SPECT/CT of Total Ankle Arthroplasty.

Use of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) is increasing providing additional information in patients with inconclusive clinical examination and unremarkable imaging findings presenting with chronic pain after total ankle arthroplasty. To differentiate the cause of pain after total ankle arthroplasty can be challenging. SPECT/CT combines structural and metabolic imaging as a hybrid tool leading to higher specificity and overall diagnostic accuracy presumably in cases of gutter impingement, prosthetic loosening, and osteoarthritis of adjacent joints. Moreover, SPECT/CT can complement diagnostic work up in periprosthetic joint infections. Basal tracer enhancement has to be considered for the interpretation of imaging findings.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg−/−) mice and ten wild-type animals (Ahsg+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (µCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg−/− mice compared with corresponding Ahsg+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg−/− mice were significantly increased (p = 0.002) compared with Ahsg+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment.

Medium Activity Prevents Periprosthetic Bone Mass Loss in the Medial Metaphyseal Region of the Tibia after Posterior-Stabilized TKA: A 5-Year Follow-up Study of 110 Knees.

OBJECTIVE: The bone mass around the prosthesis plays an important role in the stability of the prosthesis. This study aimed to assess the effect of postoperative activity on bone mineral density (BMD) in the proximal tibia 5 years after total knee arthroplasty (TKA). To provide a scientific guidance for postoperative functional exercise. METHODS: 110 patients underwent unilateral primary TKA were divided into three groups based on the University of California Los Angeles (UCLA) activity scale: low activity group (LA group, UCLA = 4, 5); medium activity group (MA group, UCLA = 6, 7); and high activity group (HA group, UCLA = 8, 9). The primary observation was a comparison of the BMD and BMD change percentage (ΔBMD (%)) in the periprosthetic tibia among the LA, MA and HA groups at 1 year, 3 years and 5 years. The secondary observations were radiographic evaluation (prosthetic stability, periprosthetic fractures, aseptic loosening and periprosthetic joint infection) and clinical evaluation (Knee Society Score (KSS), visual analogue score scores and range of motion (ROM)). A one-way ANOVA was used to compare the clinical scores and BMD among the three groups. RESULTS: The BMD of medial region decreased by 10.80%, 12.64%, 13.61% at 1, 3, and 5 years respectively; these were 5.72%, 6.26%, 7.83% in lateral region and 1.42%, 1.78%, 3.28% in diaphyseal region. For medial metaphyseal region, the BMD of the MA group was significantly greater than that of the LA and HA groups at 1 and 3 years (108.9 ± 5.2 vs. 106.1 ± 6.69 vs. 105.4 ± 5.2 and 108.5 ± 6.0 vs. 101.2 ± 6.76 vs. 103.0 ± 6.8, P < 0.01 and P < 0.001), and the BMD changes (ΔBMD (%)) in the MA group were significantly smaller than those in the LA and HA groups (8.75 ± 5.36 vs. 11.92 ± 5.49 vs. 12.70 ± 5.21 and 9.11 ± 5.11 vs. 16.04 ± 4.79 vs. 14.82 ± 4.26, P < 0.01 and P < 0.001). Regarding secondary observations, all of the prostheses were assessed as stable, without periprosthetic fractures, aseptic loosening and periprosthetic joint infection. Regarding KSS scores, there was no significant difference among the three groups. However, the VAS and ROM of the HA group were better than those of the MA and LA groups (1.65 ± 0.79 vs. 2.63 ± 0.77 vs. 3.00 ± 1.17, p < 0.001, and 111.90 ± 9.17 vs. 110.20 ± 6.78 vs. 102.90 ± 8.48, P < 0.001). CONCLUSION: Medium activity prevented periprosthetic bone loss in the medial metaphyseal region of the tibia after posterior-stabilized TKA, and moderate-intensity exercise is recommended for patients after TKA to reduce periprosthetic bone loss.

Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis.

Background: Aseptic loosening of prosthesis (ALP) is one of the most common long-term complications of knee and hip arthroplasty. Wear particle-induced osteoclastogenesis and subsequent periprosthetic osteolysis account for the morbidity of ALP. Here, we investigate the potential of cimifugin (CIM), a natural extract from Cimicifuga racemosa and Saposhnikovia divaricata, as a bone-protective drug in the treatment of ALP. Method: First, we performed cell viability and osteoclast formation assays to assess the effect of noncytotoxic CIM on osteoclast differentiation in vitro. Bone slice resorption and F-actin ring immunofluorescence assays were adopted to assess the effects of CIM on bone-resorption function. Then, quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to further assess the repressive effects of CIM on osteoclastogenesis at the gene expression level. To elucidate the mechanisms underlying the above findings, Western blot and luciferase reporter gene assays were used to assess the regulatory effects of CIM on the NF-κB and MAPK signaling pathways. Moreover, a Ti particle-induced murine calvarial osteolysis model and subsequent histomorphometric analysis via micro-CT and immunohistochemical staining were used to elucidate the effect of CIM on periprosthetic osteolysis in vivo. Result: CIM dose-dependently inhibited both bone marrow-derived macrophage (BMM)- and RAW264.7 cell-derived osteoclastogenesis and bone resorption pit formation in vitro, which was further supported by the reduced expression of F-actin and osteoclast-specific genes. According to the Western blot analysis, inhibition of IκBα phosphorylation in the NF-κB signaling pathway, not the phosphorylation of MAPKs, was responsible for the suppressive effect of CIM on osteoclastogenesis. Animal experiments demonstrated that CIM alleviated Ti particle-induced bone erosion and osteoclast accumulation in murine calvaria. Conclusion: The current study suggested for the first time that CIM can inhibit RANKL-induced osetoclastogenesis by suppressing the NF-κB signaling pathway in vitro and prevent periprosthetic osteolysis in vivo. These findings suggest the potential of CIM as a therapeutic in ALP.

SPHK Inhibitors and Zoledronic Acid Suppress Osteoclastogenesis and Wear Particle-Induced Osteolysis.

Background: Inflammatory osteolysis induced by wear particles is the major cause of prosthetic loosening after artificial joint replacement, and its prevention and treatment are difficult worldwide. Our previous study confirmed that sphingosine kinases (SPHKs) are important mediators regulating the wear particle-induced macrophage inflammatory response. However, it is unclear whether SPHKs can modulate chronic inflammation and alleviate osteolysis. Zoledronic acid (ZA), an imidazole-containing bisphosphonate, directly affects osteoclasts and prevents bone mineral-related diseases. However, the effects of SPHK inhibitors and ZA used to treat periprosthetic osteolysis are unknown. Methods: We applied tartrate-resistant acid phosphatase (TRAP) staining to evaluate bone destruction in the interface membranes of patients with aseptic loosening and a control group. A murine calvarial osteolysis model was used to examine the preventative effect of SPHK inhibitors and ZA on osteolysis. Micro-CT scanning, immunohistochemistry (IHC), and histomorphometric analysis were conducted to determine the variations in inflammatory osteolysis. The effects of different drug concentrations on cell viability were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to confirm the reduced expression of osteoclast-specific genes after drug and titanium treatment. The osteoclast formation and functions of the drugs were analyzed using TRAP staining in vivo and in vitro. The effect of SPHKs/S1P-TRAF2-BECN1 signaling pathways was verified via RT-qPCR and tissue IHC. Results: In this study, we found that SPHK inhibitors (ABC294640 and FTY720) combined with ZA decreased the degree of inflammatory osteolysis in vivo. However, ABC294640 and ZA suppressed osteoclast differentiation and osteoclast-specific genes in vitro. SPHKs regulate the inflammatory osteolysis induced by wear particles by increasing the expression of SPHKs/S1P-TRAF2-BECN1. Conclusion: Our study revealed that wear particles could induce inflammatory osteolysis by upregulating SPHKs/S1P-TRAF2-BECN1 and SPHK inhibitors/ZA inhibit osteoclastogenesis in vitro and prevent inflammatory osteolysis in vivo, suggesting that SPHK inhibitors and ZA can be a new perspective and scientific basis for the prevention and treatment of prosthesis loosening.

Occult Hip Prosthetic Loosening Diagnosed by [18F] Fluoride-PET/CT.

BACKGROUND: Positron emission tomography using the [18F] fluoride metabolite combined with computerized tomography (F-PET/CT) can be used to analyze the metabolic status of the periprosthetic bone after surgery for total hip arthroplasty. METHODS: To obtain normal PET referent values, 44 patients with 5 models of well-functioning hip prosthetic components were analyzed by F-PET/CT, radiography, and clinical score. Another group of patients having painful total hip arthroplasty, but whose radiography showed no conclusive signs of loosening, was analyzed by F-PET/CT scans before revision surgery. RESULTS: Preoperative median F-PET scores of the bone metabolic activity were 6.65 (3.3-9.0) for the painful stem group and 1.85 (1.2-3.9) (P < .01) for the referent group having the same stem model. At revision surgery, the stems in the painful group were assessed to be loose. At 2-year follow-up, the revised patients were all pain free. CONCLUSION: F-PET/CT may be a new diagnostic tool for assessing occult loose stems that are not seen by radiography.

Tussilagone Inhibits Osteoclastogenesis and Periprosthetic Osteolysis by Suppressing the NF-κB and P38 MAPK Signaling Pathways.

BACKGROUND: Aseptic prosthetic loosening is one of the main factors causing poor prognosis of limb function after joint replacement and requires troublesome revisional surgery. It is featured by wear particle-induced periprosthetic osteolysis mediated by excessive osteoclasts activated in inflammatory cell context. Some natural compounds show antiosteoclast traits with high cost-efficiency and few side effects. Tussilagone (TUS), which is the main functional extract from Tussilago farfara generally used for relieving cough, asthma, and eliminating phlegm in traditional medicine has been proven to appease several RAW264.7-mediated inflammatory diseases via suppressing osteoclast-related signaling cascades. However, whether and how TUS can improve aseptic prosthetic loosening via modulating osteoclast-mediated bone resorption still needs to be answered. METHODS: We established a murine calvarial osteolysis model to detect the preventative effect of TUS on osteolysis in vivo. Micro-CT scanning and histomorphometric analysis were used to determine the variation of bone resorption and osteoclastogenesis. The anti-osteoclast-differentiation and anti-bone-resorption bioactivities of TUS in vitro were investigated using bone slice resorption pit evaluation, and interference caused by cytotoxicity of TUS was excluded according to the CCK-8 assay results. Quantitative polymerase chain reaction (qPCR) analysis was applied to prove the decreased expression of osteoclast-specific genes after TUS treatment. The inhibitory effect of TUS on NF-κB and p38 MAPK signaling pathways was testified by Western blot and NF-κB-linked luciferase reporter gene assay. RESULTS: TUS better protected bones against osteolysis in murine calvarial osteolysis model with reduced osteoclasts than those in the control group. In vitro studies also showed that TUS exerted antiosteoclastogenesis and anti-bone-resorption effects in both bone marrow macrophages (BMMs) and RAW264.7 cells, as evidenced by the decline of osteoclast-specific genes according to qPCR. Western blotting revealed that TUS treatment inhibited IκBα degradation and p38 phosphorylation. CONCLUSIONS: Collectively, our studies proved for the first time that TUS inhibits osteoclastogenesis by suppressing the NF-κB and p38 MAPK signaling pathways, therefore serving as a potential natural compound to treat periprosthetic osteolysis-induced aseptic prosthetic loosening.

DAPT inhibits titanium particle-induced osteolysis by suppressing the RANKL/Notch2 signaling pathway.

Artificial prosthesis is wildly used in clinical medicine for degenerative disease such as osteoclast-related diseases. However, the material wear particles released from the surface of prostheses cause prosthetic loosening as a result of aseptic osteolysis in long-term use. Therefore, it is important to find an agent that inhibits the formation and function of osteoclast for therapeutic use. Notch signaling pathway plays a lot of roles in cell proliferation, differentiation, and apoptosis. However, the role of Notch signaling pathway in osteoclastogenesis remains unclear. The aim of this study is to assess the effects of γ-secretase inhibitor DAPT on osteoclastogenesis via Notch signaling pathway in vitro and titanium particle-induced osteolysis in vivo. In animal experiments, the inhibitory effect of DAPT on titanium particle-induced osteolysis in a mouse calvaria model was demonstrated. Interestingly, few resorption pits were observed following administration of DAPT and almost no osteoclasts formed at high concentration of DAPT. in vitro experiments revealed the mechanism of the effects of DAPT on osteoclastogenesis. DAPT inhibited the formation and function of osteoclast by blocking RANKL-induced Notch2-NF-κB complex signaling pathway. In conclusion, these results indicated that DAPT could prevent and cure titanium particle-induced prosthetic loosening and other osteoclast-related diseases.

Is early migration enough to explain late clinical loosening of hip prostheses?

Prosthetic loosening has been debated for decades, both in terms of the timing and nature of the triggering events. Multiple radiostereometric studies of hip prostheses have now shown that early migration poses a risk of future clinical failure, but is this enough to explain late clinical loosening?To answer this question, the progression of loosening from initiation to radiographic detection is described; and the need for explanations other than early prosthetic loosening is analysed, such as stress-shielding, particle disease, and metal sensitivity.Much evidence indicates that prosthetic loosening has already been initiated during or shortly after the surgery, and that the subsequent progression of loosening is affected by biomechanical factors, fluid pressure fluctuations and inflammatory responses to necrotic cells and cell fragments, i.e. the concept of late loosening appears to be a misinterpretation of late-detected loosening.Clinical implications: atraumatic surgery and initial prosthetic stability are crucial in ensuring low risk of prosthetic loosening. Cite this article: EFORT Open Rev 2020;5:113-117. DOI: 10.1302/2058-5241.5.190014.

Bone mineral density as a marker of hip implant longevity: a prospective assessment of a cementless stem with dual-energy X-ray absorptiometry at twenty years.

PURPOSE: Bone remodeling around the femoral component after total hip arthroplasty (THA) is considered to be an important factor in long-term stability and seems to be strictly related to the stem design, coating, and fixation. Stress shielding, micro-movement, and high intra-articular fluid pressure might activate macrophages and osteoclasts, causing progressive bone density decreases. Here we analyze the bone mineral density (BMD) around a cementless femoral stem during a 20-year period to better understand the adaptive bone changes around such implants during long-term follow-up. METHODS: In this retrospective study, 14 patients treated by THA were reviewed from a cohort of 84. Clinical evaluation with Harris Hip Score and radiographic assessment were performed throughout a 20-year follow-up. To evaluate the bone remodeling around the stem, we monitored the femoral BMD in four regions of interest with a dual-energy X-ray absorptiometry (DEXA) post-operatively and at one, two, three, five and 20 years of follow-up. RESULTS: The main BMD changes between the post-operative examination and the 20-year follow-up varied between + 11.19% and + 24.30%. Patients with signs of loosening, low Harris Hip Scores, and pain showed decreasing BMD values. CONCLUSIONS: The correlation between the clinical result and BMD values could suggest DEXA results as a predictor of implant loosening or longevity.

Arctigenin inhibits RANKL-induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle-induced bone loss in vivo.

Wear particle-induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle-induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle-induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti-inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle-induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle-induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow-derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast-related signaling pathways. The results showed that arctigenin inhibited RANKL-induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose-dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF-κB) ligand-induced NF-κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast-related osteolytic diseases caused by excessive osteoclast formation.

Utility of radiolabeled leukocyte and bone marrow scintigraphy with SPECT/CT in the diagnostic work-up- of the painful prosthetic joint: A single-institution experience

@#In tbhe assessment of prosthetic joint pains, differentiating between aseptic loosening and infection can be challenging due to their similarities in clinical presentation and histopathology. Combined radiolabeled leukocyte and bone marrow scintigraphy and SPECT/CT is considered the most suitable nuclear imaging modality for this purpose. However, this is infrequently performed in our local setting. We present two cases where these studies were appropriately performed with different scan outcomes. The first case involved a 67-year-old male with painful right knee prosthesis and an alleged history of recurrent periprosthetic joint infection (PJI). The leukocyte tagging scan and marrow scan images were found to be congruent, which was more compatible with aseptic loosening. No emergent surgical intervention was done in our hospital, and the patient returned to this home territory for further management. The second case was a 72-year-old male with progressive pain in his left prosthetic hiip which began after surgery a year prior. Scan images were incongruent, suggestive of PJI; this was confired on joint aspiration and eventual surgical revision. Despite this imaging study's high sensitvity and high specificity, it has not been well-received in management algorihms of PJI. Collaboration between clinicans and nuclear imaging specilists is key in increasing the general use of these procedures.

Low-field magnetic resonance imaging offers potential for measuring tibial component migration.

BACKGROUND: Roentgen stereophotogrammetric analysis (RSA) is used to measure early prosthetic migration and to predict future implant failure. RSA has several disadvantages, such as the need for perioperatively inserted tantalum markers. Therefore, this study evaluates low-field MRI as an alternative to RSA. The use of traditional MRI with prostheses induces disturbing metal artifacts which are reduced by low-field MRI. The purpose of this study is to assess the feasibility to use low-field (0.25 Tesla) MRI for measuring the precision of zero motion. This was assessed by calculating the virtual prosthetic motion of a zero-motion prosthetic reconstruction in multiple scanning sessions. Furthermore, the effects of different registration methods on these virtual motions were tested. RESULTS: The precision of zero motion for low-field MRI was between 0.584 mm and 1.974 mm for translation and 0.884° and 3.774° for rotation. The manual registration method seemed most accurate, with µ ≤ 0.13 mm (σ ≤ 0.931 mm) for translation and µ ≤ 0.15° (σ ≤ 1.63°) for rotation. CONCLUSION: Low-field MRI is not yet as precise as today's golden standard (marker based RSA) as reported in the literature. However, low-field MRI is feasible of measuring the relative position of bone and implant with comparable precision as obtained with marker-free RSA techniques. Of the three registration methods tested, manual registration was most accurate. Before starting clinical validation further research is necessary and should focus on improving scan sequences and registration algorithms.

Hot issues related to modern hip prosthetic materials / 医学研究生学报

Artificial prosthetic material is one of the important factors determining the effect of artificial hip replacement.There are mainly three types of interfaces in the prosthetic materials: the fixed in-terface,the friction interface,and the interface between the modular prostheses.Porous metals improve the osseointegration of the bio-logical fixed interface.High crosslinking polyethylene and composite ceramics significantly reduce the wear of the friction interface.The modular prostheses of ceramic ball head can reduce the wear particles and corrosion.However,the prosthesis loosening,wear and metal corrosion are still the most important factors affecting the medium-long term effects of artificial hip replacement.This article reviews the research progress of artificial hip prosthesis materials from the perspective of the three prosthetic interfaces.

Imaging in peri-prosthetic assessment: an orthopaedic perspective.

As imaging techniques are ever-evolving, this article aims to provide a brief overview of the various modalities including their limitations. The ability of imaging for evaluation of implant osseo-integration will be addressed and also the role of imaging in assessing septic and aseptic loosening, with a particular focus on adverse tissue reactions, will be discussed. Specific features when imaging the big joints such as shoulder, hip, knee and ankle joint will also be outlined.Overall, a lack of standardisation and validity was noted and despite the gross variety of imaging modalities, there is no technique covering all aspects required for evaluation of implant fixation and septic and aseptic loosening. Each imaging modality has a role, depending on the information required and anticipated. The choice of imaging technique should not be primarily based on medical considerations but also on availability, accessibility, expertise and costs. Plain radiographs alone have been recommended in cases of suspected peri-prosthetic joint infections, given the lack of evidence for additional imaging techniques in this context. For aseptic loosening, ultrasound and plain radiographs may serve as initial screening tools. Metal artefact reducing sequences (MARS) MRI are advancing cross-sectional imaging and are likely to promote their role in patient evaluation.We conclude that imaging is one essential part in the work-up of patients with total joint replacements, within a specific clinical context. Close teamwork between experienced radiologists and orthopaedic surgeons is required for optimal patient care. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160058. Originally published online at www.efortopenreviews.org.

Hypericin suppresses osteoclast formation and wear particle-induced osteolysis via modulating ERK signalling pathway.

Osteoclast-induced bone resorption and wear-particle-induced osteolysis leads to prosthetic loosening, one of the most common causes of joint implant failure, resulting in revision surgery. Thus, inhibition of osteoclastic bone resorption, which further prevents wear particle-induced osteolysis, is a potential treatment strategy for prosthetic loosening. Here, we examined the therapeutic effect of hypericin (HP), which was photosensitive, on osteoclastogenesis and wear particle-induced osteolysis in the absence of visible light. HP inhibited RANKL-induced osteoclast differentiation in bone marrow macrophages (BMMs) and RAW264.7 cell line without any evidence of cytotoxicity. The bone-resorbing activity of mature osteoclasts was significantly inhibited by HP. As HP has been previously reported to inhibit signalling pathway such as ERK and NF-κB in other cells, which is also important in osteoclast differentiation. We thus examined the molecular mechanism and showed that HP significantly inhibited the ERK/mitogen-activated protein kinase (MAPK) signalling pathway without affecting nuclear factor kappaB (NF-κB), c-Jun N-terminal kinase (JNK) and p38 signalling in RANKL-stimulated BMMs. Further in vivo studies revealed HP attenuated osteoclast formation and subsequently prevented wear particle-induced bone erosion. Taken together, the results suggest that HP inhibits RANKL-mediated osteoclastogenesis via affecting ERK signalling in vitro and suppresses wear particle-induced osteolysis in vivo. We therefore conclude that HP may be an innovative and safe alternative treatment for osteoclast-related prosthetic loosening.

The effect of enoxacin on osteoclastogenesis and reduction of titanium particle-induced osteolysis via suppression of JNK signaling pathway.

The aim of this study was to assess the effect of enoxacin on osteoclastogenesis and titanium particle-induced osteolysis. Wear particles liberated from the surface of prostheses are associated with aseptic prosthetic loosening. It is well established that wear particles induce inflammation, and that extensive osteoclastogenesis plays a critical role in peri-implant osteolysis and subsequent prosthetic loosening. Therefore, inhibiting extensive osteoclast formation and bone resorption could be a potential therapeutic target to prevent prosthetic loosening. In this study, we demonstrated that enoxacin, a fluoroquinolone antibiotic, exerts potent inhibitory effects on titanium particle-induced osteolysis in a mouse calvarial model. Interestingly, the number of mature osteoclasts decreased after treatment with enoxacin in vivo, suggesting that osteoclast formation might be inhibited by enoxacin. We then performed in vitro studies to confirm our hypothesis and revealed the mechanism of action of enoxacin. Enoxacin inhibited osteoclast formation by specifically abrogating RANKL-induced JNK signaling. Collectively, these results suggest that enoxacin, an antibiotic with few side effects that is widely used in clinics, had significant potential for the treatment of particle-induced peri-implant osteolysis and other diseases caused by excessive osteoclast formation and function.