Periprosthetic Bone Resorption Research Articles

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.

The Effects of Different Femoral Component Materials on Bone and Implant Response in Total Knee Arthroplasty: A Finite Element Analysis.

Due to the high stiffness of the biomaterials used in total knee arthroplasty, stress shielding can lead to decreased periprosthetic bone mineral density and bone resorption. As different materials and 3D-printed highly porous surfaces are available for knee femoral components from the industry nowadays, this study aimed to compare the effects of two same-design cruciate-retaining femoral components, made with CoCr and titanium alloy, respectively, on periprosthetic bone stresses through a finite element model of the implanted knee in order to evaluate the induced stress shielding. Moreover, the effect of the cementless highly porous surface of the titanium implant was analyzed in comparison to the cemented interface of the CoCr implant. The von Mises stresses were analyzed in different periprosthetic regions of interest of the femur with different configurations and knee flexion angles. The titanium component induced higher bone stresses in comparison with the CoCr component, mostly in the medial compartment at higher knee flexion angles; therefore, the CoCr component led to more stress shielding. The model was revealed to be effective in describing the effects of different femoral component materials on bone stress, highlighting how a cementless, highly porous titanium femoral component might lead to less stress shielding in comparison to a cemented CoCr implant with significant clinical relevance and reduced bone resorption after total knee arthroplasty.

Numerical Evaluations of an Uncemented Acetabular Component in Total Hip Arthroplasty: Effects of Loading and Interface Conditions.

Using finite element (FE) models of intact and implanted hemipelvises, the study aimed to investigate the influences of musculoskeletal loading and implant-bone interface conditions on preclinical analysis of an uncemented acetabular component after total hip arthroplasty (THA). A new musculoskeletal loading dataset, corresponding to daily activities of sitting up-down, stairs up-down and normal walking, for a pelvic bone was generated based on previously validated Gait2392 model. Three implant-bone interface conditions, fully bonded and debonded having two rim press-fits (1 mm and 2 mm), were analyzed. High tensile (2000-2415 μϵ) and compressive strains (900-1035 μϵ) were predicted for 2 mm press-fit, which might evoke microdamage in pelvic cortex. Strain shielding in periprosthetic cancellous bone was higher for bonded condition during sitting up activity, compared to other combinations of interface and loading conditions. Only the nodes around acetabular rim (less than 6%) were susceptible to interfacial debonding. Although maximum micromotion increased with increase in press-fit, postoperatively for all load cases, these were within a favorable range (52-143 μm) for bone ingrowth. Micromotions reduced (39-105 μm) with bone remodeling, indicating lesser chances of implant migration. Bone apposition was predominant around acetabular rim, compared to dome, for all interface conditions. Periprosthetic bone resorption of 10-20% and bone apposition of 10-15% were predicted for bonded condition. Whereas for press-fit (1 mm and 2 mm), predominant bone apposition of 200-300% was observed. This study highlights the importance of variations in loading and interface conditions on in silico evaluations of an uncemented acetabular component.

Comparison of short-term effectiveness of Prodisc-C Vivo artificial disc replacement and Zero-P fusion for treatment of single-segment cervical spondylosis

To compare the short-term effectiveness and the impact on cervical segmental range of motion using Prodisc-C Vivo artificial disc replacement and Zero-P fusion for the treatment of single-segment cervical spondylosis. The clinical data of 56 patients with single-segment cervical spondylosis who met the selection criteria between January 2015 and December 2018 were retrospectively analyzed, and they were divided into study group (27 cases, using Prodisc-C Vivo artificial disc replacement) and control group (29 cases, using Zero-P fusion) according to different surgical methods. There was no significant difference between the two groups in terms of gender, age, type of cervical spondylosis, disease duration, involved segments and preoperative pain visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), surgical segments range of motion, upper and lower adjacent segments range of motion, overall cervical spine range of motion, and cervical curvature (P>0.05). The operation time, intraoperative blood loss, postoperative hospitalization stay, time of returning to work, clinical effectiveness indicators (VAS score, JOA score, NDI, and improvement rate of each score), and imaging indicators (surgical segments range of motion, upper and lower adjacent segments range of motion, overall cervical spine range of motion, and cervical curvature, prosthesis position, bone absorption, heterotopic ossification, etc.) were recorded and compared between the two groups. There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05); the postoperative hospitalization stay and time of returning to work in the study group were significantly shorter than those in the control group (P<0.05). Both groups were followed up 12-64 months, with an average of 26 months. There was no complication such as limb or organ damage, implant failure, and severe degeneration of adjacent segments requiring reoperation. The VAS score, JOA score, and NDI of the two groups at each time point after operation significantly improved when compared with those before operation (P<0.05); there was no significant difference in the above scores at each time point after operation between the two groups (P>0.05); there was no significant difference in the improvement rate of each score between the two groups at last follow-up (P>0.05). The surgical segments range of motion in the study group maintained to varying degrees after operation, while it in the control group basically disappeared after operation, showing significant differences between the two groups (P<0.05). At last follow-up, there was no significant difference in the upper and lower adjacent segments range of motion in the study group when compared with preoperative ones (P>0.05), while the upper adjacent segments range of motion in the control group increased significantly (P<0.05). The overall cervical spine range of motion and cervical curvature of the two groups decreased at 3 months after operation, and increased to varying degrees at last follow-up, but there was no significant difference between groups and within groups (P>0.05). At last follow-up, X-ray films and CT examinations showed that no prosthesis loosening, subsidence, or displacement was found in all patients; there were 2 cases (7.4%) of periprosthetic bone resorption and 3 cases (11.1%) of heterotopic ossification which did not affect the surgical segments range of motion. Both the Prodisc-C Vivo artificial disc replacement and Zero-P fusion have satisfactory short-term effectiveness in treatment of single-segment cervical spondylosis. Prodisc-C Vivo artificial disc replacement can also maintain the cervical spine range of motion to a certain extent, while reducing the occurrence of excessive motion of adjacent segments after fusion.

Diagnostic Performance of Advanced Metal Artifact Reduction MRI for Periprosthetic Shoulder Infection.

The diagnosis of periprosthetic shoulder infection (PSI) in patients with a painful arthroplasty is challenging. Magnetic resonance imaging (MRI) may be helpful, but shoulder implant-induced metal artifacts degrade conventional MRI. Advanced metal artifact reduction (MARS) improves the visibility of periprosthetic bone and soft tissues. The purpose of our study was to determine the reliability, repeatability, and diagnostic performance of advanced MARS-MRI findings for diagnosing PSI. Between January 2015 and December 2019, we enrolled consecutive patients suspected of having PSI at our academic hospital. All 89 participants had at least 1-year clinical follow-up and underwent standardized clinical, radiographic, and laboratory evaluations and advanced MARS-MRI. Two fellowship-trained musculoskeletal radiologists retrospectively evaluated the advanced MARS-MRI studies for findings associated with PSI in a blinded and independent fashion. Both readers repeated their evaluations after a 2-month interval. Interreader reliability and intrareader repeatability were assessed with κ coefficients. The diagnostic performance of advanced MARS-MRI for PSI was quantified using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). When applying the International Consensus Meeting (ICM) 2018 criteria, of the 89 participants, 22 (25%) were deemed as being infected and 67 (75%) were classified as being not infected (unlikely to have PSA and not requiring a surgical procedure during 1-year follow-up). The interreader reliability and intrareader repeatability of advanced MARS-MRI findings, including lymphadenopathy, joint effusion, synovitis, extra-articular fluid collection, a sinus tract, rotator cuff muscle edema, and periprosthetic bone resorption, were good (κ = 0.61 to 0.80) to excellent (κ > 0.80). Lymphadenopathy, complex joint effusion, and edematous synovitis had sensitivities of >85%, specificities of >90%, odds ratios of >3.6, and AUC values of >0.90 for diagnosing PSI. The presence of all 3 findings together yielded a PSI probability of >99%, per logistic regression analysis. Our study shows the clinical utility of advanced MARS-MRI for diagnosing PSI when using the ICM 2018 criteria as the reference standard. Although the reliability and diagnostic accuracy were high, these conclusions are based on our specific advanced MARS-MRI protocol interpreted by experienced musculoskeletal radiologists. Investigations with larger sample sizes are needed to confirm these results. Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Computational prediction of the long-term behavior of the femoral density after THR using the Silent Hip stem

Aseptic loosening due to the progressive periprosthetic bone resorption following total hip replacement is a crucial concern, that causes complications and failure of the arthroplasty surgery. The mismatch in stiffness between the hip implant and the surrounding femoral bone is one of the key factors leading to bone density resorption. This paper aimed to investigate the long-term response of the femoral bone after THR using the Silent Hip stem. For this purpose, a validated thermodynamic-based computational model was used to compute the change in bone density before and after THR. This model incorporated essential factors involved in bone remodeling process, such as mechanical loading, and biochemical affinities. The results of the numerical simulations using 3D finite element analysis were analyzed in five zones of interest qualitatively and quantitatively. Bone density predictions showed notable bone resorption in cervical areas, specifically in zone 1 and zone 5 of −18.7% and −14%, respectively. Conversely, bone formation was observed in the greater trochanter area (zone 2) of +25%. Stress shielding seemed to occur at cervical area due to the reduction in the mechanical loading in this region. Based on the quantitative analysis of the bone density distribution throughout the femoral bone, it appears that the Silent Hip stem achieved less bone resorption compared to conventional hip stem designs reported in the literature, which could be used for active patients.

Bone Remodeling after Ulna Head Replacement in Distal Radioulnar Joint Arthroplasty: A Radiographic Comparison between a Partial and a Total Ulna Head Concept.

Background Ulna head arthroplasty has become an eligible solution for injury or disease in the distal radioulnar joint. Bone resorption beneath the prosthetic head is often reported, but mechanism poorly understood. Purpose The aims were to evaluate bone remodeling and radiological instability in two conceptually different distal radioulnar joint arthroplasties: the total and the partial ulna head replacement. Patients and Methods We conducted a retrospective radiographic assessment of 51 ulna head arthroplasties; 26 Herbert ulna (total ulna head replacement) and 25 First Choice (partial ulna head replacement), to analyze periprosthetic bone resorption and radiologic instability. Intraoperative/immediate postoperative and 1-year radiographs were reviewed by two independent assessors. The radiographic follow-up averaged 13 (10-17) months. The size of the stem in relation to the diameter of the ulna (filling ratio) was measured on the intraoperative/immediate postoperative radiographs. Bone resorption beneath the collar of the prothesis was measured on the 1-year radiographs and expressed as a bone resorption index (BRI) between the length of the resorption and the length of the implant stem. Radiological stability was measured on both the preoperative and the 1-year lateral radiographs. Results The total ulna head prothesis presented with more extensive bone resorption beneath the prosthetic head than the partial ulna head prothesis at 1-year post surgery ( p <0.001). The filling ratio did not influence the 1-year bone resorption and there was no difference regarding radiological instability between the two prosthetic designs. Conclusion The pattern of bone adaptions after an ulna head prothesis may differ due to design and concept of the prosthesis.

Mechanical interaction between additive-manufactured metal lattice structures and bone in compression: implications for stress shielding of orthopaedic implants

One of the main biomechanical causes for aseptic failure of orthopaedic implants is the stress shielding. This is caused by an uneven load distribution across the bone normally due to a stiff metal prosthesis component, leading to periprosthetic bone resorption and to implant loosening. To reduce the stress shielding and to improve osseointegration, biocompatible porous structures suitable for orthopaedic applications have been developed. Aim of this study was to propose a novel in-vitro model of the mechanical interaction between metal lattice structures and bovine cortical bone in compression. Analysis of the strain distribution between metal structure and bone provides useful information on the potential stress shielding of orthopaedic implants with the same geometry of the porous scaffold. Full density and lattice structures obtained by the repetition of 1.5 mm edge cubic elements via Laser Powder Bed Fusion of CoCrMo powder were characterized for mechanical properties using standard compressive testing. The two porous geometries were characterized by 750 μm and 1000 μm pores resulting in a nominal porosity of 43.5% and 63.2% respectively. Local deformation and strains of metal samples coupled with fresh bovine cortical bone samples were evaluated via Digital Image Correlation analysis up to failure in compression. Visualization and quantification of the local strain gradient across the metal-bone interface was used to assess differences in mechanical behaviour between structures which could be associated to stress-shielding. Overall stiffness and local mechanical properties of lattice and bone were consistent across samples. Full-density metal samples appeared to rigidly transfer the compression force to the bone which was subjected to large deformations (2.2 ± 0.3% at 15 kN). Larger porosity lattice was associated to lower stiffness and compressive modulus, and to a smoother load transfer to the bone. While tested on a limited sample size, the proposed in-vitro model appears robust and repeatable to assess the local mechanical interaction of metal samples suitable for orthopaedic applications with the bone tissue. CoCrMo scaffolds made of 1000 μm pores cubic cells may allow for a smoother load transfer to the bone when used as constitutive material of orthopaedic implants.

Identification of Thymidine Phosphorylase as a Potential Therapeutic Target for Bone Loss Associated Periprosthetic Osteolysis

Background: Macrophage-derived factors are generally thought to play a key role in the pathogenesis of aseptic loosening though initiating periprosthetic inflammation and pathological bone resorption. Therefore, the aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. Methods: We examined the effects of 12 macrophage-derived factors that were identified by RNA sequencing analysis of stimulated macrophages on osteoclast differentiation in vitro. The identified molecule was characterized as osteoclastogenic factor in vitro and in vivo. RNA-seq for the induced-osteoclasts was performed in an effort to understand its action mode. Therapeutic effects of Src kinase inhibitor were evaluated in implant particles-induced osteolysis murine model. Findings: Thymidine phosphorylase (TYMP) was found to induce the production of significant numbers of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP silencing by siRNA reduced the number of osteoclasts in macrophages that had been stimulated with implant particles, suggesting a potential role in periprosthetic osteolysis. High levels of TYMP were detected in the serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. Interestingly, TYMP stimulation appeared to activate the tyrosine kinase Fyn signaling associated with cell fusion and osteoclast formation. The oral administration of saracatinib, an FYN kinase inhibitor, significantly and consistently suppressed the formation of bone osteolytic lesions in implant wear particles-induced osteolysis model. Interpretation: Our findings highlight a novel molecular target for therapeutic intervention in implant loosening. Funding Information: Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research C;17K10993), Akiyama Life Science, Foundation and Kobayashi Foundation, and Japan Agencyfor Medical Research and Development (JP20gm6210004). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The institutional review boards of Hokkaido University and hospital approved the study protocols for the use of human samples (approval ID: 016-0002). All participants signed an informed consent form for research use. Procedures for animal experiments were performed following protocols approved by the Institute of Animal Care and Use Committee of the Hokkaido University Graduate School of Medicine (no. 17-0085).

A three-dimensional finite element analysis on the effects of implant materials and designs on periprosthetic tibial bone resorption.

Implant material is a more important factor for periprosthetic tibial bone resorption than implant design after total knee arthroplasty (TKA). The virtual perturbation study was planned to perform using single case of proximal tibia model. We determined whether the implant materials' stiffness affects the degree of periprosthetic tibial bone resorption, and whether the effect of material change with the same implant design differed according to the proximal tibial plateau areas. This three-dimensional finite element analysis included two cobalt-chromium (CoCr) and two titanium (Ti) tibial implants with different designs. They were implanted into the proximal tibial model reconstructed using extracted images from computed tomography. The degree of bone resorption or formation was measured using the strain energy density after applying axial load. The same analysis was performed after exchanging the materials while maintaining the design of each implant. The degree of periprosthetic tibial bone resorption was not determined by the type of implant materials alone. When the implant materials were changed from Ti to CoCr, the bone resorption in the medial compartment increased and vice versa. The effect of material composition's change on anterior and posterior areas varied accordingly. Although the degree of bone resorption was associated with implant materials, it differed depending on the design of each implant. The effect on the degree of bone resorption according to the materials after TKA should be evaluated while concomitantly considering design.

The effect of strontium ranelate on titanium particle-induced periprosthetic osteolysis regulated by WNT/β-catenin signaling in vivo and in vitro.

Aseptic loosening following periprosthetic osteolysis is the primary complication that limits the lifetime of total joint arthroplasty (TJA). The wear particles trigger a chronic inflammation response in the periprosthetic tissue and turn over the bone balance to bone resorption. The present study aimed to investigate the possible effect and mechanism of strontium ranelate (SR), a clinically safe drug for osteoporosis, on particle-induced periprosthetic osteolysis. Thirty-six female C57BL/6j mice underwent tibial Ti-nail implantation to establish an animal model of aseptic loosening. After 12 weeks, micro-CT results showed that strontium ranelate could inhibit periprosthetic bone resorption. In vitro, Ti particles were used to stimulate RAW264.7 cell line to collect conditioned medium, and co-culture MC3T3-E1 cell line with conditioned medium to establish a cell model of aseptic loosening. The results of alkaline phosphatase (ALP) detection, immunofluorescence, and flow cytometry demonstrated that strontium ranelate could regulate the expression of OPG/RANKL, promote differentiation and mineralization, and inhibit apoptosis in osteoblasts. Moreover, we revealed that SR’s exerted its therapeutic effect by down-regulating sclerostin, thereby activating the Wnt/β-catenin signal pathway. Therefore, this research suggests that strontium ranelate could be a potential drug for the prevention and treatment of particle-induced aseptic loosening post-TJA.

Prospective and longitudinal evolution of postoperative periprosthetic findings on metal artifact\u2013reduced MR imaging in asymptomatic patients after uncemented total hip arthroplasty

ObjectiveTo prospectively assess the evolution of postoperative MRI findings in asymptomatic patients after total hip arthroplasty (THA) over 24 months (mo).MethodsThis prospective cohort study included 9 asymptomatic patients (56.7 ± 15.0 years) after THA. Metal artifact–reduced 1.5-T MRI was performed at 3, 6, 12, and 24 mo after surgery. The femoral stem and acetabular cup were assessed by two readers for bone marrow edema (BME), periprosthetic bone resorption, and periosteal edema in addition to periarticular soft tissue edema and joint effusion.ResultsBME was common around the femoral stem in all Gruen zones after 3 mo (range: 50–100%) and 6 mo (range: 33–100%) and in the acetabulum in DeLee and Charnley zone II after 3 mo (100%) and 6 mo (33%). BME decreased substantially after 12 mo (range: 0–78%) and 24 mo (range: 0–50%), may however persist in particular in Gruen zones 1 + 7. Periosteal edema along the stem was common 3 mo postoperatively (range: 63–75%) and rare after 24 mo: 13% only in Gruen zones 2 and 5. Twelve months and 24 mo postoperatively, periprosthetic bone resorption was occasionally present around the femoral stem (range: 11–33% and 13–38%, respectively). Soft tissue edema occurred exclusively along the surgical access route after 3 mo (100%) and 6 mo (89%) and never at 12 mo or 24 mo (0%).ConclusionAround the femoral stem, BME (33–100%) and periosteal edema (0–75%) are common until 6 mo after THA, decreasing substantially in the following period, may however persist up to 24 mo (BME: 0–50%; periosteal edema: 0–13%) in few non-adjoining Gruen zones. Soft tissue edema along the surgical access route should have disappeared 12 mo after surgery.

Denosumab prevents periprosthetic bone mineral density loss in the tibial metaphysis in total knee arthroplasty

BackgroundPeriprosthetic bone quality is one of the most important factors preventing early prosthesis migration and long-term failure. Although denosumab, which binds to the receptor activator of nuclear factor kappa-B ligand (RANKL), has been linked with periprosthetic bone mineral density (BMD), the effectiveness of denosumab against bone loss remains unclear. We hypothesized that denosumab treatment after total knee arthroplasty (TKA) could prevent periprosthetic bone resorption. MethodsIn this prospective cohort study, 28 patients with primary knee osteoarthritis were divided into two groups: denosumab (denosumab and vitamin D) and control (vitamin D only) groups. All patients underwent TKA with the same implant model and received medication after surgery. We used dual-energy X-ray absorptiometry to measure periprosthetic BMD after TKA. ResultsIn the control group, the BMD of the proximal medial tibia decreased drastically at 12 months after TKA (−19.7%). Denosumab treatment significantly preserved this BMD loss (0.7%). The linear regression analysis revealed that denosumab intervention had the highest significantly positive relationship with BMD. ConclusionsOur results indicate that denosumab treatment significantly reduces periprosthetic BMD loss, even at the early stages after TKA. This therapeutic strategy may facilitate early stable fixation of the prosthesis which, in turn, may help to prevent early implant migration and reduce the need for revision surgery.

Evidence for Gender-Specific Bone Loss Mechanisms in Periprosthetic Osteolysis.

Osteolysis adjacent to total hip replacement (THR) prostheses is a major cause of their eventual failure. Periprosthetic osteolysis is associated with the production of bioactive particles, produced by the wear of articulating prosthesis surfaces. Wear particles invade the periprosthetic tissue, inducing inflammation and bone resorption. Previous studies have shown that osteocytes, the most numerous cell type in mineralised bone, can respond to wear particles of multiple orthopaedic material types. Osteocytes play important roles in bone resorption, regulating bone resorption by osteoclasts and directly through osteocytic osteolysis, also known as perilacunar remodelling. In this study, we perform a histological analysis of bone biopsies obtained from cohorts of male and female patients undergoing either primary THR surgery or revision THR surgery for aseptic loosening. The osteocyte lacunae area (Ot.Lac.Ar) and percentage lacunar area/bone area (%Ot.Lac.Ar/B.Ar) were significantly larger overall in revision THR bone than bone from similar sites in primary THR. Analysis by patient gender showed that increased Ot.Lac.Ar, indicative of increased perilacunar remodelling, was restricted to female revision samples. No significant differences in osteoclast parameters were detectable between the cohorts. These findings suggest previously unrecognised gender-specific mechanisms of bone loss in orthopaedic wear particle-induced osteolysis in humans.

Inflammation time-axis in aseptic loosening of total knee arthroplasty: A preliminary study.

ObjectiveAseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15–20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists.DesignThe inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry.ResultsAL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages.ConclusionsOur study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient’s response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.

Leptin Increases Particle-Induced Osteolysis in Female ob/obMice

Particles generated from wear of prosthesis joint bearing surfaces induce inflammation-mediated periprosthetic bone resorption (osteolysis). Morbidly obese leptin-deficient ob/ob mice are resistant to polyethylene particle-induced bone loss, suggesting that leptin, a hormone produced by adipocytes that circulates in concentrations proportional to total body adiposity, increases osteolysis. To confirm that particles induce less osteolysis in leptin-deficient mice after controlling for cold stress (room temperature)-induced bone loss, ob/ob mice on a C57BL/6 (B6) background and colony B6 wildtype (WT) mice housed at thermoneutral temperature were randomized to control or particle treatment groups (N = 5/group). Polyethylene particles were implanted over calvaria and mice sacrificed 2 weeks later. Compared to particle-treated WT mice, particle-treated ob/ob mice had lower osteolysis score, less infiltration of immune cells, and less woven bone formation. To determine the role of leptin in particle-induced osteolysis, ob/ob mice were randomized into one of 4 groups (n = 6–8/group): (1) control, (2) particles, (3) particles + continuous leptin (osmotic pump, 6 μg/d), or (4) particles + intermittent leptin (daily injection, 40 μg/d). Leptin treatment increased particle-induced osteolysis in ob/ob mice, providing evidence that the adpiokine may play a role in inflammation-driven bone loss. Additional research is required to determine whether altering leptin levels within the physiological range results in corresponding changes in polyethylene-particle-induced osteolysis.

Probing Cytocompatibility, Hemocompatibility, and Quantitative Inflammatory Response in Mus musculus toward Oxide Bioceramic Wear Particulates and a Comparison with CoCr.

Peri-prosthetic bone resorption and loosening of artificial joints have been widely recognized to limit the performance of the load-bearing implants. Therefore, the present study probes into the cyto-, hemo-, and histocompatibility of the small sized wear particulates of ZrO2-toughened Al2O3 (ZTA). In order to develop a comprehensive, yet clinically relevant understanding, a comparison is made with two baseline ceramics (Al2O3 and ZrO2) and metallic material (CoCr), all in particulateforms. Whilein vitro cytotoxicity assessment was carried out with mouse osteoblast cells, preclinical testing of intra-articularly injected particulates up to the concentration 25 wt % in PBS over the period of 12 weeks was performed in mouse model. Interestingly, mouse osteoblast cells, cultured in media with ZTA, Al2O3, and ZrO2 particulates of three different concentrations (0.25, 2.5, and 25 mg/mL) exhibited uncompromised cell viability and considerable cell spreading, up to the time frame of 72 h. In contrast, similar experiments with CoCr particulates demonstrated significant decrease in cellular growth with drastic change in osteoblast proliferation behavior. Furthermore, the decrease in RBC damage after contact with ZTA, Al2O3, and ZrO2 particulates at 25 mg/mL of dose level illustrated 4.4, 5.8, and 1.25% hemolysis, respectively, confirming clinically acceptable hemocompatibility. However, hematic activity of CoCr particles was reflected with 15.6% of hemolysis. In vivo, the absence of any significant effect of intra-articularly injected ceramic (Al2O3, ZrO2, ZTA) as well as metallic (CoCr) particulates on complete hemogram and serum biochemistry of Balb/C mice was recorded at all the time points up to 12 weeks. The extensive histological analysis confirmed the absence of any signature of the tissue-level toxicity at all time points. The pro-inflammatory cytokine analysis using TNF-α and IL-1β markers provided complementary evidence toward nongranulomatous and nonimmunogenic response of synovial membrane of knee joint and other vital organs of mice that were exposed to Al2O3, ZrO2, ZTA, and CoCr particulates. Taken together, our results establish the nontoxic nature of oxide ceramic particulates to bone cells, in vitro, as well as to periprosthetic tissue, in vivo.

Vitamin E-stabilized UHMWPE: Biological response on human osteoblasts to wear debris

UHMWPE doped with vitamin E was introduced to provide oxidation resistance upon sterilization, without affecting UHMWPE's mechanical properties. Particle-induced macrophage activation leads to periprosthetic bone resorption, requiring total joint replacements. During osteolysis, osteoblasts produce osteoimmunological factors such as RANKL and OPG, and the inhibitors of the Wnt pathway DKK-1 and Sclerostin. This study investigated in vitro how vitamin E-blended-UHMWPE wear debris might affect osteoblast-mediated osteolysis and the production of RANKL, OPG, Sclerostin and DKK-1, compared to conventional UHMWPE wear debris.Human osteoblastic SaOS2 cells were incubated with wear particles from Vitamin E doped and conventional UHMWPE and the gene expression and protein production of IL-6, RANKL, OPG, DKK-1, and Sclerostin was evaluated, RANKL, a bone erosion marker, was reduced, while OPG, a bone protective marker, were increased by the vitamin E-blended UHMWPE compared to conventional UHMWPE.Vitamin E doped UHMWPE reduced Sclerostin level, and partially affected DKK-1 production, thereby protecting against bone erosion. In conclusion, Vitamin E-blended UHMWPE induced an osteoimmunological response in bone cells that had positive effects on the osteolysis induced by wear debris, reducing aseptic loosening of the implants.In conclusion, this is the first study showing that Vitamin E-blended UHMWPE induced an osteoimmunological response in bone cells that positively affect the osteolysis induced by wear debris, thereby reducing the aseptic loosening of the implants.

Medial Tibial Periprosthetic Bone Resorption and Its Effect on Clinical Outcomes After Total Knee Arthroplasty: Cobalt-Chromium vs Titanium Implants

BackgroundRecently, concerns arose over the medial tibial bone resorption of a novel cobalt-chromium implant. This study aimed at investigating the effects of tibial component material, design, and patient factors on periprosthetic bone resorption and at determining its association with clinical outcomes after total knee arthroplasty (TKA). MethodsA total of 462 primary TKAs using 5 types of implants were included. To evaluate tibial periprosthetic bone resorption, we assessed radiolucent lines and change in bone mineral density at the medial tibial condyle (BMDMT). Factors related to bone resorption were assessed using regression analysis. Clinical outcomes were also evaluated with respect to periprosthetic bone resorption. ResultsCompared to titanium implants, cobalt-chromium implants showed a higher incidence of complete radiolucent lines (23.1% vs 7.9% at 2 years post-TKA) and a greater degree of BMDMT reduction. However, there was no significant difference between the implants made of the same material. Increased medial tibial bone resorption was associated with male sex, osteoporosis, larger preoperative varus deformity, longer follow-up period, and lower body mass index. The periprosthetic bone resorption was not associated with clinical outcomes including changes in range of motion and Western Ontario and McMaster Universities Osteoarthritis Index score. Furthermore, no cases warranted additional surgery. ConclusionPeriprosthetic bone resorption was associated with implant material but not with implant design. Moreover, patient factors were related to the medial tibial bone resorption post-TKA. However, the periprosthetic bone resorption was not associated with short-term clinical outcomes. We contend that researchers should incorporate integrative considerations when developing and assessing novel implants.

The efficiency of risedronate in reducing bone resorption after total hip arthroplasty: a meta-analysis of randomized control trials at a minimum of 6\xa0months\u2019 follow-up

BackgroundRecently risedronate is suggested to be effective for the prevention and treatment of for osteoporosis in total hip arthroplasty. This meta-analysis aimes to evaluate the efficacy of risedronate in reducing femoral periprosthetic bone mineral density loss in patients undergoing primary total hip arthroplasty.MethodsA systematic search was performed in Medline (1966-31 October 2017), PubMed (1966-31 October 2017), Embase (1980-31 October 2017), ScienceDirect (1985-31 October 2017) and the Cochrane Library. Only randomized controlled trial (RCT) were included. Fixed/random effect model was used according to the heterogeneity tested by I2 statistic. Meta-analysis was performed using Stata 11.0 software. The outcome measures included periprosthetic bone mineral density, length of stay and adverse effects.ResultsFour RCTs including 198 patients met the inclusion criteria. The present meta-analysis showed that there were significant differences between treatment groups in terms of periprosthetic bone mineral density in Gruen zones 1 (standard mean difference (SMD) = 0.758, 95% CI 0.469 to 1.047, P = 0.000), 2 (SMD = 0.814, 95% CI 0.523 to 1.106, P = 0.000), 3 (SMD = 0.340, 95% CI 0.059 to 0.622, P = 0.018), 6 (SMD = 2.400, 95% CI 2.029 to 2.771, P = 0.000), and 7 (SMD = 2.400, 95% CI 2.029 to 2.771, P = 0.000).ConclusionOral risedronate could significantly reduce periprosthetic bone resorption around an uncemented femoral stem (Gruen zones 1, 2, 3, 6, and 7) up to 6 months after THA. In addition, no severe adverse events were identified. Future trials of risedronate treatment after THA should focus on clinically relevant end points such as the risks of fracture and revision arthroplasty.