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Bone & Joint Research
Vol. 14, Issue 2 | Pages 124 - 135
20 Feb 2025
Huang J Zheng J Yin J Lin R Wu J Xu H Zhu J Zhang H Wang G Cai D

Aims. To examine how eukaryotic translation initiation factor 5A (eIF5A) regulates osteoarthritis (OA) during mechanical overload and the specific mechanism. Methods. Histological experiments used human bone samples and C57BL/6J mice knee samples. All cell experiments were performed using mice primary chondrocytes. Messenger RNA (mRNA) sequencing was performed on chondrocytes treated with 20% cyclic tensile strain for 24 hours. Western blot (WB) and quantitative polymerase chain reaction were employed to detect relevant indicators of cartilage function in chondrocytes. We created the destabilization of the medial meniscus (DMM) model and the mechanical overload-induced OA model and injected with overexpressing eIF5A adenovirus (eIF5A-ADV). Cartilage degeneration was evaluated using Safranin O/Fast Green staining. Relative protein levels were ascertained by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Results. After OA initiation, eIF5A caused an upregulation of type II collagen (COL2) and a downregulation of matrix metalloproteinase 13 (MMP13), P16, and P21, which postponed the aggravation of OA. Further sequencing and experimental findings revealed that eIF5A knockdown accelerated the progression of OA by boosting the expression of histone acetyltransferase cyclic-adenosine monophosphate response element binding protein (CREB)-binding protein (CREBBP) to mediate activation of the Notch pathway. Conclusion. Our findings identified a crucial functional mechanism for the onset of OA, and suggest that intra-articular eIF5A injections might be a useful therapeutic strategy for OA treatment. Cite this article: Bone Joint Res 2025;14(2):124–135


Bone & Joint Research
Vol. 14, Issue 2 | Pages 136 - 142
20 Feb 2025
Walter N Loew T Hinterberger T Mohokum M Alt V Rupp M

Aims. Fracture-related infections (FRIs) are a major concern for patients and healthcare systems, yet their impact on mental health has been largely overlooked. This study aimed to assess the longitudinal impact of FRI on patients’ quality of life. Methods. A prospective study was conducted at a level 1 trauma centre between January 2020 and December 2022. In total, 56 patients participated, with quality of life assessed at five timepoints: one week preoperatively, and one, three, six, and 12 months postoperatively. Statistical analysis was performed using repeated measures analysis of variance (ANOVA) with adjusted post-hoc analysis. Results. The preoperative Physical Component Summary score on the 36-Item Short-Form Health Survey questionnaire (SF-36) was 26.71, increasing to 30.40 at one month, remaining stable at three months. A modest increase was observed at six months (32.45, p = 0.003), but it decreased to 29.72 at 12 months. The preoperative Mental Component Summary score (SF-36) was 46.48, decreasing to 39.89 at one month (p = 0.027) and to 36.03 at three months (p ≤ 0.001). However, it improved at six (42.74) and 12 months (44.05). Positive changes were seen in EuroQol five-dimension questionnaire (EQ-5D) subdimensions, such as mobility, self-care, usual activities, and pain/discomfort, while anxiety/depression scores decreased over time. The EQ-5D visual analogue scale (VAS) score increased to 62.79 at six months (p ≤ 0.001) and decreased to 58.2 at 12 months (p = 0.011). Conclusion. FRIs substantially affect mental health and quality of life, particularly during the initial three months of treatment. This study emphasizes the importance of addressing psychological aspects early in FRI management, advocating for holistic care encompassing both physical and psychological aspects of treatment. Cite this article: Bone Joint Res 2025;14(2):136–142


Bone & Joint Open
Vol. 6, Issue 2 | Pages 206 - 214
18 Feb 2025
Iken AR Gademan MGJ Snoeker BAM Vliet Vlieland TPM Poolman RW

Aims

To develop a multidisciplinary health research agenda (HRA) utilizing expertise from various disciplines to identify and prioritize evidence uncertainties in orthopaedics, thereby reducing research waste.

Methods

We employed a novel, structured framework to develop a HRA. We started by systematically collecting all evidence uncertainties from stakeholders with an interest in orthopaedic care, categorizing them into 13 sub-themes defined by the Dutch Orthopaedic Association (NOV). Subsequently, a modified two-phased Delphi study (two rounds per phase), adhering to the Conducting and REporting DElphi Studies (CREDES) guideline, was conducted. In Phase 1, board members assessed the collected evidence uncertainties on a three-point Likert scale to confirm knowledge gaps. In Phase 2, diverse stakeholders, including orthopaedic surgeons, rated the confirmed knowledge gaps on a seven-point Likert scale. Panel members rated one self-selected sub-theme and two randomly assigned sub-themes. The results from Phase 2 were ranked based on the overall average score for each uncertainty. Finally, a focus group discussion with patient associations’ representatives identified their top-ranked uncertainty from a predefined consensus process, leading to the final HRA. An advisory board, the Federation of Medical Specialists, and the NOV research coordinator oversaw the process.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 111 - 123
18 Feb 2025
Wang J Shan L Hang J Li H Meng Y Cao W Gu C Dai J Tao L

Aims

We aimed to develop and validate a novel prediction model for osteoporosis based on serotonin, fat-soluble vitamins, and bone turnover markers to improve prediction accuracy of osteoporosis.

Methods

Postmenopausal women aged 55 to 65 years were recruited and divided into three groups based on DXA (normal, osteopenia, and osteoporosis). A total of 109 participants were included in this study and split into healthy (39/109, 35.8%), osteopenia (35/109, 32.1%), and osteoporosis groups (35/109, 32.1%). Serum concentrations of serotonin, fat-soluble vitamins, and bone turnover markers of participants were measured. Stepwise discriminant analysis was performed to identify efficient predictors for osteoporosis. The prediction model was developed based on Bayes and Fisher’s discriminant functions, and validated via leave-one-out cross-validation. Normal and empirical volume under the receiver operating characteristic (ROC) surface (VUS) tests were used to evaluate predictive effects of variables in the prediction model.


Bone & Joint Open
Vol. 6, Issue 2 | Pages 195 - 205
14 Feb 2025
Selim A Dass D Govilkar S Brown AJ Bonde S Burston B Thomas G

Aims

The conversion of previous hip fracture surgery to total hip arthroplasty (CTHA) can be surgically challenging with unpredictable outcomes; reported complication rates vary significantly. This study aimed to establish the medium-term survival and outcomes of CTHA performed following a previous hip fracture surgery.

Methods

All CTHAs performed at our tertiary orthopaedic institution between January 2008 and January 2020 following previous ipsilateral hip fracture surgery were included. Patients were followed up clinically using Oxford Hip Scores (OHS), and radiologically until death or revision surgery. Postoperative complications, radiological implant failure, and indications for revision surgery were reviewed.


Bone & Joint Open
Vol. 6, Issue 2 | Pages 186 - 194
13 Feb 2025
Battaglia AG D'Apolito R Ding BTK Tonolini S Ramazzotti J Zagra L

Aims. Revision hip arthroplasty for femoral stem loosening remains challenging due to significant bone loss and deformities requiring specialized revision stems. The aim of this study was to evaluate the clinical and radiological outcomes, and survival, of a consecutive series of femoral revisions performed using a primary cementless stem with tapered geometry and rectangular cross-section at medium-term follow-up. Methods. We retrospectively evaluated 113 patients (115 hips) with intraoperative Paprosky type I (n = 86) or II (n = 29) defects, who underwent femoral revision with Alloclassic Zweymüller SL stem for one-stage aseptic revision or two-stage septic revision from January 2011 to December 2020. The mean follow-up was 77.9 months (SD 33.8). Nine patients were lost to follow-up (deceased or not available), leaving 104 patients (106 hips) for the clinical and radiological analysis. Clinical assessment was performed with Harris Hip Score (HHS) and visual analogue scale (VAS) before surgery and at final follow-up. Results. There were 60 males and 53 females with a mean age at time of surgery of 71.2 years (SD 12.6). The mean HHS and VAS significantly improved at final follow-up, from 33.7 (SD 13.0) and 5.8 (SD 1.8) preoperatively to 66.4 (SD 16.8) and 2.1 (SD 1.8) postoperatively, respectively (p = 0.001 and p = 0.001). Overall, 28 patients (25%) showed non-progressive radiolucent lines at the level of proximal femur without radiological or clinical signs of loosening. One patient had a recurrence of periprosthetic joint infection after a two-stage procedure requiring re-revision surgery. One patient underwent exchange of modular components for recurrent dislocation, and another case of dislocation was treated conservatively. The survival with aseptic loosening as endpoint was 100%, while stem revision for any reason was 99.1% at up to 152 months’ follow-up. Conclusion. Alloclassic Zweymüller SL primary stem showed favourable medium-term results and survival for revision total hip arthroplasty in Paprosky type I and II defects. Cite this article: Bone Jt Open 2025;6(2):186–194


Bone & Joint Open
Vol. 6, Issue 2 | Pages 164 - 177
10 Feb 2025
Clement ND Scott CEH Macpherson GJ Simpson PM Leitch G Patton JT

Aims

Unicompartmental knee arthroplasty (UKA) is associated with an accelerated recovery, improved functional outcomes, and retention of anatomical knee kinematics when compared to manual total knee arthroplasty (mTKA). UKA is not universally employed by all surgeons as there is a higher revision risk when compared to mTKA. Robotic arm-assisted (ra) UKA enables the surgeon to position the prosthesis more accurately when compared to manual UKA, and is associated with improved functional outcomes and a lower early revision risk. Non-randomized data suggests that, when compared to mTKA, raUKA has a clinically meaningful greater functional benefit. This protocol describes a randomized controlled trial that aims to evaluate the clinical and cost-effectiveness of raUKA compared to mTKA for individuals with isolated medial compartment osteoarthritis (OA).

Methods

The total versus robotic-assisted unicompartmental knee arthroplasty (TRAKER) trial is a patient- and assessor-blinded, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary knee arthroplasty for primary medial compartment OA at a single NHS hospital (ClinicalTrials.gov NCT05290818). Participants will be randomly allocated on a 1:2 basis to either raUKA or mTKA, respectively. The primary analysis will compare the Oxford Knee Score (OKS) six months after surgery. Secondary outcomes measured at three, six, and 12 months include the OKS, Forgotten Joint Score, patient expectations, EuroQol five-dimension questionnaire (EQ-5D), and EQ-visual analogue scale (EQ-VAS), patient satisfaction, range of motion, postoperative complications, need for further surgery, resource use, and financial costs. Cost-effectiveness will be measured over a ten-year time span. A total of 159 patients will be randomized (n = 53 raUKA vs n = 106 mTKA) to obtain 80% power to detect a five-point difference in OKS between the groups six months after surgery.


Bone & Joint Open
Vol. 6, Issue 2 | Pages 147 - 154
7 Feb 2025
Clement ND Qaddoura B Coppola A Akram N Pendyala S Jones S Afzal I Kader DF

Aims

Control of acute pain following knee arthroplasty (KA) with a perioperative peripheral nerve block (PNB) may improve functional outcomes and reduce the risk of chronic postoperative knee pain (CPKP). The aims of this study were to assess whether a PNB influences patient-reported outcomes and risk of CPKP at one year following KA.

Methods

A retrospective study was conducted over a two-year period and included 3,338 patients who underwent KA, of whom 1,434 (43.0%) had a lower limb PNB. A total of 2,588 patients (77.6%) completed and returned their one-year follow-up questionnaire. The Oxford Knee Score (OKS) and pain component (OKS-PS), EuroQol five-dimension questionnaire (EQ-5D), and EQ-visual analogue scale (VAS) were collected preoperatively and at one year postoperatively. Patient satisfaction was also recorded at one year. The OKS-PS was used to define CPKP at one year.


Bone & Joint Research
Vol. 14, Issue 2 | Pages 93 - 96
6 Feb 2025
Wignadasan W Fontalis A Shaeir M Haddad FS


Bone & Joint Research
Vol. 14, Issue 2 | Pages 97 - 110
6 Feb 2025
Zhang D Zhu T Bai J Chen C Wen J Zhou Y Guan X

Aims. In our previous research, we have found that melatonin (MEL) affects the osteoporotic process. By balancing bone remoulding, autophagy is involved in age-related bone loss. However, as a regulator of autophagy, whether MEL influences senile osteoporosis via regulating autophagy remains unclear. Methods. Cellular, radiological, and histopathological evaluations were performed on 36 16-month-old male C57BL6/L mice or aged bone marrow-derived mesenchymal stem cells. A MEL-gelatin methacrylamide system was constructed to aid osteoporotic fracture healing. Results. In this study, we found that bone loss, low level of MEL, and decreased autophagy coexisted in aged C57BL6/L mice. A physiological (low, 10 nM but not 100 nM) concentration of MEL restored bone loss, transformed the cytokine framework, and increased the autophagic level in aged mice, whereas inhibition of autophagy unfavourably reduced the positive effects of MEL on bone mass. The autophagy-conducted increased osteogenic lineage commitment and extracellular matrix mineralization, but not matrix synthesis of aged bone marrow-derived mesenchymal stem cells, was responsible for MEL anabolic effects on bone. PIK3C-AKT-MTOR signal was tested to be a main pathway that is involved in MEL-induced autophagy. Conclusion. Our data suggest that the application of MEL can restore degenerative osteogenesis of aged bone marrow-derived mesenchymal stem cells, and has the potential to regain bone mass in aged mice through activating autophagy via the PIK3C-AKT-MTOR pathway. MEL therefore may serve as a potential clinical therapy to treat senile osteoporosis. Cite this article: Bone Joint Res 2025;14(2):97–110


Bone & Joint Research
Vol. 14, Issue 2 | Pages 77 - 92
4 Feb 2025
Spanninga BJ Hoelen TA Johnson S Cheng B Blokhuis TJ Willems PC Arts JJC

Aims

Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system.

Methods

PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 268 - 276
1 Feb 2025
Hedley PL Lausten-Thomsen U Conway KM Hindsø K Romitti PA Christiansen M

Aims

In this study, we aimed to evaluate incidence trends and potential risk factors associated with Perthes’ disease in Denmark, using publicly available data.

Methods

Our population-based case-control study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,924,292 infants born between 1985 and 2016. We estimated age-specific incidence rates for four birth periods of equal duration (1985 to 1992, 1993 to 2000, 2001 to 2008, and 2009 to 2016) and investigated associations with perinatal conditions, congenital malformations, coagulation defects, autism spectrum disorders (ASD), and attention deficit hyperactivity disorders (ADHD).


Aims

Sagittal lumbar pelvic alignment alters with posterior pelvic tilt (PT) following total hip arthroplasty (THA) for developmental dysplasia of the hip (DDH). The individual value of pelvic sagittal inclination (PSI) following rebalancing of lumbar-pelvic alignment is unknown. In different populations, PT regresses in a linear relationship with pelvic incidence (PI). PSI and PT have a direct relationship to each other via a fixed individual angle ∠γ. This study aimed to investigate whether the new PI created by acetabular component positioning during THA also has a linear regression relationship with PT/PSI when lumbar-pelvic alignment rebalances postoperatively in patients with Crowe type III/IV DDH.

Methods

Using SPINEPARA software, we measured the pelvic sagittal parameters including PI, PT, and PSI in 61 patients with Crowe III/IV DDH. Both PSI and PT represent the pelvic tilt state, and the difference between their values is ∠γ (PT = PSI + ∠γ). The regression equation between PI and PT at one year after THA was established. By substituting ∠γ, the relationship between PI and PSI was also established. The Bland-Altman method was used to evaluate the consistency between the PSI calculated by the linear regression equation (ePSI) and the actual PSI (aPSI) measured one year postoperatively.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 139 - 148
1 Feb 2025
Goh EL Khatri A Costa AB Ting A Steiner K Png ME Metcalfe D Cook JA Costa ML

Aims

Older adults with hip fractures are at high risk of experiencing complications after surgery, but estimates of the rate of specific complications vary by study design and follow-up period. The aim of this systematic review was to determine the prevalence of complications in older adults after hip fracture surgery.

Methods

MEDLINE, Embase, CINAHL, and CENTRAL databases were searched from inception until 30 June 2023. Studies were included if they reported prevalence data of complications in an unselected, consecutive population of older adults (aged ≥ 60 years) undergoing hip fracture surgery.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 239 - 245
1 Feb 2025
Evenhuis RE Bus MPA van Nes J Walter SG Cabrolier J Fiocco M van der Wal RJP Broekhuis D Sellevold S van de Sande MAJ

Aims

Over time, the locking mechanism of Modular Universal Tumour and Revision System (MUTARS) knee arthroplasties changed from polyethylene (PE) to polyether-ether-ketone Optima (PEEK) and metal-on-metal (MoM) in an attempt to reduce the risk of mechanical failure. In this study, we aimed to assess the cumulative incidence of locking mechanism revision for symptomatic instability by type of material, and assess potential associated risk factors.

Methods

The MUTARS Orthopaedic Registry Europe was used for a retrospective review of 316 patients (54% male (n = 170), median age 44 years (IQR 23 to 61)) who underwent a MUTARS knee arthroplasty for oncological indications between December 1995 and January 2023. The minimum follow-up was 12 months, and the median follow-up was 7.9 years (IQR 3.3 to 13.0). A competing risk model was used to estimate the cumulative incidence of first locking mechanism revision with death and revision for any other reason as competing events. Possible risk factors were assessed employing a univariate cause-specific hazards regression model.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 246 - 252
1 Feb 2025
Jeys LM Morris GV Kurisunkal VJ Botello E Boyle RA Ebeid W Houdek MT Puri A Ruggieri P Brennan B Laitinen MK

Aims

The Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma.

Methods

With representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting’s process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries. Supported by major orthopaedic oncology organizations, the meeting used a modified Delphi process to develop consensus statements through online questionnaires, thematic groupings, narrative reviews, and anonymous pre-meeting polling.


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 135 - 138
1 Feb 2025
Costa ML Greenwood C Nixon J

Hip fractures commonly occur in older patients, with high levels of frailty and comorbidity. Many of these patients have limited mobility before their fracture, and even after surgery, their mobility may remain limited. It is therefore not surprising that they are at a high risk of developing pressure sores, particularly on their heels, and a variety of devices and interventions have been proposed to reduce this risk. Foam or air mattresses, designed to reduce contact pressure on the patient’s whole body, are now routinely used in many healthcare systems. However, there is wide variation in their design. We developed the WHiTE 14;PRESSURE 3 trial to address the lack of evidence in this area. This is a three-arm multicentre randomized trial including health economic evaluation and recruiting patients from NHS hospitals in the UK. The trial compares standard strategies for the prevention of pressure sores with standard care plus a constant low-pressure device and with standard care plus a heel off-loading device. This annotation describes the development of this trial. Cite this article: Bone Joint J 2025;107-B(2):135–138


The Bone & Joint Journal
Vol. 107-B, Issue 2 | Pages 261 - 267
1 Feb 2025
Theunissen WWES van der Steen MC Klerkx T Schonck C Besselaar AT van Douveren FQMP Tolk JJ

Aims

Worldwide controversy exists on the optimal treatment of stable dysplastic hips. The most common treatment options are abduction brace treatment and active surveillance. The primary aim of this study was to assess the effect of active surveillance in stable hip dysplasia, by investigating the percentage of Graf IIb stable dysplastic hips that recover spontaneously without abduction brace treatment. The second aim was to identify prognostic factors for spontaneous recovery of stable dysplastic hips.

Methods

A single-centre, prospective cohort study was conducted at the Máxima Medical Center between 1 March 2019 and 1 March 2023. Infants aged three to 4.5 months at the first outpatient clinic visit, diagnosed with Graf IIb hip dysplasia, and treated with active surveillance were included. Spontaneous recovery was defined as infants who had a normalized hip on ultrasound (α-angle ≥ 60°) after six weeks of active surveillance without receiving abduction brace treatment. Baseline infant characteristics and ultrasound measurements were used as potential predictor variables for spontaneous recovery in logistic regression analyses.


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

Aims

The development of lumbar lordosis has been traditionally examined using angular measurements of the spine to reflect its shape. While studies agree regarding the increase in the angles during growth, the growth rate is understudied, and sexual dimorphism is debated. In this study, we used a novel method to estimate the shape of the lumbar curve (LC) using the landmark-based geometric morphometric method to explore changes in LC during growth, examine the effect of size and sex on LC shape, and examine the associations between angular measurements and shape.

Methods

The study population included 258 children aged between 0 and 20 years (divided into five age groups) who underwent a CT scan between the years 2009 and 2019. The landmark-based geometric morphometric method was used to capture the LC shape in a sagittal view. Additionally, the lordosis was measured via Cobb and sacral slope angles. Multivariate and univariate statistical analyses were carried out to examine differences in shape between males and females and between the age groups.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 46 - 57
24 Jan 2025
Abdulhadi Alagha M Cobb J Liddle AD Malchau H Rolfson O Mohaddes M

Aims

While cementless fixation offers potential advantages over cemented fixation, such as a shorter operating time, concerns linger over its higher cost and increased risk of periprosthetic fractures. If the risk of fracture can be forecasted, it would aid the shared decision-making process related to cementless stems. Our study aimed to develop and validate predictive models of periprosthetic femoral fracture (PPFF) necessitating revision and reoperation after elective total hip arthroplasty (THA).

Methods

We included 154,519 primary elective THAs from the Swedish Arthroplasty Register (SAR), encompassing 21 patient-, surgical-, and implant-specific features, for model derivation and validation in predicting 30-day, 60-day, 90-day, and one-year revision and reoperation due to PPFF. Model performance was tested using the area under the curve (AUC), and feature importance was identified in the best-performing algorithm.