes. Long-term denosumab administration reduced osteocyte OPG mRNA, suggesting that OPG expression declines as osteocytes age. Consistent with this, osteocyte expression of OPG was more prevalent near the surface of cortical bone in humans and mice. These results suggest that new osteocytes are an important source of OPG in remodeling bone and that suppression of remodeling reduces OPG abundance by reducing new osteocyte formation. The lack of new osteocytes and the OPG they produce may contribute to rebound resorption after denosumab discontinuation.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

Linking the relation between gut microbiota and glucocorticoid-induced osteoporosis.

Osteoporosis (OP) is the most prevalent metabolic bone disease, characterized by the low bone mass and microarchitectural deterioration of bone tissue. Glucocorticoid (GC) clinically acts as one of the anti-inflammatory, immune-modulating, and therapeutic drugs, whereas the long-term use of GC may cause rapid bone resorption, followed by prolonged and profound suppression of bone formation, resulting in the GC-induced OP (GIOP). GIOP ranks the first among secondary OP and is a pivotal risk for fracture, as well as high disability rate and mortality, at both societal and personal levels, vital costs. Gut microbiota (GM), known as the "second gene pool" of human body, is highly correlated with maintaining the bone mass and bone quality, and the relation between GM and bone metabolism has gradually become a research hotspot. Herein, combined with recent studies and based on the cross-linking relationship between GM and OP, this review is aimed to discuss the potential mechanisms of GM and its metabolites on the OP, as well as the moderating effects of GC on GM, thereby providing an emerging thought for prevention and treatment of GIOP.

Site-specific characteristics of bone and progenitor cells in control and ovariectomized rats.

One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.

Neuropathic (Charcot) Arthropathy of the Knee.

Neuropathic arthropathy of the knee (Charcot knee) is a rare pathology defined by progressive destruction of bone and soft tissue in a patient with underlying peripheral neuropathy. Historically, Charcot knee was associated with neurosyphilis, but it has been increasingly described as a late stage of diabetes. The pathophysiology of the disease is not completely understood, but theories include repetitive microtrauma and an abnormal neurovascular response. Patients present with a warm, swollen, and unstable joint and have rapid bone resorption and characteristic findings on pathology. Nonsurgical options for pain and dysfunction include total contact casting and bracing treatment. Pharmacologic management includes diphosphonates, although this use is considered off-label. Surgical management historically included knee fusion. However, recent case series have suggested that newer prostheses allow for successful arthroplasty in this cohort, although complications are higher when compared with joint arthroplasty in patients with normal neurologic function.

A Case of Mandibular Prognathism with Generalized Aggressive Periodontitis and Crowding

Aggressive periodontitis during adolescence has a poor prognosis due to rapid alveolar bone resorption. Few studies have investigated long-term follow-up after surgical orthodontic treatment performed in conjunction with that for invasive periodontitis. Here, we report a case of mandibular prognathism accompanied by generalized aggressive periodontitis and crowding. A 31-year-old woman was referred to our department for treatment of masticatory dysfunction due to reverse overjet. The patient exhibited a class III molar relationship, protrusion of the ANB of －6.0°, and severe maxillary crowding. Initial periodontal examination revealed deep periodontal pockets and extensive inflammation. Mandibular prognathism accompanied by generalized aggressive periodontitis and crowding was diagnosed. Therefore, it was necessary to adopt an interdisciplinary approach involving surgical, orthodontic, and periodontal treatment. Prior to commencement of orthodontic treatment, plaque control, scaling, and root planing of all teeth were performed by a periodontist to suppress inflammation and reduce probing depth. During pre-surgical orthodontic treatment, the maxillary first premolars were extracted to reduce crowding of the maxillary incisors. To correct the mandibular prognathism, the mandible was repositioned by sagittal split ramus osteotomy. Proper occlusion of the incisors and maximum intercuspation were achieved by post-surgical orthodontic treatment. After completion of active orthodontic treatment, acceleration of inflammation was observed together with aggravated resorption of the alveolar bone surrounding the molars. However, reduction of probing depth and inflammation were observed after scaling and root planing. The surgical-orthodontic treatment time was 1 year and 11 months, which was followed by a 2-year retention period. There was no tooth loss due to periodontitis, and an overall satisfactory outcome was achieved.

Is This Rapid Destructive Hip Osteoarthritis ?

Rapid destructive hip osteoarthritis is a diagnosis by exclusion. It should be differentiated from septic arthritis, osteonecrosis, neuropathic arthritis and other aetiologies causing rapid bone resorption or destruction around the hip. The present study aims to review the incidence of rapid destructive hip osteoarthritis among those patients who request total hip arthroplasty for end stage arthrosis.A retrospective review of radiographs of all patients who scheduled for total hip arthroplasty from January 2010 to March 2019 were analysed by 3 orthopaedic fellows. Of 174 hips of 146 patients, 35 hips of 29 patients were considered by at least 2 orthopaedic fellows to have rapid destructive hip osteoarthritis based on radiographic criteria of rapid joint space narrowing or rapid destruction of femoral head with or without acetabular involvement. Clinical history and physical finding, blood biochemistry, cultures and pathology with or without frozen section are reviewed.Early total hip arthroplasty, rather than routine operation in the long waiting list, is recommended for rapid destructive hip osteoarthritis to prevent technical difficulty in dealing with the bone loss or defect associated with rapid destructive hip osteoarthritis. However, one must exclude septic arthritis before proceeding to total hip arthroplasty. In clinically highly suspected cases, staged total hip arthroplasty was done despite of normal initial blood investigationsand negative hip aspiration with equivocal frozen section on table. In one such patient, the culture was initially negative, but became positive only after extended period of culture. On the other hand, rapid destruction of acetabulum requiring impaction bone grafting and acetabular augmentation for total hip arthroplasty was needed in one patient. Malignancy was suspected in another patient, but there was no evidence of malignancy or infection in the femoral head and tissue obtained by excisional arthroplasty of hip. One patient with hip pain and bilateral hip involvement was found to have Charcot joint.Rapid destruction hip osteoarthritis represents an uncommon subset of arthrosis with rapid progression. A delicate balance between correct diagnosis and timely early operation should be exercised to prevent rapid loss of bone stock making delayed total hip arthroplasty become technical difficult with possible compromised outcomes.

Influences of gallium substitution on the phase stability, mechanical strength and cellular response of β-tricalcium phosphate bioceramics

β-tricalcium phosphate (β-TCP), a well-accepted synthetic bone grafting biomaterial, is confronted with limitations of poor phase stability and lacking the capacity to mediate the biological functions. In the current study, gallium (Ga) was substituted for calcium in the β-TCP, and the influences of Ga substitution on the phase stability, compressive strength and cellular response of β-TCP bioceramics were investigated. The results indicated that substitution of at least 2.5 mol% Ga for calcium prevented the β-TCP from transforming into α-TCP at 1250 °C. The β-TCP bioceramics substituted with 2.5 mol% Ga attained the highest compressive strength. The β-TCP bioceramics substituted with 2.5 and 5 mol% Ga showed good cytocompatibility, and suppressed in vitro osteoclastic activity as well as osteoblastic differentiation. Considering the favorable mechanical strength and the inhibitory effect on the osteoclastic activity, the β-TCP bioceramics substituted with 2.5 mol% Ga are promising for treating the bone defect in the pathological state of excessively rapid bone resorption.

Effects of combined chemical design (Cu addition) and topographical modification (SLA) of Ti-Cu/SLA for promoting osteogenic, angiogenic and antibacterial activities

Cu has been proved to possess various beneficial biological activities, while sandblasting and acid etching (SLA) is widely used to modify the commercial dental implant in order to improve osseointegration. Based on the above, a novel antimicrobial dental implant material, Ti-Cu alloy, was treated with SLA, to combine chemical design (Cu addition) and topographical modification (SLA). In this work, the effects of SLA treated Ti-Cu alloys (Ti-Cu/SLA) on osteogenesis, angiogenesis and antibacterial properties were evaluated from both in vitro and in vivo tests, and Ti/SLA and Ti-Cu (without SLA) were served as control groups. Benefiting by the combined effects of chemical design (Cu addition) and micro-submicron hybrid structures (SLA), Ti-Cu/SLA had significantly improved inhibitory effects on oral anaerobic bacteria (P. gingivalis and S. mutans) and could induce upregulation of osteogenic-related and angiogenic-related genes expression in vitro. More importantly, in vivo studies also demonstrated that Ti-Cu/SLA implants had wonderful biological performance. In the osseointegration model, Ti-Cu/SLA implant promoted osseointegration via increasing peri-implant bone formation and presenting good bone-binding, compared to Ti/SLA and Ti-Cu implants. Additionally, in the peri-implantitis model, Ti-Cu/SLA effectively resisted the bone resorption resulted from bacterial infection and meanwhile promoted osseointegration. All these results suggest that the novel multiple functional Ti-Cu/SLA implant with rapid osseointegration and bone resorption inhibition abilities has the potential application in the future dental implantation.

Facial alveolar bone alterations and gray value changes based on cone beam computed tomography around maxillary anterior implants: A clinical retrospective study of 1-3years.

The purpose of this cone beam computed tomography (CBCT) study was to describe facial alveolar bone alterations and gray value (GV) changes around implants in aesthetic anterior maxilla with simultaneous guided bone regeneration (GBR) and to investigate potential influence of factors related to vertical alveolar bone stability, such as particle sizes of the deproteinized bovine bone mineral (DBBM) used. A retrospective study design was adopted. Four facio-palatal cross-sectional CBCT images of 166 implants from 124 patients who had maxillary anterior implants were obtained. Measurements of the vertical facial alveolar bone level (VFBL), horizontal facial alveolar bone thickness (HFBT), and GV were identified of 1-3years. Then, correlation coefficients for those parameters were calculated. Finally, linear mixed models were established to investigate potential factors influencing vertical alveolar bone resorption. Facial alveolar bone underwent fast bone modeling and remodeling during the first 6months, with decreases of 1.00±1.19 and 0.74±0.86mm in VFBL and HFBT in implant shoulder, respectively, and there was positive and significant correlation between the alterations in VFBL and HFBT1 (rs =.516, p=.000). Linear mixed models identified particle size of DBBM as a critical factor associated with vertical bone resorption (p=.000). The GV gradually increased during the follow-up period. Rapid and unavoidable peri-implant bone resorption usually happened during the first 6months after implant placement. GBR is a predictable treatment for maxillary anterior implants, since GV has an increasing trend. Large bone particles of DBBM help maintain vertical alveolar bone stability.

How Autoantibodies Regulate Osteoclast Induced Bone Loss in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by autoimmunity that triggers joint inflammation and tissue destruction. Traditional concepts of RA pathogenesis have strongly been focused on inflammation. However, more recent evidence suggests that autoimmunity per se modulates the disease and in particular bone destruction during the course of RA. RA-associated bone loss is caused by increased osteoclast differentiation and activity leading to rapid bone resorption. Autoimmunity in RA is based on autoantibodies such as rheumatoid factor (RF) and autoantibodies against citrullinated proteins (ACPA). These autoantibodies exert effector functions on immune cells and on bone resorbing osteoclasts, thereby facilitating bone loss. This review summarizes potential pathways involved in increased destruction of bone tissue in RA, particularly focusing on the direct and indirect actions of autoantibodies on osteoclast generation and function.

Characterization of ligature-induced experimental periodontitis.

We sought to better characterize the progression of periodontal tissue breakdown in rats induced by a ligature model of experimental periodontal disease (PD). A total of 60 male Sprague-Dawley rats were evenly divided into an untreated control group and a PD group induced by ligature bilaterally around first and second maxillary molars. Animals were sacrificed at 1, 3, 5, 7, 14, and 21 days after the induction of PD. Alveolar bone loss was evaluated by histomorphometry and microcomputed tomography (μCT). The immune-inflammatory process in the periodontal tissue was assessed using descriptive histologic analysis and quantitative polymerase chain reaction (qPCR). This ligature model resulted in significant alveolar bone loss and increased inflammatory process of the periodontal tissues during the initial periods of evaluation (0-14 days). A significant increase in the gene expression of pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and proteins involved in osteoclastogenesis, receptor activator of nuclear factor-k B ligand (RANKL) and osteoprotegerin (OPG) was observed in the first week of analysis. In the later periods of evaluation (14-21 days), no significant alterations were noted with regard to inflammatory processes, bone resorption, and expression of cytokine genes. The ligature-induced PD model resulted in progressive alveolar bone resorption with two different phases: Acute (0-14 days), characterized by inflammation and rapid bone resorption, and chronic (14-21 days) with no significant progression of bone loss. Furthermore, the gene expressions of IL-6, IL-1β, TNF-α, RANKL, and OPG were highly increased during the progress of PD in the early periods. RESEARCH HIGHLIGHTS: Ligature-induced bone resorption in rats occurred in the initial periods after disease induction The bone resorption was characterized by two distinct phases: Acute (0-14 days), with pronounced inflammation and alveolar bone loss Chronic phase (14-21 days): No further disease progression Several pro-inflammatory cytokines were increased during the progress of periodontitis.

Analysis of bone metabolism during early stage and clinical benefits of early intervention with alendronate in patients with systemic rheumatic diseases treated with high-dose glucocorticoid: Early DIagnosis and Treatment of OsteopoRosis in Japan (EDITOR-J) study.

We conducted a prospective multicenter study to assess early changes in the dynamics of bone metabolism in patients with systemic connective tissue diseases following commencement of high-dose glucocorticoid therapy and the benefits of early treatment with bisphosphonate and vitamin D analogue. The subjects of this randomized controlled trial were 106 female patients with systemic connective tissue diseases treated for the first time with glucocorticoids at doses equivalent to prednisolone ≥20mg/day (age≥18years). One week after initiation of glucocorticoid therapy, patients were randomly assigned to treatment with alfacalcidol at 1μg/day (n=33), alendronate 35mg/week (n=37), and alfacalcidol plus alendronate (n=36). The primary endpoints were changes in lumbar spine bone density at 6months of treatment and the frequency of bone fracture at 12months. Commencement of glucocorticoid therapy was associated with a rapid and marked bone resorption within 1week. The combination of alfacalcidol and alendronate administered after the first week of glucocorticoid therapy halted the pathological processes affecting bone metabolism, increased bone density, and reduced the incidence of bone fracture over a period of 12months. Taken together, the use of the combination of alfacalcidol and alendronate improved bone metabolism, increased bone density, and significantly reduced the incidence of bone fracture during 1-year high-dose glucocorticoid therapy.

Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation.

Fibroblast growth factor 23 (FGF23), a central regulator of phosphate and vitamin D metabolism, is mainly produced by osteocytes in bone and exerts its effects on distant organs. Despite its endocrine function, the mechanism controlling serum FGF23 levels is not fully understood. Here we tested the hypothesis that osteoclastic bone resorption may play a role in regulating circulating levels of FGF23, using a mouse model where injections of interleukin (IL)-1β into the subcutaneous tissue over the calvaria induced rapid bone resorption. A significant amount of FGF23 was detected in the extracts from mouse bones, which supports the idea that FGF23 stays in bone for a while after its production. IL-1β-induced bone resorption was associated with elevated serum FGF23 levels, an effect abolished by pre-treatment with pamidronate. Fgf23 expression was not increased in either the calvariae or tibiae of IL-1β-injected mice, which suggests that IL-1β facilitated the entry of FGF23 protein into circulation by accelerating bone resorption rather than increasing its gene expression. The direct effect of IL-1β on bone was confirmed when it increased FGF23 levels in the conditioned media of mouse calvariae in organ culture. Repeated treatment of the cultured calvariae with IL-1β led to a refractory phase, where FGF23 was not mobilized by IL-1β anymore. Consistent with the in vivo results, treatment with IL-1β failed to increase Fgf23 mRNA in isolated primary osteocytes and osteoblasts. These results suggest that FGF23 produced by osteocytes remains in bone, and that rapid bone resorption facilitates its entry into the bloodstream.

Successful rehabilitation of partial edentulous maxilla and mandible with new type of implants: molecular precision implants.

The extraction of teeth results in rapid bone resorption both vertically and horizontally in the first month. The loss of alveolar ridge reduces the chance of implant rehabilitation. Atraumatic extraction, implant placement in extraction socket, and an immediate prosthesis have been proposed as alternative therapies to maintain the volume and contours tissue and reduce time and cost of treatment. The immediate load of implants is a universally practiced procedure; nevertheless a successful procedure requires expertise in both the clinical and the reconstructive stages using a solid implant system. Excellent primary stability and high bone-implant contact are only minimal requirements for any type of implant procedure. In this paper we present a case report using a new type of implants. The new type of implants, due to its sophisticated control system of production, provides to the implantologist a safe and reliable implant, with a macromorphology designed to ensure a close contact with the surrounding bone.

Residual bone height measured by panoramic radiography in older edentulous Korean patients

PURPOSEThe aim of this study was to obtain statistical data on the residual bone height at different natural tooth positions by panoramic radiography in edentulous Korean patients aged 60-90 years.MATERIALS AND METHODSThe study included the diagnostic panoramic radiographs of 180 randomly selected edentulous patients without systemic diseases affecting bone. The radiographic selection criteria included absence of obvious facial asymmetry, clearly visible anatomic structures, and no surgical and fracture history. The panoramic radiographs of 79 patients met these criteria and were used in the analysis. The same researcher processed all the radiographs by using a standardized method. The height of the residual bone was measured at 18 predetermined sites (7 in the maxilla and 11 in the mandible) on digitized and printed radiographs by using a Digimatic caliper, triangle, and ruler. Gender- and age-related differences were statistically analyzed by using the t-test and rank-sum test (α=0.05).RESULTSThe maxillary residual bone height did not show significant gender-related differences, but male patients had significantly higher residual bone in the mandible(P<.05). No significant height differences at the measured sites were noted among the 60s, 70s, and 80s age groups.CONCLUSIONDentists should pay greater attention to older female edentulous patients because they are more prone to rapid residual bone resorption. Residual bone resorption may not be affected by age.

Evaluasi Pemberian Bahan Allograft dan Alloplast pada Penderita Periodontitis Agresif Menyeluruh dengan Genotipe Positif Alel 2 (+3954) Interleukin-1 Beta

Generalized aggressive periodontitis is a disease or a disorder of periodontium that occurs in people below 30 years old. These patients usually have several immune response disorders, such as defects in chemotaxis, phagocytic of neturophils and monocytes, and genetic defect. Clinically, there are generalized losses of tissue attachment with extensive, rapid and progressive alveolar bone resorption. In order to repair bone destruction, treatment that produce bone regeneration is needed, i.e. full thickness flap with bone grafting. In these cases, allograft and alloplast bone grafts were used. Allograft is derived from subjects within the same species but different individuals, whereas alloplast is foreign body embedded into the tissue (e.g. hydroxylapatite). In this report, pocket depth, papillae bleeding index (PBI), and clinical attachment were evaluated. Six month after surgery and bone grafting, there were + 4 mm decrease of pocket depths, bleeding on probing index and 3-4 mm increase of clinical attachment. Unstimulated wholes saliva were also collected for DNA isolation. The IL-1beta(+3954) genotypes were performed by Polymerase chain reaction, digested with TagI restriction enzyme and separated by gel electrophoresis. Results showed both patients bearing allele 2 homozygous of IL-1B+3954 genotype. This genotype has been identified as the one of immunogenetic factor that could affect the severity of periodontal disease. Successful treatment depends on the adequacy of oral hygiene. Patients were advised to maintain optimal oral hygiene and to do periodic check every 2-3 months. DOI: 10.14693/jdi.v15i2.70

Differential regulation of HIF‐mediated pathways increases mitochondrial metabolism and ATP production in hypoxic osteoclasts

Inappropriate osteoclast activity instigates pathological bone loss in rheumatoid arthritis. We have investigated how osteoclasts generate sufficient ATP for the energy-intensive process of bone resorption in the hypoxic microenvironment associated with this rheumatic condition. We show that in human osteoclasts differentiated from CD14+ monocytes, hypoxia (24 h, 2% O2): (a) increases ATP production and mitochondrial electron transport chain activity (Alamar blue, O2 consumption); (b) increases glycolytic flux (glucose consumption, lactate production); and (c) increases glutamine consumption. We demonstrate that glucose, rather than glutamine, is necessary for the hypoxic increase in ATP production and also for cell survival in hypoxia. Using siRNA targeting specific isoforms of the hypoxia-inducible transcription factor HIF (HIF-1α, HIF-2α), we show that employment of selected components of the HIF-1α-mediated metabolic switch to anaerobic respiration enables osteoclasts to rapidly increase ATP production in hypoxia, while at the same time compromising long-term survival. We propose this atypical HIF-driven metabolic pathway to be an adaptive mechanism to permit rapid bone resorption in the short term while ensuring curtailment of the process in the absence of re-oxygenation. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Charcot arthropathy presenting with primary bone resorption

BackgroundThe clinical presentation of acute Charcot arthropathy in the diabetic population usually follows the Eichenholtz classification. We present three usual cases of Charcot arthropathy presenting with rapid primary bone resorption in the absence of subluxation, dislocation and/or fracture. MethodsA review of the literature was performed. To our knowledge Charcot arthropathy has not been previously described as primary bone resorption. Case reportsThree cases encountered at our specialist multidisciplinary High Risk Foot Clinic (HRFC) presented with primary bony resorption without features of subluxation, dislocation and/or fracture. DiscussionAggressive primary bone resorption was initially thought due to infection; a diagnostic dilemma that delayed optimal treatment. Late bone resorption in typical Charcot is linked to unregulated proinflammatory cytokines (IL-1β, IL-6 and TNFα) that lead to increased osteoclastic activity. The pathophysiology of osteolysis in aggressive primary bony resorption may relate to a disturbance in the balance between RANK-L and OPG. ConclusionPrimary resorption of bone without subluxation, dislocation and/or fracture can represent an active Charcot process. Prudent use of serial radiography and early MRI to look for the widespread bone and soft tissue oedema is recommended.