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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_13 | Pages 8 - 8
1 Oct 2018
Du JY Flanagan CD Bensusan JS Knusel KD Akkus O Rimnac CM
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Background. Structural bone allografts are an established treatment method for long-bone structural defects arising from such conditions as trauma, sarcoma, and osteolysis following total joint replacement. However, the quality of structural bone allografts is difficult to non-destructively assess prior to use. The functional lifetime of structural allografts depend on their ability to resist cyclic loading, which can lead to fracture even at stress levels well below the yield strength. Because allograft bone has limited capacity for remodeling, optimizing allograft selection for bone quality could decrease long-term fracture risk. Raman spectroscopy biomarkers can non-destructively assess the three primary components of bone (collagen, mineral, and water), and may predict the resistance of donor bone allografts to fracture from cyclic loads. The purpose of this study was to prospectively assess the ability of Raman biomarkers to predict number of cycles to fracture (“cyclic fatigue life”) of human allograft cortical bone. Methods. Twenty-one cortical bone specimens were from the mid-diaphysis of human donor bone tissue (bilateral femurs from 4 donors: 63M, 61M, 51F, 48F) obtained from the Musculoskeletal Transplant Foundation. Six Raman biomarkers were analyzed: collagen disorganization, type B carbonate substitution (a surrogate for mineral maturation), matrix mineralization, and 3 water compartments. Specimens underwent cyclic fatigue testing under fully reversed conditions at 35 and 45MPa (physiologically relevant stress levels for structural allografts). Specimens were tested to fracture or to 30 million cycles (“run-out”), simulating 15 years of moderate activity (i.e., 6000 steps per day). Multivariate regression analysis was performed using a tobit model (censored linear regression) for prediction of cyclic fatigue life. Specimens were right-censored at 30 million cycles. Results. All of the 6 biomarkers that were evaluated were independently associated with cyclic fatigue life (p < 0.05). The multivariate model explained 70% of the variance in cyclic fatigue life (R2=0.695, p<0.001,). Increasing disordered collagen (p<0.001) and loosely collagen-bound water compartments (p<0.001) were associated with decreased cyclic fatigue life. Increasing type B carbonate substitution (p<0.001), matrix mineralization (p<0.001), tightly collagen-bound water (p<0.001), and mineral-bound water (p=0.002) were associated with increased cyclic fatigue life. In the predictive model, 42% of variance in cyclic fatigue life was attributable to degree of collagen disorder, all bound water compartments accounted for 6%, and age and sex accounted for 17%. Conclusions. Raman biomarkers of three bone components (collagen, mineral, and water) predict cyclic fatigue life of human cortical bone. Increased baseline collagen disorder was associated with decreased cyclic fatigue life, and was the strongest determinant of cyclic fatigue life. Increased matrix mineralization and mineral maturation were associated with increased cyclic fatigue life. Bound-water compartments of bone contributed minimally to cyclic fatigue life. These results are complementary with prior Raman studies of monotonic testing of bone that reported decreased toughness and strength with increased collagen disorder and increased stiffness with increased bone mineralization and mineral maturation. This model should be prospectively validated. Raman analysis is a promising tool for the non-destructive evaluation of structural bone allograft quality and may be useful as a screening tool for selection of allograft bone. Acknowledgements. Supported by a grant from the Musculoskeletal Transplant Foundation. The Dudley P. Allen Fellowship (JYD), Wilbert J. Austin Professor of Engineering Chair (CMR) and the Leonard Case Jr. Professor of Engineering Chair (OA) are gratefully acknowledged


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 6 | Pages 769 - 776
1 Jun 2011
Hogervorst T Bouma H de Boer SF de Vos J

We examined the morphology of mammalian hips asking whether evolution can explain the morphology of impingement in human hips. We describe two stereotypical mammalian hips, coxa recta and coxa rotunda. Coxa recta is characterised by a straight or aspherical section on the femoral head or head-neck junction. It is a sturdy hip seen mostly in runners and jumpers. Coxa rotunda has a round femoral head with ample head-neck offset, and is seen mostly in climbers and swimmers. Hominid evolution offers an explanation for the variants in hip morphology associated with impingement. The evolutionary conflict between upright gait and the birth of a large-brained fetus is expressed in the female pelvis and hip, and can explain pincer impingement in a coxa profunda. In the male hip, evolution can explain cam impingement in coxa recta as an adaptation for running


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_1 | Pages 29 - 29
1 Jan 2018
Cobb J Clarke S Jeffers J Wozencroft R Halewood C Amis A
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Hip resurfacing remains a safe and effective option according to registry data. Results in women were less reliable, in part owing to soft tissue impingement. Biolox Delta ceramic bearing couples are now in widespread use with very low complication rates. We set about merging these three elements to develop a novel hip resurfacing arthroplasty. Contours of both acetabular and femoral components were generated from biometric data, adapted to the constraints of ceramic machining, to ensure that radii blended from the bearing surface avoiding any sharp boundaries. Plasma spray coating with titanium and hydroxyapatite direct onto ceramic was developed and tested using shear, tensile and taber abrasion testing. Wear testing was carried out to 5 million cycles according to the ASTM. Destructive testing was carried out in a variety of test conditions and angles. Cadaveric testing demonstrated stability using a single use disposable instruments for both conventional and patient specific procedures. Very low dose CT enabled the entire interface to be observed as the Ceramic is radiolucent, enhancing migration analysis, which will be undertaken at 4 intervals to confirm stability. Functional scores and gait analysis will be used in the safety study. The CE study recruitment is underway, with first in human trials starting in summer 2017. PMA submission will follow the safety study. Commercial release of the device in Europe is unlikely before 2019, and in the USA may not be until 2027. The path to novel device development in 2017 is very costly in time and money


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_12 | Pages 1 - 1
1 Nov 2015
Cassar-Gheiti A Byrne D Muhall K
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Objective. The objective of this study was to assess the biomechanical stability of three types of chondral flap repair and a hydrogel scaffold implantation on the acetabular articular surface using a physiological human cadaveric model. Methods. Chondral flaps were created in the antero-superior zone of the acetabulum in a series of human cadaveric hip joints. The chondral flap was repaired by fibrin glue, cyanoacrylate, suture technique and an agarose hydrogel scaffold sealed with fibrin glue using 6 hips in each case. After each repair, the specimens were mounted in a validated jig and tested for 1500 gait cycles. In order to determine the stability of the repair, specimens were evaluated arthroscopically at specific intervals. Results. The fibrin glue and cyanoacrylate techniques were technically the easiest to perform arthroscopically, all flaps repaired with fibrin were detached at 50 cycles while those repaired with cyanoacrylate lasted for an average of 635 cycles. On the other hand, both the suture repair and scaffold implantation techniques were more technically challenging but were both stable till the endpoint of 1500 cycles. Conclusion. Fibrin glue on its own does not provide sufficient fixation to repair chondral flaps on the acetabular surface. Cyanoacrylate repairs universally failed midway through the testing protocol employed here, raising doubts as to the effectiveness of that technique. The suture and hydrogel scaffold technique were the most reliable for chondral repair at any given cycle. The results of this biomechanical study demonstrate the relative effectiveness of chondral repair and fixation techniques with sutures and hydrogel scaffolds on the acetabular chondral surface


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 3 | Pages 363 - 365
1 Apr 2003
Fleming P Lenehan B O’Rourke S McHugh P Kaar K McCabe JP

Injuries to the sciatic nerve are an occasional complication of surgery to the hip and acetabulum, and traction is frequently the causative mechanism. In vitro and animal experiments have shown that increased tensile strain on peripheral nerves, when applied for prolonged periods, impairs nerve function. We have used video-extensometry to measure strain on the human sciatic nerve during total hip replacement (THR). Ten consecutive patients with a mean age of 72 years undergoing primary THR by the posterior approach were recruited, and strains in the sciatic nerve were measured in different combinations of flexion and extension of the hip and knee, before dislocation of the hip. Significant increases (p = 0.02) in strain in the sciatic nerve were observed in flexion of the hip and extension of the knee. The mean increase was 26% (19% to 30%). In animal studies increases of this magnitude have been shown to impair electrophysiological function in peripheral nerves. Our results suggest that excessive flexion of the hip and extension of the knee should be avoided during THR


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 261 - 268
1 Mar 2023
Ruhr M Huber G Niki Y Lohner L Ondruschka B Morlock MM

Aims. The aim of the study was to investigate whether the primary stability of press-fit acetabular components can be improved by altering the impaction procedure. Methods. Three impaction procedures were used to implant acetabular components into human cadaveric acetabula using a powered impaction device. An impaction frequency of 1 Hz until complete component seating served as reference. Overimpaction was simulated by adding ten strokes after complete component seating. High-frequency implantation was performed at 6 Hz. The lever-out moment of the acetabular components was used as measure for primary stability. Permanent bone deformation was assessed by comparison of double micro-CT (µCT) measurements before and after impaction. Acetabular component deformation and impaction forces were recorded, and the extent of bone-implant contact was determined from 3D laser scans. Results. Overimpaction reduced primary acetabular component stability (p = 0.038) but did not significantly increase strain release after implantation (p = 0.117) or plastic deformations (p = 0.193). Higher press-fits were associated with larger polar gaps for the 1 Hz reference impaction (p = 0.002, R. 2. = 0.77), with a similar trend for overimpaction (p = 0.082, R. 2. = 0.31). High-frequency impaction did not significantly increase primary stability (p = 0.170) at lower impaction forces (p = 0.001); it was associated with smaller plastic deformations (p = 0.035, R. 2. = 0.34) and a trend for increased acetabular component relaxation between strokes (p = 0.112). Higher press-fit was not related to larger polar gaps for the 6 Hz impaction (p = 0.346). Conclusion. Overimpaction of press-fit acetabular components should be prevented since additional strokes can be associated with increased bone damage and reduced primary stability as shown in this study. High-frequency impaction at 6 Hz was shown to be beneficial compared with 1 Hz impaction. This benefit has to be confirmed in clinical studies. Cite this article: Bone Joint J 2023;105-B(3):261–268


Bone & Joint Open
Vol. 4, Issue 7 | Pages 472 - 477
1 Jul 2023
Xiang W Tarity TD Gkiatas I Lee H Boettner F Rodriguez JA Wright TM Sculco PK

Aims. When performing revision total hip arthroplasty using diaphyseal-engaging titanium tapered stems (TTS), the recommended 3 to 4 cm of stem-cortical diaphyseal contact may not be available. In challenging cases such as these with only 2 cm of contact, can sufficient axial stability be achieved and what is the benefit of a prophylactic cable? This study sought to determine, first, whether a prophylactic cable allows for sufficient axial stability when the contact length is 2 cm, and second, if differing TTS taper angles (2° vs 3.5°) impact these results. Methods. A biomechanical matched-pair cadaveric study was designed using six matched pairs of human fresh cadaveric femora prepared so that 2 cm of diaphyseal bone engaged with 2° (right femora) or 3.5° (left femora) TTS. Before impaction, three matched pairs received a single 100 lb-tensioned prophylactic beaded cable; the remaining three matched pairs received no cable adjuncts. Specimens underwent stepwise axial loading to 2600 N or until failure, defined as stem subsidence > 5 mm. Results. All specimens without cable adjuncts (6/6 femora) failed during axial testing, while all specimens with a prophylactic cable (6/6) successfully resisted axial load, regardless of taper angle. In total, four of the failed specimens experienced proximal longitudinal fractures, three of which occurred with the higher 3.5° TTS. One fracture occurred in a 3.5° TTS with a prophylactic cable yet passed axial testing, subsiding < 5 mm. Among specimens with a prophylactic cable, the 3.5° TTS resulted in lower mean subsidence (0.5 mm (SD 0.8)) compared with the 2° TTS (2.4 mm (SD 1.8)). Conclusion. A single prophylactic beaded cable dramatically improved initial axial stability when stem-cortex contact length was 2 cm. All implants failed secondary to fracture or subsidence > 5 mm when a prophylactic cable was not used. A higher taper angle appears to decrease the magnitude of subsidence but increased the fracture risk. The fracture risk was mitigated by the use of a prophylactic cable. Cite this article: Bone Jt Open 2023;4(7):472–477


Bone & Joint Open
Vol. 4, Issue 3 | Pages 182 - 187
14 Mar 2023
Sheridan GA Hanlon M Welch-Phillips A Spratt K Hagan R O'Byrne JM Kenny PJ Kurmis AP Masri BA Garbuz DS Hurson CJ

Aims. Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. Methods. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Results. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. Conclusion. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making. Cite this article: Bone Jt Open 2023;4(3):182–187


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_4 | Pages 26 - 26
1 Apr 2022
Gormley C Dunning M Peffers M Wilkinson M
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In a recent phase 2 superiority clinical trial we demonstrated that a single dose of 60mg of the human monoclonal antibody denosumab inhibits osteolytic lesion activity in patients undergoing revision total hip arthroplasty (THA), demonstrating proof of biological efficacy for this clinical application. Here, we examined the effect that denosumab has on disease biology at the osteolysis tissue level. Osteolytic tissue taken from the prosthesis-bone lesion interface at revision surgery in patients with osteolysis (n=10 participants that had received a single 60 mg dose of denosumab 8 weeks prior to revision surgery and n=10 that had received placebo) was examined for total genetic message activity and protein levels using whole genome sequencing and mass spectrometry, respectively. The top five upregulated enriched pathways with denosumab treatment included inflammatory response, myeloid cell activation, myeloid leukocyte migration, neutrophil and granulocyte activation (p<6.26 × 10. −28. ). Cell morphogenesis was amongst the most downregulated pathways (p<3.42 ×10. −23. ). Finally, comparison of the trial mRNA and protein data versus mouse single cell RNA sequencing data of the same pathway blockade in mouse tibia showed the same direction of effect, suggesting that giving the drug causes then cells responsible for osteolysis to disperse into a more immature form (128 of 189 genes (z=4.87, P<0.0001) disease and functional pathways at the mRNA level and 10 of 11 (z=2.72, P=0.0065) at the protein level). In this first-in-man study we identify multiple genes and pathways within periprosthetic osteolysis tissue that are affected by denosumab treatment. The dominant pathways involved upregulation of innate inflammatory signaling and downregulation of cell morphogenesis. We also found enrichment of similar disease and functional pathways at both the mRNA and protein levels versus mRNA pathway enrichment found in mouse osteomorphs. These data provide the first human data of the mechanistic effect of denosumab treatment on inflammatory osteolytic lesion activity after joint replacement that is necessary to support its clinical application. ∗Winner of The Bone & Joint Journal prize∗


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 36 - 36
19 Aug 2024
Ma C Goodnough LH Zhao L Chow SK Wang Y Chan CKF Goodman SB
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Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure. We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities. We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P<0.01), an effect not reversible even with the addition of BMP2. Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 26 - 26
2 May 2024
Al-Naib M Afzal I Radha S
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As patient data continues to grow, the importance of efficient and precise analysis cannot be overstated. The employment of Generative Artificial Intelligence (AI), specifically Chat GPT-4, in the realm of medical data interpretation has been on the rise. However, its effectiveness in comparison to manual data analysis has been insufficiently investigated. This quality improvement project aimed to evaluate the accuracy and time-efficiency of Generative AI (GPT-4) against manual data interpretation within extensive datasets pertaining to patients with orthopaedic injuries. A dataset, containing details of 6,562 orthopaedic trauma patients admitted to a district general hospital over a span of two years, was reviewed. Two researchers operated independently: one utilised GPT-4 for insights via prompts, while the other manually examined the identical dataset employing Microsoft Excel and IBM® SPSS® software. Both were blinded on each other's procedures and outcomes. Each researcher answered 20 questions based on the dataset including injury details, age groups, injury specifics, activity trends and the duration taken to assess the data. Upon comparison, both GPT-4 and the manual researcher achieved consistent results for 19 out of the 20 questions (95% accuracy). After a subsequent review and refined prompts (prompt engineering) to GPT-4, the answer to the final question aligned with the manual researcher's findings. GPT-4 required just 30 minutes, a stark contrast to the manual researcher's 9-hour analytical duration. This quality improvement project emphasises the transformative potential of Generative AI in the domain of medical data analysis. GPT-4 not only paralleled the accuracy of manual analysis but also achieved this in significantly less time. For optimal accurate results, data analysis by AI can be enhanced through human oversight. Adopting AI-driven approaches, particularly in orthopaedic data interpretation, can enhance efficiency and ultimately improve patient care. We recommend future investigations on large and more varied datasets to reaffirm these outcomes


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 24 - 24
2 May 2024
Lawrence J Woods S Roberts K Tuck E Balogh P Predeus A He P Polanski K Prigmore E Zhou D Webb S Jardine L
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The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4). We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes. We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells. We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation. Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._. Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._. This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_14 | Pages 24 - 24
1 Nov 2021
Wilkinson J
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To date there is no medical treatment alternative to surgery for osteolysis after THA. In this proof-of-concept clinical trial we examined the effect of a human monoclonal antibody against osteoclasts versus placebo on osteolytic lesion activity in patients undergoing revision surgery. Patients scheduled for revision for symptomatic osteolysis were randomised (1:1) to receive either denosumab 60mg or placebo subcutaneously eight weeks prior to operation. At surgery, biopsies from the osteolytic membrane-bone interface were taken for histomorphometric analysis of osteoclast number. Secondary outcome measures included systemic bone turnover markers. 22 subjects completed the study (10 denosumab). The denosumab group had 83% (−63 to −97), P=0.011 fewer osteoclasts at osteolytic lesion sites, 87% lower osteoclast surface (−65 to −95, P=0.009), and 72% lower eroded surface (−35 to −93, P=0.020) versus the placebo group. At surgery, serum CTX-I, TRAP5b and PINP were 80% (−65 to −95, p<0.001), 57% (−40 to −90, p<0.001), and 44% (−41 to −65, p<0.001) lower in the denosumab versus placebo groups, respectively. The rate of adverse events (denosumab 6, placebo 7) were similar between groups (P>0.05). These data provide a biological basis for a definitive clinical trial using pain, function and prosthesis survival as the study endpoints. As osteolysis/ aseptic loosening is the leading cause of prosthesis failure world-wide, the establishment of a non-surgical solution would reduce patient suffering and dramatically reducing the cost to healthcare economies


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_14 | Pages 35 - 35
1 Nov 2021
Chisari E Cho J Wouthuyzen-Bakker M Friedrich A Parvizi J
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A growing number of recent investigations on the human genome, gut microbiome, and proteomics suggests that the loss of mucosal barrier function, particularly in the gastrointestinal tract, may substantially affect antigen trafficking, ultimately influencing the close bidirectional interaction between the gut microbiome and the immune system. This cross-talk is highly influential in shaping the host immune system and ultimately clinical infections. The hypothesis of the current study was that a change in microbiome and/or breach in GI epithelial barrier could be partially responsible for development of periprosthetic joint infections (PJI). Multiple biomarkers of gut barrier disruption were tested in parallel in plasma samples collected as part of a prospective cohort study of patients undergoing revision arthroplasty for aseptic failures or PJI (As defined by the 2018 ICM criteria). All blood samples were collected before any antibiotic was administered. Samples were tested for Zonulin, soluble CD14 (sCD14), and lipopolysaccharide (LPS) using commercially available enzyme-linked immunosorbent assays. Statistical analysis consisted of descriptive statistics, Mann-Whitney t-test, and Kruskal-Wallis test. A total of 134 patients were consented and included in the study. 44 were classified as PJI (30 chronic and 14 acute), and 90 as aseptic failures (26 primaries and 64 aseptic revisions). Both Zonulin and sCD14, but not LPS, were found to be significantly increased in the PJI group compared to non-infected cases (p<0.001; p=0.003). Higher levels of Zonulin were found in acute infections compared to chronic PJI (p=0.005. This prospective ongoing study reveals a possible link between gut permeability and the ‘gut-immune-joint axis’ in PJI. If this association continues to be born out with larger cohort recruitment and more in-depth analysis, it would have an immense implication in managing patients with PJI. In addition to administering antimicrobials, patients with PJI and other orthopedic infections may require gastrointestinal modulators such as pro and prebiotics


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_10 | Pages 2 - 2
1 Aug 2021
Seewoonarain S Stavri R Behforootan S Abel R
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Hip fractures are associated with poor outcomes and high mortality rates of 30%. The current gold standard to measure bone fragility is a Dual-Energy X-ray Absorptiometry (DEXA) scan measuring bone mineral density. Yet DEXA under-diagnoses bone fragility by 50% (1). To combat the burden of bone fragility, this experimental study combined ultrasound (US) with a sophisticated computational algorithm, namely full wave inversion (FWI), to evaluate femoral bone structure. The aims were to assess the association of bone structure between the proximal femoral diaphysis and femoral neck; secondly to evaluate whether transverse ultrasound could assess bone structure of the proximal femoral diaphysis. Bone structure of 19 ex vivo human femora was assessed by micro-CT analysis (mean age 88.11 years, male:female 13:6)(Nikon HMXST 225). Using ImageJ/BoneJ, three 10.2mm subsections of proximal diaphysis and femoral neck underwent analysis: the total bone volume fraction, cortical parameters (bone volume fraction, porosity, thickness) and trabecular parameters (porosity, thickness, spacing and connectivity). A unique US prototype was developed to analyse fifteen femoral diaphyseal subsections using two P4-1 transducers with a novel tomography sequence (Verasonics, Matlab ver R2019a, FWI TRUST protocol). Comparative quantitative analysis of US and Micro-CT measurements was assessed (Graphpad Prism 8.3.1). Micro-CT analysis of the proximal femoral diaphysis demonstrated low correlation to the femoral neck (Pearson r −0.54 to 0.55). US was able to capture cortical structure, though a wide limit of agreement seen when compared to micro-CT analysis (Bland-Altman range 36–59% difference). This novel US technique was able to capture cortical bone structure. Improvements in methodology and technology are required to improve the analysis of trabecular bone and overall accuracy. Further evaluation of US and FWI is required to develop the technique and determine its role in clinical practice


Bone & Joint Research
Vol. 13, Issue 12 | Pages 741 - 749
6 Dec 2024
Blichfeldt-Eckhardt MR Varnum C Lauridsen JT Rasmussen LE Mortensen WCP Jensen HI Vaegter HB Lambertsen KL

Aims

Better prediction of outcome after total hip arthroplasty (THA) is warranted. Systemic inflammation and central neuroinflammation are possibly involved in progression of osteoarthritis and pain. We explored whether inflammatory biomarkers in blood and cerebrospinal fluid (CSF) were associated with clinical outcome, and baseline pain or disability, 12 months after THA.

Methods

A total of 50 patients from the Danish Pain Research Biobank (DANPAIN-Biobank) between January and June 2018 were included. Postoperative outcome was assessed as change in Oxford Hip Score (OHS) from baseline to 12 months after THA, pain was assessed on a numerical rating scale, and disability using the Pain Disability Index. Multiple regression models for each clinical outcome were included for biomarkers in blood and CSF, respectively, including age, sex, BMI, and Kellgren-Lawrence score.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 479 - 488
6 Jun 2024
Paksoy A Meller S Schwotzer F Moroder P Trampuz A Imiolczyk J Perka C Hackl M Plachel F Akgün D

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

Methods

This was a prospective pilot study, including 24 patients divided into three groups, with eight patients each undergoing revision of their hip arthroplasty due to aseptic reasons, and low- and high-grade PJI, respectively. The number of intraoperative samples and the incidence of positive cultures were recorded for each patient. Additionally, venous blood samples and periarticular tissue samples were collected from each patient to determine miRNA expressions between the groups. MiRNA screening was performed by small RNA-sequencing using the miRNA next generation sequencing (NGS) discovery (miND) pipeline.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_12 | Pages 11 - 11
1 Oct 2019
Wyles CC Paradise CR Masters TL Patel R Abdel MP Trousdale RT Sierra RJ
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Introduction. Adverse local tissue reactions (ALTR) can result in devastating soft tissue and osseous destruction, while potentially increasing the risk of concomitant periprosthetic joint infection (PJI). The aims of this study were to evaluate cobalt (Co) and chromium (Cr) levels generated in simulators from metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) constructs, and determine their impact on native tissues and PJI risk through evaluation of human adipose-derived mesenchymal stem cells (AMSCs) and Staphylococcus epidermidis isolates. Methods. Ten hip simulator constructs were assembled with 36-mm high-offset femoral heads, highly cross-linked polyethylene liners, and titanium stems. Five constructs used CoCr femoral heads and five used ceramic. Constructs were submerged in bovine serum (BS) and run for 1,000,000 cycles. Samples of BS were collected and evaluated for CoCr concentration. Various concentrations of CoCr were chosen for further assessment of cytotoxicity and growth impact on AMSCs and S. epidermidis and compared to inert SiO2. Results. After 1,000,000 cycles, mean MoP and CoP Co concentration was 2264 ng/mL and 0.6 ng/mL, respectively (p<0.001). Mean MoP and CoP Cr concentration was 217 ng/mL and 4.3 ng/mL, respectively (p<0.001). Mean MoP Co:Cr ratio was 10. Co nanoparticles were significantly more toxic to human AMSCs than control SiO2 in a dose-response manner (p<0.001). S. epidermidis growth was not significantly impacted by Co concentrations derived from the simulators. Conclusions. MoP constructs built in ideal conditions generated substantial CoCr debris, highlighting a baseline risk with these implants that may be exacerbated by host factors or imperfect surgical technique. Evaluation of impact on AMSCs suggests that debris levels produced under ideal conditions can be cytotoxic. Additionally, these concentrations did not potentiate or inhibit S. epidermidis growth, suggesting elevated PJI rates with ALTR may be related to other factors potentially associated with tissue necrosis. For any tables or figures, please contact the authors directly


The Bone & Joint Journal
Vol. 105-B, Issue 9 | Pages 946 - 952
1 Sep 2023
Dhawan R Young DA Van Eemeren A Shimmin A

Aims

The Birmingham Hip Resurfacing (BHR) arthroplasty has been used as a surgical treatment of coxarthrosis since 1997. We present 20-year results of 234 consecutive BHRs performed in our unit.

Methods

Between 1999 and 2001, there were 217 patients: 142 males (65.4%), mean age 52 years (18 to 68) who had 234 implants (17 bilateral). They had patient-reported outcome measures collected, imaging (radiograph and ultrasound), and serum metal ion assessment. Survivorship analysis was performed using Kaplan-Meier estimates. Revision for any cause was considered as an endpoint for the analysis.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 198 - 204
16 Mar 2023
Ramsay N Close JCT Harris IA Harvey LA

Aims

Cementing in arthroplasty for hip fracture is associated with improved postoperative function, but may have an increased risk of early mortality compared to uncemented fixation. Quantifying this mortality risk is important in providing safe patient care. This study investigated the association between cement use in arthroplasty and mortality at 30 days and one year in patients aged 50 years and over with hip fracture.

Methods

This retrospective cohort study used linked data from the Australian Hip Fracture Registry and the National Death Index. Descriptive analysis and Kaplan-Meier survival curves tested the unadjusted association of mortality between cemented and uncemented procedures. Multilevel logistic regression, adjusted for covariates, tested the association between cement use and 30-day mortality following arthroplasty. Given the known institutional variation in preference for cemented fixation, an instrumental variable analysis was also performed to minimize the effect of unknown confounders. Adjusted Cox modelling analyzed the association between cement use and mortality at 30 days and one year following surgery.