ABSTRACT
Osteolytic bone lesion is a major cause of lower quality of life and poor prognosis in patients with multiple myeloma (MM), but molecular pathogenesis of the osteolytic process in MM remains elusive. Fms-like tyrosine kinase 3 ligand (FLT3L) was reported to be elevated in bone marrow (BM) and blood of patients with advanced MM who often show osteolysis. Here, we investigated a functional link of FLT3L to osteolytic process in MM. We recruited 86, 306, and 52 patients with MM, acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), respectively. FLT3L levels of patients with hematologic malignancies were measured in BM-derived plasma and found to be significantly higher in MM than in AML or ALL, which rarely show osteolysis. FLT3L levels were further elevated in MM patients with bone lesion compared with patients without bone lesion. In vitro cell-based assays showed that the administration of FLT3L to HEK293T, HeLa, and U2OS cells led to an increase in the DKK1 transcript level through STAT3 phosphorylation at tyrosine 705. WNT reporter assay showed that FLT3L treatment reduced WNT signaling and nuclear translocation of ß-catenin. These results collectively show that the FLT3L-STAT3-DKK1 pathway inhibits WNT signaling-mediated bone formation in MM, which can cause osteolytic bone lesion. Finally, transcriptomic profiles revealed that FLT3L and DKK1 were predominantly elevated in the hyperdiploidy subtype of MM. Taken together, FLT3L can serve as a promising biomarker for predicting osteolytic bone lesion and also a potential therapeutic target to prohibit the progression of the osteolytic process in MM with hyperdiploidy.
Subject(s)
Multiple Myeloma , Osteolysis , Humans , Multiple Myeloma/genetics , Multiple Myeloma/pathology , Multiple Myeloma/metabolism , Osteolysis/pathology , Osteolysis/genetics , Osteolysis/etiology , Wnt Signaling Pathway , Male , Female , Middle Aged , Aged , Cell Line, Tumor , STAT3 Transcription Factor/metabolism , STAT3 Transcription Factor/genetics , Neoplasm Staging , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , AdultABSTRACT
INTRODUCTION: A recent study reported a 34% mid-term revision rate after M6-C™ cervical total disc replacement (CTDR) for wear-related osteolysis. Here, we aim to investigate the prevalence, risk factors, and radiographic characteristics of periprosthetic bony changes and implant failure of the M6-C™ artificial disc. METHODS: We retrospectively analysed radiographic (conventional X-ray, CT scan) and clinical outcomes (EQ-5D-5L, Neck Disability Index (NDI), and Visual Analog Scale (VAS) for neck and arm pain) data collected during routine follow-up of patients who underwent CTDR with the M6-C™ between 2011 and 2015. RESULTS: In total, 85 patients underwent CTDR with the M6-C™. Follow-up data were available for 43 patients (54% female, mean age 44 years) with 50 implants and a mean follow-up of 8.1 years (6.5-11 years). Implant failure with the presence of severe osteolysis was identified in 5 (12%) patients who were all male (p = 0.016) and implanted at the C5/6 level (p = 0.11). All failed implants required revision surgery. The overall prevalence of osteolysis was 44% (22/50 implants) and 34% (17/50 implants) for significant heterotopic ossification. Patients with high-grade osteolysis showed higher VAS arm pain (p = 0.05) and lower EQ-5D-VAS health VAS (p = 0.03). CONCLUSION: We report a lower reoperation rate for failed M6-C™ implants than previously published, but confirmed that osteolysis and heterotopic ossification are common following CTDR with the M6-C™ and may be asymptomatic. Therefore, we strongly recommend ongoing clinical and radiographic monitoring after CTDR with the M6-C™, particularly for male patients implanted at the C5/6 level.
Subject(s)
Intervertebral Disc Degeneration , Ossification, Heterotopic , Osteolysis , Total Disc Replacement , Humans , Male , Female , Adult , Total Disc Replacement/adverse effects , Treatment Outcome , Follow-Up Studies , Intervertebral Disc Degeneration/surgery , Retrospective Studies , Osteolysis/diagnostic imaging , Osteolysis/epidemiology , Osteolysis/etiology , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Neck Pain/etiology , Ossification, Heterotopic/diagnostic imaging , Ossification, Heterotopic/epidemiology , Ossification, Heterotopic/etiologyABSTRACT
BACKGROUND: Particle-induced osteolysis resulting from polyethylene wear remains a source of implant failure in anatomic total shoulder designs. Modern polyethylene components are irradiated in an oxygen-free environment to induce cross-linking, but reducing the resulting free radicals with melting or heat annealing can compromise the component's mechanical properties. Vitamin E has been introduced as an adjuvant to thermal treatments. Anatomic shoulder arthroplasty models with a ceramic head component have demonstrated that vitamin E-enhanced polyethylene show improved wear compared with highly cross-linked polyethylene (HXLPE). This study aimed to assess the biomechanical wear properties and particle size characteristics of a novel vitamin E-enhanced highly cross-linked polyethylene (VEXPE) glenoid compared to a conventional ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid against a cobalt chromium molybdenum (CoCrMo) head component. METHODS: Biomechanical wear testing was performed to compare the VEXPE glenoid to UHMWPE glenoid with regard to pristine polyethylene wear and abrasive endurance against a polished CoCrMo alloy humeral head in an anatomic shoulder wear-simulation model. Cumulative mass loss (milligrams) was recorded, and wear rate calculated (milligrams per megacycle [Mc]). Under pristine wear conditions, particle analysis was performed, and functional biologic activity (FBA) was calculated to estimate particle debris osteolytic potential. In addition, 95% confidence intervals for all testing conditions were calculated. RESULTS: The average pristine wear rate was statistically significantly lower for the VEXPE glenoid compared with the HXLPE glenoid (0.81 ± 0.64 mg/Mc vs. 7.00 ± 0.45 mg/Mc) (P < .05). Under abrasive wear conditions, the VEXPE glenoid had a statistically significant lower average wear rate compared with the UHMWPE glenoid comparator device (18.93 ± 5.80 mg/Mc vs. 40.47 ± 2.63 mg/Mc) (P < .05). The VEXPE glenoid demonstrated a statistically significant improvement in FBA compared with the HXLPE glenoid (0.21 ± 0.21 vs. 1.54 ± 0.49 (P < .05). CONCLUSIONS: A new anatomic glenoid component with VEXPE demonstrated significantly improved pristine and abrasive wear properties with lower osteolytic particle debris potential compared with a conventional UHMWPE glenoid component. Vitamin E-enhanced polyethylene shows early promise in shoulder arthroplasty components. Long-term clinical and radiographic investigation needs to be performed to verify if these biomechanical wear properties translate to diminished long-term wear, osteolysis, and loosening.
Subject(s)
Arthroplasty, Replacement, Shoulder , Materials Testing , Polyethylenes , Prosthesis Design , Prosthesis Failure , Shoulder Prosthesis , Vitamin E , Humans , Arthroplasty, Replacement, Shoulder/methods , Biomechanical Phenomena , Particle Size , Osteolysis/etiology , Osteolysis/prevention & control , Shoulder Joint/surgeryABSTRACT
BACKGROUND: Clavicular hook plates are extensively used in the treatment of acromioclavicular dislocation. Subacromial osteolysis is a typical complication following hook plate fixation. We performed a systematic review and meta-analysis to determine the incidence of subacromial osteolysis and analyzed the associated characteristics of subacromial osteolysis to guide surgeons. METHODS: PubMed, EMBASE, and Cochrane Library databases were comprehensively searched for relevant literature. We screened the literature based on the eligibility criteria, extracted relevant data, and assessed the quality of the included studies. Pooled odds ratios or mean differences with 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. Heterogeneity was evaluated by the chi-squared test and I2 statistics. A meta-regression analysis was performed to explore the potential source of heterogeneity. RESULTS: Thirty-two studies met the inclusion criteria. The total pooled incidence of subacromial osteolysis was 29% and the only covariate that could influence the incidence of subacromial osteolysis was the radiological measurement method (P = .017). Patients in the hook plate fixation with coracoclavicular ligament reconstruction group had lower odds of subacromial osteolysis (odds ratio, 2.54, 95% CI 1.54-4.18; P < .001). There were no significant differences in the Constant-Murley scores at the final follow-up between patients with and without subacromial osteolysis (standardized mean difference, -0.17; 95% CI, -0.50 to 0.15; P = .294). CONCLUSIONS: Subacromial osteolysis has a relatively high and variable incidence, and the primary factor influencing the reported incidence is the radiological assessment method. The current analysis suggests coracoclavicular ligament reconstruction as an effective surgical approach for decreasing the incidence of subacromial osteolysis. The presence or absence of subacromial osteolysis did not significantly impact the functional outcomes observed during the final follow-up period.
Subject(s)
Acromioclavicular Joint , Bone Plates , Osteolysis , Humans , Acromioclavicular Joint/surgery , Acromioclavicular Joint/injuries , Osteolysis/etiology , Osteolysis/epidemiology , Bone Plates/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Joint Dislocations/surgeryABSTRACT
BACKGROUND: Aseptic loosening around the prosthesis is a common cause of failure in total joint arthroplasty. Polyethylene wear particles trigger the release of inflammatory factors by macrophages. Key mediators involved in osteoclastogenesis include interleukin-6, tumor necrosis factor-α, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and bone protection hormone (Osteoprotegerin [OPG]). The purpose of our experiment was to see whether melittin can slow down the release of inflammatory mediators through the NF-kB pathway, regulate the RANKL/OPG ratio, reduce osteoclast formation, and delay the onset of arthritis in rats. METHODS: A total of 20 male Sprague-Dawley rats (10 months, Specific Pathogen Free, 350 g ± 20 g) were randomly divided into 5 groups: sham group, model group, melittin concentration 1 group (0.2 mg/kg), concentration 2 group (0.4 mg/kg), and concentration 3 group (0.6 mg/kg). All rats were implanted with TA2 high-purity titanium rods. A drill was used to create a bone canal along the long axis of the femur in the intercondylar notch. The model group and experimental groups were exposed to polyethylene particles, while the sham group did not receive any particles. RESULTS: The melittin group exhibited significantly increased serum levels of serum P, calcium-phosphorus product, OPG, PINP, PINP/CTX-I, and OPG/RANKKL (P < .05). In the experimental group, micro computed tomography scanning results revealed a decrease in the amount of bone defect around the prosthesis. Immunofluorescence analysis demonstrated a decrease in the expression of IKKα and P65, while the expression of OPG showed an upward trend. Both Hematoxylin-Eosin and Tartrate-Resistant Acid Phosphatase staining revealed less osteoclast and inflammatory cell infiltration in bone resorption pits. CONCLUSIONS: Our study demonstrates that melittin has the ability to inhibit the NF-kB pathway in a rat model, and reduce the impact of RANKL/OPG, thereby delaying osteoclast activity and alleviating periprosthetic osteolysis.
Subject(s)
Disease Models, Animal , Melitten , NF-kappa B , Osteolysis , Osteoprotegerin , RANK Ligand , Rats, Sprague-Dawley , Animals , Male , Osteolysis/etiology , Osteolysis/prevention & control , RANK Ligand/metabolism , Osteoprotegerin/metabolism , Rats , Melitten/pharmacology , NF-kappa B/metabolism , Titanium , Osteoclasts/drug effects , Signal Transduction/drug effects , Polyethylene , Prosthesis FailureABSTRACT
INTRODUCTION: The aim of the present study is to analyze the clinical-radiological outcomes of patients undergoing knee prosthesis revision surgery using constrained condylar prosthesis (LCCK; Zimmer-Biomet). MATERIAL AND METHODS: Retrospective study of 89 patients operated on between the years 2008 and 2020 with a minimum of 2 years of follow-up. Clinical outcomes were evaluated using the WOMAC Index score and KOOS scales. Radiological results (radiolucent lines, osteolysis, and cortical hypertrophy) were evaluated by two independent observers. Implant survival was analyzed using the Kaplan-Meier method. RESULTS: At the end of follow-up, a mean WOMAC Index score of 78.67 and KOOS score of 68.8 were obtained. Radiolucent lines (both non-progressive and progressive) were detected in 83.3% of the patients in the sample. Areas of osteolysis > 5 mm around the components were present in 6.75%. Cortical hypertrophy was seen around the femoral stem in 20.3% of cases, around the tibial stem in 20.3% and around both components in 6.76%. No statistically significant relationship was found between the presence of radiolucent lines, osteolysis or cortical hypertrophy with functional results. Implant survival was 88.1% at 13 years. CONCLUSION: The present study shows high survival of LCCK prosthesis in revision surgery. The progressive radiolucencies, were associated with worst clinical outcome.
Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Prosthesis Design , Prosthesis Failure , Reoperation , Humans , Knee Prosthesis/adverse effects , Arthroplasty, Replacement, Knee/methods , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/instrumentation , Reoperation/statistics & numerical data , Female , Male , Retrospective Studies , Aged , Middle Aged , Aged, 80 and over , Radiography , Osteolysis/etiology , Osteolysis/diagnostic imaging , Knee Joint/surgery , Knee Joint/diagnostic imaging , Knee Joint/physiopathology , AdultSubject(s)
Osteolysis , Female , Humans , Male , Middle Aged , Osteolysis/diagnostic imaging , Osteolysis/surgery , Osteolysis/etiology , Treatment OutcomeABSTRACT
CASE: A 15-year-old girl known with osteogenesis imperfecta presented with left femoral pain. She had been treated with multiple Fassier-Duval intramedullary nails, which were still in situ. Radiographic imaging demonstrated focal osteolysis and periosteal reaction at the telescopic junction of the rod in the distal femur. She underwent implant removal. Intraoperative sampling demonstrating acute sterile inflammation and presence of brownish colored particles consistent with metal debris and osteolysis. Explant analysis confirmed corrosion of the stainless-steel telescopic nail as the underlying cause. CONCLUSION: Osteolysis and periosteal reaction because of corrosion should be considered in conjunction with other more common causes of pain, such as fracture or infection, in patients treated with telescopic intramedullary nails.
Subject(s)
Osteolysis , Female , Humans , Adolescent , Osteolysis/diagnostic imaging , Osteolysis/etiology , Corrosion , Device Removal , Femur , PainABSTRACT
Aims: Oxidized zirconium (OxZi) and highly cross-linked polyethylene (HXLPE) were developed to minimize wear and risk of osteolysis in total hip arthroplasty (THA). However, retrieval studies have shown that scratched femoral heads may lead to runaway wear, and few reports of long-term results have been published. The purpose of this investigation is to report minimum ten-year wear rates and clinical outcomes of THA with OxZi femoral heads on HXLPE, and to compare them with a retrospective control group of cobalt chrome (CoCr) or ceramic heads on HXLPE. Methods: From 2003 to 2006, 108 THAs were performed on 96 patients using an OxZi head with a HXLPE liner with minimum ten-year follow-up. Harris Hip Scores (HHS) were collected preoperatively and at the most recent follow-up (mean 13.3 years). Linear and volumetric liner wear was measured on radiographs of 85 hips with a minimum ten-year follow-up (mean 14.5 years). This was compared to a retrospective control group of 45 THAs using ceramic or CoCr heads from October 1999 to February 2005, with a minimum of ten years' follow-up. Results: Average HHS improved from 50.8 to 91.9 and 51.0 to 89.8 in the OxZi group and control group, respectively (p = 0.644), with no osteolysis in either group. Linear and volumetric wear rates in the OxZi group averaged 0.03 mm/year and 3.46 mm3/year, respectively. There was no statistically significant difference in HHS scores, nor in linear or volumetric wear rate between the groups, and no revision for any indication. Conclusion: The radiological and clinical outcomes, and survivorship of THA with OxZi femoral heads and HXLPE liners, were excellent, and comparable to CoCr or ceramic heads at minimum ten-year follow-up. Wear rates are below what would be expected for development of osteolysis. OxZi-HXLPE is a durable bearing couple with excellent long-term outcomes.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Osteolysis , Humans , Polyethylene , Zirconium , Retrospective Studies , Femur Head/surgery , Osteolysis/etiology , Osteolysis/surgery , Prosthesis Failure , Prosthesis Design , Chromium AlloysABSTRACT
Aims: Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear. Methods: Data were retrieved for all patients who underwent isolated acetabular component liner exchange surgery with a HXLPE component in our institute between August 2000 and January 2015. Patients were classified according to the fixation method used (original locking mechanism (n = 36) or cemented (n = 50)). Survival and revision rates were compared. A total of 86 revisions were performed and the mean duration of follow-up was 13 years. Results: A total of 20 patients (23.3%) had complications, with dislocation alone being the most common (8.1%; 7/86). Ten patients (11.6%) required re-revision surgery. Cementing the HXLPE liner (8.0%; 4/50) had a higher incidence of re-revision due to acetabular component liner-related complications than using the original locking mechanism (0%; 0/36; p = 0.082). Fixation using the original locking mechanism was associated with re-revision due to acetabular component loosening (8.3%; 3/36), compared to cementing (0%; 0/50; p = 0.038). Overall estimated mean survival was 19.2 years. There was no significant difference in the re-revision rate between the original locking mechanism (11.1%; 4/36) and cementing (12.0%; 6/50; p = 0.899). Using Kaplan-Meier survival analysis, the revision-free survival of HXLPE fixed with the original locking mechanism and cementing was 94.1% and 93.2%, respectively, at ten years, and 84.7% and 81.3%, respectively, at 20 years (p = 0.840). Conclusion: The re-revision rate and the revision-free survival following acetabular component liner exchange revision surgery using the HXLPE liner were not influenced by the fixation technique used. Both techniques were associated with good survival at a mean follow-up of 13 years. Careful patient selection is necessary for isolated acetabular component liner exchange revision surgery in order to achieve the best outcomes.
Subject(s)
Acetabulum , Arthroplasty, Replacement, Hip , Hip Prosthesis , Osteolysis , Polyethylene , Prosthesis Design , Prosthesis Failure , Reoperation , Humans , Arthroplasty, Replacement, Hip/methods , Arthroplasty, Replacement, Hip/instrumentation , Osteolysis/etiology , Female , Male , Middle Aged , Aged , Acetabulum/surgery , Retrospective Studies , Adult , Aged, 80 and over , Follow-Up StudiesABSTRACT
Total ankle arthroplasty (TAA) has become a popular management option for ankle arthritis. Periprosthetic osteolysis is one of the most common causes for reoperation in TAA. A CT scan should be done in all suspected osteolysis cases to confirm location, quantify size and aid in surgical planning. These patients are often asymptomatic with limited evidence regarding appropriate management. Smaller lesions should be monitored for progression in size. Periprosthetic cysts measuring 10-15mm in all three axes should be considered for debridment and curettage with autogenous bone grafting. The authors believe that bone grafting of large asymptomatic periprosthetic cysts could prevent implant failure.
Subject(s)
Arthroplasty, Replacement, Ankle , Cysts , Joint Prosthesis , Osteolysis , Humans , Ankle/surgery , Bone Transplantation , Osteolysis/etiology , Retrospective Studies , Arthroplasty, Replacement, Ankle/adverse effects , Joint Prosthesis/adverse effects , Cysts/complications , Cysts/surgery , Ankle Joint/surgery , Curettage/adverse effects , Reoperation/adverse effectsABSTRACT
Numerous interference screws of different compositions exist including titanium screws, bioabsorbable screws, and polyetheretherketone (PEEK) screws. PEEK-based implants are frequently used in orthopaedic surgery due to their biocompatibility, similar elastic modulus to cortical bone, and purported negligible risk of osteolysis compared with bioabsorbable screws. In this case report, we present the case of a 48-year-old healthy female who experienced a massive osteolytic reaction in the talus and fibula after 11 weeks following implantation of PEEK-based interference screws during lateral ankle ligament reconstruction. The patient subsequently underwent removal of the PEEK screws and specimens were sent for microbiological and histopathological analysis. The specimens report demonstrated fibrotic tenosynovial soft tissue with patchy chronic inflammation, oedematous reactive changes, and histiocytic reaction, with no evidence of any significant acute inflammation. The patient recovered well and was asymptomatic at 6 months postoperatively. To our knowledge, this is the first case report of a massive osteolytic reaction to PEEK-based interference screws.
Subject(s)
Benzophenones , Bone Screws , Fibula , Ketones , Osteolysis , Polyethylene Glycols , Polymers , Talus , Humans , Female , Middle Aged , Osteolysis/etiology , Bone Screws/adverse effects , Ketones/adverse effects , Polyethylene Glycols/adverse effects , Polymers/adverse effects , Fibula/surgery , Talus/surgery , Biocompatible Materials/adverse effectsABSTRACT
We report a rarely occurring hematologic neoplasm in a young adult. Hematologic neoplasms were first described in 2008 and are now included in both accepted tumor classification systems, i.e., International Consensus Classification and World Health Organization. This hematologic neoplasm shows a characteristic ALK positivity in immunohistochemical examination and correspondingly, ALK fusion genes in the molecular analysis. Pathologists should be aware of this entity, particularly as it is challenging to differentiate from other more frequent neoplasms of the same disease group or mesenchymal neoplasm with ALK aberration.
Subject(s)
Osteolysis , Humans , Diagnosis, Differential , Osteolysis/pathology , Osteolysis/diagnosis , Osteolysis/diagnostic imaging , Osteolysis/etiology , Mandibular Neoplasms/pathology , Mandibular Neoplasms/diagnosis , Mandibular Neoplasms/genetics , Male , Adult , Anaplastic Lymphoma Kinase/genetics , Young Adult , FemaleABSTRACT
INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.
Subject(s)
Bone Cements , Bone Neoplasms , Pelvic Bones , Humans , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Bone Neoplasms/complications , Bone Cements/therapeutic use , Osteolysis/etiology , Cementation , Treatment Outcome , Female , Pelvic Neoplasms/secondary , MaleABSTRACT
Periprosthetic tissue inflammation is a challenging complication arising in joint replacement surgeries, which is often caused by wear debris from polyethylene (PE) components. In this study, we examined the potential biological effects of grafting a [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSAH) polymer onto the surface of PE through a solvent-evaporation technique. J774A.1 macrophage-like cells and primary cultured mouse osteoblasts were treated with PE powder with or without the MEDSAH coating. MEDSAH grafting on PE substantially reduced the expression of pro-inflammatory cytokines and other mediators in primary cultured mouse osteoblasts, but did not significantly impact macrophage-mediated inflammation. Our findings suggest that a MEDSAH coating on PE-based materials has potential utility in mitigating periprosthetic tissue inflammation and osteolysis and preventing aseptic loosening in total joint replacements. Further research, including large-scale clinical trials and biomechanical analyses, is needed to assess the long-term performance and clinical implications of MEDSAH-coated PE-based materials in total joint arthroplasty.
Subject(s)
Inflammation , Osteoblasts , Polyethylene , Animals , Mice , Inflammation/pathology , Osteoblasts/metabolism , Osteoblasts/drug effects , Macrophages/metabolism , Cell Line , Cytokines/metabolism , Osteolysis/etiology , Osteolysis/pathology , Coated Materials, Biocompatible/chemistry , Methacrylates/chemistry , Arthroplasty, Replacement/adverse effectsABSTRACT
The use of highly crosslinked ultra-high molecular weight polyethylene (XLPE) has significantly reduced the volumetric wear of acetabular liners, thereby reducing the incidence of osteolysis. However, contemporary components tend to generate smaller wear particles, which can no longer be identified using conventional histology. This technical limitation can result in imprecise diagnosis. Here, we report on two uncemented total hip arthroplasty cases (~7 years in situ) revised for periprosthetic fracture of the femur and femoral loosening, respectively. Both liners exhibited prominent wear. The retrieved pseudocapsular tissue exhibited a strong macrophage infiltration without microscopically identifiable polyethylene particles. Yet, using Fourier-transform infrared micro-spectroscopic imaging (FTIR-I), we demonstrated the prominent intracellular accumulation of polyethylene debris in both cases. This study shows that particle induced osteolysis can still occur with XLPE liners, even under 10 years in situ. Furthermore, we demonstrate the difficulty of determining the presence of polyethylene debris within periprosthetic tissue. Considering the potentially increased bioactivity of finer particles from XLPE compared to conventional liners, an accurate detection method is required, and new histopathological hallmarks of particle induced osteolysis are needed. FTIR-I is a great tool to that end and can help the accurate determination of foreign body tissue responses.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Prosthesis Failure , Humans , Arthroplasty, Replacement, Hip/adverse effects , Spectroscopy, Fourier Transform Infrared/methods , Hip Prosthesis/adverse effects , Female , Polyethylenes/chemistry , Osteolysis/etiology , Osteolysis/pathology , Osteolysis/diagnosis , Aged , Male , Reoperation , Polyethylene/chemistry , Polyethylene/adverse effects , Middle AgedABSTRACT
Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.
Subject(s)
Bone Neoplasms , Osteolysis , Animals , Mice , X-Ray Microtomography/methods , Bone Neoplasms/complications , Bone Neoplasms/secondary , Bone and Bones/diagnostic imaging , Osteolysis/diagnostic imaging , Osteolysis/etiology , Osteolysis/pathology , Disease Models, Animal , Cell Line, TumorABSTRACT
Background: Periprosthetic osteolysis is a prevalent complication following total ankle arthroplasty (TAA), implicating various cytokines in osteoclastogenesis as pivotal in this process. This study aimed to evaluate the relationship between osteolysis and the concentrations of osteoclastogenesis-related cytokines in synovial fluid and investigate its clinical value following TAA. Methods: Synovial fluid samples from 23 ankles that underwent revision surgery for osteolysis following TAA were analyzed as the osteolysis group. As a control group, we included synovial fluid samples obtained from 23 ankles during primary TAA for osteoarthritis. The receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio in these samples was quantified using sandwich enzyme-linked immunosorbent assay techniques, and a bead-based multiplex immunoassay facilitated the detection of specific osteoclastogenesis-related cytokines. Results: RANKL levels averaged 487.9 pg/mL in 14 of 23 patients in the osteolysis group, with no detection in the control group's synovial fluid. Conversely, a significant reduction in OPG levels was observed in the osteolysis group (p = 0.002), resulting in a markedly higher mean RANKL/OPG ratio (0.23) relative to controls (p = 0.020). Moreover, the osteolysis group had increased concentrations of various osteoclastogenesis-related cytokines (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, IP-10, and monocyte chemotactic protein-1) in the synovial fluid relative to the control group. Conclusions: Our results demonstrated that periprosthetic osteolysis was associated with osteoclastogenesis activation through an elevated RANKL/OPG ratio following TAA. We assume that RANKL and other osteoclastogenesis-related cytokines in the synovial fluid have clinical value as a potential marker for the development and progression of osteolysis following TAA.
Subject(s)
Arthroplasty, Replacement, Ankle , Biomarkers , Osteolysis , Osteoprotegerin , RANK Ligand , Synovial Fluid , Humans , Synovial Fluid/metabolism , Synovial Fluid/chemistry , Osteolysis/metabolism , Osteolysis/etiology , Male , Female , RANK Ligand/metabolism , Aged , Middle Aged , Arthroplasty, Replacement, Ankle/adverse effects , Osteoprotegerin/metabolism , Osteoprotegerin/analysis , Biomarkers/metabolism , Biomarkers/analysis , Aged, 80 and over , Cytokines/metabolism , Cytokines/analysis , ReoperationABSTRACT
ABSTRACT: Ovarian cancer with bone involvement occurs rarely with an incidence of 0.1-0.12%. The common sites of bone metastasis are vertebrae, pelvic bones, and the skull. Patients present with severe localized bone pain, swelling, and difficulty in walking. We report a rare case of a 53-year-old female with metastatic epithelial serous adenocarcinoma of the ovary presented with multiple bony lesions in pelvic bones involving the sacrum, bilateral ilium, ischium and pubic bones and the right femur in the region of greater trochanter, smaller lesions in the left femur, and dorso lumbar vertebral metastasis while undergoing treatment as a part of distant spread. Radiologically, the osteolytic lesions are the most common, but in our case, the lesions are osteoblastic, which is rare.