Periprosthetic Osteolysis Research Articles

Particle-induced osteolysis is mediated by endoplasmic reticulum stress-associated osteoblast apoptosis

Osteoblast dysfunction plays a crucial role in periprosthetic osteolysis and aseptic loosening, and endoplasmic reticulum (ER) stress is recognized as an important causal factor of wear particle-induced osteolysis. However, the influence of ER stress on osteoblast activity during osteolysis and its underlying mechanisms remain elusive. This study aims to investigate whether ER stress is involved in the detrimental effects of wear particles on osteoblasts. Through our investigation, we observed elevated expression levels of ER stress and apoptosis markers in particle-stimulated bone specimens and osteoblasts. To probe further, we employed the ER stress inhibitor, 4-PBA, to treat particle-stimulated osteoblasts. The results revealed that 4-PBA effectively alleviated particle-induced osteoblast apoptosis and mitigated osteogenic reduction. Furthermore, our study revealed that wear particle-induced ER stress in osteoblasts coincided with mitochondrial damage, calcium overload, and oxidative stress, all of which were effectively alleviated by 4-PBA treatment. Encouragingly, 4-PBA administration also improved bone formation and attenuated osteolysis in a mouse calvarial model. In conclusion, our results demonstrate that ER stress plays a crucial role in mediating wear particle-induced osteoblast apoptosis and impaired osteogenic function. These findings underscore the critical involvement of ER stress in wear particle-induced osteolysis and highlight ER stress as a potential therapeutic target for ameliorating wear particle-induced osteogenic reduction and bone destruction.

ROS-mediated mitophagy and necroptosis regulate osteocytes death caused by TCP particles in MLO-Y4 cells

Our previous data have revealed TCP particles caused cell death of osteocytes, comprising over 95 % of all bone cells, which contribute to periprosthetic osteolysis, joint loosening and implant failure, but its mechanisms are not fully understood. Here, we reported that TCP particles inhibited cell viability of osteocytes MLO-Y4, and caused cell death. TCP particles caused mitochondrial impairment and increased expressions of LC-3 II, Parkin and PINK 1, accompanied by the elevation of autophagy flux and intracellular acidic components, the accumulation of LC-3II, PINK1 and Parkin in damaged mitochondria, and p62 reduction. The increased LC-3II expression and cell death extent were significantly enhanced by the autophagy inhibitor Baf A1, compared with Baf A1 (or TCP particles) alone, indicating that TCP particles increase autophagic flux and lead to cell even death of MLO-Y4 cells, closely associated with mitophagy. Furthermore, TCP particles induced propidium iodide (PI) uptake and the phosphorylation of RIP1, RIP3 and MLKL, thereby increasing necroptosis in MLO-Y4 cells. The pro-necroptotic effect was alleviated by the RIP1 inhibitor Nec-1 or the MLKL inhibitor NSA. Additionally, TCP particles promoted the production of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS), and increased TXNIP expression, but decreased protein levels of TRX1, Nrf2, HO-1 and NQO1, leading to oxidative stress. The ROS scavenger NAC remarkably reversed mitophagy and necroptosis caused by TCP particles, suggesting that ROS is responsible for mitophagy and necroptosis. Collectively, ROS-mediated mitophagy and necroptosis regulate osteocytes death caused by TCP particles in MLO-Y4 cells, which enhances osteoclastogenesis and periprosthetic osteolysis.

Metallic artifact suppression with MAVRIC-SL in magnetic resonance imaging for assessing chronic pain after hip or knee arthroplasty.

To analyze the association between osteolysis at the prosthesis interfaces, as determined by magnetic resonance imaging (MRI) with multiacquisition variable-resonance image combination selective (MAVRIC-SL) sequences, and clinical severity after knee or hip arthroplasty, as well as to assess interobserver and intraobserver agreement on periprosthetic bone resorption. This was a cross-sectional study of 47 patients (49 joints) under postoperative follow-up after knee or hip arthroplasty, with chronic pain, between March 2019 and August 2020. All of the patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. The component interfaces were evaluated and ordered into two groups: osseointegrated and osteolytic. Nonparametric tests were used. There were significant differences between the two groups in terms of the mean WOMAC scores: total (p = 0.010); stiffness domain (p = 0.047); and function (p = 0.011) domains. There was substantial interobserver and intraobserver agreement for most analyses of the components. Periprosthetic osteolysis appears to be associated with clinical complaints of pain in the post-arthroplasty scenario, and MAVRIC-SL provides reproducible assessments. It could prove to be an important tool for orthopedists to use in the evaluation of challenging cases of chronic pain after arthroplasty.

Effect of diabetes mellitus on the outcomes of total ankle arthroplasty: is controlled diabetes mellitus a risk factor?

BackgroundIt is still uncertain whether diabetes mellitus (DM) is a risk factor for poor outcomes and increased complications after total ankle arthroplasty (TAA). The objective of this study was to compare clinical outcomes and complication rates of TAA in patients with and without DM.MethodsThis study enrolled patients with symptomatic end-stage ankle osteoarthritis with a minimum follow-up period of 24 months after TAA. A total of 252 patients (266 ankles) were classified into two groups according to the presence of DM: (1) DM group (59 patients, 67 ankles) and (2) non-DM group (193 patients, 199 ankles). We defined controlled diabetes as (1) HbA1c level < 7.0%, or (2) fasting glucose level < 130 mg/dL with HbA1c level ≥ 7.0% for hospitalization period. Clinical outcomes data (Ankle Osteoarthritis Scale, American Orthopedic Foot and Ankle Society ankle-hindfoot score, Short Form-36 Physical Component Summary score, and visual analog scale for pain) were compared preoperatively and at the final follow-up between the two groups. Complications following TAA were also compared between the two groups.ResultsAll clinical variables had improved in both groups by the final follow-up (mean follow-up = 77.8 months). There was no significant difference in any clinical variable between the two groups at the final follow-up (P > 0.05). Of the 266 ankles, 73 ankles (19 in the DM group, 54 in the non-DM group) developed periprosthetic osteolysis. Although the DM group showed a higher prevalence of aseptic loosening or subsidence, the difference between the two groups was not statistically significant (P = 0.236).ConclusionsIn the intermediate-term follow-up, TAA in patients with controlled DM showed clinical outcomes and complication rates comparable to patients without DM. Our results suggest that TAA can be done safely in diabetic patients if the DM is controlled in the perioperative period.Level of evidence: Therapeutic Level III.

Kaempferol attenuates wear particle-induced inflammatory osteolysis via JNK and p38-MAPK signaling pathways

Ethnopharmacological relevanceWear particle-induced inflammatory osteoclast activation is a master contributor to periprosthetic osteolysis, which can cause pathological bone loss and destruction. Hence, inhibiting inflammation and osteoclastogenesis is an important strategy for preventing wear particle-induced osteolysis. To date, there are no FDA-approved non-surgical pharmacotherapies for arresting periprosthetic osteolysis. Kaempferol (KAE), a natural flavonol abundant in many traditional Chinese herbal medicines, has been shown to have protective effects against inflammatory bone diseases such as rheumatoid arthritis, but no previous study has evaluated the effects of KAE on wear particle-induced osteolysis. Aim of the studyThe study aimed to investigate the effects of KAE on wear particle-induced inflammatory osteolysis and osteoclast activation, and further explore the underlying mechanisms. Materials and methodsTiAl6V4 metal particles (TiPs) were retrieved from the prosthesis of patients who underwent revision hip arthroplasty due to aseptic loosening. A mouse calvarial osteolysis model was used to investigate the effects of KAE on wear particle-induced inflammatory osteolysis in vivo. Primary bone marrow-derived macrophages (BMMs) were used to explore the effects of KAE on osteoclast differentiation and bone-resorbing activity as well as the underlying mechanisms in vitro. ResultsIn the present study, we found that KAE alleviated wear particle-induced inflammatory bone loss in vivo and inhibited osteoclast differentiation and function in vitro. Furthermore, we revealed that KAE exerted anti-osteoclastogenic effects by downregulating JNK and p38-MAPK signaling as well as the downstream NFATc1 expression. ConclusionsKAE is an alternative therapeutic agent for preventing and treating periprosthetic osteolysis and aseptic loosening.

Macrophage-derived exosomes modulate wear particle-induced osteolysis via miR-3470b targeting TAB3/NF-κB signaling

Aseptic prosthesis loosening (APL) is one of the most prevalent complications associated with arthroplasty. The main cause is the periprosthetic osteolysis induced by wear particles. However, the specific mechanisms of crosstalk between immune cells and osteoclasts/osteoblasts during osteolysis are unclear. In this study, we report the role and mechanism of macrophage-derived exosomes in wear particle-induced osteolysis. The results of exosomes up-taken experiments revealed that osteoblast and mature osteoclasts capture macrophage-derived exosomes (M-Exo). Next-generation sequencing and RT-qPCR on M-Exo revealed that exosomal microRNA miR-3470b was downregulated in wear particle-induced osteolysis. The results of analysis on Luciferase reporter assays/fluorescence in situ hybridization (FISH)/immunofluorescence (IF)/immunohistochemistry (IHC) and co-culture experiments demonstrated that wear particles induced osteoclast differentiation by increasing the expression of NFatc1 via M-Exo miR-3470b targeting TAB3/ NF-κB signaling. We also illustrate that engineered exosomes enriching miR-3470b facilitated to suppressed the osteolysis; the microenvironment enriching with miR-3470b could suppress wear particle-induced osteolysis via inhibition of TAB3/ NF-κB in vivo. In summary, our findings indicate that macrophage-derived exosomes transfer to osteoclasts to induce osteolysis in wear particle-induced APL. Engineering exosomes enriching with miR-3470b might be a novel strategy for the targeting treatment of bone resorption-related diseases.

Osteocytes Exposed to Titanium Particles Inhibit Osteoblastic Cell Differentiation via Connexin 43

Periprosthetic osteolysis (PPO) induced by wear particles is the most severe complication of total joint replacement; however, the mechanism behind PPO remains elusive. Previous studies have shown that osteocytes play important roles in wear-particle-induced osteolysis. In this study, we investigated the effects of connexin 43 (Cx43) on the regulation of osteocyte-to-osteoblast differentiation. We established an in vivo murine model of calvarial osteolysis induced by titanium (Ti) particles. The osteolysis characteristic and osteogenesis markers in the osteocyte-selective Cx43 (CKO)-deficient and wild-type (WT) mice were observed. The calvarial osteolysis induced by Ti particles was partially attenuated in CKO mice. The expression of β-catenin and osteogenesis markers increased significantly in CKO mice. In vitro, the osteocytic cell line MLO-Y4 was treated with Ti particles. The co-culturing of MLO-Y4 cells with MC3T3-E1 osteoblastic cells was used to observe the effects of Ti-treated osteocytes on osteoblast differentiation. When Cx43 of MLO-Y4 cells was silenced or overexpressed, β-catenin was detected. Additionally, co-immunoprecipitation detection of Cx43 and β-catenin binding in MLO-Y4 cells and MC3T3-E1 cells was performed. Finally, β-catenin expression in MC3T3-E1 cells and osteoblast differentiation were evaluated after 18α-glycyrrhetinic acid (18α-GA) was used to block the intercellular communication of Cx43 between MLO-Y4 and MC3T3-E1 cells. Ti particles increased Cx43 expression and decreased β-catenin expression in MLO-Y4 cells. The silencing of Cx43 increased the β-catenin expression, and the over-expression of Cx43 decreased the β-catenin expression. In the co-culture model, Ti treatment of MLO-Y4 cells inhibited the osteoblastic differentiation of MC3T3-E1 cells and Cx43 silencing in MLO-Y4 cells attenuated the inhibitory effects on osteoblastic differentiation. With Cx43 silencing in the MLO-Y4 cells, the MC3T3-E1 cells, co-cultured alongside MLO-Y4, displayed decreased Cx43 expression, increased β-catenin expression, activation of Runx2, and promotion of osteoblastic differentiation in vitro co-culture. Finally, Cx43 expression was found to be negatively correlated to the activity of the Wnt signaling pathway, mostly through the Cx43 binding of β-catenin from its translocation to the nucleus. The results of our study suggest that Ti particles increased Cx43 expression in osteocytes and that osteocytes may participate in the regulation of osteoblast function via the Cx43 during PPO.

Macrophages-bone marrow mesenchymal stem cells crosstalk in bone healing.

Bone healing is associated with many orthopedic conditions, including fractures and osteonecrosis, arthritis, metabolic bone disease, tumors and periprosthetic particle-associated osteolysis. How to effectively promote bone healing has become a keen topic for researchers. The role of macrophages and bone marrow mesenchymal stem cells (BMSCs) in bone healing has gradually come to light with the development of the concept of osteoimmunity. Their interaction regulates the balance between inflammation and regeneration, and when the inflammatory response is over-excited, attenuated, or disturbed, it results in the failure of bone healing. Therefore, an in-depth understanding of the function of macrophages and bone marrow mesenchymal stem cells in bone regeneration and the relationship between the two could provide new directions to promote bone healing. This paper reviews the role of macrophages and bone marrow mesenchymal stem cells in bone healing and the mechanism and significance of their interaction. Several new therapeutic ideas for regulating the inflammatory response in bone healing by targeting macrophages and bone marrow mesenchymal stem cells crosstalk are also discussed.

The utilization of a perioperative muscle free flap in total ankle arthroplasty: A case report and brief review of the literature

Ankle arthrodesis and total ankle arthroplasty (TAA) are both approaches to surgical treatment of ankle arthroses, with the latter becoming increasingly popular as it maintains ankle mobility. TAA has been associated with complications, including wound persistence, periprosthetic osteolysis, infection, and implant failure, which can be attributed to the area's poor vascularization and soft-tissue quality. In particular, the anterior compartment - solely supplied by the anterior tibial artery – explains the heightened risk of poor outcomes in ankle surgery. The effect of a secondary reconstructive procedure, such as a skin graft or a muscle flap for prosthesis salvage, has been well described in the literature. Muscle flaps are indicated in soft tissue reconstructive procedures because they provide a reliable blood supply and significant tissue volume where there is dead space. Here we outline a case where a 53-year-old male patient received a gracilis muscle free flap after TAA to improve outcomes and as an alternative orthoplastic procedure for patients who otherwise would undergo limb amputation. After several months of physical therapy, the patient is pain-free and active. With this, it can be concluded that a free muscle flap has the potential to be used perioperatively in higher-risk patients to improve TAA outcomes and as an alternative to other procedures that can reduce a patient's quality of life, such as ankle arthrodesis or amputation.

The Effect of Preoperative Bisphosphonate Use on Total Hip Arthroplasty Outcomes

BackgroundPatients undergoing total hip arthroplasty (THA) commonly have osteoporosis for which bisphosphonates (BPs) are Food and Drug Administration (FDA)-approved for treatment. Bisphosphonate use post-THA is associated with decreased periprosthetic bone loss or revisions, and increased longevity of implants. However, evidence is lacking for preoperative bisphosphonate use in THA recipients. This study investigated the association between bisphosphonate use pre-THA and outcomes. MethodsA retrospective review of a national administrative claims database was conducted. Among THA recipients who had a prior diagnosis of hip osteoarthritis and osteoporosis/osteopenia, the treatment group (BP-exposed) consisted of patients who had a history of bisphosphonate use at least 1 year before THA; controls (BP-naive) comprised patients who did not have preoperative bisphosphonate use. The BP-exposed were matched to BP-naive in a 1:4 ratio by age, sex, and comorbidities. Logistic regressions were used to calculate the odds ratio for intraoperative and 1-year postoperative complications. ResultsThe BP-exposed group had significantly higher rates of intraoperative and 1-year postoperative periprosthetic fractures (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.23, 1.57) and revisions (OR: 1.14, 95% CI: 1.04, 1.25) compared with the BP-naive controls. BP-exposed also experienced higher rates of aseptic loosening, dislocation, periprosthetic osteolysis, and stress fracture of the femur or hip/pelvis compared to the BP-naive controls, but these values were not statistically significant. ConclusionThe use of bisphosphonates in THA patients preoperatively is associated with higher rates of intraoperative and 1-year postoperative complications. These findings may impact the management of patients undergoing THA who have a prior diagnosis of osteoporosis/osteopenia and use of bisphosphonates. Level of evidenceRetrospective Cohort Study (Level 3).

Is it possible to stop the osteolysis of the periprosthetic bone during re-endoprosthetics of the hip joint against the background of osteoporosis?

Revision interventions due to aseptic instability show a marked upward trend, and one of the reasons is an increase in the number of people with osteoporosis in the population. The impaired bone metabolism in these cases persist even after re-endoprosthetics. The authors aim to draw attention of trauma orthopaedists to the need to treat osteoporosis either before or immediately after the re-endoprosthetic surgery. A clinical case is presented. A 65-year-old patient T., 5 months after surgery, complained of persistent pain in the left hip joint radiating to the left knee joint, which intensified when walking, lameness, inability to move without additional support (two crutches), limited range of motion within the left hip joint that had undergone surgery (endoprosthesis). The patient had a history of femoral neck fracture associated with a low energy fall. The left hip joint re-endoprosthetics was performed due to aseptic instability of the femoral and acetabular components of the prosthetic implant. The diagnosed diseases included secondary osteoporosis, D-deficiency, hypocalcemia, and periprosthetic osteolysis. Given the increased intensity of resorption and the fact that the femoral neck fracture occurred with underlying secondary osteoporosis, it was decided to prescribe antiresorptive therapy with denosumab 60 mg once every 6 months combined with alfacalcidol and calcium supplement. Despite an objective 3-month delay in antiresorptive therapy initiation, the treatment result was achieved in the observed patient. In summary, denosumab 60 mg increases the effectiveness of re-endoprosthetics with underlying osteoporosis by reducing activity of the periprosthetic bone osteolysis.

SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis

The most common cause for prosthetic revision surgery is wear particle-induced periprosthetic osteolysis, which leads to aseptic loosening of the prosthesis. Both SOST gene and its synthetic protein, sclerostin, are hallmarks of osteocytes. According to our previous findings, blocking SOST induces bone formation and protects against bone loss and deformation caused by titanium (Ti) particles by activating the Wnt/β-catenin cascade. Although SOST has been shown to influence osteoblasts, its ability to control wear-particle-induced osteolysis via targeting osteoclasts remains unclear. Mice were subjected to development of a cranial osteolysis model. Micro CT, HE staining, and TRAP staining were performed to evaluate bone loss in the mouse model. Bone marrow-derived monocyte-macrophages (BMMs) made from the C57BL/6 mice were exposed to the medium of MLO-Y4 (co-cultured with Ti particles) to transform them into osteoclasts. Bioinformatics methods were used to predict and validate the interaction among SOST, Wnt/β-catenin, RANKL/OPG, TNF-α, and IL-6. Local bone density and bone volume improved after SOST inhibition, both the number of lysis pores and the rate of skull erosion decreased. Histological research showed that β-catenin and OPG expression were markedly increased after SOST inhibition, whereas TRAP and RANKL levels were markedly decreased. In-vitro, Ti particle treatment elevated the expression of sclerostin, suppressed the expression of β-catenin, and increased the RANKL/OPG ratio in the MLO-Y4 cell line. TNF-α and IL-6 also elevated after treatment with Ti particles. The expression levels of NFATc1, CTSK, and TRAP in osteoclasts were significantly increased, and the number of positive cells for TRAP staining was increased. Additionally, the volume of bone resorption increased at the same time. In contrast, when SOST expression was inhibited in the MLO-Y4 cell line, these effects produced by Ti particles were reversed. All the results strongly show that SOST inhibition triggered the osteocyte Wnt/β-catenin signaling cascade and prevented wear particle-induced osteoclastogenesis, which might reduce periprosthetic osteolysis.Key messagesSOST is a molecular regulator in maintaining bone homeostasis.SOST plays in regulating bone homeostasis through the Wnt/β-catenin signaling pathway.SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.

Therapeutic effects of curcumin liposomes and nanocrystals on inflammatory osteolysis: In vitro and in vivo comparative study

Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent than that of Cur-NCs, both in vitro and in vivo, although the cellular uptake of Cur-NCs was quicker. In conclusion, the results demonstrate that Cur-LPs have great potential for the clinical treatment of inflammatory osteolysis and that the therapeutic effect is closely related to the liposomal dosage form.

Fabricating Stiffness-Matched Three Dimensional -Printed Metal Implants for Total Wrist Arthroplasty.

Total wrist arthroplasty (TWA) is a motion-sparing treatment for pancarpal arthritis; however, complication rates up to 50% have limited widespread use. Implant micromotion, stress shielding, and periprosthetic osteolysis result in implant failure and revision to arthrodesis. Metal 3-dimensional (3D) printing allows for more accurate matching of surrounding bone biomechanical properties, theoretically reducing periprosthetic osteolysis. Herein, we use computed tomography to characterize the relationship of relative stiffness along the length of the distal radius with patient demographic factors. After institutional review, wrist computed tomography scans at a single institution between 2013 and 2021 were identified. Exclusion criteria were history of radius or carpal trauma or fracture. Collected demographics included age, sex, and comorbidities (including osteoporosis/osteopenia). Scans were analyzed using Materialize Mimics Innovation Suite 24.0 (Leuven, Belgium). Distal radius cortical density (in Hounsfield units) and medullary volume (in cubic millimeters) with relation to distance from the radiocarpal joint were recorded. Average values for each variable were used to 3D-printed distal radius trial components with stiffness matched to bone density by length. Thirty-two patients met inclusion criteria. Distal radius cortical bone density progressively increased proximal to the radiocarpal joint, whereas medullary volume decreased; changes in both plateaued 20 mm proximal to the joint. Distal radius material properties differed by age, sex, and comorbidities. Total wrist arthroplasty implants were fabricated to match these variables as proof of concept. Distal radius material properties vary along the bone length; conventional implants do not account for this variance. This study showed 3D-printed implants can be created to match bone properties along the length of the implant.

PROSTHETIC LOOSENING IN A TOTAL HIP ARTHROPLASTY PATIENT AFTER BREAST CANCER CHEMOTHERAPY AND HORMONOTHERAPY: A CASE REPORT

Total joint replacement (TJR) was one of the most revolutionary breakthroughs in joint surgery. The majority studies had shown that most implants could last about 25 years, anyway, there is still variation in the longevity of implants. In US, for all the hip revisions from 2012 to 2017 in the United States, 12.0% of the patients were diagnosed as aseptic loosening. Variable studies have showed that any factor that could cause a systemic or partial bone loss, might be the risk of periprosthetic osteolysis and aseptic loosening.Breast cancer is the most frequent malignancy in women, more than 2.1 million women were newly diagnosed with breast cancer, 626,679 women with breast cancer died in 2018. It's been reported that the mean incidence of THA was 0.29% for medicare population with breast cancer in USA, of which the incidence was 3.46% in Norwegian. However, the effects of breast cancer chemotherapy and hormonotherapy, such as aromatase inhibitors (AI), significantly increased the risk of osteoporosis, and had been proved to become a great threat to hip implants survival.In this case, a 46-year-old female undertook chemotherapy and hormonotherapy of breast cancer 3 years after her primary THA, was diagnosed with aseptic loosening of the hip prosthesis. Her treatment was summarized and analyzed.Breast cancer chemotherapy and hormonotherapy might be a threat to the stability of THA prosthesis. More attention should be paid when a THA paitent occurred with breast cancer. More studies about the effect of breast cancer treatments on skeleton are required.

Targeted therapy for peri-prosthetic osteolysis using macrophage membrane-encapsulated human urine-derived stem cell extracellular vesicles.

Aseptic loosening of the prosthesis is a severe complication after joint replacement. It is of great practical significance and social value to discover the prevention and treatment strategies for this condition. Exosomes from urine-derived stem cells (Exos) have great potential in promoting bone repair, reconstruction, and regulating bone metabolism. However, they are easily eliminated by macrophages and incapable of targeting the osteolysis zone. In this study, based on macrophage "homing" into periprosthetic osteolysis region and cell membrane encapsulating nanotechnology, exosomes from urine-derived stem cells were encapsulated with macrophage membrane (MM) to prevent periprosthetic osteolysis. We found that macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effectiveness of Exos, which alleviated wear particles-induced calvarial osteolysis. Furthermore, MM-Exos could provide immunological camouflage and allow the Exos to avoid phagocytosis by macrophages and stimulate cellular uptake by bone marrow-derived stem cells (BMSCs). Therefore, we demonstrated the unique ability of the macrophage membrane as a targeted transport of exosomes from urine-derived stem cells for the prevention and treatment of periprosthetic osteolysis. These biomimetic nanoparticles provided a new therapeutic exosome delivery system for preventing wear particles-induced osteolysis. STATEMENT OF SIGNIFICANCE: Macrophage membrane encapsulated urine-derived stem cell-derived exosomes (MM-Exos) can be targeted delivery to the osteolysis zone and enhance the therapeutic effect of Exos on peri‑prosthetic osteolysis prevention. MM-Exos could allow the Exos to avoid phagocytosis by macrophages and promote the uptake of Exos by BMSCs.

Hip and Knee Arthroplasty: A Review of Complications and Advances in Imaging

Arthroplasty-related complications are challenging to diagnose as they often present with nonspecific signs and symptoms, and can lead to long-term morbidity if inadequately managed. The difficulty in imaging implants is compounded by its intrinsic propensity to artifacts. Strategies to reduce this include: Judicious use of the appropriate imaging modality for the relevant clinical indication; knowledge of optimizing imaging acquisition parameters; and use of metal artifact reduction (MAR) software. We review the literature on expected normal appearances of hip and knee arthroplasties, findings of arthroplasty-related complications on various imaging modalities, advances in imaging techniques, and subsequently, suggest an algorithm for painful arthroplasty assessment. Serial radiographs remain key in identifying subtle changes in component position, hardware failure, periprosthetic osteolysis, and potential for loosening, given their ready availability, high resolution, and minimal metal-related artifact. Computed tomography with MAR provides 3D assessment and information on bone stock for surgical planning and custom implants. Magnetic resonance imaging with MAR can identify complications at earlier stages, such as loosening, capsular dehiscence in instability, and periprosthetic edema in nondisplaced fractures. It has high diagnostic performance in infection (lamellated synovitis), particle disease, adverse reactions to metal debris, in addition to demonstrating impingement on neurovascular structures. Nuclear medicine imaging is used as a problem-solving tool and is valuable in its high negative predictive value. Novel imaging techniques can further reduce artifacts and improve visualization of the implant-bone interface, and machine learning can facilitate image interpretation although attaining sufficient data and clinical validation will be challenging.

The dual role of autophagy in periprosthetic osteolysis.

Periprosthetic osteolysis (PPO) induced by wear particles is an important cause of aseptic loosening after artificial joint replacement, among which the imbalance of osteogenesis and osteoclastic processes occupies a central position. The cells involved in PPO mainly include osteoclasts (macrophages), osteoblasts, osteocytes, and fibroblasts. RANKL/RANK/OGP axis is a typical way for osteolysis. Autophagy, a mode of regulatory cell death and maintenance of cellular homeostasis, has a dual role in PPO. Although autophagy is activated in various periprosthetic cells and regulates the release of inflammatory cytokines, osteoclast activation, and osteoblast differentiation, its beneficial or detrimental role remains controversy. In particular, differences in the temporal control and intensity of autophagy may have different effects. This article focuses on the role of autophagy in PPO, and expects the regulation of autophagy to become a powerful target for clinical treatment of PPO.

Ten to 13-Year Results of Delta Ceramic-on-Ceramic Total Hip Arthroplasty in Patients Less Than 30 Years Old.

We previously reported mid-term results of total hip arthroplasty (THA) using Delta ceramic-on-ceramic (CoC) bearings in 72 patients (86 hips) who were <30 years old. Noise was noted in 8 (9.3%) of the hips, no osteolysis or loosening was detected, and no patient required reoperation. The purpose of this study was to assess clinical and radiographic outcomes, complications, and survivorship at >10 years after THA using Delta CoC bearings in patients who were <30 years old. Cementless THA with a Delta CoC bearing was performed between March 2008 and January 2012 in 91 hips of 76 patients who were <30 years old. Eighty-five hips in 71 patients (44 men and 27 women) with a mean age of 25.9 years (range, 16 to 29 years) at surgery were followed for a mean of 10.9 years (range, 10 to 13 years). No ceramic bearings fractured. The incidence of squeaking increased to 5.9% (5 of 85), but the squeaking was not reproducible within individual patients. Periprosthetic osteolysis developed in 3 hips (3 patients): around the stem in 2 and around the metal shell in 1. The stem in 1 hip underwent revision because of a Vancouver type-B2 periprosthetic femoral fracture. One patient with systemic lupus erythematosus underwent irrigation and debridement for periprosthetic joint infection. Survivorship free of reoperation for any reason was 92.4% (95% confidence interval, 82.4% to 100%) at 13 years. The long-term results and survivorship of Delta CoC THA in patients <30 years old were favorable. Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty

PurposeThis study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA).MethodsThis study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated.ResultsThe average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007).ConclusionIn the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.