Effect of vitamin E-enhanced highly cross-linked polyethylene on wear rate and particle debris in anatomic total shoulder arthroplasty: a biomechanical comparison to ultrahigh-molecular-weight polyethylene.

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.

Uncemented total hip arthroplasty using alumina ceramic bearings at a minimum of 14 years of follow-up.

INTRODUCTION: The effectiveness of modern ceramic bearings has been well established in reducing the osteolysis associated with wear of the bearing surfaces in total hip arthroplasty (THA). However, there are limited mid- to long-term follow-up data for complications associated with ceramic bearings. MATERIALS AND METHODS: This case series analyzed 124 consecutive primary uncemented THAs in 108 patients with a mean age of 61 years using alumina ceramic-on-alumina ceramic bearing couples. Seventy THAs (56%) were evaluated at a minimum 14 years of follow-up; the mean follow-up period was 16 ± 1 years (14-20 years). Kaplan-Meier survivorship was determined with revision surgery for any reason as the end point. Complications were recorded focusing on osteolysis, ceramic fracture, and abnormal sounds until the final follow-up. Clinical data were scored according to the Merle d'Aubigne and Postel hip score at 14 years after THA. RESULTS: The survivorship was 93.5% (95% CI 86.7-97.0%) at 14-years postoperatively. Five patients (4.0%) underwent revision surgery due to instability or infection before 1-year postoperatively. Two patients (1.6%) underwent revision surgery due to ceramic liner fracture at 9- and 12-years postoperatively, respectively. There was no radiographic evidence of osteolysis. A total of 27 complications occurred: dislocations (n = 7/124), squeaking sounds (n = 3/124), clicking sounds (n = 6/124), ceramic liner fractures (n = 2/124), periprosthetic fractures (n = 4/124), deep infections (n = 2/124), transient sciatic nerve palsy (n = 2/124), and femoral stem breakage (n = 1/124). The Merle d'Aubigne and Postel hip score was 16.8 ± 1.4 points. CONCLUSIONS: The survivorship analysis demonstrates the uncemented THA using alumina ceramic bearings may provide favorable clinical outcome and can offer minimal wear at a minimum 14-year follow-up. Revision surgery was mostly required due to instability and infection in the short-term, and implant breakage in the mid- to long-term.

Astragalus polysaccharide attenuates LPS-related inflammatory osteolysis by suppressing osteoclastogenesis by reducing the MAPK signalling pathway.

Bacterial products can stimulate inflammatory reaction and activate immune cells to enhance the production of inflammatory cytokines, and finally promote osteoclasts recruitment and activity, leading to bone destruction. Unfortunately, effective preventive and treatment measures for inflammatory osteolysis are limited and usually confuse the orthopedist. Astragalus polysaccharide (APS), the main extractive of Astragali Radix, has been widely used for treating inflammatory diseases. In the current study, in vitro and in vivo experimental results demonstrated that APS notably inhibited osteoclast formation and differentiation dose-dependently. Moreover, we found that APS down-regulated RANKL-related osteoclastogenesis and levels of osteoclast marker genes, such as NFATC1, TRAP, c-FOS and cathepsin K. Further underlying mechanism investigation revealed that APS attenuated activity of MAPK signalling pathways (eg ERK, JNK and p38) and ROS production induced by RANKL. Additionally, APS was also found to suppress LPS-related inflammatory osteolysis by decreasing inflammatory factors' production in vivo. Overall, our findings demonstrate that APS effectively down-regulates inflammatory osteolysis due to osteoclast differentiation and has the potential to become an effective treatment of the disorders associated with osteoclast.

Zoledronic acid and teriparatide have a complementary therapeutic effect on aseptic loosening in a rabbit model.

BACKGROUND: Revisions are mainly caused by wear debris-induced aseptic loosening. How to effectively suppress debris-induced periprosthetic osteolysis has become an urgent problem. Both zoledronic acid and teriparatide can increase the bone mass around prostheses and increase the stability of prostheses. A hypothesis was proposed: the combination of the two drugs may have a better treatment effect than the use of either drug alone. METHODS: We created a rabbit model to study the effect and mechanism of the combination of zoledronic acid and teriparatide in the treatment of aseptic loosening. Thirty-two adult male New Zealand white rabbits were selected and treated with TKA surgery, and a titanium rod prosthesis coated evenly with micrometre-sized titanium debris was implanted into the right femoral medullary cavity. All rabbits were randomized into four groups (control group = 8, zoledronic acid group = 8, teriparatide group = 8, and zoledronic acid + teriparatide group = 8). All the animals were sacrificed in the 12th week, and X-ray analyses, H&E staining, Goldner-Masson trichrome staining, von Kossa staining, and RT-PCR and Western blotting of the mRNA and protein of OCN, OPG, RANKL and TRAP5b in the interface membrane tissues around the prostheses were immediately carried out. RESULTS: The results shown that both zoledronic acid and teriparatide could inhibit debris-induced peri-prosthetic osteolysis and promote new bone formation. Zoledronic acid was more capable of inhibiting osteoclast activation and peri-prosthetic osteolysis, while teriparatide was more capable of promoting osteoblast function and peri-prosthetic bone integration. CONCLUSION: This research confirmed that the combination of zoledronic acid and teriparatide could prevent and treat aseptic loosening of the prosthesis more effectively. However, the safety of this combination and the feasibility of long-term application have not been ensured, and the clinical application requires further experiments and clinical research support.

Whole-Body Imaging of Multiple Myeloma: Diagnostic Criteria.

Multiple myeloma (MM) is a clonal plasma cell proliferative disorder characterized by primary infiltration of bone marrow and excessive production of abnormal immunoglobulin. This disease is the second most common hematologic malignancy (after lymphoma), and its spectrum of characteristic features are widely known by the acronym CRAB (hypercalcemia, renal impairment, anemia, and bone lesions). Traditionally, the diagnosis and treatment of MM have been triggered by clear end-organ damage. However, owing to recently introduced treatment options that can extend patient survival and the increasing recognition of biomarkers that can be used to identify patients at high risk of progression to active disease, the diagnostic criteria have been revised. Bone disease is one of the most prominent features of MM, and imaging has an important role in diagnosis and follow-up, with each whole-body imaging modality having different indications in distinct disease situations. Skeletal survey has been the standard imaging procedure used during the past decade, but it should no longer be used unless it is the only option. Whole-body low-dose CT is a reasonable and cost-effective initial imaging approach. Whole-body MRI is the most sensitive technique for detecting bone involvement and assessing painful complications. PET/CT is the best tool for evaluating treatment response. The importance of radiologists has increased in this scenario. Therefore, to properly assist hematologists and improve the care of patients with MM, it is essential that radiologists know the updated diagnostic criteria for MM, indications for and limitations of each imaging option, and recommendations for follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

[Photodynamic intramedullary bone stabilization of pathological fractures]. / Fotodynamische intramedulläre Knochenstabilisierung bei pathologischen Frakturen.

Pathological fractures of long tubular bones are stabilized with conventional implants. Essentially, plates and intramedullary nails are used for stabilization and are two different techniques, which compete with each other with respect to the surgical treatment. A large number of such means of osteosynthesis are commercially available but are primarily focused on acute fractures in otherwise biologically healthy bones. The pathological fracture or the treatment of impending pathological fractures due to metastatic osteolysis differs from the treatment of healthy bones in some fundamental aspects. The characteristics of pathological fractures make the development of new technologies that meet the specific needs of both the patient and the surgeon desirable. A new approach in treatment is stabilization of internal long bone fractures by the use of a cylindrical balloon implant, which is introduced into the bone via a small proximal or distal hole and then filled and expanded to a much larger diameter with a liquid monomer. The curing process is initiated with the application of blue light forming a rigid implant by polymerization (IlluminOss™). Many of the well-known disadvantages of conventional implants can be eliminated with this technology. Specifically, with respect to the irregular shape of the natural medullary canal it is possible to completely fill the medullary canal of the tubular bone. The filling of the canal provides torsional stability without the use of interlocking screws. Similarly, the use of the balloon technique enables minimally invasive surgery and furthermore permits the additive use of conventional metallic plates whenever necessary. The new balloon techniques show high primary stability in the treatment of pathological shaft fractures. In particular cases, the addition of a supplemental plate osteosynthesis is recommended.

Results of 200 Consecutive Ceramic-on-Ceramic Cementless Hip Arthroplasties in Patients Up To 50 Years of Age: A 5-24 Years of Follow-Up Study.

BACKGROUND: Ceramic-on-ceramic (CoC) bearings due to their mechanical properties can be used in primary total hip arthroplasty (THA) especially in young patients requiring a long-lasting implant. The goal of this study is to analyze the results of a series of 200 consecutive CoC THAs in patients aged 50 years or less at the time of surgery. METHODS: A retrospective study was conducted on the first 200 consecutive CoC arthroplasties performed using the direct lateral approach on 105 females and 81 males (14 bilateral cases) with an average age of 44.2 (16-50) years. The diagnosis was primary or post-traumatic osteoarthritis in 94 cases, avascular necrosis of the femoral head in 47, displaced intracapsular femoral neck fracture in 29, osteoarthritis secondary to developmental dysplasia of the hip/Legg-Calvè-Perthes disease/slipped capital femoral epiphysis in 20, and rheumatic diseases in 10 cases. The preoperative Harris Hip Score was 32.5 on average (range 15-55). All the implants were cementless. In 177 THAs the coupling was alumina-on-alumina, and in 23 cases the coupling was AMC-on-AMC (alumina matrix composite). RESULTS: Twenty-five patients with 28 THAs were lost at the final follow-up, 2 stems were revised due to subsidence, 1 cup was revised due to malposition, 1 femoral head was changed because of impingement, and 1 THA was revised for periprosthetic infection. Three patients sustained a Vancouver B1 periprosthetic femoral fracture. At the final follow-up (mean 14.9 years; minimum 5 years to maximum 24 years), 172 THAs were eligible for clinical and radiographic evaluation: none was revised for wear and/or breakage of the ceramic components. Harris Hip Score rose up to a mean value of 90.1 (52-100). CONCLUSION: The present report demonstrates that CoC coupling offers excellent long-term results in THA performed in young patients with very low wear and no adverse effects caused by the material.

Effects of sequential treatment with intermittent parathyroid hormone and zoledronic acid on particle-induced implant loosening: Evidence from a rat model.

Particle-induced implant loosening is a major challenge to long-term survival of joint prostheses. Administration of intermittent parathyroid hormone (PTH) has shown potential in the treatment of cases of early-stage periprosthetic osteolysis, while sequential administration of intermittent PTH (iPTH) and bisphosphonates (Bps) has achieved significant effects on treatment of postmenopausal osteoporosis. The objective of this study was to determine whether sequential treatment could preserve bone mass and implant fixation during a pathological course of peri-implant osteolysis in a rat model. Ninety male Sprague Dawley rats were randomly divided into nine groups, four of which were used for confirmation of establishment of the peri-implant osteolysis model at two time points, while the other five were used to determine the efficiency of the sequential treatment on peri-implant osteolysis. Implant fixation and peri-implant bone mass were evaluated using biomechanical testing, micro-CT analysis, and histology at 6 and 12 weeks postoperative. The biomechanical test demonstrated that the maximum loading force during a push-out test was significantly elevated in the sequential treatment group compared to the osteolysis group and iPTH withdrawal group at 12 weeks. Peri-implant bone morphology also indicated a robust increase in bone volume in the sequential treatment group. Sequential administration of iPTH and Bps was effective in preventing experimental peri-implant osteolysis, resulting in improved implant fixation and increased peri-implant bone volume. Clinical significance: The innovative application of sequential treatment in peri-implant osteolysis could be used clinically to improve the prognosis of patients with early-stage periprosthetic osteolysis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1489-1497, 2019.

Clinical Outcomes and Bearing-Specific Complications Following Fourth-Generation Alumina Ceramic-on-Ceramic Total Hip Arthroplasty: A Single-Surgeon Series of 749 Hips at a Minimum of 5-Year Follow-Up.

BACKGROUND: The purpose of this study is to evaluate the minimum 5-year outcomes and bearing-specific complications in a single surgeon series of fourth-generation alumina ceramic-on-ceramic total hip arthroplasties (THAs). METHODS: We retrospectively analyzed 667 patients (749 hips) who underwent primary THAs by a single surgeon using fourth-generation alumina ceramic bearings. There were 315 men and 352 women with a mean age of 54.2 years. The surgeon used cementless prostheses with an identical design and BIOLOX Delta ceramics in all hips, using a 36-mm head in 472 hips (63%) and a 32-mm head in 227. The mean follow-up duration was 6.5 years (range, 5 to 8 years). RESULTS: The mean Harris hip score improved from 45.6 points preoperatively to 91.3 points at final follow-up. All but 1 acetabular cup and all femoral stems were well fixed. No radiographic evidence of osteolysis was identified at final follow-up. There were 2 (0.3%) ceramic liner fractures and no ceramic head fractures. A total of 48 hips (6.4%) exhibited audible noise (29 clickings and 19 squeakings), but no patient required revision. Other complications were 1 dislocation, 1 deep infection, 3 iliopsoas tendonitis, and 6 periprosthetic femoral fractures. Kaplan-Meier survivorship for revision for any reason was 98.6% (95% confidence interval, 97.7-99.5) at 6.5 years. CONCLUSION: Delta ceramic-on-ceramic THAs had a high rate of survivorship without radiographic evidence of osteolysis at 6.5-year follow-up. However, we found 0.3% ceramic liner fractures and 6.4% audible noises associated with the use of Delta ceramics.

Paeoniflorin Inhibits Receptor Activator for Nuclear Factor κB (RANK) Ligand-Induced Osteoclast Differentiation In Vitro and Particle-Induced Osteolysis In Vivo.

BACKGROUND Paeoniflorin (PF), a glucoside isolated from the dried root of Paeonia lactiflora Pall, has been reported to have a number of pharmacological properties, including immunity-regulation, anticancer activities, and neuroprotective effect. However, PF's pharmacological role in bone disorder has been seldom reported. Hence, this study was designed to investigate the effects of PF on osteoclast differentiation and osteolysis diseases. MATERIAL AND METHODS The bone marrow macrophages were isolated from C57BL/6 mice and incubated with RANK ligand (RANKL) and various concentrations of PF. After 5 days of incubation, tartrate-resistant acid phosphatase (+) cells and bone resorption pits were counted. Effects of PF on expression of osteoclast-specific protein and gene were investigated via Western blot, q-PCR, and immunofluorescence assay. The osteoprotective effect of PF in vivo was evaluated in a calvarial osteolysis model via micro-CT scan and histological stain. RESULTS In vitro, PF intervention inhibited osteoclast formation and resorption activity. PF also impaired RANKL-induced NF-κB phosphorylation and immigration to the nucleus. PF suppressed osteoclast-marker protein and gene expression. In vivo, PF inhibited cobalt-chromium-molybdenum alloy particle-induced osteolysis and reduced osteoclast number in tissue slice. CONCLUSIONS PF is a potential agent against osteolysis-related diseases caused by excessive osteoclast activity.

The Ideal Total Hip Replacement Bearing Surface in the Young Patient: A Prospective Randomized Trial Comparing Alumina Ceramic-On-Ceramic With Ceramic-On-Conventional Polyethylene: 15-Year Follow-Up.

BACKGROUND: The optimum bearing surface for total hip arthroplasty remains debatable. We have previously published our outcome at 10 years and this represents the 15-year follow-up. METHODS: A total of 58 hips (in 57 patients with a mean age of 42 years) were randomized to receive either ceramic-on-ceramic (CoC) or ceramic-on-polyethylene (CoP) total hip arthroplasty. We prospectively followed for survivorship, functional outcomes (using the Harris Hip Score and the St Michael's Hip Score [SMH]), and radiological outcomes. RESULTS: At a minimum of 15 years, 3 patients had died, but not been revised. Seven were lost to follow-up. Five cases from the CoP group were revised (4 for polyethylene wear and osteolysis). Four from the CoC were revised; one each for head fracture, instability, infection, and trunnionosis. Both groups showed statistically significant improvements in Harris Hip Score scores and SMH functional scores, with no difference between the 2 bearings. For the CoP group, there was an improvement from 15.6 to 21.5 in the SMH and from 48.8 to 88.7 (P > .05); and for CoC, this improvement was 15.8 to 23.5 and 50.3 to 94.6 (P > .05), respectively. Mean wear rate of the polyethylene was 0.092 mm/y and for the CoC was 0.018 mm/y. Two patients in the CoC group had evidence of acetabular osteolysis vs 3 in the CoP. Six patients had femoral osteolysis in the CoC group and 12 in the CoP group. CONCLUSION: Survivorship and function of the 2 bearing groups remains comparable; while the polyethylene wear and osteolysis may represent issues in the future.

A Minimum Ten Years of Follow-Up of Alumina Head on Delta Liner Total Hip Arthroplasty.

BACKGROUND: In the early days when delta ceramics were developed, there was a period of using delta ceramic liner and alumina ceramic head. Therefore, the purpose of this study is to investigate the clinical and radiological outcomes of total hip arthroplasty using delta ceramic liner on alumina ceramic head after a minimum of 10 years of follow-up and to evaluate problems of early delta ceramic liner. METHODS: Alumina on delta cementless total hip arthroplasty was performed in 92 hips (85 patients) from August 2005 to March 2007 at our hospital. Bilateral total hip arthroplasty were performed in 7 patients, 30 patients on the left side and 48 patients on the right side. Preoperative diagnosis was osteonecrosis of the femoral head in 34 hips (37%), degenerative arthritis in 31 hips (33.7%), femur neck fracture in 21 hips (22.8%), and rheumatoid arthritis in 6 hips (6.5%). All surgeries were carried out with anterolateral approach. For the clinical evaluation, Harris hip score (HHS), pain, and range of motion were assessed. Radiographs were reviewed by the authors to search for any signs of osteolysis, loosening of implants, and heterotopic ossification. RESULTS: HHS was compared between preoperative and final follow-ups. The mean HHS improved from preoperative 58.3 points (range 27-76) to 92.7 points (range 78-98) on the final follow-up (P = .02). The mean range of hip motion at the final follow-up was flexion 116.9°, adduction 23.8°, abduction 34.6°, internal rotation 16.3°, and external rotation 39.2°. As for the postoperative pain, 1 patient complained of inguinal pain and 4 patients complained of thigh pain. Because of trauma, 3 cases of dislocation were observed in all cases. There are 3 cases with dislocation and 2 cases were treated with conservative treatment without recurrence, but 1 case was required for surgical treatment due to eccentric rim wear of delta liner. The aseptic loosening of acetabular cup and femoral stem was each 1 hip. CONCLUSION: Alumina head-on-delta liner cementless THA, using a large femoral head 32-36 mm in diameter, demonstrated satisfactory clinical and radiological results in the minimum 10 years of follow-up. Eccentric rim wear can occur even in delta ceramic liners that are known to have high strength, and this can lead to dislocation which can, in turn, increase the possibility of linear fracture.

Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study.

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis.

Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO. Therefore, the present study aimed to further clarify the impact of VE-UHMWPE wear particles on the osseous microenvironment and to identify the potential modulatory pathways involved. Using an established murine calvaria model, mice were subjected to sham operation (SHAM group), or treated with UHMWPE or VE-UHMWPE particles for different experimental durations (7, 14 and 28 days; n=6/group). Morphometric analysis by micro-computed tomography detected significant (p<0.01) and comparable signs of PIO in all particle-treated groups, whereas markers of inflammation [tumor necrosis factor (TNF)-α/tartrate resistant acid phosphatase (TRAP) staining] and bone remodeling [Dickkopf-related protein 1 (DKK-1)/osteoprotegerin (OPG)] were most affected in the early stages following surgery. Taking the present data into account, VE-UHMWPE appears to have a promising biocompatibility and increased ageing resistance. According to the α-CGRP serum levels and immunohistochemistry, the impact of vitamin E on neuropeptidergic signaling and its chance for regenerative approaches requires further investigation.

Alumina Delta-on-Highly Crosslinked-Remelted Polyethylene Bearing in Cementless Total Hip Arthroplasty in Patients Younger than 50 Years.

BACKGROUND: The purpose of this retrospective study was to determine the clinical and radiographic results, prevalence of polyethylene wear and osteolysis, and fracture of alumina delta ceramic femoral head or highly crosslinked, remelted polyethylene (HXLPE) liner associated with the use of alumina delta ceramic femoral head-on-HXLPE bearing in cementless total hip arthroplasty in patients younger than 50 years. METHODS: We reviewed the cases of 119 patients (130 hips) who underwent a cementless total hip arthroplasty using alumina delta ceramic-on-HXLPE bearing when they were 50 years or younger at the time of surgery. The most common diagnoses were osteonecrosis (51%) and osteoarthritis secondary to developmental dysplastic hip (39%). Osteolysis and polyethylene wear rates were evaluated with use of radiography and computed tomography. In addition, prevalence of fracture of alumina delta ceramic head and polyethylene line was documented. The mean follow-up was 8.3 years (range, 7-9 years). RESULTS: The mean Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index score, University of California, Los Angeles activity score were 94 points, 14 points, and 8.1 points, respectively, at the final follow-up. No patient had thigh pain. All acetabular components and all but one femoral components were well fixed. The mean annual penetration rate of femoral head was 0.022 ± 0.003 mm/year. No hip had osteolysis or ceramic head or HXLPE liner fracture. CONCLUSION: Our average 8.3-year results with the use of alumina delta ceramic-on-HXLPE bearing in the patients younger than 50 years suggest that cementless acetabular and femoral components provide a high survival rate without evidence of osteolysis or ceramic head or AXLPE liner fracture.

Long-Term Results of Third-Generation Ceramic-on-Ceramic Bearing Cementless Total Hip Arthroplasty in Young Patients.

BACKGROUND: The results of third-generation of alumina-on-alumina ceramic bearing in a large number of patient cohorts are limited. The purpose of this study was to determine clinical and radiologic outcome, prevalence of osteolysis detected with radiographs and computerized tomographic scan, and survivorship of a cementless total hip arthroplasty using a third-generation of alumina-on-alumina ceramic bearing in a large number of active patients aged younger than 65 years. METHODS: We reviewed the cases of 871 patients (1131 hips) who underwent a cementless total hip arthroplasty when they were aged 65 years or younger at the time of surgery. The most common diagnoses were osteonecrosis (53%) and osteoarthritis (20%). Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, and University of California, Los Angeles activity scores were recorded. Radiographic and computerized tomographic evaluations were used to evaluate implant fixation and osteolysis. The mean follow-up interval was 18.8 years (range, 15-20 years). RESULTS: At the time of final follow-up, the mean Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index score, and University of California, Los Angeles activity score were 90 points, 15 points, and 8 points, respectively. All the femoral stem and acetabular components were well-fixed at the time of final follow-up. No hip had aseptic loosening or osteolysis or fracture of ceramic material at the time of the final follow-up. CONCLUSION: The current results with the use of the third-generation of alumina-on-alumina ceramic bearings in young patients suggest that cementless acetabular and femoral components provide outstanding long-term fixation and provide a high rate of survivorship without evidence of osteolysis.

Alumina Delta-on-Alumina Delta Bearing in Cementless Total Hip Arthroplasty in Patients Aged <50 Years.

BACKGROUND: There are limited studies to evaluate long-term clinical and radiographic outcomes of alumina delta ceramic-on-ceramic bearings in cementless total hip arthroplasty (THA). The purpose of this study was to evaluate the clinical and radiographic results, prevalence of osteolysis, squeaking, and fracture of ceramic material associated with the use of the alumina delta ceramic-on-alumina delta ceramic bearing in cementless THA in patients aged <50 years. METHODS: We reviewed the cases of 277 patients (334 hips) who underwent a cementless THA using alumina delta ceramic-on-alumina delta ceramic when they were 50 years or younger at the time of surgery. Demographic data; Harris Hip Score; Western Ontario McMaster Universities Osteoarthritis Index; and University of California, Los Angeles activity score were recorded. Radiographic and computerized tomographic evaluations were used to evaluate implant fixation and osteolysis. Squeaking sound and ceramic fracture were documented. The mean follow-up was 13.1 years (range, 10-14). RESULTS: The mean postoperative Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index score, University of California, Los Angeles activity score were 93 points, 15 points, and 8.6 points, respectively. Two patients had thigh pain (grade 7 points). All acetabular components and all but 2 femoral components were well fixed. Thirty-three hips (10%) exhibited clicking sound, and 2 hips (0.6%) exhibited squeaking sound. No hip had osteolysis or ceramic head or liner fracture. CONCLUSION: Our minimum 10-year follow-up results with the use of alumina delta ceramic-on-alumina delta ceramic bearings in patients aged <50 years suggest that cementless THA provides a high rate of survivorship without evidence of osteolysis or fracture of ceramic material.

Local delivery of mutant CCL2 protein-reduced orthopaedic implant wear particle-induced osteolysis and inflammation in vivo.

Total joint replacement (TJR) has been widely used as a standard treatment for late-stage arthritis. One challenge for long-term efficacy of TJR is the generation of ultra-high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle-induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle-induced osteolysis and the effects of 7ND treatment were evaluated using micro-CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle-induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle-induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs.

Gambogic acid inhibits multiple myeloma mediated osteoclastogenesis through suppression of chemokine receptor CXCR4 signaling pathways.

Bone disease, characterized by the presence of lytic lesions and osteoporosis is the hallmark of multiple myeloma (MM). Stromal cell-derived factor 1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4), has been implicated as a regulator of bone resorption, suggesting that agents that can suppress SDF1α/CXCR4 signaling might inhibit osteoclastogenesis, a process closely linked to bone resorption. We, therefore, investigated whether gambogic acid (GA), a xanthone, could inhibit CXCR4 signaling and suppress osteoclastogenesis induced by MM cells. Through docking studies we predicted that GA directly interacts with CXCR4. This xanthone down-regulates the expression of CXCR4 on MM cells in a dose- and time-dependent manner. The down-regulation of CXCR4 was not due to proteolytic degradation, but rather GA suppresses CXCR4 mRNA expression by inhibiting nuclear factor-kappa B (NF-κB) DNA binding. This was further confirmed by quantitative chromatin immunoprecipitation assay, as GA inhibits p65 binding at the CXCR4 promoter. GA suppressed SDF-1α-induced chemotaxis of MM cells and downstream signaling of CXCR4 by inhibiting phosphorylation of Akt, p38, and Erk1/2 in MM cells. GA abrogated the RANKL-induced differentiation of macrophages to osteoclasts in a dose- and time-dependent manner. In addition, we found that MM cells induced differentiation of macrophages to osteoclasts, and that GA suppressed this process. Importantly, suppression of osteoclastogenesis by GA was mediated through IL-6 inhibition. Overall, our results show that GA is a novel inhibitor of CXCR4 expression and has a strong potential to suppress osteoclastogenesis mediated by MM cells.

High survivorship with a titanium-encased alumina ceramic bearing for total hip arthroplasty.

BACKGROUND: Although ceramic-on-ceramic bearings for total hip arthroplasty (THA) show promising results in terms of bearing-surface wear, fracture of the bearing, insertional chips, and squeaking remain a concern. QUESTIONS/PURPOSES: Our primary objective of this report was to determine overall survivorship of a titanium-encased ceramic-on-ceramic bearing couple. Our secondary objectives were to evaluate for ceramic fracture, insertional chips, osteolysis, and device squeaking. METHODS: Six surgeons at six institutions implanted 194 patients (209 hips) with an average age of 52 years with cementless hips and alumina ceramic bearings. One hundred thirty-seven patients (146 hips) have 10-year followup (70%). We determined Kaplan-Meier survivorship of the bearing surface and implant system and collected radiographic and clinical data to evaluate for osteolysis and squeaking. RESULTS: Survivorship using revision for any reason as the end point was 97% at 10 years and survivorship end point bearing surface failure or aseptic loosening of 99%. There was one ceramic insert fracture (0.5%), there were no insertional chips, there was no visible osteolysis on AP and lateral radiographs, and there was a 1% patient-self-reported incidence of squeaking at the last clinical followup. Six hips underwent revision (3.7%). CONCLUSIONS: Ceramic bearings for THA with a titanium-encased insert have high survivorship at 10 years followup and a fracture risk of 0.5%. We found at last followup on routine radiographs no evidence of osteolysis, and no patient has been revised for squeaking or has reported dissatisfaction with the clinical result because of noise. IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.