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Bone & Joint Research
Vol. 14, Issue 1 | Pages 58 - 68
27 Jan 2025
Pelleg-Kallevag R Borgel S Kedar E Peled N May H

Aims. The development of lumbar lordosis has been traditionally examined using angular measurements of the spine to reflect its shape. While studies agree regarding the increase in the angles during growth, the growth rate is understudied, and sexual dimorphism is debated. In this study, we used a novel method to estimate the shape of the lumbar curve (LC) using the landmark-based geometric morphometric method to explore changes in LC during growth, examine the effect of size and sex on LC shape, and examine the associations between angular measurements and shape. Methods. The study population included 258 children aged between 0 and 20 years (divided into five age groups) who underwent a CT scan between the years 2009 and 2019. The landmark-based geometric morphometric method was used to capture the LC shape in a sagittal view. Additionally, the lordosis was measured via Cobb and sacral slope angles. Multivariate and univariate statistical analyses were carried out to examine differences in shape between males and females and between the age groups. Results. The overall shape of the LC overlapped between males and females in most age groups, except for the nine- to 12-year age group. However, size did not affect LC shape. LC shape changed significantly during growth from straight to curved, reaching its mature shape earlier in females. This corresponded with the results obtained by the lordosis and sacral slope angles. A significant positive correlation was found between the LC shape and angles, although the angles demonstrated poor distinction between age groups, as opposed to the LC shape. Conclusion. New insights into LC shape development were achieved using the geometric morphometric method. The LC shape was sex-independent in most age groups. However, the LC reached its mature shape earlier in females than males. The method and data of this study are beneficial for future studies examining aetiological factors for spinal pathologies and maldevelopment. Cite this article: Bone Joint Res 2025;14(1):58–68


Bone & Joint Open
Vol. 3, Issue 11 | Pages 913 - 923
28 Nov 2022
Hareendranathan AR Wichuk S Punithakumar K Dulai S Jaremko J

Aims. Studies of infant hip development to date have been limited by considering only the changes in appearance of a single ultrasound slice (Graf’s standard plane). We used 3D ultrasound (3DUS) to establish maturation curves of normal infant hip development, quantifying variation by age, sex, side, and anteroposterior location in the hip. Methods. We analyzed 3DUS scans of 519 infants (mean age 64 days (6 to 111 days)) presenting at a tertiary children’s hospital for suspicion of developmental dysplasia of the hip (DDH). Hips that did not require ultrasound follow-up or treatment were classified as ‘typically developing’. We calculated traditional DDH indices like α angle (α. SP. ), femoral head coverage (FHC. SP. ), and several novel indices from 3DUS like the acetabular contact angle (ACA) and osculating circle radius (OCR) using custom software. Results. α angle, FHC, and ACA indices increased and OCR decreased significantly by age in the first four months, mean α. SP. rose from 62.2° (SD 5.7°) to 67.3° (SD 5.2°) (p < 0.001) in one- to eight- and nine- to 16-week-old infants, respectively. Mean α. SP. and mean FHC. SP. were significantly, but only slightly, lower in females than in males. There was no statistically significant difference in DDH indices observed between left and right hip. All 3DUS indices varied significantly between anterior and posterior section of the hip. Mean 3D indices of α angle and FHC were significantly lower anteriorly than posteriorly: α. Ant. = 58.2° (SD 6.1°), α. Post. = 63.8° (SD 6.3°) (p < 0.001), FHC. Ant. = 43.0 (SD 7.4), and FHC. Post. = 55.4° (SD 11.2°) (p < 0.001). Acetabular rounding measured byOCR indices was significantly greater in the anterior section of the hip (p < 0.001). Conclusion. We used 3DUS to show that hip shape and normal growth pattern vary significantly between anterior and posterior regions, by magnitudes similar to age-related changes. This highlights the need for careful selection of the Graf plane during 2D ultrasound examination. Whole-joint evaluation by obtaining either 3DUS or manual ‘sweep’ video images provides more comprehensive DDH assessment. Cite this article: Bone Jt Open 2022;3(11):913–923


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 79 - 79
2 Jan 2024
Roncada T Kelly D
Full Access

Cartilage lacks the ability to self-repair when damaged, which can lead to the development of degenerative joint disease. Despite intensive research in the field of cartilage tissue engineering, there is still no regenerative treatment that consistently promotes the development of hyaline cartilage. Extracellular matrix (ECM) derived hydrogels have shown to support cell adhesion, growth and differentiation [1,2]. In this study, porcine articular cartilage was decellularized, solubilised and subsequently modified into a photo-crosslinkable methacrylated cartilage ECM hydrogel. Bone marrow derived mesenchymal stem/stromal cells (MSCs) were encapsulated into both methacrylated ECM hydrogels (ECM-MA) and gelatin methacryloyl (GelMA) as control hydrogel, and their chondrogenic potential was assessed using biochemical assays and histological analysis. We found that successful decellularization of the cartilage tissue could be achieved while preserving key ECM components, including collagen and glycosaminoglycans. A live-dead assay demonstrated good viability of MSCs withing both GelMA and ECM-MA hydrogels on day 7. Large increases in sGAG accumulation was observed after 21 days of culture in chondrogenic media in both groups. Histological analysis revealed the presence of a more fibrocartilage tissue in the GelMA group, while cells embedded within the ECM-MA showed a round and chondrocytic-like morphology. Both groups stained positively for proteoglycans and collagen, with limited evidence of calcium deposition following Alizarin Red staining. These results show that ECM-MA hydrogels support a hyaline cartilage phenotype and robust cartilaginous matrix production. Future studies will focus on the printability of ECM-MA hydrogels to enable their use as bioinks for the biofabrication of functional tissues


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. 105-B, Issue SUPP_17 | Pages 15 - 15
24 Nov 2023
Trenkwalder K Erichsen S Weisemann F Augat P Militz M Hackl S
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Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 78 - 78
14 Nov 2024
Moore A Whitehouse M Wylde V Walsh N Beswick A Jameson C Blom A
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Introduction. Hip prosthetic joint infection (PJI) is a debilitating complication following joint replacement surgery, with significant impact on patients and healthcare systems. The INFection ORthopaedic Management: Evidence into Practice (INFORM: EP) study, builds upon the 6-year INFORM programme by developing evidence-based guidelines for the identification and management of hip PJI. Methods. A panel of 21 expert stakeholders collaborated to develop best practice guidelines based on evidence from the previous INFORM research programme. An expert consensus process was used to refine guidelines using RAND/UCLA criteria. The guidelines were then implemented over a 12-month period through a Learning Collaborative of 24 healthcare professionals from 12 orthopaedic centres in England. Qualitative interviews were conducted with 17 members of the collaborative and findings used to inform the development of an implementation support toolkit. Patient and public involvement contextualised the implementation of the guidelines. The study is registered with the ISCRTN (34710385). Result. The INFORM guidelines, structured around the stages of PJI management, were largely supported by surgeons, although barriers included limited awareness among non-surgical team members, lack of job planning for multidisciplinary teams, and challenges in ensuring timely referrals from primary care. Psychological support for patients was identified as a critical gap. Advanced Nurse Practitioners and multidisciplinary team (MDT) coordinators were seen as potential bridges to address these knowledge gaps. The guidelines were also viewed as a useful tool for service development. Conclusions. This study presents the first evidence-based guidelines for hip PJI management, offering a comprehensive approach to prevention, treatment, and postoperative care. Effective implementation is crucial, involving wider dissemination amongst primary and community care, as well as non-specialist treatment centres. Further resources are needed to ensure job planning for MDTs and psychological support for patients. Overall, this study lays the foundation for improved PJI management, benefiting patients and healthcare systems


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 40 - 40
2 May 2024
Moore A Whitehouse M Wylde V Walsh N Beswick A Jameson C Blom A
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Hip prosthetic joint infection (PJI) is a debilitating complication following joint replacement surgery, with significant impact on patients and healthcare systems. The INFection ORthopaedic Management: Evidence into Practice (INFORM:EP) study, builds upon the 6-year INFORM programme by developing evidence-based guidelines for the identification and management of hip PJI. A panel of 21 expert stakeholders collaborated to develop best practice guidelines based on evidence from INFORM \[1\]. An expert consensus process was used to refine guidelines using RAND/UCLA criteria. The guidelines were then implemented over a 12-month period through a Learning Collaborative of 24 healthcare professionals from 12 orthopaedic centres in England. Qualitative interviews were conducted with 17 members of the collaborative and findings used to inform the development of an implementation support toolkit. Patient and public involvement contextualised the implementation of the guidelines. The study is registered with the ISCRTN (34710385). The INFORM guidelines, structured around the stages of PJI management, were largely supported by surgeons, although barriers included limited awareness among non-surgical team members, lack of job planning for multidisciplinary teams, and challenges in ensuring timely referrals from primary care. Psychological support for patients was identified as a critical gap. Advanced Nurse Practitioners and multidisciplinary team (MDT) coordinators were seen as potential bridges to address these knowledge gaps. The guidelines were also viewed as a useful tool for service development. This study presents the first evidence-based guidelines for hip PJI management, offering a comprehensive approach to prevention, treatment, and postoperative care. Effective implementation is crucial, involving wider dissemination amongst primary and community care, as well as non-specialist treatment centres. Further resources are needed to ensure job planning for MDTs and psychological support for patients. Overall, this study lays the foundation for improved PJI management, benefiting patients and healthcare systems


Bone & Joint Research
Vol. 10, Issue 8 | Pages 474 - 487
2 Aug 2021
Duan M Wang Q Liu Y Xie J

Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_15 | Pages 68 - 68
7 Nov 2023
Hohmann E Paschos N Keough N Molepo M Oberholster A Erbulut D Tetsworth K Glat V Gueorguiev B
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The purpose of this study was to develop a quality appraisal tool for the assessment of laboratory basic science biomechanical studies. Materials andScore development comprised of the following phases: item identification/development, item reduction, content/face/criterion validity, weighting, test-retest reliability and internal consistency. For item identification/development, the panel was asked to independently list criteria and factors they considered important for cadaver study and generate items that should be used to appraise cadaver study quality. For content validity, the content validity ratio (CVR) was calculated. The minimum accepted content validity index (CVI) was set to 0.85. For weighting, equal weight for each item was 6.7% [15 items]. Based on these figures the panel was asked to either upscale or downscale the weight for each item ensuring that the final sum for all items was 100%. Face validity was assessed by each panel member using a Likert scale from 1–7. Strong face validity was defined as a mean score of >5. Test-retest reliability was assessed using 10 randomly selected studies. Criterion validity was assessed using the QUACS scale as standard. Internal consistency was assessed using Cronbach's alpha. Five items reached a CVI of 1 and 10 items a CVI of 0.875. For weighting five items reached a final weight of 10% and ten items 5%. The mean score for face validity was 5.6. Test-retest reliability ranged from 0.78–1.00 with 9 items reaching a perfect score. Criterion validity was 0.76 and considered to be strong. Cronbach's alpha was calculated to be 0.71 indicating acceptable internal consistency. The new proposed quality score for basic science studies consists of 15 items and has been shown to be reliable, valid and of acceptable internal consistency. It is suggested that this score should be utilised when assessing basic science studies


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_3 | Pages 120 - 120
23 Feb 2023
Guo J Blyth P Baillie LJ Crawford HA
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The treatment of paediatric supracondylar humeral fractures is likely one of the first procedures involving X-ray guided wire insertion that trainee orthopaedic surgeons will encounter. Pinning is a skill that requires high levels of anatomical knowledge, spatial awareness, and hand-eye coordination. We developed a simulation model using silicone soft-tissue and 3D-printed bones to allow development and practice of this skill at no additional risk to patients. For this model, we have focused on reusability and lowering raw-material costs without compromising fidelity. To achieve this, the initial bone model was extracted from open-source computed tomography scans and modified from adult to paediatric size. Muscle of appropriate robustness was then sculpted around the bones using 3D modelling software. A cutaneous layer was developed to mimic oedema using clay sculpturing on a plaster-casted paediatric forearm. These models were then used for 3D-printing and silicone casting respectively. The bone models were printed with settings to imitate cortical and cancellous densities and give high-fidelity tactile feedback upon drilling. Each humerus costs NZD $0.30 in material to print and can be used 1–3 times. Silicone casting of the soft-tissue layers imitates differing relative densities between muscle and oedematous cutaneous tissue, thereby increasing skill necessary to accurately palpate landmarks. Each soft-tissue sleeve cost NZD $70 in material costs to produce and can be used 20+ times. The resulting model is modular, reusable, and replaceable, with each component standardised and easily reproduced. It can be used to practice land-mark palpation and Kirschner wire pinning and is especially valuable in smaller centres which may not be able to afford traditional Saw Bones models. This low-cost model thereby improves equity while maintaining quality of simulation training


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 130 - 130
2 Jan 2024
Ergene E Liman G Demirel G Yilgor P
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Skeletal muscle tissue engineering has made progress towards production of functional tissues in line with the development in materials science and fabrication techniques. In particular, combining the specificity of 3D printing with smart materials has introduced a new concept called the 4D printing. Inspired by the unique properties of smart/responsive materials, we designed a bioink made of gelatin, a polymer with well-known cell compatibility, to be 3D printed on a magnetically responsive substrate. Gelatin was made photocrosslinkable by the methacrylate reaction (GELMA), and its viscosity was finetuned by blending with alginate which was later removed by alginate lyase treatment, so that the printability of the bioink as well as the cell viability can be finetuned. C2C12 mouse myoblasts-laden bioink was then 3D printed on a magnetic substrate for 4D shape-shifting. The magnetic substrate was produced using silicon rubber (EcoFlex) and carbonyl iron powders. After 3D printing, the bioink was crosslinked on the substrate, and the substrate was rolled with the help of a permanent magnet. Unrolled (Open) samples were used as the control group. The stiffness of the bioink matrix was found to be in the range of 13–45 kPa, which is the appropriate value for the adhesion of C2C12 cells. In the cell viability analysis, it was observed that the cells survived and could proliferate within the 7-day duration of the experiment. As a result of the immunofluorescence test, compared to the Open Group, more cell nuclei were observed overlapping MyoD1 expression in the Rolled Group; this indicated that the cells in these samples had more cell-cell interactions and therefore tended to form more myotubes. Acknowledgements: This research was supported by the TÜBİTAK 2211-A and YÖK 100/2000 scholarship programs


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 66 - 66
11 Apr 2023
Sebastian S Collin M Liu Y Raina D Tägil M Lidgren L
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There is a lack of carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotic for Staphylococcus aureus deep bone infections (DBIs). RIF is also associated with systemic side effects, and known for causing rapid development of antibiotic resistance when given as monotherapy. We evaluated a clinically usedbi-phasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). It was hypothesized that this combined approach could provide improved biofilm eradication and prevent the development of RIF resistance. Methods: 1) Biofilm eradication: Using a modified crystal violet staining biofilm quantification method, the antibiotics released at different time points (Day 1, 3, 7, 14, 21, 28 and 35) from the hemispherical pellets of CaS/HA(500 mg)-VAN (24.57 mg) / GEN (10.35 mg) composites with or without RIF (8.11 mg) were tested for their ability to disrupt the preformed 48-h old biofilms of S. aureus ATCC 25923, and S. aureus clinical strain P-3 in 96-well microtitre plate. For each tested group of antibiotic fractions, five separate wells were used (n=5). 2) Testing for resistance development: Similar to the method mentioned above the 48-h biofilm embeded bacteria exposed to antibiotic fractions from different time points continuously for 7 days. The biofilms remained were then tested for RIF resistant strains of bacteria. Overall, there was clear antibiofilm biofilm activity observed with CaS/HA-VAN/GEN+RIF combinations compared with CaS/HA-VAN/GEN alone. The S. aureus strains developed resistance to RIF when biofilms were subjected to CaS/HA-RIF alone but not with combinations of CaS/HA-VAN/GEN+RIF. Enhanced antibiofilm effects without development of RIF resistance indicates that biphasic CaS/HA loaded with VAN or GEN could be used as a carrier for RIF for additional local delivery in clinically demanding DBIs. Acknowledgement: We deeply acknowledge the Royal Fysiographic Society of Lund, Landshövding Per Westlings Minnesfond and the Stina and Gunnar Wiberg fond for financial support


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 86 - 86
17 Apr 2023
Aljuaid M Alzahrani S Shurbaji S
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Acetabular morphology and orientation differs from ethnic group to another. Thus, investigating the natural history of the parameters that are used to assess both was a matter of essence. Nevertheless, clarification the picture of normal value in our society was the main aim of this study. However, Acetabular head index (AHI) and center edge angle (CEA) were the most sensitive indicative parameters for acetabular dysplasia. Hence, they were the main variables used in evaluation of acetabular development. A cross-sectional retrospective study that had been done in a tertiary center. Computed tomography abdomen scouts’ radiographs of non-orthopedics patients were included. They had no history of pelvic or hips’ related symptoms or fractures in femur or pelvis. Images’ reports were reviewed to exclude those with tumors in the femur or pelvic bones. A total of 81 patients was included with 51% of them were males. The mean of age was 10.38± 3.96. CEA was measured using Wiberg technique, means of CEA were 33.71±6.53 and 36.50±7.39 for males and females, respectively. Nonetheless, AHI means were 83.81±6.10 and 84.66±4.17 for males and females, respectively. On the other hand, CEA was increasing by a factor 0.26 for each year (3-18, range). In addition, positive significant correlation was detected between CEA and age as found by linear regression r 2 0.460 (f(df1,79) =21.232, P ≤0.0001). Also, Body mass index (BMI) was positively correlated with CEA r 0.410, P 0.004). This study shows that obesity and aging are linked to increased CEA. Each ethnic group has its own normal values that must be studied to avoid premature diagnosis


Bone & Joint Research
Vol. 12, Issue 12 | Pages 734 - 746
12 Dec 2023
Chen M Hu C Hsu Y Lin Y Chen K Ueng SWN Chang Y

Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion. EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 79 - 79
17 Apr 2023
Stockmann A Grammens J Lenz J Pattappa G von Haver A Docheva D Zellner J Verdonk P Angele P
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Partial meniscectomy patients have a greater likelihood for the development of early osteoarthritis (OA). To prevent the onset of early OA, patient-specific treatment algorithms need to be created that predict patient risk to early OA after meniscectomy. The aim of this work was to identify patient-specific risk factors in partial meniscectomy patients that could potentially lead to early OA. Partial meniscectomy patients operated between 01/2017 and 12/2019 were evaluated in the study (n=317). Exclusion criteria were other pathologies or surgeries for the evaluated knee and meniscus (n = 114). Following informed consent, an online questionnaire containing demographics and the “Knee Injury and Osteoarthritis Outcome Score” (KOOS) questionnaire was sent to the patient. Based on the KOOS pain score, patients were classified into “low” (> 75) and “high” (< 75) risk patients, indicating risk to symptomatic OA. The “high risk” patients also underwent a follow-up including an MRI scan to understand whether they have developed early OA. From 203 participants, 96 patients responded to the questionnaire (116 did not respond) with 61 patients considered “low-risk” and 35 “high-risk” patients. Groups that showed a significant increased risk for OA were patients aged > 40 years, females, overweight (BMI >25 kg/m2 ≤ 30 kg/m2), and smokers (*p < 0.05). The “high-risk”-follow-up revealed a progression of early osteoarthritic cartilage changes in seven patients, with the remaining nineteen patients showing no changes in cartilage status or pain since time of operation. Additionally, eighteen patients in the high-risk group showed a varus or valgus axis deviation. Patient-specific factors for worse postoperative outcomes after partial meniscectomy and indicators for an “early OA” development were identified, providing the basis for a patient-specific treatment approach. Further analysis in a multicentre study and computational analysis of MRI scans is ongoing to develop a patient-specific treatment algorithm for meniscectomy patients


Bone & Joint Open
Vol. 4, Issue 11 | Pages 825 - 831
1 Nov 2023
Joseph PJS Khattak M Masudi ST Minta L Perry DC

Aims. Hip disease is common in children with cerebral palsy (CP) and can decrease quality of life and function. Surveillance programmes exist to improve outcomes by treating hip disease at an early stage using radiological surveillance. However, studies and surveillance programmes report different radiological outcomes, making it difficult to compare. We aimed to identify the most important radiological measurements and develop a core measurement set (CMS) for clinical practice, research, and surveillance programmes. Methods. A systematic review identified a list of measurements previously used in studies reporting radiological hip outcomes in children with CP. These measurements informed a two-round Delphi study, conducted among orthopaedic surgeons and specialist physiotherapists. Participants rated each measurement on a nine-point Likert scale (‘not important’ to ‘critically important’). A consensus meeting was held to finalize the CMS. Results. Overall, 14 distinct measurements were identified in the systematic review, with Reimer’s migration percentage being the most frequently reported. These measurements were presented over the two rounds of the Delphi process, along with two additional measurements that were suggested by participants. Ultimately, two measurements, Reimer’s migration percentage and femoral head-shaft angle, were included in the CMS. Conclusion. This use of a minimum standardized set of measurements has the potential to encourage uniformity across hip surveillance programmes, and may streamline the development of tools, such as artificial intelligence systems to automate the analysis in surveillance programmes. This core set should be the minimum requirement in clinical studies, allowing clinicians to add to this as needed, which will facilitate comparisons to be drawn between studies and future meta-analyses. Cite this article: Bone Jt Open 2023;4(11):825–831


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 54 - 54
14 Nov 2024
Pann P Taheri S Schilling AF Graessel S
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Introduction. Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. Method. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted. Result. OARSI scoring confirmed OA induction 4 weeks post-DMM surgery, with forced exercise exacerbating cartilage degradation regardless of intensity. No significant genotype-dependent differences were observed. Serum analysis revealed elevated cytokine levels associated with OA and inflammation in KO mice compared to WT mice 4 and 8 weeks post-surgery (VEGF-A, MCP-1, CXCL10, RANTES, MIP1-alpha, MIP1-beta, and RANKL). The observed effects were often exacerbated by intense exercise but rarely by DMM surgery. NanoCT analysis demonstrated increased sclerotic bone changes after 6 weeks of forced exercise in KO mice compared to WT mice. Conclusion. Our results suggest an OA promoting effect of exercise in early disease stages of posttraumatic OA. Intense exercise induced inflammatory processes correlated to increased cytokine levels in the serum that might exacerbate OA pathogenesis in later stages. The neuropeptide alpha-CGRP might play a role in protecting against these adverse effects


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 38 - 38
1 Dec 2022
Sheridan G Hanlon M Welch-Phillips A Spratt K Hagan R O'Byrne J Kenny P Kurmis A Masri B Garbuz D Hurson C
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Hip resurfacing may be a useful surgical procedure when patient selection is correct and only implants with superior performance are used. In order to establish a body of evidence in relation to hip resurfacing, pseudotumour formation and its genetic predisposition, we performed a case-control study investigating the role of HLA genotype in the development of pseudotumour around MoM hip resurfacings. All metal-on-metal (MoM) hip resurfacings performed in the history of the institution were assessed. A total of 392 hip resurfacings were performed by 12 surgeons between February 1st 2005 and October 31st 2007. In all cases, pseudotumour was confirmed in the preoperative setting on Metal Artefact Reduction Sequencing (MARS) MRI. Controls were matched by implant (ASR or BHR) and absence of pseudotumour was confirmed on MRI. Blood samples from all cases and controls underwent genetic analysis using Next Generation Sequencing (NGS) assessing for the following alleles of 11 HLA loci (A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPB1, DPA1). Statistical significance was determined using a Fisher's exact test or Chi-Squared test given the small sample size to quantify the clinical association between HLA genotype and the need for revision surgery due to pseudotumour. Both groups were matched for implant type (55% ASR, 45% BHR in both the case and control groups). According to the ALVAL histological classification described by Kurmis et al., the majority of cases (63%, n=10) were found to have group 2 histological findings. Four cases (25%) had group 3 histological findings and 2 (12%) patients had group 4 findings. Of the 11 HLA loci analysed, 2 were significantly associated with a higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) and 4 were noted to be protective against pseudotumour formation (DQA1*03:01:01, DRB1*04:04:01, C*01:02:01, B*27:05:02). These findings further develop the knowledge base around specific HLA genotypes and their role in the development of pseudotumour formation in MoM hip resurfacing. Specifically, the two alleles at higher risk of pseudotumour formation (DQB1*05:03:01 and DRB1*14:54:01) in MoM hip resurfacing should be noted, particularly as patient-specific genotype-dependent surgical treatments continue to develop in the future


The Bone & Joint Journal
Vol. 102-B, Issue 4 | Pages 495 - 500
1 Apr 2020
Milligan DJ Cosgrove AP

Aims

To monitor the performance of services for developmental dysplasia of the hip (DDH) in Northern Ireland and identify potential improvements to enhance quality of service and plan for the future.

Methods

This was a prospective observational study, involving all infants treated for DDH between 2011 and 2017. Children underwent clinical assessment and radiological investigation as per the regional surveillance policy. The regional radiology data was interrogated to quantify the use of ultrasound and ionizing radiation for this population.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 124 - 124
14 Nov 2024
Lin Y Lian W Chen Y Wang F
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Introduction. Osteoporosis accounts for a major risk factor of fracture-associated disability or premature death in the elderly. Enhancement of bone anabolism for slowing osteoporosis is highly demanding. Exerkine fibronectin type III domain containing 5 (FNDC5) regulates energy metabolism, inflammation, and aging. This study was aimed to investigate whether Fndc5 signaling in osteoblasts changed estrogen deficiency-mediated bone loss or microarchitecture deterioration. Method. Female osteoblast-specific Fndc5 transgenic mice (Fndc5Tg), which overexpressed Fndc5 under the control of key osteoblast marker osteocalcin promoter, were given bilateral ovariectomy to induce estrogen deficiency-mediated osteoporosis. Bone mass, microstructures, and biomechanical properties were quantified using μCT imaging and material testing. Dynamic bone formation was traced using fluorescence calcein. Osteogenic differentiation and adipocyte formation of bone-marrow mesenchymal cells were investigated using von Kossa staining and Nile red staining, respectively. Serum osteocalcin, CTX-1 and TRAP5b levels were quantified using designated ELISA kits. Mitochondrial respiration was investigated using Seahorse Extracellular Flux Analyzer. Result. Fndc5Tg mice developed relatively higher bone mass and microarchitecture than wild-type mice. Fndc5 overexpression attenuated the losses of bone mineral density and trabecular network, including trabecular volume, thickness, and trabecular number, and improved cortical thickness and porosity in ovariectomized mice. Gain of Fndc5 function preserved biomechanical characteristics (maximum load, breaking force, and energy), serum bone formation marker osteocalcin levels, and bone formation rate, whereas it reduced serum bone resorption makers CTX-1 and TRAP5b levels, osteoclast overburden, and marrow adiposis. In vitro, Fndc5 reversed the estrogen deficiency-mediated mineralized matrix underproduction and adipocyte formation of bone-marrow mesenchymal cells, and inhibited osteoclast formation in osteoporotic bone. Mechanistically, Fndc5 activated AMPK signaling, promoting mitochondrial respiration and ATP production to enhance osteoblastic activity. Conclusion. Fndc5 signaling exerted bone-protective actions delaying estrogen deficiency-mediated osteoporosis. This study highlighted a new molecular remedial option for osteoporosis development by manipulating Fndc5 functions