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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 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 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.


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.


Bone & Joint Research
Vol. 14, Issue 1 | Pages 42 - 45
21 Jan 2025
Fontalis A Wignadasan W Kayani B Haddad FS


Bone & Joint Research
Vol. 14, Issue 1 | Pages 20 - 32
17 Jan 2025
Chen Z Zhou T Yin Z Duan P Zhang Y Feng Y Shi R Xu Y Pang R Tan H

Aims. Magnesium ions (Mg. 2+. ) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg. 2+. combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg. 2+. in cartilage repair. Methods. A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg. 2+. treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg. 2+. was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results. The histological results showed that the 0.5 mol/L Mg. 2+. group had deeper positive staining in haematoxylin-eosin (H&E), safranin O, Alcian blue, and type II collagen staining. The new cartilage coverage in the injury area was more complete, and the regeneration of hyaline cartilage was higher. The RT-qPCR results showed that sirtuin 1/bone morphogenetic protein-2/sex-determining region Y box 9 (SIRT1/BMP-2/SOX-9) and hypoxia-inducible factor 1-alpha (HIF-1α) messenger RNA levels were up-regulated after Mg. 2+. injection. Conclusion. MFX combined with Mg. 2+. treatment has a positive effect on cartilage repair. The Mg. 2+. injection dose of 0.5 mol/L is most effective in enhancing microfracture-mediated cartilage repair. Cite this article: Bone Joint Res 2025;14(1):20–32


Bone & Joint Research
Vol. 14, Issue 1 | Pages 16 - 19
15 Jan 2025
Jones S Tyson S


Bone & Joint Research
Vol. 14, Issue 1 | Pages 5 - 15
1 Jan 2025
Tanveer M Klein K von Rechenberg B Darwiche S Dailey HL

Aims

The “2 to 10% strain rule” for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.

Methods

MicroCT scans of eight female sheep with plated mid-shaft tibial osteotomies were used to create image-based finite element models. Virtual mechanical testing was used to compute postoperative gap-closing and 3D continuum strains representing compression (volumetric strain) and shear deformation (distortional strain). Callus mineralization was measured in zones in and around the osteotomy gap.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 790 - 792
17 Dec 2024
Mangwani J Brockett C Pegg E

Cite this article: Bone Joint Res 2024;13(12):790–792.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 779 - 789
16 Dec 2024
Zou H Hu F Wu X Xu B Shang G An D Qin D Zhang X Yang A

Aims. The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis. Methods. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments. Results. LINC01089 expression was reinforced in serum samples of OP patients, but it gradually diminished while hMSCs underwent osteogenic differentiation. LINC01089 knockdown facilitated hMSC osteogenic differentiation. This was substantiated by: the increase in ALP activity; ALP, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) messenger RNA (mRNA) levels; and level of ARS staining. Meanwhile, LINC01089 upregulation resulted in the opposite effects. LINC01089 targeted miR-1287-5p, and the LINC01089 knockdown-induced hMSC osteogenic differentiation was repressed by miR-1287-5p depletion. HSPA4 is a downstream function molecule of the LINC01089/miR-1287-5p pathway; miR-1287-5p negatively modulated HSPA4 levels and attenuated its functional effects. Conclusion. LINC01089 negatively regulated hMSC osteogenic differentiation, at least in part, via governing miR-1287-5p/HSPA4 signalling. These findings provide new insights into hMSC osteogenesis and bone metabolism. Cite this article: Bone Joint Res 2024;13(12):779–789


Bone & Joint Research
Vol. 13, Issue 12 | Pages 764 - 778
12 Dec 2024
Huang Q Zhuo Y Duan Z Long Y Wang J Zhang Z Fan S Huang Y Deng K Xin H

Aims

Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.

Methods

In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 750 - 763
11 Dec 2024
Xie C Gong J Zheng C Zhang J Gao J Tian C Guo X Dai S Gao T

Aims

This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.

Methods

The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment.

Cite this article: Bone Joint Res 2024;13(12):725–740.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 716 - 724
4 Dec 2024
Cao S Chen Y Zhu Y Jiang S Yu Y Wang X Wang C Ma X

Aims

This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation.

Methods

A total of 16 subjects with CAI (eight without OLT and eight with OLT) and eight healthy subjects underwent gait analysis in a stair descent setting. Inverse dynamic analysis was applied to ground reaction forces and marker trajectories using the AnyBody Modeling System. One-dimensional statistical parametric mapping was performed to compare ankle joint reaction force and joint moment curve among groups.


Bone & Joint Research
Vol. 13, Issue 12 | Pages 703 - 715
3 Dec 2024
Raza IGA Snelling SJB Mimpen JY

Aims

Extracellular matrix (ECM) is a critical determinant of tissue mechanobiology, yet remains poorly characterized in joint tissues beyond cartilage in osteoarthritis (OA). This review aimed to define the composition and architecture of non-cartilage soft joint tissue structural ECM in human OA, and to compare the changes observed in humans with those seen in animal models of the disease.

Methods

A systematic search strategy, devised using relevant matrix, tissue, and disease nomenclature, was run through the MEDLINE, Embase, and Scopus databases. Demographic, clinical, and biological data were extracted from eligible studies. Bias analysis was performed.