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The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 50 - 55
1 Jan 2018
Kono K Tomita T Futai K Yamazaki T Tanaka S Yoshikawa H Sugamoto K

Aims. In Asia and the Middle-East, people often flex their knees deeply in order to perform activities of daily living. The purpose of this study was to investigate the 3D kinematics of normal knees during high-flexion activities. Our hypothesis was that the femorotibial rotation, varus-valgus angle, translations, and kinematic pathway of normal knees during high-flexion activities, varied according to activity. Materials and Methods. We investigated the in vivo kinematics of eight normal knees in four male volunteers (mean age 41.8 years; 37 to 53) using 2D and 3D registration technique, and modelled the knees with a computer aided design program. Each subject squatted, kneeled, and sat cross-legged. We evaluated the femoral rotation and varus-valgus angle relative to the tibia and anteroposterior translation of the medial and lateral side, using the transepicodylar axis as our femoral reference relative to the perpendicular projection on to the tibial plateau. This method evaluates the femur medially from what has elsewhere been described as the extension facet centre, and differs from the method classically applied. . Results. During squatting and kneeling, the knees displayed femoral external rotation. When sitting cross-legged, femurs displayed internal rotation from 10° to 100°. From 100°, femoral external rotation was observed. No significant difference in varus-valgus angle was seen between squatting and kneeling, whereas a varus position was observed from 140° when sitting cross-legged. The measure kinematic pathway using our methodology found during squatting a medial pivoting pattern from 0° to 40° and bicondylar rollback from 40° to 150°. During kneeling, a medial pivot pattern was evident. When sitting cross-legged, a lateral pivot pattern was seen from 0° to 100°, and a medial pivot pattern beyond 100°. Conclusion. The kinematics of normal knees during high flexion are variable according to activity. Nevertheless, our study was limited to a small number of male patients using a different technique to report the kinematics than previous publications. Accordingly, caution should be observed in generalizing our findings. Cite this article: Bone Joint J 2018;100-B:50–5


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1238 - 1247
1 Oct 2019
Soreide E Denbeigh JM Lewallen EA Thaler R Xu W Berglund L Yao JJ Martinez A Nordsletten L van Wijnen AJ Kakar S

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Materials and Methods

A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6).


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 998 - 1006
1 Jul 2012
Kodama A Kamei N Kamei G Kongcharoensombat W Ohkawa S Nakabayashi A Ochi M

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.


Bone & Joint Research
Vol. 10, Issue 11 | Pages 714 - 722
1 Nov 2021
Qi W Feng X Zhang T Wu H Fang C Leung F

Aims. To fully verify the reliability and reproducibility of an experimental method in generating standardized micromotion for the rat femur fracture model. Methods. A modularized experimental device has been developed that allows rat models to be used instead of large animal models, with the aim of reducing systematic errors and time and money constraints on grouping. The bench test was used to determine the difference between the measured and set values of the micromotion produced by this device under different simulated loading weights. The displacement of the fixator under different loading conditions was measured by compression tests, which was used to simulate the unexpected micromotion caused by the rat’s ambulation. In vivo preliminary experiments with a small sample size were used to test the feasibility and effectiveness of the whole experimental scheme and surgical scheme. Results. The bench test showed that a weight loading < 500 g did not affect the operation of experimental device. The compression test demonstrated that the stiffness of the device was sufficient to keep the uncontrollable motion between fracture ends, resulting from the rat’s daily activities, within 1% strain. In vivo results on 15 rats prove that the device works reliably, without overburdening the experimental animals, and provides standardized micromotion reproductively at the fracture site according to the set parameters. Conclusion. Our device was able to investigate the effect of micromotion parameters on fracture healing by generating standardized micromotion to small animal models. Cite this article: Bone Joint Res 2021;10(11):714–722


Bone & Joint Research
Vol. 11, Issue 11 | Pages 835 - 842
17 Nov 2022
Wiesli MG Livio F Achermann Y Gautier E Wahl P

Aims. There is a considerable challenge in treating bone infections and orthopaedic device-associated infection (ODAI), partly due to impaired penetration of systemically administrated antibiotics at the site of infection. This may be circumvented by local drug administration. Knowledge of the release kinetics from any carrier material is essential for proper application. Ceftriaxone shows a particular constant release from calcium sulphate (CaSO. 4. ) in vitro, and is particularly effective against streptococci and a large portion of Gram-negative bacteria. We present the clinical release kinetics of ceftriaxone-loaded CaSO. 4. applied locally to treat ODAI. Methods. A total of 30 operations with ceftriaxone-loaded CaSO. 4. had been performed in 28 patients. Ceftriaxone was applied as a single local antibiotic in 21 operations and combined with vancomycin in eight operations, and in an additional operation with vancomycin and amphotericin B. Sampling of wound fluid was performed from drains or aspirations. Ceftriaxone concentrations were measured by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results. A total of 37 wound fluid concentrations from 16 operations performed in 14 patients were collected. The ceftriaxone concentrations remained approximately within a range of 100 to 200 mg/l up to three weeks. The median concentration was 108.9 mg/l (interquartile range 98.8 to 142.5) within the first ten days. No systemic adverse reactions were observed. Conclusion. Our study highlights new clinical data of locally administered ceftriaxone with CaSO. 4. as carrier material. The near-constant release of ceftriaxone from CaSO. 4. observed in vitro could be confirmed in vivo. The concentrations remained below known local toxicity thresholds. Cite this article: Bone Joint Res 2022;11(11):835–842


Bone & Joint Research
Vol. 10, Issue 10 | Pages 639 - 649
19 Oct 2021
Bergiers S Hothi H Henckel J Di Laura A Belzunce M Skinner J Hart A

Aims. Acetabular edge-loading was a cause of increased wear rates in metal-on-metal hip arthroplasties, ultimately contributing to their failure. Although such wear patterns have been regularly reported in retrieval analyses, this study aimed to determine their in vivo location and investigate their relationship with acetabular component positioning. Methods. 3D CT imaging was combined with a recently validated method of mapping bearing surface wear in retrieved hip implants. The asymmetrical stabilizing fins of Birmingham hip replacements (BHRs) allowed the co-registration of their acetabular wear maps and their computational models, segmented from CT scans. The in vivo location of edge-wear was measured within a standardized coordinate system, defined using the anterior pelvic plane. Results. Edge-wear was found predominantly along the superior acetabular edge in all cases, while its median location was 8° (interquartile range (IQR) -59° to 25°) within the anterosuperior quadrant. The deepest point of these scars had a median location of 16° (IQR -58° to 26°), which was statistically comparable to their centres (p = 0.496). Edge-wear was in closer proximity to the superior apex of the cups with greater angles of acetabular inclination, while a greater degree of anteversion influenced a more anteriorly centred scar. Conclusion. The anterosuperior location of edge-wear was comparable to the degradation patterns observed in acetabular cartilage, supporting previous findings that hip joint forces are directed anteriorly during a greater portion of walking gait. The further application of this novel method could improve the current definition of optimal and safe acetabular component positioning. Cite this article: Bone Joint Res 2021;10(10):639–649


Bone & Joint Research
Vol. 11, Issue 9 | Pages 669 - 678
1 Sep 2022
Clement RGE Hall AC Wong SJ Howie SEM Simpson AHRW

Aims. Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection. Methods. Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 10. 7. colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling. Results. Chondrocyte death was greater with 8325-4 (96.2% (SD 5.5%); p < 0.001) than DU1090 (28.9% (SD 16.0%); p = 0.009) and both were higher than controls (3.8% (SD 1.2%)). Histology revealed cartilage/bone damage with 8325-4 or DU1090 compared to controls (p = 0.010). Both infected groups lost weight (p = 0.006 for both) and experienced limb swelling (p = 0.043 and p = 0.018, respectively). Joints inoculated with bacteria showed significant alterations in gait cycle with a decreased stance phase, increased swing phase, and a corresponding decrease in swing speed. Conclusion. Murine joints inoculated with Hla-producing 8325-4 experienced significantly more chondrocyte death than those with DU1090, which lack the toxin. This was despite similar immune responses, indicating that Hla was the major cause of chondrocyte death. Hla-deficient DU1090 also elevated chondrocyte death compared to controls, suggesting a smaller additional deleterious role of the immune system on cartilage. Cite this article: Bone Joint Res 2022;11(9):669–678


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1527 - 1534
3 Nov 2020
Orita K Minoda Y Sugama R Ohta Y Ueyama H Takemura S Nakamura H

Aims. Vitamin E-infused highly cross-linked polyethylene (E1) has recently been introduced in total knee arthroplasty (TKA). An in vitro wear simulator study showed that E1 reduced polyethylene wear. However there is no published information regarding in vivo wear. Previous reports suggest that newly introduced materials which reduce in vitro polyethylene wear do not necessarily reduce in vivo polyethylene wear. To assist in the evaluation of the newly introduced material before widespread use, we established an in vivo polyethylene wear particle analysis for TKA. The aim of this study was to compare in vivo polyethylene wear particle generation between E1 and conventional polyethylene (ArCom) in TKA. Methods. A total of 34 knees undergoing TKA (17 each with ArCom or E1) were investigated. Except for the polyethylene insert material, the prostheses used for both groups were identical. Synovial fluid was obtained at a mean of 3.4 years (SD 1.3) postoperatively. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined by scanning electron microscopy. Results. The total number of polyethylene wear particles obtained from the knees with E1 (mean 6.9, SD 4.0 × 10. 7. counts/knee) was greater than that obtained from those with ArCom (mean 2.2, SD 2.6 × 10. 7. counts/knee) (p = 0.001). The particle size (equivalent circle of diameter) from the knees with E1 was smaller (mean 0.5 μm, SD 0.1) than that of knees with ArCom (mean 1.5, SD 0.3 μm) (p = 0.001). The aspect ratio of particles from the knees with E1 (mean 1.3, SD 0.1) was smaller than that with ArCom (mean 1.4, SD 0.1) (p < 0.001 ). Conclusion. This is the first report of in vivo wear particle analysis of E1. E1 polyethylene did not reduce the number of in vivo polyethylene wear particles compared with ArCom in early clinical stage. Further careful follow-up of newly introduced E1 for TKA should be carried out. Cite this article: Bone Joint J 2020;102-B(11):1527–1534


Bone & Joint Research
Vol. 12, Issue 12 | Pages 712 - 721
4 Dec 2023
Dantas P Gonçalves SR Grenho A Mascarenhas V Martins J Tavares da Silva M Gonçalves SB Guimarães Consciência J

Aims. Research on hip biomechanics has analyzed femoroacetabular contact pressures and forces in distinct hip conditions, with different procedures, and used diverse loading and testing conditions. The aim of this scoping review was to identify and summarize the available evidence in the literature for hip contact pressures and force in cadaver and in vivo studies, and how joint loading, labral status, and femoral and acetabular morphology can affect these biomechanical parameters. Methods. We used the PRISMA extension for scoping reviews for this literature search in three databases. After screening, 16 studies were included for the final analysis. Results. The studies assessed different hip conditions like labrum status, the biomechanical effect of the cam, femoral version, acetabular coverage, and the effect of rim trimming. The testing and loading conditions were also quite diverse, and this disparity limits direct comparisons between the different researches. With normal anatomy the mean contact pressures ranged from 1.54 to 4.4 MPa, and the average peak contact pressures ranged from 2 to 9.3 MPa. Labral tear or resection showed an increase in contact pressures that diminished after repair or reconstruction of the labrum. Complete cam resection also decreased the contact pressure, and acetabular rim resection of 6 mm increased the contact pressure at the acetabular base. Conclusion. To date there is no standardized methodology to access hip contact biomechanics in hip arthroscopy, or with the preservation of the periarticular soft-tissues. A tendency towards improved biomechanics (lower contact pressures) was seen with labral repair and reconstruction techniques as well as with cam correction. Cite this article: Bone Joint Res 2023;12(12):712–721


The Bone & Joint Journal
Vol. 103-B, Issue 7 Supple B | Pages 9 - 16
1 Jul 2021
Hadden WJ Ibrahim M Taha M Ure K Liu Y Paish ADM Holdsworth DW Abdelbary H

Aims. The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods. Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results. All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion. This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16


The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 59 - 65
1 Jun 2020
Kwon Y Arauz P Peng Y Klemt C

Aims. The removal of the cruciate ligaments in total knee arthroplasty (TKA) has been suggested as a potential contributing factor to patient dissatisfaction, due to alteration of the in vivo biomechanics of the knee. Bicruciate retaining (BCR) TKA allows the preservation of the cruciate ligaments, thus offering the potential to reproduce healthy kinematics. The aim of this study was to compare in vivo kinematics between the operated and contralateral knee in patients who have undergone TKA with a contemporary BCR design. Methods. A total of 29 patients who underwent unilateral BCR TKA were evaluated during single-leg deep lunges and sit-to-stand tests using a validated computer tomography and fluoroscopic imaging system. In vivo six-degrees of freedom (6DOF) kinematics were compared between the BCR TKA and the contralateral knee. Results. During single-leg deep lunge, BCR TKAs showed significantly less mean posterior femoral translation (13 mm; standard deviation (SD) 4) during terminal flexion, compared with the contralateral knee (16.6 mm, SD 3.7; p = 0.001). Similarly, BCR TKAs showed significantly less mean femoral rollback (11.6 mm (SD 4.5) vs 14.4 mm (SD 4.6); p < 0.043) during sit-to-stand. BCR TKAs showed significantly reduced internal rotation during many parts of the strenuous flexion activities particularly during high-flexion lunge (4° (SD 5.6°) vs 6.5° (SD 6.1°); p = 0.051) and during sit-to-stand (4.5° (SD 6°) vs 6.9° (SD 6.3°); p = 0.048). Conclusion. The contemporary design of BCR TKA showed asymmetrical flexion-extension and internal-external rotation, suggesting that the kinematics are not entirely reproduced during strenuous activities. Future studies are required to establish the importance of patient factors, component orientation and design, in optimizing kinematics in patients who undergo BCR TKA. Cite this article: Bone Joint J 2020;102-B(6 Supple A):59–65


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims. Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Methods. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining. Results. In vitro testing showed that the secreted ECM oriented itself along the fibre in multi-layered scaffolds. Both types of CG scaffolds supported cell viability, growth, and matrix synthesis. In vitro chondrogenesis on scaffold showed an around 400-fold increase in collagen type 2 (COL2A1) expression in both CG scaffolds, but the total glycosaminoglycan (GAG)/DNA deposition was 1.39-fold higher in the multi-layered scaffold than the randomly aligned scaffold. In vivo cartilage formation occurred in both multi-layered and randomly aligned scaffolds treated with and without cells, and was shown to be of hyaline phenotype on immunostaining. The defects treated with multi-layered + cells, however, showed significantly thicker cartilage formation than the randomly aligned scaffold. Conclusion. We demonstrated that MSCs loaded CG scaffold with multi-layered zonal architecture promoted superior hyaline AC regeneration. Cite this article: Bone Joint Res 2020;9(9):601–612


The Bone & Joint Journal
Vol. 101-B, Issue 11 | Pages 1348 - 1355
1 Nov 2019
Gascoyne T Parashin S Teeter M Bohm E Laende E Dunbar M Turgeon T

Aims. A retrospective study was conducted to measure short-term in vivo linear and volumetric wear of polyethylene (PE) inserts in 101 total knee arthroplasty (TKA) patients using model-based radiostereometric analysis (MBRSA). Patients and Methods. Nonweightbearing supine RSA exams were performed postoperatively and at six, 12, and 24 months. Weightbearing standing RSA exams were performed on select patients at 12 and 24 months. Wear was measured both linearly (joint space) and volumetrically (digital model overlap) at each available follow-up. Precision of both methods was assessed by comparing double RSA exams. Patient age, sex, body mass index, and Oxford Knee Scores were analyzed for any association with PE wear. Results. Linear wear occurred at 0.015 mm/year (supine) and 0.220 mm/year (standing). Volumetric wear occurred at 10.3 mm. 3. /year (supine) and 39.3 mm. 3. /year (standing). Wear occurred primarily on the medial side of the joint. Weightbearing imaging greatly improved the reliability of measurement. Clinical precision of volumetric wear was 34 mm. 3. No significant associations were found between patient demographics or function scores and measured wear. Conclusion. In vivo volumetric wear of TKAs can be assessed at short-term follow-up using MBRSA. Cite this article: Bone Joint J 2019;101-B:1348–1355


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims. Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants. Methods. pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 10. 9. particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs. Results. Significantly higher content of DNA and collagen was observed for the pEV-treated group compared to control and cEV groups. No differences were found in GAG quantification nor in EVs uptake within any treated group. Conclusion. In conclusion, pEVs showed better performance than cEVs in our in vitro OA model. Although further studies are needed, pEVs are shown as a potential alternative to cEVs for cell-free regenerative medicine. Cite this article: Bone Joint Res 2023;12(10):667–676


Bone & Joint Research
Vol. 5, Issue 12 | Pages 610 - 618
1 Dec 2016
Abubakar AA Noordin MM Azmi TI Kaka U Loqman MY

In vivo animal experimentation has been one of the cornerstones of biological and biomedical research, particularly in the field of clinical medicine and pharmaceuticals. The conventional in vivo model system is invariably associated with high production costs and strict ethical considerations. These limitations led to the evolution of an ex vivo model system which partially or completely surmounted some of the constraints faced in an in vivo model system. The ex vivo rodent bone culture system has been used to elucidate the understanding of skeletal physiology and pathophysiology for more than 90 years. This review attempts to provide a brief summary of the historical evolution of the rodent bone culture system with emphasis on the strengths and limitations of the model. It encompasses the frequency of use of rats and mice for ex vivo bone studies, nutritional requirements in ex vivo bone growth and emerging developments and technologies. This compilation of information could assist researchers in the field of regenerative medicine and bone tissue engineering towards a better understanding of skeletal growth and development for application in general clinical medicine. Cite this article: A. A. Abubakar, M. M. Noordin, T. I. Azmi, U. Kaka, M. Y. Loqman. The use of rats and mice as animal models in ex vivo bone growth and development studies. Bone Joint Res 2016;5:610–618. DOI: 10.1302/2046-3758.512.BJR-2016-0102.R2


The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1505 - 1510
2 Nov 2020
Klemt C Limmahakhun S Bounajem G Xiong L Yeo I Kwon Y

Aims. The complex relationship between acetabular component position and spinopelvic mobility in patients following total hip arthroplasty (THA) renders it difficult to optimize acetabular component positioning. Mobility of the normal lumbar spine during postural changes results in alterations in pelvic tilt (PT) to maintain the sagittal balance in each posture and, as a consequence, markedly changes the functional component anteversion (FCA). This study aimed to investigate the in vivo association of lumbar degenerative disc disease (DDD) with the PT angle and with FCA during postural changes in THA patients. Methods. A total of 50 patients with unilateral THA underwent CT imaging for radiological evaluation of presence and severity of lumbar DDD. In all, 18 patients with lumbar DDD were compared to 32 patients without lumbar DDD. In vivo PT and FCA, and the magnitudes of changes (ΔPT; ΔFCA) during supine, standing, swing-phase, and stance-phase positions were measured using a validated dual fluoroscopic imaging system. Results. PT, FCA, ΔPT, and ΔFCA were significantly correlated with the severity of lumbar DDD. Patients with severe lumbar DDD showed marked differences in PT with changes in posture; there was an anterior tilt (-16.6° vs -12.3°, p = 0.047) in the supine position, but a posterior tilt in an upright posture (1.0° vs -3.6°, p = 0.005). A significant decrease in ΔFCA during stand-to-swing (8.6° vs 12.8°, p = 0.038) and stand-to-stance (7.3° vs 10.6°,p = 0.042) was observed in the severe lumbar DDD group. Conclusion. There were marked differences in the relationship between PT and posture in patients with severe lumbar DDD compared with healthy controls. Clinical decision-making should consider the relationship between PT and FCA in order to reduce the risk of impingement at large ranges of motion in THA patients with lumbar DDD. Cite this article: Bone Joint J 2020;102-B(11):1505–1510


Bone & Joint Research
Vol. 6, Issue 6 | Pages 366 - 375
1 Jun 2017
Neves N Linhares D Costa G Ribeiro CC Barbosa MA

Objectives. This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods. A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results. A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions. This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1


Bone & Joint Research
Vol. 1, Issue 4 | Pages 42 - 49
1 Apr 2012
Kwon Y Mellon SJ Monk P Murray DW Gill HS

Objectives. Pseudotumours (abnormal peri-prosthetic soft-tissue reactions) following metal-on-metal hip resurfacing arthroplasty (MoMHRA) have been associated with elevated metal ion levels, suggesting that excessive wear may occur due to edge-loading of these MoM implants. This study aimed to quantify in vivo edge-loading in MoMHRA patients with and without pseudotumours during functional activities. Methods. The duration and magnitude of edge-loading in vivo was quantified during functional activities by combining the dynamic hip joint segment contact force calculated from the three-dimensional (3D) motion analysis system with the 3D reconstruction of orientation of the acetabular component and each patient’s specific hip joint centre, based on CT scans. Results. Edge-loading in the hips with pseudotumours occurred with a four-fold increase in duration and magnitude of force compared with the hips without pseudotumours (p = 0.02). Conclusions. The study provides the first in vivo evidence to support that edge-loading is an important mechanism that leads to localised excessive wear (edge-wear), with subsequent elevation of metal ion levels in MoMHRA patients with pseudotumours


Bone & Joint Research
Vol. 5, Issue 4 | Pages 137 - 144
1 Apr 2016
Paterson SI Eltawil NM Simpson AHRW Amin AK Hall AC

Objectives. During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying in vivo are poorly understood. We used an animal model to investigate the subsequent effects of joint drying on cartilage and chondrocytes. Methods. The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively. Results. Joint drying caused extensive chondrocyte death within the superficial regions of cartilage. Histology of dried cartilage demonstrated a loss of surface integrity at four weeks, fibrillations at eight weeks, and an increased modified Mankin score (p < 0.001). Cartilage thickness increased (p < 0.001), whereas chondrocyte density decreased at four weeks (p < 0.001), but then increased towards sham-operated levels (p < 0.01) at eight weeks. By week eight, chondrocyte pairing/clustering and cell volume increased (p < 0.05; p < 0.001, respectively). Conclusions. These in vivo results demonstrated for the first time that as a result of laminar airflow, cartilage degeneration occurred which has characteristics similar to those seen in early osteoarthritis. Maintenance of adequate cartilage hydration during open orthopaedic surgery is therefore of paramount importance. Cite this article: Dr A. Hall. Drying of open animal joints in vivo subsequently causes cartilage degeneration. Bone Joint Res 2016;5:137–144. DOI: 10.1302/2046-3758.54.2000594


Bone & Joint Research
Vol. 7, Issue 5 | Pages 362 - 372
1 May 2018
Ueda Y Inui A Mifune Y Sakata R Muto T Harada Y Takase F Kataoka T Kokubu T Kuroda R

Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2


The Bone & Joint Journal
Vol. 97-B, Issue 7 | Pages 933 - 938
1 Jul 2015
Sola M Dahners L Weinhold P Svetkey van der Horst A Kallianos S Flood D

This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague–Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live–dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone. Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity. Cite this article: Bone Joint J 2015; 97-B:933–8


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 11 | Pages 1493 - 1497
1 Nov 2005
Price AJ Short A Kellett C Beard D Gill H Pandit H Dodd CAF Murray DW

Polyethylene particulate wear debris continues to be implicated in the aetiology of aseptic loosening following knee arthroplasty. The Oxford unicompartmental knee arthroplasty employs a spherical femoral component and a fully congruous meniscal bearing to increase contact area and theoretically reduce the potential for polyethylene wear. This study measures the in vivo ten-year linear wear of the device, using a roentgenstereophotogrammetric technique. In this in vivo study, seven medial Oxford unicompartmental prostheses, which had been implanted ten years previously were studied. Stereo pairs of radiographs were acquired for each patient and the films were analysed using a roentgen stereophotogrammetric analysis calibration and a computer-aided design model silhouette-fitting technique. Penetration of the femoral component into the original volume of the bearing was our estimate of linear wear. In addition, eight control patients were examined less than three weeks post-insertion of an Oxford prosthesis, where no wear would be expected. The control group showed no measured wear and suggested a system accuracy of 0.1 mm. At ten years, the mean linear wear rate was 0.02 mm/year. The results from this in vivo study confirm that the device has low ten-year linear wear in clinical practice. This may offer the device a survival advantage in the long term


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 34 - 44
1 Jan 2022
Beckers L Dandois F Ooms D Berger P Van Laere K Scheys L Vandenneucker H

Aims

Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs.

Methods

In total, 34 patients (13 female, 21 male; mean age 62 years (41 to 79); BMI 29.7 kg/m2 (23.6 to 42.1)) with 38 medial Oxford partial UKAs (20 left, 18 right; 19 cementless, 14 cemented, and five hybrid) were prospectively followed with sequential 99mTc-hydroxymethane diphosphonate single photon emission CT (SPECT)/CT preoperatively, and at one and two years postoperatively. Changes in mean osteoblastic activity were investigated using a tracer localization scheme with volumes of interest (VOIs), reported by normalized mean tracer values. A SPECT/CT registration platform additionally explored cortical tracer evolution in zones of interest identified by previous experimental research.


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 276 - 282
1 Feb 2017
Mumith A Coathup M Chimutengwende-Gordon M Aston W Briggs T Blunn G

Aims

Massive endoprostheses rely on extra-cortical bone bridging (ECBB) to enhance fixation. The aim of this study was to investigate the role of selective laser sintered (SLS) porous collars in augmenting the osseointegration of these prostheses.

Materials and Methods

The two novel designs of porous SLS collars, one with small pores (Ø700 μm, SP) and one with large pores (Ø1500 μm, LP), were compared in an ovine tibial diaphyseal model. Osseointegration of these collars was compared with that of a clinically used solid, grooved design (G). At six months post-operatively, the ovine tibias were retrieved and underwent radiological and histological analysis.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 1 | Pages 120 - 127
1 Jan 2002
Musgrave DS Pruchnic R Bosch P Ziran BH Whalen J Huard J

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 10 | Pages 1426 - 1433
1 Oct 2005
Kobayashi T Watanabe H Yanagawa T Tsutsumi S Kayakabe M Shinozaki T Higuchi H Takagishi K

Human bone-marrow mesenchymal stem cells have an important role in the repair of musculoskeletal tissues by migrating from the bone marrow into the injured site and undergoing differentiation. We investigated the use of autologous human serum as a substitute for fetal bovine serum in the ex vivo expansion medium to avoid the transmission of dangerous transfectants during clinical reconstruction procedures. Autologous human serum was as effective in stimulating growth of bone-marrow stem cells as fetal bovine serum. Furthermore, medium supplemented with autologous human serum was more effective in promoting motility than medium with fetal bovine serum in all cases. Addition of B-fibroblast growth factor to medium with human serum stimulated growth, but not motility. Our results suggest that autologous human serum may provide sufficient ex vivo expansion of human bone-marrow mesenchymal stem cells possessing multidifferentiation potential and may be better than fetal bovine serum in preserving high motility


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 633 - 638
1 May 2007
Matthews TJW Smith SR Peach CA Rees JL Urban JPG Carr AJ

We have undertaken an in vivo assessment of the tissue metabolism and cellular activity in torn tendons of the rotator cuff. Cellular oxygen consumption was measured in 13 patients undergoing mini-open repair of small, medium, large and massive full-thickness tears. Measurements were also taken from three control patients who were undergoing open stabilisation of the shoulder with grossly normal tendons. The level of oxygen and nitrous oxide was measured amperometrically using silver needle microelectrodes at the apex of the tear and 1.5 cm from its edge. With nitrous oxide indicating the degree of perfusion, oxygen consumption was calculated at each location to reflect cellular activity. All of the torn tendons had lower levels of cellular activity than the control group. This activity was lower still in the tissue nearest to the edge of the tear with the larger tears showing the lowest activity. This indicated reduced levels of tissue metabolism and infers a reduction in tendon viability. Our findings suggest that surgical repair of torn tendons of the rotator-cuff should include the more proximal, viable tissue, and may help to explain the high rate of re-rupture seen in larger tears


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 6 | Pages 752 - 760
1 Jun 2007
Yamada Y Toritsuka Y Horibe S Sugamoto K Yoshikawa H Shino K

We used three-dimensional movement analysis by computer modelling of knee flexion from 0° to 50° in 14 knees in 12 patients with recurrent patellar dislocation and in 15 knees in ten normal control subjects to compare the in vivo three-dimensional movement of the patella. Flexion, tilt and spin of the patella were described in terms of rotation angles from 0°. The location of the patella and the tibial tubercle were evaluated using parameters expressed as percentage patellar shift and percentage tubercle shift. Patellar inclination to the femur was also measured and patellofemoral contact was qualitatively and quantitatively analysed. The patients had greater values of spin from 20° to 50°, while there were no statistically significant differences in flexion and tilt. The patients also had greater percentage patellar shift from 0° to 50°, percentage tubercle shift at 0° and 10° and patellar inclination from 0° to 50° with a smaller oval-shaped contact area from 20° to 50° moving downwards on the lateral facet. Patellar movement analysis using a three-dimensional computer model is useful to clearly demonstrate differences between patients with recurrent dislocation of the patella and normal control subjects


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1245 - 1251
1 Sep 2006
Pendegrass CJ Oddy MJ Sundar S Cannon SR Goodship AE Blunn GW

We examined the mechanical properties of Vicryl (polyglactin 910) mesh in vitro and assessed its use in vivo as a novel biomaterial to attach tendon to a hydroxyapatite-coated metal implant, the interface of which was augmented with autogenous bone and marrow graft. This was compared with tendon re-attachment using a compressive clamp device in an identical animal model. Two- and four-ply sleeves of Vicryl mesh tested to failure under tension reached 5.13% and 28.35% of the normal ovine patellar tendon, respectively. Four-ply sleeves supported gait in an ovine model with 67.05% weight-bearing through the operated limb at 12 weeks, without evidence of mechanical failure. Mesh fibres were visible at six weeks but had been completely resorbed by 12 weeks, with no evidence of chronic inflammation. The tendon-implant neoenthesis was predominantly an indirect type, with tendon attached to the bone-hydroxyapatite surface by perforating collagen fibres


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 8 | Pages 1194 - 1198
1 Nov 2002
Felländer-Tsai L Högberg E Wredmark T Arner P

We have used in vivo microdialysis to monitor postoperative physiological events in the synovial membrane after arthroscopy. The levels of lactate were significantly higher in the synovial membrane than in the reference tissue (subcutaneous fat) and there was a significant increase in lactate after operation. Blood flow, measured as the ethanol ratio, was stable in both tissues. Our findings show that there was an increase in the local production of lactate since the levels of lactate in blood and the reference tissue were comparable and did not show a significant increase. There was also a consumption of glucose in the synovial membrane which was not observed in the reference tissue. The levels of pyruvate were higher in the synovial membrane. A state of reperfusion occurs in the synovial membrane after moderate trauma such as standard arthroscopy of the knee. Microdialysis should be further evaluated in studies of the in vivo physiology of the synovial membrane


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 2 | Pages 254 - 258
1 Mar 1993
Kabo J Gebhard J Loren G Amstutz H

Polyethylene acetabular cups retrieved at revision surgery were measured by a shadowgraph technique to determine linear wear, and the values were compared with those obtained from radiographs. There was a close correlation between them, although the radiographic measurements slightly underestimated the true wear. Average linear wear rates for surface-replacement components were much greater than those for conventional prostheses with femoral heads up to 32 mm in diameter. Volumetric wear, calculated using a new formula, was found to be less than previously reported in vivo, and similar in magnitude to the results of experimental wear tests in vitro. The volumetric wear rates were greatest for the surface-replacement components and, for conventional components, were found to increase in a linear manner with component diameter


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 9 | Pages 1257 - 1262
1 Sep 2009
Sundar S Pendegrass CJ Oddy MJ Blunn GW

We used demineralised bone matrix (DBM) to augment re-attachment of tendon to a metal prosthesis in an in vivo ovine model of reconstruction of the extensor mechanism at the knee. We hypothesised that augmentation of the tendon-implant interface with DBM would enhance the functional and histological outcomes as compared with previously reported control reconstructions without DBM. Function was assessed at six and 12 weeks postoperatively, and histological examination was undertaken at 12 weeks. A significant increase of 23.5% was observed in functional weight-bearing at six weeks in the DBM-augmented group compared with non-augmented controls (p = 0.004). By 12 weeks augmentation with DBM resulted in regeneration of a more direct-type enthesis, with regions of fibrocartilage, mineralised fibrocartilage and bone. In the controls the interface was predominantly indirect, with the tendon attached to the bone graft-hydroxyapatite base plate by perforating collagen fibres


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 8 | Pages 1106 - 1113
1 Aug 2008
Richards L Brown C Stone MH Fisher J Ingham E Tipper JL

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated. We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles


Bone & Joint Research
Vol. 8, Issue 11 | Pages 535 - 543
1 Nov 2019
Mohammad HR Campi S Kennedy JA Judge A Murray DW Mellon SJ

Objectives

The aim of this study was to determine the polyethylene wear rate of Phase 3 Oxford Unicompartmental Knee Replacement bearings and to investigate the effects of resin type and manufacturing process.

Methods

A total of 63 patients with at least ten years’ follow-up with three bearing types (1900 resin machined, 1050 resin machined, and 1050 resin moulded) were recruited. Patients underwent full weight-bearing model-based radiostereometric analysis to determine the bearing thickness. The linear wear rate was estimated from the change in thickness divided by the duration of implantation.


Bone & Joint Research
Vol. 3, Issue 11 | Pages 317 - 320
1 Nov 2014
Basso T Klaksvik J Foss OA

Objective. In ex vivo hip fracture studies femoral pairs are split to create two comparable test groups. When more than two groups are required, or if paired femurs cannot be obtained, group allocation according to bone mineral density (BMD) is sometimes performed. In this statistical experiment we explore how this affects experimental results and sample size considerations. Methods. In a hip fracture experiment, nine pairs of human cadaver femurs were tested in a paired study design. The femurs were then re-matched according to BMD, creating two new test groups. Intra-pair variance and paired correlations in fixation stability were calculated. A hypothetical power analysis was then performed to explore the required sample size for the two types of group allocation. . Results. The standard deviation (. sd. ) of the mean paired difference in fixation stability increased from 2 mm in donor pairs to 5 mm in BMD-matched pairs. Intra-pair correlation was 0.953 (Pearson’s r) in donor pairs and non-significant at -0.134 (Pearson’s r) in BMD-matched pairs. Required sample size to achieve a statistical power of 0.8 increased from ten pairs using donor pairs to 54 pairs using BMD-matched pairs. Conclusion. BMD cannot be used to create comparable test groups unless sample size is increased substantially and paired statistics are no longer valid. Cite this article: Bone Joint Res 2014;3:317–20


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 1 | Pages 131 - 137
1 Jan 2000
Menetrey J Kasemkijwattana C Day CS Bosch P Vogt M Fu FH Moreland MS Huard J

Injury to muscles is very common. We have previously observed that basic fibroblast growth factor (b-FGF), insulin growth factor type 1 (IGF-1) and nerve growth factor (NGF) are potent stimulators of the proliferation and fusion of myoblasts in vitro. We therefore injected these growth factors into mice with lacerations of the gastrocnemius muscle. The muscle regeneration was evaluated at one week by histological staining and quantitative histology. Muscle healing was assessed histologically and the contractile properties were measured one month after injury. Our findings showed that b-FGF, IGF and to a less extent NGF enhanced muscle regeneration in vivo compared with control muscle. At one month, muscles treated with IGF-1 and b-FGF showed improved healing and significantly increased fast-twitch and tetanus strengths. Our results suggest that b-FGF and IGF-1 stimulated muscle healing and may have a considerable effect on the treatment of muscle injuries


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 4 | Pages 601 - 613
1 May 2000
Roach HI Clarke NMP

Chondrocytes at the lower zone of the growth plate must be eliminated to facilitate longitudinal growth; this is generally assumed to involve apoptosis. We attempted to provide definitive electron-microscopic evidence of apoptosis in chondrocytes of physes and chondroepiphyses in the rabbit. We were, however, unable to find a single chondrocyte with the ultrastructure of ‘classical’ apoptosis in vivo, although such a cell was found in vitro. Instead, condensed chondrocytes had a convoluted nucleus with patchy chromatin condensations while the cytoplasm was dark with excessive amounts of endoplasmic reticulum. These cells were termed ‘dark chondrocytes’. A detailed study of their ultrastructure combined with localisation methods in situ suggested a different mechanism of programmed cell death. In addition, another type of death was identified among the immature chondrocytes of the chondroepiphysis. These cells had the same nucleus as dark chondrocytes, but the lumen of the endoplasmic reticulum had expanded to fill the entire non-nuclear space, and all cytoplasm and organelles had been reduced to dark, worm-like inclusions. Since these cells appeared to be ‘in limbo’, they were termed ‘paralysed’ cells. It is proposed that ‘dark chondrocytes’ and ‘paralysed cells’ are examples of physiological cell death which does not involve apoptosis. It is possible that the confinement of chondrocytes within their lacunae, which would prevent phagocytosis of apoptotic bodies, necessitates different mechanisms of elimination


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 4 | Pages 591 - 594
1 May 2000
Milgrom C Finestone A Simkin A Ekenman I Mendelson S Millgram M Nyska M Larsson E Burr D

Mechanical loading during physical activity produces strains within bones. It is thought that these forces provide the stimulus for the adaptation of bone. Tibial strains and rates of strain were measured in vivo in six subjects during running, stationary bicycling, leg presses and stepping and were compared with those of walking, an activity which has been found to have only a minimal effect on bone mass. Running had a statistically significant higher principal tension, compression and shear strain and strain rates than walking. Stationary bicycling had significantly lower tension and shear strains than walking. If bone strains and/or strain rates higher than walking are needed for tibial bone strengthening, then running is an effective strengthening exercise for tibial bone


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 5 | Pages 767 - 773
1 Jul 2002
Skoglund B Larsson L Aspenberg PA

Wear particles commonly used for experiments may carry adherent endotoxin on their surfaces, which may be responsible for the observed effects. In this study, we attached titanium plates to the tibiae of 20 rats. After osseointegration, endotoxin-contaminated or uncontaminated high-density-polyethylene (HDPE) particles were applied. Contaminated specimens showed a dramatic resorption of bone after seven days but new bone filled the site again at 21 days. Uncontaminated specimens showed no resorption. In 18 rats we implanted intramuscularly discs of ultra-high-molecular-weight polyethylene (UHMWPE) with baseline or excess contamination of endotoxin. Excess endotoxin disappeared within 24 hours and the amount of endotoxin remained at baseline level (contamination from production). Uncontaminated titanium discs did not adsorb endotoxin in vivo. The endotoxin was measured by analytical chemistry. Locally-applied endotoxin stimulated bone resorption similarly to that in experiments with wear particles. Endotoxin on the surface of implants and particles appeared to be inactivated in situ. A clean implant surface did not adsorb endotoxin. Our results suggest that endotoxin adhering to orthopaedic implants is not a major cause for concern


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1200 - 1208
1 Nov 2004
Borden M Attawia M Khan Y El-Amin SF Laurencin CT

We have evaluated in vivo a novel, polymer-based, matrix for tissue engineering of bone. A segmental defect of 15 mm was created in the ulna of New Zealand white rabbits to determine the regenerative properties of a porous polylactide-co-glycolide matrix alone and in combination with autogenous marrow and/or the osteoinductive protein, BMP-7. In this study four implant groups were used: 1) matrix alone; 2) matrix with autogenous marrow; 3) matrix with 20 μg of BMP-7; and 4) matrix with 20 μg of BMP-7 and autogenous marrow. The results showed that the degree of bone formation was dependent on the properties of the graft material. The osteoconductive sintered matrix structure showed significant formation of bone at the implant-bone interface. The addition of autogenous marrow increased the penetration of new bone further into the central area of the matrix and also increased the degree of revascularisation. The osteoinductive growth factor BMP-7 induced penetration of new bone throughout the entire structure of the implant. The most effective treatment was with the combination of marrow cells and osteoinductive BMP-7


The Journal of Bone & Joint Surgery British Volume
Vol. 62-B, Issue 2 | Pages 230 - 237
1 May 1980
Moreland M

In order to study the effect of pure torsional forces upon the rotational development of the growing tibia, 35 immature rabbits underwent torsional loading of one tibia in vivo with a spring-loaded cylinder while the other tibia was a control. The radiographic results showed rotation occurring only at the epiphysial plate. Histologically this was assocaited with angulation of the hypertrophic cartilage columns occurring as little as 24 hours after loading which with longer periods of loading produced angled primary and secondary trabeculae. Radiographic and histological analyses of the diaphysis using tetracycline labelling and Spalteholtz injection techniques failed to show any evidence of cortical remodelling or reorientation of the cortical vessels of a rotational nature, suggesting that rotational modelling occurs solely at the epiphysial plate


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 4 | Pages 592 - 599
1 May 2002
Maier M Milz S Tischer T Münzing W Manthey N Stäbler A Holzknecht N Weiler C Nerlich A Refior HJ Schmitz C

There is little information about the effects of extracorporeal shock-wave about application the effects (ESWA) of on normal bone physiology. We have therefore investigated the effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500 shock-wave pulses each of different energy flux densities (EFD) on either the left or right femur or remained untreated. The effects were studied by bone scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5 mJ/mm. 2. and 0.9 mJ/mm. 2. EFD), local blood flow and bone metabolism were decreased, but were increased 28 days after ESWA (0.9 mJ/mm. 2. ). One day after ESWA with 0.9 mJ/mm. 2. EFD but not with 0.5 mJ/mm. 2. , there were signs of soft-tissue oedema, epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of haemosiderin were found epiperiosteally and within the marrow cavity ten days after ESWA. We conclude that ESWA with both 0.5 mJ/mm. 2. and 0.9 mJ/mm. 2. EFD affected the normal bone physiology in the distal rabbit femur. Considerable damaging side-effects were observed with 0.9 mJ/mm. 2. EFD on periosteal soft tissue and tissue within the bone-marrow cavity


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 7 | Pages 948 - 951
1 Sep 2000
Sychterz CJ Engh CA Young AM Hopper RH Engh CA

At yearly intervals we compared the radiological wear characteristics of 81 alumina ceramic femoral heads with a well-matched group of 43 cobalt-chrome femoral heads. Using a computer-assisted measurement system we assessed two-dimensional penetration of the head into the polyethylene liner. We used linear regression analysis of temporal data of the penetration of the head to calculate the true rates of polyethylene wear for both groups. At a mean of seven years the true rate of wear of the ceramic group was slightly greater (0.09 mm/year, SD 0.07) than that of the cobalt-chrome group (0.07 mm/year, SD 0.04). Despite the numerous theoretical advantages of ceramic over cobalt-chrome femoral heads, the wear performance in vivo of these components was similar


The Bone & Joint Journal
Vol. 100-B, Issue 12 | Pages 1592 - 1599
1 Dec 2018
Galea VP Connelly JW Shareghi B Kärrholm J Sköldenberg O Salemyr M Laursen MB Muratoglu O Bragdon C Malchau H

Aims

The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high molecular weight polyethylene (ModXLPE) in patients five years after primary total hip arthroplasty (THA). The secondary aim was to assess the clinical results of patients treated with VEPE by evaluating patient-reported outcome measures (PROMs), radiological evidence of fixation, and the incidence of mechanical failure.

Patients and Methods

A total of 208 patients (221 THAs) from four international centres were recruited into a prospective study involving radiostereometric analysis (RSA) and the assessment of clinical outcomes. A total of 193 hips (87%) were reviewed at the five-year follow-up. Of these, 136 (70%) received VEPE (vs ModXLPE) liners and 68 (35%) received ceramic (vs metal) femoral heads. PROMs and radiographs were collected preoperatively and at one, two, and five years postoperatively. In addition, RSA images were collected to measure PE wear postoperatively and at one, two, and five years after surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 7 | Pages 865 - 874
1 Jul 2012
Mills LA Simpson AHRW

This review is aimed at clinicians appraising preclinical trauma studies and researchers investigating compromised bone healing or novel treatments for fractures. It categorises the clinical scenarios of poor healing of fractures and attempts to match them with the appropriate animal models in the literature.

We performed an extensive literature search of animal models of long bone fracture repair/nonunion and grouped the resulting studies according to the clinical scenario they were attempting to reflect; we then scrutinised them for their reliability and accuracy in reproducing that clinical scenario.

Models for normal fracture repair (primary and secondary), delayed union, nonunion (atrophic and hypertrophic), segmental defects and fractures at risk of impaired healing were identified. Their accuracy in reflecting the clinical scenario ranged greatly and the reliability of reproducing the scenario ranged from 100% to 40%.

It is vital to know the limitations and success of each model when considering its application.


Aims

The Intraosseous Transcutaneous Amputation Prosthesis (ITAP) may improve quality of life for amputees by avoiding soft-tissue complications associated with socket prostheses and by improving sensory feedback and function. It relies on the formation of a seal between the soft tissues and the implant and currently has a flange with drilled holes to promote dermal attachment. Despite this, infection remains a significant risk. This study explored alternative strategies to enhance soft-tissue integration.

Materials and Methods

The effect of ITAP pins with a fully porous titanium alloy flange with interconnected pores on soft-tissue integration was investigated. The flanges were coated with fibronectin-functionalised hydroxyapatite and silver coatings, which have been shown to have an antibacterial effect, while also promoting viable fibroblast growth in vitro. The ITAP pins were implanted along the length of ovine tibias, and histological assessment was undertaken four weeks post-operatively.


The Journal of Bone & Joint Surgery British Volume
Vol. 82-B, Issue 4 | Pages 499 - 505
1 May 2000
Uvehammer J Kärrholm J Brandsson S

We studied the kinetics of the knee in 20 patients (22 knees) 12 months after total knee arthroplasty (TKA), by using three-dimensional radiostereometry and film-exchanger techniques. Eleven knees had a concave (constrained) tibial implant and 11 a posterior-stabilised prosthesis. Eleven normal knees served as a control group.

In the posterior-stabilised knees there was less proximal and posterior displacement of the centre of the tibial plateau during extension from 45° to 15°, with a decrease in the anterior translation of the femoral condyles of 4 mm at 45°. There was less internal tibial rotation and increased distal positioning of the centre of the tibial plateau with both designs when compared with the normal knees, and in both the centre of the plateau was displaced posteriorly by more than 1 cm.

Increased AP translation has been recorded in all prosthetic designs so far studied by radiostereometry. The use of a posterior-stabilised design of tibial insert could reduce this translation but not to that of the normal knee.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 1 | Pages 123 - 123
1 Jan 2008
HEMS TEJ


Bone & Joint Research
Vol. 2, Issue 12 | Pages 255 - 263
1 Dec 2013
Zhang Y Xu J Wang X Huang J Zhang C Chen L Wang C Ma X

Objective

The objective of this study was to evaluate the rotation and translation of each joint in the hindfoot and compare the load response in healthy feet with that in stage II posterior tibial tendon dysfunction (PTTD) flatfoot by analysing the reconstructive three-dimensional (3D) computed tomography (CT) image data during simulated weight-bearing.

Methods

CT scans of 15 healthy feet and 15 feet with stage II PTTD flatfoot were taken first in a non-weight-bearing condition, followed by a simulated full-body weight-bearing condition. The images of the hindfoot bones were reconstructed into 3D models. The ‘twice registration’ method in three planes was used to calculate the position of the talus relative to the calcaneus in the talocalcaneal joint, the navicular relative to the talus in talonavicular joint, and the cuboid relative to the calcaneus in the calcaneocuboid joint.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 1 | Pages 33 - 39
1 Jan 2001
Dennis DA Komistek RD Walker SA Cheal EJ Stiehl JB

We carried out weight-bearing video radiological studies on 40 patients with a total knee arthroplasty (TKA), to determine the presence and magnitude of femoral condylar lift-off. Half (20) had posterior-cruciate-retaining (PCR) and half (20) posterior-cruciate-substituting (PS) prostheses. The selected patients had successful arthroplasties with no pain or instability. Each carried out successive weight-bearing knee bends to maximum flexion, and the radiological video tapes were analysed using an interactive model-fitting technique.

Femoral lift-off was seen at some increment of knee flexion in 75% of patients (PCR TKA 70%; PS TKA 80%). The mean values for lift-off were 1.2 mm with a PCR TKA and 1.4 mm with a PS TKA. Lift-off occurred mostly laterally with the PCR TKA, and both medially and laterally with the PS TKA. Separation between the femoral condyles and the articular surface of the tibia was recorded at 0°, 30°, 60° and 90° of flexion. Femoral condylar lift-off may contribute to eccentric polyethylene wear, particularly in designs of TKA which have flatter condyles. Coronal conformity is an important consideration in the design of a TKA.