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Bone & Joint Open
Vol. 5, Issue 4 | Pages 304 - 311
15 Apr 2024
Galloway R Monnington K Moss R Donaldson J Skinner J McCulloch R

Aims. Young adults undergoing total hip arthroplasty (THA) largely have different indications for surgery, preoperative function, and postoperative goals compared to a standard patient group. The aim of our study was to describe young adult THA preoperative function and quality of life, and to assess postoperative satisfaction and compare this with functional outcome measures. Methods. A retrospective cohort analysis of young adults (aged < 50 years) undergoing THA between May 2018 and May 2023 in a single tertiary centre was undertaken. Median follow-up was 31 months (12 to 61). Oxford Hip Score (OHS) and focus group-designed questionnaires were distributed. Searches identified 244 cases in 225 patients. Those aged aged under 30 years represented 22.7% of the cohort. Developmental dysplasia of the hip (50; 45.5%) and Perthes’ disease (15; 13.6%) were the commonest indications for THA. Results. Preoperatively, of 110 patients, 19 (17.2%) were unable to work before THA, 57 (52%) required opioid analgesia, 51 (46.4%) were reliant upon walking aids, and 70 (63.6%) had sexual activity limited by their pathology. One patient required revision due to instability. Mean OHS was 39 (9 to 48). There was a significant difference between the OHS of cases where THA met expectation, compared with the OHS when it did not (satisfied: 86 (78.2%), OHS: 41.2 (36.1%) vs non-satisfied: 24 (21%), OHS: 31.6; p ≤ 0.001). Only one of the 83 patients (75.5%) who returned to premorbid levels of activity did so after 12 months. Conclusion. Satisfaction rates of THA in young adults is high, albeit lower than commonly quoted figures. Young adults awaiting THA have poor function with high requirements for mobility aids, analgesia, and difficulties in working and undertaking leisure activities. The OHS provided a useful insight into patient function and was predictive of satisfaction rates, although it did not address the specific demands of young adults undertaking THA. Function at one year postoperatively is a good indication of overall outcomes. Cite this article: Bone Jt Open 2024;5(4):304–311


Bone & Joint Research
Vol. 9, Issue 11 | Pages 789 - 797
2 Nov 2020
Seco-Calvo J Sánchez-Herráez S Casis L Valdivia A Perez-Urzelai I Gil J Echevarría E

Aims. To analyze the potential role of synovial fluid peptidase activity as a measure of disease burden and predictive biomarker of progression in knee osteoarthritis (KOA). Methods. A cross-sectional study of 39 patients (women 71.8%, men 28.2%; mean age of 72.03 years (SD 1.15) with advanced KOA (Ahlbäck grade ≥ 3 and clinical indications for arthrocentesis) recruited through the (Orthopaedic Department at the Complejo Asistencial Universitario de León, Spain (CAULE)), measuring synovial fluid levels of puromycin-sensitive aminopeptidase (PSA), neutral aminopeptidase (NAP), aminopeptidase B (APB), prolyl endopeptidase (PEP), aspartate aminopeptidase (ASP), glutamyl aminopeptidase (GLU) and pyroglutamyl aminopeptidase (PGAP). Results. Synovial fluid peptidase activity varied significantly as a function of clinical signs, with differences in levels of PEP (p = 0.020), ASP (p < 0.001), and PGAP (p = 0. 003) associated with knee locking, PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p = 0.000) with knee failure, and PEP (p = 0.006), ASP (p = 0.001), GLU (p = 0.037), and PGAP (p < 0.001) with knee effusion. Further, patients with the greatest functional impairment had significantly higher levels of APB (p = 0.005), PEP (p = 0.005), ASP (p = 0.006), GLU (p = 0.020), and PGAP (p < 0.001) activity, though not of NAP or PSA, indicating local alterations in the renin-angiotensin system. A binary logistic regression model showed that PSA was protective (p = 0.005; Exp (B) 0.949), whereas PEP (p = 0.005) and GLU were risk factors (p = 0.012). Conclusion. These results suggest synovial fluid peptidase activity could play a role as a measure of disease burden and predictive biomarker of progression in KOA. Cite this article: Bone Joint Res 2020;9(11):789–797


Bone & Joint Research
Vol. 8, Issue 5 | Pages 207 - 215
1 May 2019
Key S Scott G Stammers JG Freeman MAR Pinskerova V Field RE Skinner J Banks SA

Objectives. The medially spherical GMK Sphere (Medacta International AG, Castel San Pietro, Switzerland) total knee arthroplasty (TKA) was previously shown to accommodate lateral rollback while pivoting around a stable medial compartment, aiming to replicate native knee kinematics in which some coronal laxity, especially laterally, is also present. We assess coronal plane kinematics of the GMK Sphere and explore the occurrence and pattern of articular separation during static and dynamic activities. Methods. Using pulsed fluoroscopy and image matching, the coronal kinematics and articular surface separation of 16 well-functioning TKAs were studied during weight-bearing and non-weight-bearing, static, and dynamic activities. The closest distances between the modelled articular surfaces were examined with respect to knee position, and proportions of joint poses exhibiting separation were computed. Results. Overall, 1717 joint poses were analyzed. At a 1.0 mm detection threshold, 37 instances of surface separation were observed in the lateral compartment and four medially (p < 0.001). Separation was activity-dependent, both laterally and medially (p < 0.001), occurring more commonly during static deep flexion in the lateral compartment, and during static rotation in the medial compartment. Lateral separation occurred more frequently than medial during kneeling (7/14 lateral vs 1/14 medial; p = 0.031) and stepping (20/1022 lateral vs 0/1022 medial; p < 0.001). Separation varied significantly between individuals during dynamic activities. Conclusion. No consistent association between closest distances of the articular surfaces and knee position was found during any activity. Lift-off was infrequent and depended on the activity performed and the individual knee. Lateral separation was consistent with the design rationale. Medial lift-off was rare and mostly in non-weight-bearing activities. Cite this article: S. Key, G. Scott, J. G. Stammers, M. A. R. Freeman†, V. Pinskerova, R. E. Field, J. Skinner, S. A. Banks. Does lateral lift-off occur in static and dynamic activity in a medially spherical total knee arthroplasty? A pulsed-fluoroscopic investigation. Bone Joint Res 2019;8:207–215. DOI: 10.1302/2046-3758.85.BJR-2018-0237.R1


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. 103-B, Issue 3 | Pages 522 - 529
1 Mar 2021
Nichol T Callaghan J Townsend R Stockley I Hatton PV Le Maitre C Smith TJ Akid R

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529


Bone & Joint Research
Vol. 5, Issue 10 | Pages 492 - 499
1 Oct 2016
Li X Li M Lu J Hu Y Cui L Zhang D Yang Y

Objectives. To elucidate the effects of age on the expression levels of the receptor activator of the nuclear factor-κB ligand (RANKL) and osteoclasts in the periodontal ligament during orthodontic mechanical loading and post-orthodontic retention. Materials and Methods. The study included 20 male Sprague-Dawley rats, ten in the young group (aged four to five weeks) and ten in the adult group (aged 18 to 20 weeks). In each rat, the upper-left first molar was subjected to a seven-day orthodontic force loading followed by a seven-day retention period. The upper-right first molar served as a control. The amount of orthodontic tooth movement was measured after seven-day force application and seven-day post-orthodontic retention. The expression levels of RANKL and the tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts were evaluated on day 7 (end of mechanical force loading) and day 14 (after seven days of post-orthodontic retention). Statistical analysis was performed using the t-test, and significance was set at p < 0.05. Results. There was no significant difference between the amount of tooth movement in the young group (0.96, standard deviation (. sd. ) 0.30mm) and that in the adult group (0.80mm, . sd. 0.28) (p > 0.05) after the seven-day force application. On the compression side, the expression of RANKL and TRAP-positive osteoclasts in both the young and the adult groups increased after the application of force for seven days, and then decreased at the end of the seven-day retention period. However, by the end of the period, the expression of RANKL on the compression side dropped to the control level in the young group (p > 0.05), while it was still higher than that on the control side in the adult group (p < 0.05). The expression of RANKL on the compression side did not show significant difference between the young and the adult groups after seven-day force application (p > 0.05), but it was significantly higher in the adult group than that in the young group after seven-day post-orthodontic retention (p < 0.05). Similarly, the decreasing trend of TRAP-positive osteoclasts during the retention period in the adult group was less obvious than that in the young group. Conclusions. The bone-resorptive activity in the young rats was more dynamic than that in the adult rats. The expression of RANKL and the number of osteoclasts in adult rats did not drop to the control level during the post-orthodontic retention period while RANKL expression and the number of osteoclasts in young rats had returned to the baseline. Cite this article: X. Li, M. Li, J. Lu, Y. Hu, L. Cui, D. Zhang, Y. Yang. Age-related effects on osteoclastic activities after orthodontic tooth movement. Bone Joint Res 2016;5:492–499. DOI: 10.1302/2046-3758.510.BJR-2016-0004.R2


Bone & Joint Research
Vol. 7, Issue 8 | Pages 517 - 523
1 Aug 2018
Tsang STJ Gwynne PJ Gallagher MP Simpson AHRW

Objectives. Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. Materials and Methods. Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours. Results. The MBEC of acetic acid was found to be: 15%, 11%, 3.2%, and 0.8% following a ten-minute, 20-minute, 180-minute, and 24-hour treatment, respectively. Conclusion. This study found that the MBEC of acetic acid following a 10- or 20-minute treatment time exceeded its safety threshold, making these concentrations unsuitable as a topical debridement adjunct. However, a clinically acceptable concentration (5%) was still found to eliminate 96.1% of biofilm-associated MSSA following a 20-minute treatment time. Cite this article: S. T. J. Tsang, P. J. Gwynne, M. P. Gallagher, A. H. R. W. Simpson. The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection. Bone Joint Res 2018;7:517–523. DOI: 10.1302/2046-3758.78.BJR-2018-0045.R1


Bone & Joint 360
Vol. 5, Issue 2 | Pages 1 - 1
1 Apr 2016
Ollivere B


Bone & Joint Research
Vol. 13, Issue 3 | Pages 91 - 100
1 Mar 2024
Yamamoto Y Fukui T Sawauchi K Yoshikawa R Takase K Kumabe Y Maruo A Niikura T Kuroda R Oe K

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100


Bone & Joint Open
Vol. 4, Issue 12 | Pages 964 - 969
19 Dec 2023
Berwin JT Duffy SDX Gargan MF Barnes JR

Aims. We assessed the long-term outcomes of a large cohort of patients who have undergone a periacetabular osteotomy (PAO), and sought to validate a patient satisfaction questionnaire for use in a PAO cohort. Methods. All patients who had undergone a PAO from July 1998 to February 2013 were surveyed, with several patient-reported outcome measures (PROMs) and radiological measurements of preoperative acetabular dysplasia and postoperative correction also recorded. Patients were asked to rate their level of satisfaction with their operation in achieving pain relief, restoration of activities of daily living, ability to perform recreational activity, and their overall level of satisfaction with the procedure. Results. A total of 143 PAOs were performed between 1998 and 2013. Of those, 90 postoperative surveys were returned. Only 65 patients (73 hips) had both pre- and postoperative radiographs available for measurement. The mean time to follow-up was 15 years (6.5 to 20). Most patients were female (91%), with a mean age of 26.4 years (14.9 to 48.3) at the time of their surgery. A statistically significant improvement in radiological correction was detected in all hips (p < 0.001). A total of 67 patients (92.3%) remained either very satisfied or satisfied with their PAO. The internal consistency of the patient satisfaction questionnaire, measured using Cronbach’s α, ranged from 0.89 to 0.94 indicating ‘good’ to ‘excellent’ reliability. Conclusion. Outcomes of importance to patients undergoing a PAO include several key domains: pain relief, improve activities of daily living, and improve recreational ability. Our study demonstrates high rates of long-term patient satisfaction in all domains, and found the patient satisfaction questionnaire to be a valid and reliable instrument for use in this cohort. Cite this article: Bone Jt Open 2023;4(12):964–969


Bone & Joint Research
Vol. 13, Issue 3 | Pages 101 - 109
4 Mar 2024
Higashihira S Simpson SJ Morita A Suryavanshi JR Arnold CJ Natoli RM Greenfield EM

Aims. Biofilm infections are among the most challenging complications in orthopaedics, as bacteria within the biofilms are protected from the host immune system and many antibiotics. Halicin exhibits broad-spectrum activity against many planktonic bacteria, and previous studies have demonstrated that halicin is also effective against Staphylococcus aureus biofilms grown on polystyrene or polypropylene substrates. However, the effectiveness of many antibiotics can be substantially altered depending on which orthopaedically relevant substrates the biofilms grow. This study, therefore, evaluated the activity of halicin against less mature and more mature S. aureus biofilms grown on titanium alloy, cobalt-chrome, ultra-high molecular weight polyethylene (UHMWPE), devitalized muscle, or devitalized bone. Methods. S. aureus-Xen36 biofilms were grown on the various substrates for 24 hours or seven days. Biofilms were incubated with various concentrations of halicin or vancomycin and then allowed to recover without antibiotics. Minimal biofilm eradication concentrations (MBECs) were defined by CFU counting and resazurin reduction assays, and were compared with the planktonic minimal inhibitory concentrations (MICs). Results. Halicin continued to exert significantly (p < 0.01) more antibacterial activity against biofilms grown on all tested orthopaedically relevant substrates than vancomycin, an antibiotic known to be affected by biofilm maturity. For example, halicin MBECs against both less mature and more mature biofilms were ten-fold to 40-fold higher than its MIC. In contrast, vancomycin MBECs against the less mature biofilms were 50-fold to 200-fold higher than its MIC, and 100-fold to 400-fold higher against the more mature biofilms. Conclusion. Halicin is a promising antibiotic that should be tested in animal models of orthopaedic infection. Cite this article: Bone Joint Res 2024;13(3):101–109


Bone & Joint Research
Vol. 11, Issue 11 | Pages 763 - 776
1 Nov 2022
Zhang Y Jiang B Zhang P Chiu SK Lee MH

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776


Bone & Joint Open
Vol. 3, Issue 9 | Pages 692 - 700
2 Sep 2022
Clement ND Smith KM Baron YJ McColm H Deehan DJ Holland J

Aims. The primary aim of our study was to assess the influence of age on hip-specific outcome following total hip arthroplasty (THA). Secondary aims were to assess health-related quality of life (HRQoL) and level of activity according to age. Methods. A prospective cohort study was conducted. All patients were fitted with an Exeter stem with a 32 mm head on highly cross-linked polyethylene (X3RimFit) cemented acetabulum. Patients were recruited into three age groups: < 65 years, 65 to 74 years, and ≥ 75 years, and assessed preoperatively and at three, 12, 24, and 60 months postoperatively. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and Hip disability and Osteoarthritis Outcome Score (HOOS), were used to assess hip-specific outcome. EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 36-Item Short Form Survey (SF-36) scores were used to assess HRQoL. The Lower Extremity Activity Scale (LEAS) and Timed Up and Go (TUG) were used to assess level of activity. Results. There were no significant (p > 0.05) differences in the WOMAC scores, HSS, HOOS, or EQ-5D-5L at any postoperative timepoint between the age groups. Patients aged ≥ 75 years had significantly lower physical function (p ≤ 0.010) and physical role (p ≤ 0.047) SF-36 scores at 12, 24, and 60 months, but were equal to that expect of an age-matched population. No differences according to age were observed for the other six domains of the SF-36 (p > 0.060). The ≥ 75 years group had a lower LEAS (p < 0.001) and longer TUG test times (p ≤ 0.032) compared to the < 65 years group, but older age groups had significant (p < 0.001) improvement relative to their preoperative baseline measures. Conclusion. Age did not influence postoperative hip-specific outcome or HRQoL (according to the EQ-5D) following THA. Despite a significant improvement, older patients had lower postoperative activity levels compared to younger patients, but this may be reflective of the overall physical effect of ageing. Cite this article: Bone Jt Open 2022;3(9):692–700


Aims. This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. Methods. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload. Results. Utilizing an OVX rat model, we observed significant alterations in bone mass and osseointegration due to VIT administration in aged rats with iron overload. The observed effects were concomitant with reductions in bone metabolism, oxidative stress, and inflammation. To elucidate whether these effects are associated with osteoclast and osteoblast activity, we conducted in vitro experiments using MC3T3-E1 cells and RAW264.7 cells. Our findings indicate that iron accumulation suppressed the activity of MC3T3-E1 while enhancing RAW264.7 function. Furthermore, iron overload significantly decreased oxidative stress levels; however, these detrimental effects can be mitigated by VIT treatment. Conclusion. Collectively, our data provide compelling evidence that VIT has the potential to reverse the deleterious consequences of iron overload on osseointegration and bone mass during ageing. Cite this article: Bone Joint Res 2024;13(9):427–440


Bone & Joint Research
Vol. 13, Issue 9 | Pages 485 - 496
13 Sep 2024
Postolka B Taylor WR Fucentese SF List R Schütz P

Aims. This study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy. Methods. Five subjects with valgus, 12 with neutral, and ten with varus limb alignment were assessed during multiple complete cycles of level walking, downhill walking, and stair descent using a combination of dynamic videofluoroscopy, ground reaction force plates, and optical motion capture. Following 2D/3D registration, tibiofemoral kinematics and kinetics were compared between the three limb alignment groups. Results. No significant differences for the rotational or translational patterns between the different limb alignment groups were found for level walking, downhill walking, or stair descent. Neutral and varus aligned subjects showed a mean centre of rotation located on the medial condyle for the loaded stance phase of all three gait activities. Valgus alignment, however, resulted in a centrally located centre of rotation for level and downhill walking, but a more medial centre of rotation during stair descent. Knee adduction/abduction moments were significantly influenced by limb alignment, with an increasing knee adduction moment from valgus through neutral to varus. Conclusion. Limb alignment was not reflected in the condylar kinematics, but did significantly affect the knee adduction moment. Variations in frontal plane limb alignment seem not to be a main modulator of condylar kinematics. The presented data provide insights into the influence of anatomical parameters on tibiofemoral kinematics and kinetics towards enhancing clinical decision-making and surgical restoration of natural knee joint motion and loading. Cite this article: Bone Joint Res 2024;13(9):485–496


Bone & Joint Research
Vol. 12, Issue 2 | Pages 133 - 137
10 Feb 2023
Liao H Tsai C

Aims. To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. Methods. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims. Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice. Methods. We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR). Results. Local delivery of NF-κB decoy ODN in vivo increased osteogenesis in males, but not females, in the presence of chronic inflammation induced by cPE. Bone resorption activity was decreased in both sexes. In vitro osteogenic and osteoclastic differentiation assays during inflammatory conditions did not reveal differences among the groups. Receptor activator of nuclear factor kappa Β ligand (Rankl) gene expression by osteoblasts was significantly decreased only in males when treated with ODN. Conclusion. We demonstrated that NF-κB decoy ODN increased osteogenesis in male mice and decreased bone resorption activity in both sexes in preclinical models of chronic inflammation. NF-κB signalling could be a therapeutic target for chronic inflammatory diseases involving bone, especially in males. Cite this article: Bone Joint Res 2024;13(1):28–39


Bone & Joint Open
Vol. 5, Issue 3 | Pages 202 - 209
11 Mar 2024
Lewin AM Cashman K Harries D Ackerman IN Naylor JM Harris IA

Aims. The aim of this study was to describe and compare joint-specific and generic health-related quality of life outcomes of the first versus second knee in patients undergoing staged bilateral total knee arthroplasty (BTKA) for osteoarthritis. Methods. This retrospective cohort study used Australian national arthroplasty registry data from January 2013 to January 2021 to identify participants who underwent elective staged BTKA with six to 24 months between procedures. The primary outcome was Oxford Knee Score (OKS) at six months postoperatively for the first TKA compared to the second TKA, adjusted for age and sex. Secondary outcomes compared six-month EuroQol five-dimension five-level (EQ-5D-5L) domain scores, EQ-5D index scores, and the EQ visual analogue scale (EQ-VAS) between knees at six months postoperatively. Results. The cohort included 635 participants (1,270 primary procedures). Preoperative scores were worse in the first knee compared to the second for all instruments; however, comparing the first knee at six months postoperatively with the second knee at six months postoperatively, the mean between-knee difference was minimal for OKS (-0.8 points; 95% confidence interval (CI) -1.4 to -0.2), EQ-VAS (3.3; 95% CI 1.9 to 4.7), and EQ-5D index (0.09 points; 95% CI 0.07 to 0.12). Outcomes for the EQ-5D-5L domains ‘mobility’, ‘usual activities’, and ‘pain/discomfort’ were better following the second TKA. Conclusion. At six months postoperatively, there were no clinically meaningful differences between the first and second TKA in either the joint-specific or overall generic health-related quality of life outcomes. However, individual domain scores assessing mobility, pain, and usual activities were notably higher after the second TKA, likely reflecting the cumulative improvement in quality of life after both knees have been replaced. Cite this article: Bone Jt Open 2024;5(3):202–209


Bone & Joint Open
Vol. 3, Issue 10 | Pages 826 - 831
28 Oct 2022
Jukes C Dirckx M Bellringer S Chaundy W Phadnis J

Aims. The conventionally described mechanism of distal biceps tendon rupture (DBTR) is of a ‘considerable extension force suddenly applied to a resisting, actively flexed forearm’. This has been commonly paraphrased as an ‘eccentric contracture to a flexed elbow’. Both definitions have been frequently used in the literature with little objective analysis or citation. The aim of the present study was to use video footage of real time distal biceps ruptures to revisit and objectively define the mechanism of injury. Methods. An online search identified 61 videos reporting a DBTR. Videos were independently reviewed by three surgeons to assess forearm rotation, elbow flexion, shoulder position, and type of muscle contraction being exerted at the time of rupture. Prospective data on mechanism of injury and arm position was also collected concurrently for 22 consecutive patients diagnosed with an acute DBTR in order to corroborate the video analysis. Results. Four videos were excluded, leaving 57 for final analysis. Mechanisms of injury included deadlift, bicep curls, calisthenics, arm wrestling, heavy lifting, and boxing. In all, 98% of ruptures occurred with the arm in supination and 89% occurred at 0° to 10° of elbow flexion. Regarding muscle activity, 88% occurred during isometric contraction, 7% during eccentric contraction, and 5% during concentric contraction. Interobserver correlation scores were calculated as 0.66 to 0.89 using the free-marginal Fleiss Kappa tool. The prospectively collected patient data was consistent with the video analysis, with 82% of injuries occurring in supination and 95% in relative elbow extension. Conclusion. Contrary to the classically described injury mechanism, in this study the usual arm position during DBTR was forearm supination and elbow extension, and the muscle contraction was typically isometric. This was demonstrated for both video analysis and ‘real’ patients across a range of activities leading to rupture. Cite this article: Bone Jt Open 2022;3(10):826–831


Bone & Joint Open
Vol. 5, Issue 9 | Pages 776 - 784
19 Sep 2024
Gao J Chai N Wang T Han Z Chen J Lin G Wu Y Bi L

Aims. In order to release the contracture band completely without damaging normal tissues (such as the sciatic nerve) in the surgical treatment of gluteal muscle contracture (GMC), we tried to display the relationship between normal tissue and contracture bands by magnetic resonance neurography (MRN) images, and to predesign a minimally invasive surgery based on the MRN images in advance. Methods. A total of 30 patients (60 hips) were included in this study. MRN scans of the pelvis were performed before surgery. The contracture band shape and external rotation angle (ERA) of the proximal femur were also analyzed. Then, the minimally invasive GMC releasing surgery was performed based on the images and measurements, and during the operation, incision lengths, surgery duration, intraoperative bleeding, and complications were recorded; the time of the first postoperative off-bed activity was also recorded. Furthermore, the patients’ clinical functions were evaluated by means of Hip Outcome Score (HOS) and Ye et al’s objective assessments, respectively. Results. The contracture bands exhibited three typical types of shape – feather-like, striped, and mixed shapes – in MR images. Guided by MRN images, we designed minimally invasive approaches directed to each hip. These approaches resulted in a shortened incision length in each hip (0.3 cm (SD 0.1)), shorter surgery duration (25.3 minutes (SD 5.8)), less intraoperative bleeding (8.0 ml (SD 3.6)), and shorter time between the end of the operation and the patient’s first off-bed activity (17.2 hours (SD 2.0)) in each patient. Meanwhile, no serious postoperative complications occurred in all patients. The mean HOS-Sports subscale of patients increased from 71.0 (SD 5.3) to 94.83 (SD 4.24) at six months postoperatively (p < 0.001). The follow-up outcomes from all patients were “good” and “excellent”, based on objective assessments. Conclusion. Preoperative MRN analysis can be used to facilitate the determination of the relationship between contracture band and normal tissues. The minimally invasive surgical design via MRN can avoid nerve damage and improve the release effect. Cite this article: Bone Jt Open 2024;5(9):776–784


Bone & Joint Open
Vol. 3, Issue 3 | Pages 236 - 244
14 Mar 2022
Oliver WM Molyneux SG White TO Clement ND Duckworth AD

Aims. The primary aim of this study was to determine the rates of return to work (RTW) and sport (RTS) following a humeral shaft fracture. The secondary aim was to identify factors independently associated with failure to RTW or RTS. Methods. From 2008 to 2017, all patients with a humeral diaphyseal fracture were retrospectively identified. Patient demographics and injury characteristics were recorded. Details of pre-injury employment, sporting participation, and levels of return post-injury were obtained via postal questionnaire. The University of California, Los Angeles (UCLA) Activity Scale was used to quantify physical activity among active patients. Regression was used to determine factors independently associated with failure to RTW or RTS. Results. The Work Group comprised 177 patients in employment prior to injury (mean age 47 years (17 to 78); 51% female (n = 90)). Mean follow-up was 5.8 years (1.3 to 11). Overall, 85% (n = 151) returned to work at a mean of 14 weeks post-injury (0 to 104), but only 60% (n = 106) returned full-time to their previous employment. Proximal-third fractures (adjusted odds ratio (aOR) 4.0 (95% confidence interval (CI) 1.2 to 14.2); p = 0.029) were independently associated with failure to RTW. The Sport Group comprised 182 patients involved in sport prior to injury (mean age 52 years (18 to 85); 57% female (n = 104)). Mean follow-up was 5.4 years (1.3 to 11). The mean UCLA score reduced from 6.9 (95% CI 6.6 to 7.2) before injury to 6.1 (95% CI 5.8 to 6.4) post-injury (p < 0.001). There were 89% (n = 162) who returned to sport: 8% (n = 14) within three months, 34% (n = 62) within six months, and 70% (n = 127) within one year. Age ≥ 60 years was independently associated with failure to RTS (aOR 3.0 (95% CI 1.1 to 8.2); p = 0.036). No other factors were independently associated with failure to RTW or RTS. Conclusion. Most patients successfully return to work and sport following a humeral shaft fracture, albeit at a lower level of physical activity. Patients aged ≥ 60 yrs and those with proximal-third diaphyseal fractures are at increased risk of failing to return to activity. Cite this article: Bone Jt Open 2022;3(3):236–244


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 880 - 887
1 Aug 2023
Onodera T Momma D Matsuoka M Kondo E Suzuki K Inoue M Higano M Iwasaki N

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887


Bone & Joint Research
Vol. 11, Issue 10 | Pages 723 - 738
4 Oct 2022
Liu Z Shen P Lu C Chou S Tien Y

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738


Bone & Joint Research
Vol. 11, Issue 5 | Pages 327 - 341
23 May 2022
Alagboso FI Mannala GK Walter N Docheva D Brochhausen C Alt V Rupp M

Aims. Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy. Methods. The human osteoblast-like Saos-2 cells infected with S. aureus EDCC 5055 strain and treated with 8 µg/ml RMP underwent osteogenic stimulation for up to 21 days. Test groups were Saos-2 cells + S. aureus and Saos-2 cells + S. aureus + 8 µg/ml RMP, and control groups were uninfected untreated Saos-2 cells and uninfected Saos-2 cells + 8 µg/ml RMP. Results. The S. aureus-infected osteoblasts showed a significant number of intracellular bacteria colonies and an unusual higher metabolic activity (p < 0.005) compared to uninfected osteoblasts. Treatment with 8 µg/ml RMP significantly eradicated intracellular bacteria and the metabolic activity was comparable to uninfected groups. The RMP-treated infected osteoblasts revealed a significantly reduced amount of mineralized extracellular matrix (ECM) at seven days osteogenesis relative to uninfected untreated osteoblasts (p = 0.007). Prolonged osteogenesis and RMP treatment at 21 days significantly improved the ECM mineralization level. Ultrastructural images of the mineralized RMP-treated infected osteoblasts revealed viable osteoblasts and densely distributed calcium crystal deposits within the extracellular organic matrix. The expression levels of prominent bone formation genes were comparable to the RMP-treated uninfected osteoblasts. Conclusion. Intracellular S. aureus infection impaired osteoblast metabolism and function. However, treatment with low dosage of RMP eradicated the intracellular S. aureus, enabling extracellular organic matrix formation and mineralization of osteoblasts at later stage. Cite this article: Bone Joint Res 2022;11(5):327–341


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims. cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. Methods. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA). Results. CREB1 was hyperactive in osteoarthritic articular cartilage, interleukin (IL)-1β-treated cartilage explants, and IL-1β- or carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-treated chondrocytes. 666-15 enhanced cell viability of OA-like chondrocytes and alleviated IL-1β- or CCCP-induced chondrocyte injury through inhibition of mitochondrial dysfunction-associated apoptosis. Moreover, inhibition of CREB1 by 666-15 suppressed expression of ADAMTS4. Additionally, 666-15 alleviated joint degeneration in an ACLT mouse model. Conclusion. Hyperactive CREB1 played a critical role in OA development, and 666-15 exerted anti-IL-1β or anti-CCCP effects in vitro as well as joint-protective effects in vivo. 666-15 may therefore be used as a promising anti-OA drug. Cite this article: Bone Joint Res 2024;13(1):4–18


Bone & Joint Open
Vol. 4, Issue 6 | Pages 408 - 415
1 Jun 2023
Ramkumar PN Shaikh HJF Woo JJ Haeberle HS Pang M Brooks PJ

Aims. The aims of the study were to report for a cohort aged younger than 40 years: 1) indications for HRA; 2) patient-reported outcomes in terms of the modified Harris Hip Score (HHS); 3) dislocation rate; and 4) revision rate. Methods. This retrospective analysis identified 267 hips from 224 patients who underwent an hip resurfacing arthroplasty (HRA) from a single fellowship-trained surgeon using the direct lateral approach between 2007 and 2019. Inclusion criteria was minimum two-year follow-up, and age younger than 40 years. Patients were followed using a prospectively maintained institutional database. Results. A total of 217 hips (81%) were included for follow-up analysis at a mean of 3.8 years. Of the 23 females who underwent HRA, none were revised, and the median head size was 46 mm (compared to 50 mm for males). The most common indication for HRA was femoroacetabular impingement syndrome (n = 133), and avascular necrosis ( (n = 53). Mean postoperative HHS was 100 at two and five years. No dislocations occurred. A total of four hips (1.8%) required reoperation for resection of heterotopic ossification, removal of components for infection, and subsidence with loosening. The overall revision rate was 0.9%. Conclusion. For younger patients with higher functional expectations and increased lifetime risk for revision, HRA is an excellent bone preserving intervention carrying low complication rates, revision rates, and excellent patient outcomes without lifetime restrictions allowing these patients to return to activity and sport. Thus, in younger male patients with end-stage hip disease and higher demands, referral to a high-volume HRA surgeon should be considered. Cite this article: Bone Jt Open 2023;4(6):408–415


Bone & Joint Research
Vol. 12, Issue 10 | Pages 624 - 635
4 Oct 2023
Harrison CJ Plessen CY Liegl G Rodrigues JN Sabah SA Beard DJ Fischer F

Aims. To map the Oxford Knee Score (OKS) and High Activity Arthroplasty Score (HAAS) items to a common scale, and to investigate the psychometric properties of this new scale for the measurement of knee health. Methods. Patient-reported outcome measure (PROM) data measuring knee health were obtained from the NHS PROMs dataset and Total or Partial Knee Arthroplasty Trial (TOPKAT). Assumptions for common scale modelling were tested. A graded response model (fitted to OKS item responses in the NHS PROMs dataset) was used as an anchor to calibrate paired HAAS items from the TOPKAT dataset. Information curves for the combined OKS-HAAS model were plotted. Bland-Altman analysis was used to compare common scale scores derived from OKS and HAAS items. A conversion table was developed to map between HAAS, OKS, and the common scale. Results. We included 3,329 response sets from 528 patients undergoing knee arthroplasty. These generally met the assumptions of unidimensionality, monotonicity, local independence, and measurement invariance. The HAAS items provided more information than OKS items at high levels of knee health. Combining both instruments resulted in higher test-level information than either instrument alone. The mean error between common scale scores derived from the OKS and HAAS was 0.29 logits. Conclusion. The common scale allowed more precise measurement of knee health than use of either the OKS or HAAS individually. These techniques for mapping PROM instruments may be useful for the standardization of outcome reporting, and pooling results across studies that use either PROM in individual-patient meta-analysis. Cite this article: Bone Joint Res 2023;12(10):624–635


Bone & Joint Research
Vol. 11, Issue 12 | Pages 854 - 861
1 Dec 2022
Park TJ Park SY Cho W Oh H Lee HJ Abd El-Aty AM Bayram C Jeong JH Jung TW

Aims. Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay. Results. We found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL-1, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3-MA reversed. Conclusion. These results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance. Cite this article: Bone Joint Res 2022;11(12):854–861


Bone & Joint Open
Vol. 5, Issue 5 | Pages 426 - 434
21 May 2024
Phelps EE Tutton E Costa ML Achten J Gibson P Moscrop A Perry DC

Aims. The aim of this study was to explore parents’ experience of their child’s recovery, and their thoughts about their decision to enrol their child in a randomized controlled trial (RCT) of surgery versus non-surgical casting for a displaced distal radius fracture. Methods. A total of 20 parents of children from 13 hospitals participating in the RCT took part in an interview five to 11 months after injury. Interviews were informed by phenomenology and analyzed using thematic analysis. Results. Analysis of the findings identified the theme “being recovered”, which conveyed: 1) parents’ acceptance and belief that their child received the best treatment for them; 2) their memory of the psychological impact of the injury for their child; and 3) their pride in how their child coped with their cast and returned to activities. The process of recovery was underpinned by three elements of experience: accepting the treatment, supporting their child through challenges during recovery, and appreciating their child’s resilience. These findings extend our framework that highlights parents’ desire to protect their child during early recovery from injury, by making the right decision, worrying about recovery, and comforting their child. Conclusion. By one year after injury, parents in both treatment groups considered their child “recovered”. They had overcome early concerns about healing, the appearance of the wrist, and coping after cast removal. Greater educational support for families during recovery would enable parents and their child to cope with the uncertainty of recovery, particularly addressing the loss of confidence, worry about reinjury, and the appearance of their wrist. Cite this article: Bone Jt Open 2024;5(5):426–434


Bone & Joint Research
Vol. 12, Issue 1 | Pages 9 - 21
9 Jan 2023
Lu C Ho C Chen S Liu Z Chou PP Ho M Tien Y

Aims. The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. Methods. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media. Results. Compared to BMSCs-only culture medium, the co-culture medium showed substantially decreased early and late apoptosis rates, attenuation of intrinsic and extrinsic apoptotic pathways, and enhanced proliferation of the hamstring tendons and tenocytes. In addition, the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes in the hamstring tendons and tenocytes significantly increased in the co-culture medium compared to that in the control medium. Conclusion. In the presence of ACLRCs and BMSCs, the hamstring tendons and tenocytes significantly attenuated apoptosis and enhanced the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes. This in vitro study suggests that the ACLRCs mixed with BMSCs could aid regeneration of the hamstring tendon graft during ACL reconstruction. Cite this article: Bone Joint Res 2023;12(1):9–21


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 501 - 507
1 May 2024
Galloway AM Keene DJ Anderson A Holton C Redmond AC Siddle HJ Richards S Perry DC

Aims. The aim of this study was to produce clinical consensus recommendations about the non-surgical treatment of children with Perthes’ disease. The recommendations are intended to support clinical practice in a condition for which there is no robust evidence to guide optimal care. Methods. A two-round, modified Delphi study was conducted online. An advisory group of children’s orthopaedic specialists consisting of physiotherapists, surgeons, and clinical nurse specialists designed a survey. In the first round, participants also had the opportunity to suggest new statements. The survey included statements related to ‘Exercises’, ‘Physical activity’, ‘Education/information sharing’, ‘Input from other services’, and ‘Monitoring assessments’. The survey was shared with clinicians who regularly treat children with Perthes’ disease in the UK using clinically relevant specialist groups and social media. A predetermined threshold of ≥ 75% for consensus was used for recommendation, with a threshold of between 70% and 75% being considered as ‘points to consider’. Results. A total of 40 participants took part in the first round, of whom 31 completed the second round. A total of 87 statements were generated by the advisory group and included in the first round, at the end of which 31 achieved consensus and were removed from the survey, and an additional four statements were generated. A total of 60 statements were included in the second round and 45 achieved the threshold for consensus from both rounds, with three achieving the threshold for ‘points to consider’. The recommendations predominantly included self-management, particularly relating to advice about exercise and education for children with Perthes’ disease and their families. Conclusion. Children’s orthopaedic specialists have reached consensus on recommendations for non-surgical treatment in Perthes’ disease. These statements will support decisions made in clinical practice and act as a foundation to support clinicians in the absence of robust evidence. The dissemination of these findings and the best way of delivering this care needs careful consideration, which we will continue to explore. Cite this article: Bone Joint J 2024;106-B(5):501–507


Bone & Joint Open
Vol. 5, Issue 2 | Pages 94 - 100
5 Feb 2024
Mancino F Kayani B Gabr A Fontalis A Plastow R Haddad FS

Anterior cruciate ligament (ACL) injuries are among the most common and debilitating knee injuries in professional athletes with an incidence in females up to eight-times higher than their male counterparts. ACL injuries can be career-threatening and are associated with increased risk of developing knee osteoarthritis in future life. The increased risk of ACL injury in females has been attributed to various anatomical, developmental, neuromuscular, and hormonal factors. Anatomical and hormonal factors have been identified and investigated as significant contributors including osseous anatomy, ligament laxity, and hamstring muscular recruitment. Postural stability and impact absorption are associated with the stabilizing effort and stress on the ACL during sport activity, increasing the risk of noncontact pivot injury. Female patients have smaller diameter hamstring autografts than males, which may predispose to increased risk of re-rupture following ACL reconstruction and to an increased risk of chondral and meniscal injuries. The addition of an extra-articular tenodesis can reduce the risk of failure; therefore, it should routinely be considered in young elite athletes. Prevention programs target key aspects of training including plyometrics, strengthening, balance, endurance and stability, and neuromuscular training, reducing the risk of ACL injuries in female athletes by up to 90%. Sex disparities in access to training facilities may also play an important role in the risk of ACL injuries between males and females. Similarly, football boots, pitches quality, and football size and weight should be considered and tailored around females’ characteristics. Finally, high levels of personal and sport-related stress have been shown to increase the risk of ACL injury which may be related to alterations in attention and coordination, together with increased muscular tension, and compromise the return to sport after ACL injury. Further investigations are still necessary to better understand and address the risk factors involved in ACL injuries in female athletes. Cite this article: Bone Jt Open 2024;5(2):94–100


Bone & Joint Research
Vol. 12, Issue 3 | Pages 189 - 198
7 Mar 2023
Ruiz-Fernández C Ait Eldjoudi D González-Rodríguez M Cordero Barreal A Farrag Y García-Caballero L Lago F Mobasheri A Sakai D Pino J Gualillo O

Aims. CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Conclusion. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state. Cite this article: Bone Joint Res 2023;12(3):189–198


Bone & Joint Research
Vol. 11, Issue 9 | Pages 652 - 668
7 Sep 2022
Lv G Wang B Li L Li Y Li X He H Kuang L

Aims. Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Methods. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot. Results. DC-exo inhibited macrophage autophagy (p = 0.002) and promoted M1 macrophage polarization (p = 0.002). DC-exo at 20 μg/ml induced collagen degradation (p < 0.001) and inflammatory cell infiltration (p = 0.023) in rats. OANCT was elevated in DC (p < 0.001) and in cartilage tissues of OA patients (p < 0.001), and positively correlated with patients’ Kellgren-Lawrence grade (p < 0.001). PIK3R5 was increased in DC-exo-treated cartilage tissues (p < 0.001), and OANCT bound to fat mass and obesity-associated protein (FTO) (p < 0.001). FTO bound to PIK3R5 (p < 0.001) to inhibit the stability of PIK3R5 messenger RNA (mRNA) (p < 0.001) and disrupt the PI3K/AKT/mTOR pathway (p < 0.001). Conclusion. Exosomal OANCT from DC could bind to FTO protein, thereby maintaining the mRNA stability of PIK3R5, further activating the PI3K/AKT/mTOR pathway to exacerbate OA. Cite this article: Bone Joint Res 2022;11(9):652–668


Bone & Joint Research
Vol. 12, Issue 5 | Pages 339 - 351
23 May 2023
Tan J Liu X Zhou M Wang F Ma L Tang H He G Kang X Bian X Tang K

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351


Bone & Joint Research
Vol. 12, Issue 3 | Pages 165 - 177
1 Mar 2023
Boyer P Burns D Whyne C

Aims. An objective technological solution for tracking adherence to at-home shoulder physiotherapy is important for improving patient engagement and rehabilitation outcomes, but remains a significant challenge. The aim of this research was to evaluate performance of machine-learning (ML) methodologies for detecting and classifying inertial data collected during in-clinic and at-home shoulder physiotherapy exercise. Methods. A smartwatch was used to collect inertial data from 42 patients performing shoulder physiotherapy exercises for rotator cuff injuries in both in-clinic and at-home settings. A two-stage ML approach was used to detect out-of-distribution (OOD) data (to remove non-exercise data) and subsequently for classification of exercises. We evaluated the performance impact of grouping exercises by motion type, inclusion of non-exercise data for algorithm training, and a patient-specific approach to exercise classification. Algorithm performance was evaluated using both in-clinic and at-home data. Results. The patient-specific approach with engineered features achieved the highest in-clinic performance for differentiating physiotherapy exercise from non-exercise activity (area under the receiver operating characteristic (AUROC) = 0.924). Including non-exercise data in algorithm training further improved classifier performance (random forest, AUROC = 0.985). The highest accuracy achieved for classifying individual in-clinic exercises was 0.903, using a patient-specific method with deep neural network model extracted features. Grouping exercises by motion type improved exercise classification. For at-home data, OOD detection yielded similar performance with the non-exercise data in the algorithm training (fully convolutional network AUROC = 0.919). Conclusion. Including non-exercise data in algorithm training improves detection of exercises. A patient-specific approach leveraging data from earlier patient-supervised sessions should be considered but is highly dependent on per-patient data quality. Cite this article: Bone Joint Res 2023;12(3):165–177


Bone & Joint Research
Vol. 13, Issue 4 | Pages 157 - 168
4 Apr 2024
Lin M Chen G Yu H Hsu P Lee C Cheng C Wu S Pan B Su B

Aims. Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. Methods. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry. Results. Benzamil suppressed growth of osteosarcoma cells by inducing apoptosis. Benzamil reduced the expression of cell surface integrins α5, αV, and β1 in MG63 cells, while it only reduced the expression of αV in U2OS cells. Benzamil suppressed the phosphorylation and activation of FAK and STAT3. In addition, mitochondrial function and ATP production were compromised by benzamil. The levels of anti-apoptotic proteins XIAP, Bcl-2, and Bcl-xL were reduced by benzamil. Correspondingly, benzamil potentiated cisplatin- and methotrexate-induced apoptosis in osteosarcoma cells. Conclusion. Benzamil exerts anti-osteosarcoma activity by inducing apoptosis. In terms of mechanism, benzamil appears to inhibit integrin/FAK/STAT3 signalling, which triggers mitochondrial dysfunction and ATP depletion. Cite this article: Bone Joint Res 2024;13(4):157–168


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1273 - 1283
1 Nov 2024
Mahmud H Wang D Topan-Rat A Bull AMJ Heinrichs CH Reilly P Emery R Amis AA Hansen UN

Aims. The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids. Methods. Intact right cadaveric shoulders from donors aged between 50 and 65 years were assigned to a ceramic group (n = 8, four male cadavers) and a metal group (n = 9, four male cadavers). A dedicated shoulder wear simulator was used to simulate daily activity by replicating the relevant joint motion and loading profiles. During testing, the joint was kept lubricated with diluted calf serum at room temperature. Each test of wear was performed for 500,000 cycles at 1.2 Hz. At intervals of 125,000 cycles, micro-CT scans of each glenoid were taken to characterize and quantify glenoid wear by calculating the change in the thickness of its articular cartilage. Results. At the completion of the wear test, the total thickness of the cartilage had significantly decreased in both the ceramic and metal groups, by 27% (p = 0.019) and 29% (p = 0.008), respectively. However, the differences between the two were not significant (p = 0.606) and the patterns of wear in the specimens were unpredictable. No significant correlation was found between cartilage wear and various factors, including age, sex, the size of the humeral head, joint mismatch, the thickness of the native cartilage, and the surface roughness (all p > 0.05). Conclusion. Although ceramic has better tribological properties than metal, we did not find evidence that its use in hemiarthroplasty of the shoulder in patients with healthy cartilage is a better alternative than conventional metal humeral heads. Cite this article: Bone Joint J 2024;106-B(11):1273–1283


Bone & Joint Open
Vol. 5, Issue 9 | Pages 799 - 805
24 Sep 2024
Fletcher WR Collins T Fox A Pillai A

Aims. The Cartiva synthetic cartilage implant (SCI) entered mainstream use in the management of first metatarsophalangeal joint (MTPJ) arthritis following the positive results of large trials in 2016. Limited information is available on the longer-term outcomes of this implant within the literature, particularly when independent from the originator. This single-centre cohort study investigates the efficacy of the Cartiva SCI at up to five years. Methods. First MTPJ arthritis was radiologically graded according to the Hattrup and Johnson (HJ) classification. Preoperative and sequential postoperative patient-reported outcome measures (PROMs) were evaluated using the Manchester-Oxford Foot Questionnaire (MOXFQ), and the activities of daily living (ADL) sub-section of the Foot and Ankle Ability Measure (FAAM). Results. Patients were followed up for a mean of 66 months (SD 7.1). Of an initial 66 cases, 16 did not return PROM questionnaires. A total of six failures were noted, with survival of 82%. Overall, significant improvement in both objective scores (MOXFQ and FAAM ADL) was maintained versus preoperatively: 18.2 versus 58.0 (p > 0.001) and 86.2 versus 41.1 (p > 0.001), respectively. The improvement was noted to be less pronounced in males. Subjective scores had deteriorated since early follow-up, with an interval decrease in patient satisfaction from 89% to 68%. Furthermore, a subset of cases demonstrated clinically important interval deterioration in objective scores. However, no specific patient factors were found to be associated with outcomes following analysis. Conclusion. This study represents the longest-term independent follow-up in the literature. It shows reassuring mid-term efficacy of the Cartiva SCI with better-than-expected survival. However, deterioration in scores for a subset of patients and lower satisfaction may predict ongoing failure in this group of patients. Additionally, males were noted to have a lower degree of improvement in scores than females. As such, ongoing observation of the SCI to assess durability and survivability, and identify predictive factors, is key to improving patient selection. Cite this article: Bone Jt Open 2024;5(9):799–805


Bone & Joint Open
Vol. 5, Issue 7 | Pages 543 - 549
3 Jul 2024
Davies AR Sabharwal S Reilly P Sankey RA Griffiths D Archer S

Aims. Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients’ decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods. Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results. Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants’ symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion. Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands. Cite this article: Bone Jt Open 2024;5(7):543–549


Bone & Joint Open
Vol. 4, Issue 2 | Pages 87 - 95
10 Feb 2023
Deshmukh SR Kirkham JJ Karantana A

Aims. The aim of this study was to develop a core outcome set of what to measure in all future clinical research on hand fractures and joint injuries in adults. Methods. Phase 1 consisted of steps to identify potential outcome domains through systematic review of published studies, and exploration of the patient perspective through qualitative research, consisting of 25 semi-structured interviews and five focus groups. Phase 2 involved key stakeholder groups (patients, hand surgeons, and hand therapists) prioritizing the outcome domains via a three-round international Delphi survey, with a final consensus meeting to agree the final core outcome set. Results. The systematic review of 160 studies identified 74 outcome domains based on the World Health Organization International Classification of Functioning, Disability, and Health. Overall, 35 domains were generated through thematic analysis of the patient interviews and focus groups. The domains from these elements were synthesised to develop 37 outcome domains as the basis of the Delphi survey, with a further four generated from participant suggestions in Round 1. The Delphi survey identified 20 outcome domains as ‘very important’ for the core outcome set. At the consensus meeting, 27 participants from key stakeholder groups selected seven outcomes for the core outcome set: pain/discomfort with activity, pain/discomfort with rest, fine hand use/dexterity, self-hygiene/personal care, return to usual work/job, range of motion, and patient satisfaction with outcome/result. Conclusion. This set of core outcome domains is recommended as a minimum to be reported in all clinical research on hand fractures and joint injuries in adults. While this establishes what to measure, future work will focus on determining how best to measure these outcomes. By adopting this patient-centred core outcome set, consistency and comparability of studies will be improved, aiding meta-analysis and strengthening the evidence base for management of these common and impactful injuries. Cite this article: Bone Jt Open 2023;4(2):87–95


Aims. The aim of this study was to compare the preinjury functional scores with the postinjury preoperative score and postoperative outcome scores following anterior cruciate ligament (ACL) reconstruction surgery (ACLR). Methods. We performed a prospective study on patients who underwent primary ACLR by a single surgeon at a single centre between October 2010 and January 2018. Preoperative preinjury scores were collected at time of first assessment after the index injury. Preoperative (pre- and post-injury), one-year, and two-year postoperative functional outcomes were assessed by using the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score, and Tegner Activity Scale. Results. We enrolled 308 males and 263 females of mean age 27 years (19 to 46). The mean preinjury and preoperative post-injury Lysholm Knee Scores were 94 (73 to 100) and 63 (25 to 85), respectively, while the respective mean scores at one and two years postoperatively were 84 (71 to 100) and 89 (71 to 100; p < 0.001). The mean Tegner preinjury and preoperative post-injury scores were 7 (3 to 9) and 3 (0 to 6), respectively, while the respective mean scores at one and two years postoperatively were 6 (1 to 8) and 6 (1 to 9) (p < 0.001). The mean KOOS scores at preinjury versus two years postoperatively were: symptoms (96 vs 84); pain (94 vs 87); activities of daily living (97 vs 91), sports and recreation function (84 vs 71), and quality of life (82 vs 69), respectively (p < 0.001). Conclusion. Functional scores improved following ACLR surgery at two years in comparison to preoperative post-injury scores. However, at two-year follow-up, the majority of patients failed to achieve their preinjury scores. The evaluation of ACLR outcomes needs to consider the preinjury scores rather than the immediate preoperative score that is usually collected. Cite this article: Bone Jt Open 2023;4(1):46–52


The Bone & Joint Journal
Vol. 106-B, Issue 5 | Pages 442 - 449
1 May 2024
Nieboer MF van der Jagt OP de Munter L de Jongh MAC van de Ree CLP

Aims. Periprosthetic proximal femoral fractures (PFFs) are a major complication after total hip arthroplasty (THA). Health status after PFF is not specifically investigated. The aim of this study is to evaluate the health status pattern over two years after sustaining a PFF. Methods. A cohort of patients with PFF after THA was derived from the Brabant Injury Outcomes Surveillance (BIOS) study. The BIOS study, a prospective, observational, multicentre follow-up cohort study, was conducted to obtain data by questionnaires pre-injury and at one week, and one, three, six, 12, and 24 months after trauma. Primary outcome measures were the EuroQol five-dimension three-level questionnaire (EQ-5D-3L), the Health Utility Index 2 (HUI2), and the Health Utility Index 3 (HUI3). Secondary outcome measures were general measurements such as duration of hospital stay and mortality. Results. A total of 70 patients with a PFF were included. EQ-5D utility scores were significantly lower on all timepoints except at six months’ follow-up compared to pre-injury. EuroQol visual analogue scale (EQ-VAS) scores at one month's follow-up were significantly lower compared to pre-injury. The percentage of reported problems at two years was higher for all dimensions except anxiety/depression when compared to pre-injury. The mean EQ-5D utility score was 0.26 higher in males compared to females (95% confidence interval (CI) 0.01 to 0.42; p = 0.003). The mean EQ-VAS score for males was 8.9 points higher when compared to females over all timepoints (95% CI 1.2 to 16.7; p = 0.027). Mortality was 10% after two years’ follow-up. Conclusion. PFF patients are a frail population with substantial functional impairment at baseline. Post-injury, they have a significant and clinically relevant lower health status two years after trauma when compared to pre-injury. Health status improves the most between one and three months after injury. Two years after PFF, more patients experience problems in mobility, self-care, usual activities, and pain/discomfort than pre-injury. Cite this article: Bone Joint J 2024;106-B(5):442–449


The Bone & Joint Journal
Vol. 105-B, Issue 10 | Pages 1052 - 1059
1 Oct 2023
El-Sahoury JAN Kjærgaard K Ovesen O Hofbauer C Overgaard S Ding M

Aims. The primary outcome was investigating differences in wear, as measured by femoral head penetration, between cross-linked vitamin E-diffused polyethylene (vE-PE) and cross-linked polyethylene (XLPE) acetabular component liners and between 32 and 36 mm head sizes at the ten-year follow-up. Secondary outcomes included acetabular component migration and patient-reported outcome measures (PROMs) such as the EuroQol five-dimension questionnaire, 36-Item Short-Form Health Survey, Harris Hip Score, and University of California, Los Angeles Activity Scale (UCLA). Methods. A single-blinded, multi-arm, 2 × 2 factorial randomized controlled trial was undertaken. Patients were recruited between May 2009 and April 2011. Radiostereometric analyses (RSAs) were performed from baseline to ten years. Of the 220 eligible patients, 116 underwent randomization, and 82 remained at the ten-year follow-up. Eligible patients were randomized into one of four interventions: vE-PE acetabular liner with either 32 or 36 mm femoral head, and XLPE acetabular liner with either 32 or 36 mm femoral head. Parameters were otherwise identical except for acetabular liner material and femoral head size. Results. A total of 116 patients participated, of whom 77 were male. The median ages of the vE-PE 32 mm and 36 mm groups were 65 (interquartile range (IQR) 57 to 67) and 63 years (IQR 56 to 66), respectively, and of the XLPE 32 mm and 36 mm groups were 64 (IQR 58 to 66) and 61 years (IQR 54 to 66), respectively. Mean total head penetration was significantly lower into vE-PE acetabular liner groups than into XLPE acetabular liner groups (-0.219 mm (95% confidence interval -0.348 to -0.090); p = 0.001). There were no differences in wear according to head size, acetabular component migration, or PROMs, except for UCLA. There were no cases of aseptic loosening or failures requiring revision at long-term follow-up. Conclusion. Significantly lower wear was observed in vE-PE acetabular liners than in XLPE acetabular liners. No difference in wear was observed between different head size or PROMs except for the UCLA at ten years. Cite this article: Bone Joint J 2023;105-B(10):1052–1059


Bone & Joint Research
Vol. 12, Issue 3 | Pages 212 - 218
9 Mar 2023
Buchalter DB Kirby DJ Anil U Konda SR Leucht P

Aims. Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. Methods. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia. Results. GIK treatment resulted in a significant protection of skeletal muscle with increased viability (GIK 22.07% (SD 15.48%)) compared to saline control (control 3.14% (SD 3.29%)) (p = 0.005). Additionally, GIK led to a statistically significant reduction in gene expression markers of cell death (CASP3, p < 0.001) and inflammation (NOS2, p < 0.001; IGF1, p = 0.007; IL-1β, p = 0.002; TNFα, p = 0.012), and a significant reduction in serum creatine kinase (p = 0.004) and creatinine (p < 0.001). GIK led to a significant reduction in IR-related pain (p = 0.030). Conclusion. Systemic GIK infusion during and after limb ischaemia protects murine skeletal muscle from cell death, kidneys from reperfusion metabolites, and reduces pain by reducing post-ischaemic inflammation. Cite this article: Bone Joint Res 2023;12(3):212–218


Bone & Joint Open
Vol. 4, Issue 2 | Pages 53 - 61
1 Feb 2023
Faraj S de Windt TS van Hooff ML van Hellemondt GG Spruit M

Aims. The aim of this study was to assess the clinical and radiological results of patients who were revised using a custom-made triflange acetabular component (CTAC) for component loosening and pelvic discontinuity (PD) after previous total hip arthroplasty (THA). Methods. Data were extracted from a single centre prospective database of patients with PD who were treated with a CTAC. Patients were included if they had a follow-up of two years. The Hip Disability and Osteoarthritis Outcome Score (HOOS), modified Oxford Hip Score (mOHS), EurQol EuroQoL five-dimension three-level (EQ-5D-3L) utility, and Numeric Rating Scale (NRS), including visual analogue score (VAS) for pain, were gathered at baseline, and at one- and two-year follow-up. Reasons for revision, and radiological and clinical complications were registered. Trends over time are described and tested for significance and clinical relevance. Results. A total of 18 females with 22 CTACs who had a mean age of 73.5 years (SD 7.7) were included. A significant improvement was found in HOOS (p < 0.0001), mOHS (p < 0.0001), EQ-5D-3L utility (p = 0.003), EQ-5D-3L NRS (p = 0.013), VAS pain rest (p = 0.008), and VAS pain activity (p < 0.0001) between baseline and final follow-up. Minimal clinically important improvement in mOHS and the HOOS Physical Function Short Form (HOOS-PS) was observed in 16 patients (73%) and 14 patients (64%), respectively. Definite healing of the PD was observed in 19 hips (86%). Complications included six cases with broken screws (27%), four cases (18%) with bony fractures, and one case (4.5%) with sciatic nerve paresthesia. One patient with concurrent bilateral PD had revision surgery due to recurrent dislocations. No revision surgery was performed for screw failure or implant breakage. Conclusion. CTAC in patients with THA acetabular loosening and PD can result in stable constructs and significant improvement in functioning and health-related quality of life at two years' follow-up. Further follow-up is necessary to determine the mid- to long-term outcome. Cite this article: Bone Jt Open 2023;4(2):53–61


Bone & Joint Research
Vol. 13, Issue 7 | Pages 332 - 341
5 Jul 2024
Wang T Yang C Li G Wang Y Ji B Chen Y Zhou H Cao L

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341


Bone & Joint Research
Vol. 12, Issue 1 | Pages 22 - 32
11 Jan 2023
Boschung A Faulhaber S Kiapour A Kim Y Novais EN Steppacher SD Tannast M Lerch TD

Aims. Femoroacetabular impingement (FAI) patients report exacerbation of hip pain in deep flexion. However, the exact impingement location in deep flexion is unknown. The aim was to investigate impingement-free maximal flexion, impingement location, and if cam deformity causes hip impingement in flexion in FAI patients. Methods. A retrospective study involving 24 patients (37 hips) with FAI and femoral retroversion (femoral version (FV) < 5° per Murphy method) was performed. All patients were symptomatic (mean age 28 years (SD 9)) and had anterior hip/groin pain and a positive anterior impingement test. Cam- and pincer-type subgroups were analyzed. Patients were compared to an asymptomatic control group (26 hips). All patients underwent pelvic CT scans to generate personalized CT-based 3D models and validated software for patient-specific impingement simulation (equidistant method). Results. Mean impingement-free flexion of patients with mixed-type FAI (110° (SD 8°)) and patients with pincer-type FAI (112° (SD 8°)) was significantly (p < 0.001) lower compared to the control group (125° (SD 13°)). The frequency of extra-articular subspine impingement was significantly (p < 0.001) increased in patients with pincer-type FAI (57%) compared to cam-type FAI (22%) in 125° flexion. Bony impingement in maximal flexion was located anterior-inferior at femoral four and five o’clock position in patients with cam-type FAI (63% (10 of 16 hips) and 37% (6 of 10 hips)), and did not involve the cam deformity. The cam deformity did not cause impingement in maximal flexion. Conclusion. Femoral impingement in maximal flexion was located anterior-inferior distal to the cam deformity. This differs to previous studies, a finding which could be important for FAI patients in order to avoid exacerbation of hip pain in deep flexion (e.g. during squats) and for hip arthroscopy (hip-preservation surgery) for planning of bone resection. Hip impingement in flexion has implications for daily activities (e.g. putting on shoes), sports, and sex. Cite this article: Bone Joint Res 2023;12(1):22–32


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims. Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. Methods. The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Results. Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Conclusion. Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis. Cite this article: Bone Joint Res 2023;12(11):677–690


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 573 - 581
1 Jun 2024
van Houtert WFC Strijbos DO Bimmel R Krijnen WP Jager J van Meeteren NLU van der Sluis G

Aims. To investigate the impact of consecutive perioperative care transitions on in-hospital recovery of patients who had primary total knee arthroplasty (TKA) over an 11-year period. Methods. This observational cohort study used electronic health record data from all patients undergoing preoperative screening for primary TKA at a Northern Netherlands hospital between 2009 and 2020. In this timeframe, three perioperative care transitions were divided into four periods: Baseline care (Joint Care, n = 171; May 2009 to August 2010), Function-tailored (n = 404; September 2010 to October 2013), Fast-track (n = 721; November 2013 to May 2018), and Prehabilitation (n = 601; June 2018 to December 2020). In-hospital recovery was measured using inpatient recovery of activities (IROA), length of stay (LOS), and discharge to preoperative living situation (PLS). Multivariable regression models were used to analyze the impact of each perioperative care transition on in-hospital recovery. Results. The four periods analyzed involved 1,853 patients (65.9% female (1,221/1,853); mean age 70.1 years (SD 9.0)). IROA improved significantly with each transition: Function-tailored (0.9 days; p < 0.001 (95% confidence interval (CI) -0.32 to -0.15)), Fast-track (0.6 days; p < 0.001 (95% CI -0.25 to -0.16)), and Prehabilitation (0.4 days; p < 0.001 (95% CI -0.18 to -0.10)). LOS decreased significantly in Function-tailored (1.1 days; p = 0.001 (95% CI -0.30 to -0.06)), Fast-track (0.6 days; p < 0.001 (95% CI -0.21 to -0.05)), and Prehabilitation (0.6 days; p < 0.001 (95%CI -0.27 to -0.11)). Discharge to PLS increased in Function-tailored (77%), Fast-track (91.6%), and Prehabilitation (92.6%). Post-hoc analysis indicated a significant increase after the transition to the Fast-track period (p < 0.001 (95% CI 3.19 to 8.00)). Conclusion. This study highlights the positive impact of different perioperative care procedures on in-hospital recovery of patients undergoing primary TKA. Assessing functional recovery, LOS, and discharge towards PLS consistently, provides hospitals with valuable insights into postoperative recovery. This can potentially aid planning and identifying areas for targeted improvements to optimize patient outcomes. Cite this article: Bone Joint J 2024;106-B(6):573–581