Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells

BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.

Research progress of bone sialoprotein in osteoclast differentiation and bone resorption

Bone sialoprotein(BSP)is an important non-collagen extracellular matrix protein(EMC)that promotes bone formation and induces bone resorption.BSP is secreted by odontoblasts,it plays an important role in cementum,alveolar bone formation and mineralization,and periodontal function.Bone resorption is controlled by a complex molecular network,and BSP can promote osteoclast differentiation and bone resorption.It is also associated with the metastasis of a range of malignancies.Osteoclasts(OC)are thought to be the only cells involved in bone resorption and play an important role in bone formation and late developmental remodeling.Osteoporosis and periodontal disease are caused by excessive bone resorption.This article will summarize the osteoclasts differentiation,the biological function of bone resorption,and explore the progress of the prevention and treatment of the related bone resorption diseases such as osteoporosis and periodontal disease through the regulation of osteoclasts.

The association between the baseline bone resorption marker CTX and incident dysglycemia after 4 years

Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.

Iguratimod, a Disease-Modifying Anti-Rheumatic Drug, Inhibits Osteoclastogenesis and Bone Resorption through Suppression of the Nuclear Factor of Activated T Cells Signaling Pathway

Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.

Estrogen enhances the functions of CD4^(+)CD25^(+)Foxp3^(+) regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro

Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).

Urine products of bone breakdown as markers of bone resorption and clinical usefulness of urinary hydroxyproline:an overview

Purpose The purpose of this study is to review the urine products of bone breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.Data Related researches published in 1985 -2000 were systematically reviewed.Results Bone markers could be used for early diagnosis of bone metabolic diseases. Biochemical markers of bone resorption that reflect osteoclast activity and/or collagen degradation provide a new and potentially important clinical tool for the assessment and monitoring of bone metabolism. Assessment of bone resorption can be achieved with measurement of urinary hydroxylysine glycosides, urinary excretion of the collagen pyridinium cross-links, urinary excretion of type I collagen telopeptide breakdown products (cross-linked telopeptides) and urinary hydroxyproline.Conclusion Urinary hydroxyproline has been in use as a marker of bone resorption, but it lacks sensitivity and specificity. It is a modified aminoacid that is a metabolic product of collagen breakdown. Hydroxyproline may be released either free or with fragments of the collagen molecule attached during bone resorption, and it is also liberated by the breakdown of complement and nonskeletal collagen.

The effects of icariine concentration on osteoclasts bone resorption induced by titanium particles in vitro

In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.

Transient bone resorption following finger replantation： a report of 3 cases

Radiographic changes consisting of al- terations in mineral content, osteopaenia or destructive neuropathy that occur following successful finger replantation have already been described. We report our experience about four fingers in three individuals in whom bone changes developed in the first three months postoperatively with complete ＂restitution ad integrum＂. Three patients, 21-49 years old （average 36 years） sustained a clean-cut amputation of four fingers. The first patient had an amputation at the base of the middle phalanx of the index finger and the second patient at the base of the proximal phalanx of the ring finger. The third had an amputation at the base of the first metacarpal bone and the proxi- mal phalanx of the small finger in a five finger amputation. In the first case, two dorsal veins and two palmar digital arteries and nerves were repaired. In the second case, one pal- mar artery and one dorsal vein were reanastomosed. In the third case at the thumb, two dorsal veins and two palmar digital arteries and nerves were reconstructed. At the small finger, one dorsal vein, one palmar digital artery and twodigital nerves were reconstructed. Bone fixation was achieved with two and three K-wires or tension-band wiring. Replantation was successful in all cases. Three weeks after replantation, the X-rays showed rapid development of osteopaenia in the juxtaarticular region and metaphyses of the bone. These changes were followed by subperiosteal, intracortical and endosteal bone resorption. No further surgical procedures or splintage were needed and hand therapy was not discontinued. At 10-13 weeks （average 12 weeks） postoperatively, the X-rays showed a complete recovery with new periosteal bone formation. We suggest that the radiographic changes after finger replantation are transient, first evident subperiosteally and progressing centrally. They may reflect small-vessel compromise and microinfarction and transient hyperemia secondary to neurovascular damage or to sympathetic progressive recovery.

Oral administration of egg white ovotransferrin prevents osteoporosis in ovariectomized rats

Ovotransferrin,an iron-binding glycoprotein,accounting for approximately 12%of egg white protein,is a member of transferrin fam ily.Our previous studies showed that ovotransferrin stimulates the proliferation and differentiation of osteoblasts,while inhibits osteoclastogenesis and resorption activity.The work aims to study the efficacy of orally administered ovotransferrin on the prevention of osteoporosis using ovariectomized(OVX)Sprague-Dawley rats.Oral administration of ovotransferrin showed no negative effect on body weight,food intake and organ weight.After 12-week treatment,feeding ovotransferrin at a dose of 1%(1 g ovotransferrin/100 g diet)prevented OVX-induced bone loss and maintained relatively high bone mineral density and integrated bone microarchitecture.The serum concentration of biomarkers indicating bone formation was increased in ovotransferrin administration groups,while the bone resorption biomarkers were decreased.Ovotransferrin feeding also decreased the production of serum cytokine TNF-αand IL-6,which are two stimulators for osteoclast differentiation.In addition to its direct regulatory role on bone turnover,ovotransferrin supplementation might benefit osteoporosis prevention by inhibiting adipogenesis,and regulating immune response.Our results suggested the potential application of ovotransferrin as a functional food ingredient on the prevention of osteoporosis.

Research Progress on the Immunomodulatory Effect of Mesenchymal Stem Cells on Chronic Periodontitis

Periodontal disease is an inflammatory and destructive disease of periodontal support tissue caused by microorganisms in dental plaque. During the development of periodontal disease, host immune regulation plays an important role, and unnecessary excessive immune regulation often exacerbates the course of chronic periodontal disease. Mesenchymal stem cells (MSCs) are adult stem cells with self replication ability and multi-directional differentiation potential. Many studies have found that MSCs have strong immunosuppressive effects on both adaptive and innate immunity. In recent years, literature has reported that MSCs are involved in the immune regulatory effect of chronic periodontal disease, inhibiting its inflammatory response and alveolar bone resorption, but the specific regulatory mechanism has not been elucidated. This article reviews the current research status of the immune regulatory effects of MSCs on chronic periodontitis.

Effects of Lanthanum on Formation and Bone-Resorbing Activity of Osteoclast-Like Cells

The effect of La^(3+) on formation of osteoclast-like cells in rabbit bone marrow cells induced by 1,25-dihydroxyvitamin D_3 and their bone-resorbing activity was evaluated by counting the number of tartrate resistant-acid phosphatase-positive [TRAP(+)] multi-nucleated cells and measuring the number and surface area of bone resorption pits with photomicrography and image analysis. The formation and morphological characteristics of osteoclast-like cells and bone resorption pits were observed under a phase contrast inverted microscope. La^(3+) promotes the formation of osteoclast-like cells at the concentration of 1.00×10^(-8)mol·L^(-1) compared with the control group(P<(0.01)), whereas no significant change in cell number is observed at higher concentrations(1.00×10^(-5), (1.00×)10^(-6) and 1.00×10^(-7) mol·L^(-1))(P>0.05). La^(3+) at the concentration of 1.00×10^(-8)mol·L^(-1) also increases the number and surface area of the resorption pits(P<0.01), but inhibits the bone-resorbing activity dose-dependently(P<0.01)at higher concentrations(1.00×10^(-5), 1.00×10^(-6) and 1.00×10^(-7) mol·L^(-1)). These findings suggest that La^(3+) may promote or inhibit the formation and bone-resorbing activity of osteoclast-like cells depending on its concentration.

Effects of Lanthanum on Bone Resorbing Activity of Rabbit Mature Osteoclasts Co-Cultured with Osteoblasts

The effects of lanthanum （Ⅲ） on the bone resorbing activity of rabbit mature osteoclasts （OCs） in the presence of osteoblasts （OBs） were studied in vitro by measuring the number and area of absorption pits. La（ Ⅲ ） at concentrations ranging from 1.00 × 10^-5 to 1.00 × 10^-8 mol·L^-1 show no effect on mature OC number （P 〉 0.05）. In the OC-OB coculture systems without La（Ⅲ ）, osteoblasts alone did not influence the pit number and area whether the two kinds of cells were in contact or not （ P 〉 0.05）. Under the OC-OB not-in-contact condition, the effect of La（ Ⅲ ） on the bone-resorbing activity of OCs was similar to that of La（Ⅲ） in the absence of OBs （P 〉 0.05）. However, while OCs were in direct contact with OBs, the inhibitory effects of La（ Ⅲ ） on OCs＇ bone-resorbing activity decreased at the concentrations of 1.00 × 10^-5, 1.00×10^-6 and 1.00×10^-7mol·L^-1, and the promotion effects increased at 1.00×10^-8mol·L^-1 （P 〈0.05）. The results suggest that direct cell-cell contact between OC and OB be essential for OBs to play their role in regulating the response of OCs to La（ Ⅲ ）.

microRNA Expression in Rat Apical Periodontitis Bone Lesion

Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various biological processes, osteoclastogenesis included. This study aims to investigate the differential expression of miRNAs in rat apical periodontitis and explore their functional target genes. Microarray analysis was used to identify differentially expressed miRNAs in apical periodontitis. Bioinformatics technique was applied for predicting the target genes of differentially expressed miRNAs and their biological functions. The result provided us with an insight into the potential biological effects of the differentially expressed miRNAs and showed particular enrichment of target genes involved in the MAPK signaling pathways. These findings may highlight the intricate and specific roles of miRNA in inflammation and osteoclastogenesis, both of which are key aspects of apical periodontitis, thus contributing to the future investigation into the etiology, under- lying mechanism and treatment of apical periodontitis.

Expression of Matrix Metalloproteinase-9 mRNA in Osteoporotic Bone Tissues

Matrix metalloproteinases (MMPs), a sort of irnportant enzymes involved in extracellular matrix metabolism, play critical r0Ies in the process of tissues remodeling, wound healing and metastasis of tumors. Dot blot and in situ hybridization were used in this study to detect the expression and localization of MMP- 9, an important proteolytic enzyme implicated in bone resorption, in bone tissues. The results showed that the level of MMP-9 mRNA expression in osteoporotic bone tissues was significantly higher than that in normal control group and the cell types that expressed MMP-9 mRNA incIuded mono- and multi-nuclear osteoclasts and some lining cells on the surface of bone matrix. It was suggested that MMP-9 play a key role in the development of bone loss in osteoporosis.

Two bone blocks sandwich technique for horizontal reconstruction of severely atrophic alveolar ridge in anterior maxilla: A case report

BACKGROUND Severe horizontal bone deficiency of the maxillary anterior region is considered a major challenge in reconstruction and successful implant placement.Various approaches have been developed to augment bone volume.Of these approaches,onlay bone graft,alveolar bone splitting,and guided bone regeneration have been suggested.CASE SUMMARY A 22-year-old female patient,with no previous medical history,presented to the Department of Oral Implantology,Wuhan University due to a missing right maxillary incisor.The X-ray results showed severe horizontal bone deficiency,with an available bone width of 3.1-4.0 mm.The two bone blocks sandwich technique was performed to augment the bone volume.After 6 months healing,X-ray results showed that the newly formed alveolar ridge dimension increased to 4.7-9.5 mm horizontally.Implant insertion surgery was performed and allceramic restorations were fabricated.The implant was stable at the 1-year followup visit after restoration,and the X-ray showed a stable bone level around the dental implant.The scores for the pink esthetic score and white esthetic score were 12 and 8,respectively,and the patient was satisfied with the esthetic outcome.CONCLUSION The two bone blocks sandwich technique may be an alternative treatment option in augmenting severe horizontal bone deficiency of the anterior maxilla.

Inhibition of Rgs10 Expression Prevents Immune Cell Infiltration in Bacteria-induced Inflammatory Lesions and Osteoclast-mediated Bone Destruction

Regulator of G-protein Signaling 10 （Rgsl0） plays an important function in osteoclast differentiation. However, the role of Rgsl0 in immune cells and inflammatory responses, which activate osteoclasts in inflam- matory lesions, such as bacteria-induced periodontal disease lesions, remains largely unknown. In this study, we used an adeno-associated virus （AAV-） mediated RNAi （AAV-shRNA-Rgs10） knockdown approach to study Rgsl0＇s function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease. We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption, in vitro and in vivo. Interestingly, local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells, T-cells and osteoclasts, and protected the periodontal tissues from local inflammatory damage and bone destruction. Importantly, AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines. Our results demonstrate that AAV- shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously. Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation, as well as the subsequent stimulation of T-cell proliferation and maturation, and osteoclast differentiation and acti- vation. Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.

Postprandial response of bone turnover markers in patients with Crohn's disease

AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.

Significant association of a single nucleotide polymorphism in the upstream region of FGFR1OP2/wit3.0 gene with residual ridge resorption of mandible in Saudis

Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis.This study aimed to investigate the role of single nucleotide polymorphisms(SNPs)in fibroblast growth factor receptor 1 oncogene partner 2(FGFR1OP2)in RRR development in Saudis.The study included 192 individuals(RRR=96;controls=96)attending outpatient clinics at the College of Dentistry,King Saud University.Demographic and clinical data were collected,the digital panoramic dental radiograph was obtained,and mandibular residual ridge height was measured.DNA was extracted from saliva and genotyping was conducted on“Sequenom MassARRAY iPLEX”.Genotype and allele frequencies of three SNPs were calculated and compared.The age at first diagnosis and bone height were compared in the three genotypes of each SNP.The age of the patients,age at first edentulism,and bone height ranged 21-80 years,12-70 years,and 13-34.6 mm,respectively.All three genotypes of the studied SNPs(rs2279351,rs78054962 and rs2306852)were identified.SNP rs2279351 associated significantly with RRR,and the mutant C allele was highly predisposing.No association was observed for the other two SNPs.The genotypes of all SNPs had an influence on age at first edentulism and bone height,but the results were not statistically different.Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity,it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone.SNP rs2279351 may alter its expression and hence RRR development.This study is limited due to small a sample size,and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.

Hip prosthetic loosening and periprosthetic osteolysis:A commentary

Prosthetic loosening and periprosthetic osteolysis have been debated for decades,both in terms of the timing and nature of the triggering events.The hypothesis of wear-particle-induced loosening states that wear particles cause a foreign-body response leading to periprosthetic osteolysis and ultimately to late prosthetic loosening,i.e.,that the osteolysis precedes the loosening.The theory of early loosening,on the other hand,postulates that the loosening is already initiated during or shortly after surgery,i.e.,that the osteolysis is secondary to the loosening.This commentary focuses on the causal relationship between prosthetic loosening and periprosthetic osteolysis.

Hip prosthetic loosening:A very personal review

Hip prosthetic loosening is often difficult to detect at an early stage,and there has been uncertainty for a long time as to when the loosening occurs and thus to the basic causes.By comparing different diagnostic methods,we found that loosening is best defined as prosthetic migration and measured by radiostereometric analysis.Convincing evidence indicates that poor interlock,poor bone quality,and resorption of a necrotic bone bed may initiate loosening during or shortly after surgery;this forms the basis of the theory of early loosening.Biomechanical factors do affect the subsequent progression of loosening,which may increase subclinically during a long period of time.Eventually,the loosening may be detected on standard radiographs and may be interpreted as late loosening but should to be interpreted as late detection of loosening.The theory of early loosening explains the rapid early migration,the development of periprosthetic osteolysis and granulomas,the causality between wear and loosening,and largely the epidemiology of clinical failure of hip prostheses.Aspects discussed are definition of loosening,the pattern of early migration,the choice of migration threshold,the current understanding of loosening,a less exothermic bone cement,cemented taper-slip stems,a new exciting computed tomography-based technique for simpler implant migration studies,and research suggestions.