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Bone & Joint Research
Vol. 12, Issue 3 | Pages 155 - 164
1 Mar 2023
McCarty CP Nazif MA Sangiorgio SN Ebramzadeh E Park S

Aims. Taper corrosion has been widely reported to be problematic for modular total hip arthroplasty implants. A simple and systematic method to evaluate taper damage with sufficient resolution is needed. We introduce a semiquantitative grading system for modular femoral tapers to characterize taper corrosion damage. Methods. After examining a unique collection of retrieved cobalt-chromium (CoCr) taper sleeves (n = 465) using the widely-used Goldberg system, we developed an expanded six-point visual grading system intended to characterize the severity, visible material loss, and absence of direct component contact due to corrosion. Female taper sleeve damage was evaluated by three blinded observers using the Goldberg scoring system and the expanded system. A subset (n = 85) was then re-evaluated following destructive cleaning, using both scoring systems. Material loss for this subset was quantified using metrology and correlated with both scoring systems. Results. There was substantial agreement in grading among all three observers with uncleaned (n = 465) and with the subset of cleaned (n = 85) implants. The expanded scoring criteria provided a wider distribution of scores which ultimately correlated well with corrosion material loss. Cleaning changed the average scores marginally using the Goldberg criteria (p = 0.290); however, using the VGS, approximately 40% of the scores for all observers changed, increasing the average score from 4.24 to 4.35 (p = 0.002). There was a strong correlation between measured material loss and new grading scores. Conclusion. The expanded scoring criteria provided a wider distribution of scores which ultimately correlated well with corrosion material loss. This system provides potential advantages for assessing taper damage without requiring specialized imaging devices. Cite this article: Bone Joint Res 2023;12(3):155–164


Bone & Joint Open
Vol. 2, Issue 7 | Pages 503 - 508
8 Jul 2021
Callaghan CJ McKinley JC

Aims. Arthroplasty has become increasingly popular to treat end-stage ankle arthritis. Iatrogenic posterior neurovascular and tendinous injury have been described from saw cuts. However, it is hypothesized that posterior ankle structures could be damaged by inserting tibial guide pins too deeply and be a potential cause of residual hindfoot pain. Methods. The preparation steps for ankle arthroplasty were performed using the Infinity total ankle system in five right-sided cadaveric ankles. All tibial guide pins were intentionally inserted past the posterior tibial cortex for assessment. All posterior ankles were subsequently dissected, with the primary endpoint being the presence of direct contact between the structure and pin. Results. All pin locations confer a risk of damaging posterior ankle structures, with all posterior ankle structures except the flexor hallucis longus tendon being contacted by at least one pin. Centrally-aligned transcortical pins were more likely to contact posteromedial neurovascular structures. Conclusion. These findings support our hypothesis that tibial guide pins pose a considerable risk of contacting and potentially damaging posterior ankle structures during ankle arthroplasty. This study is the first of its kind to assess this risk in the Infinity total ankle system. Cite this article: Bone Jt Open 2021;2(7):503–508


Bone & Joint Research
Vol. 8, Issue 2 | Pages 65 - 72
1 Feb 2019
Cowie RM Aiken SS Cooper JJ Jennings LM

Objectives. Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation. Methods. A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry. Results. There was no significant difference (p  >  0.05) between the wear rate of implants challenged with CS-BVF (3.3 mm. 3. /MC (95% confidence interval (CI) 1.8 to 4.8)) and the wear rate of those not challenged (2.8 mm. 3. /MC (95% CI 1.3 to 4.3)). However, scratching the cobalt-chrome (CoCr) significantly (p < 0.001) increased the wear rate (20.6 mm. 3. /MC (95% CI 15.5 to 25.7)). The mean surface roughness of implants challenged with CS-BVF was equivalent to negative controls both after damage simulation (p = 0.98) and at the conclusion of the study (p = 0.28). Conclusion. When used close to articulating surfaces, a low-hardness, high-purity CS-BVF had no influence on wear. When trapped between the articulating surfaces of a total knee arthroplasty, CS-BVF did not scratch the surface of CoCr femoral components, nor did it increase the wear of UHMWPE tibial inserts compared with undamaged negative controls. Cite this article: R. M. Cowie, S. S. Aiken, J. J. Cooper, L. M. Jennings. The influence of a calcium sulphate bone void filler on the third-body damage and polyethylene wear of total knee arthroplasty. Bone Joint Res 2019;8:65–72. DOI: 10.1302/2046-3758.82.BJR-2018-0146.R1


Bone & Joint Research
Vol. 6, Issue 4 | Pages 253 - 258
1 Apr 2017
Hsu C Lin C Jou I Wang P Lee J

Objectives. Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the human population. Recently, increased concentration of nitric oxide in serum and synovial fluid in patients with OA has been observed. However, the exact role of nitric oxide in the initiation of OA has not been elucidated. The aim of the present study was to investigate the role of nitric oxide in innate immune regulation during OA initiation in rats. Methods. Rat OA was induced by performing meniscectomy surgery while cartilage samples were collected 0, 7, and 14 days after surgery. Cartilage cytokine levels were determined by using enzyme-linked immunosorbent assay, while other proteins were assessed by using Western blot. Results. In the time course of the study, nitric oxide was increased seven and 14 days after OA induction. Pro-inflammatory cytokines including tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were decreased. L-NG-Nitroarginine methyl ester (L-NAME, a non-specific nitric oxide synthase inhibitor) significantly decreased cartilage nitric oxide and blocked immune suppression. Further, L-NAME decreased Matrix metalloproteinase (MMPs) and increased tissue inhibitor of metalloproteinase (TIMP) expression in meniscectomised rats. Conclusion. Nitric oxide-dependent innate immune suppression protects cartilage from damage in the early stages of OA initiation in rats. Cite this article: C-C. Hsu, C-L. Lin, I-M. Jou, P-H. Wang, J-S. Lee. The protective role of nitric oxide-dependent innate immunosuppression in the early stage of cartilage damage in rats: Role of nitric oxide in ca rtilage da mage. Bone Joint Res 2017;6:253–258. DOI: 10.1302/2046-3758.64.BJJ-2016-0161.R1


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims. Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA). Methods. Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers. Results. The 29-mer promoted expansion and chondrogenic differentiation of BM-MSCs cultured in different defined media. MIA injection caused chondrocyte death throughout the AC, with cartilage degeneration thereafter. The 29-mer/HA treatment induced extensive chondrocyte regeneration in the damaged AC and suppressed MIA-induced synovitis, accompanied by the recovery of cartilage matrix. Pharmacological inhibitors of PEDF receptor (PEDFR) and signal transducer and activator of transcription 3 (STAT3) signalling substantially blocked the chondrogenic promoting activity of 29-mer on the cultured BM-MSCs and injured AC. Conclusion. The 29-mer/HA formulation effectively induces chondrocyte regeneration and formation of cartilage matrix in the damaged AC. Cite this article: Bone Joint Res 2024;13(4):137–148


Bone & Joint Research
Vol. 11, Issue 8 | Pages 594 - 607
17 Aug 2022
Zhou Y Li J Xu F Ji E Wang C Pan Z

Aims. Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Methods. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro. Results. IL-38 was highly expressed in lentivirus vector-mediated OA mice. Meanwhile, injection of exogenous IL-38 to OA mice alleviated the cartilage damage, and reduced the levels of proinflammatory factors and chondrocyte apoptosis. TP53 was responsible for lncRNA H19-mediated upregulation of IL-38. Furthermore, it was found that the anti-inflammatory effects of IL-38 were achieved by its binding with the IL-36 receptor (IL-36R). Overexpression of H19 reduced the expression of inflammatory factors and chondrocyte apoptosis, which was abrogated by knockdown of IL-38 or TP53. Conclusion. Collectively, our findings evidenced that upregulation of lncRNA H19 attenuates inflammation and ameliorates cartilage damage and chondrocyte apoptosis in OA by upregulating TP53, IL-38, and by activating IL-36R. Cite this article: Bone Joint Res 2022;11(8):594–607


Bone & Joint Open
Vol. 3, Issue 5 | Pages 348 - 358
1 May 2022
Stokes S Drozda M Lee C

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review


Bone & Joint Research
Vol. 13, Issue 7 | Pages 362 - 371
17 Jul 2024
Chang H Liu L Zhang Q Xu G Wang J Chen P Li C Guo X Yang Z Zhang F

Aims. The metabolic variations between the cartilage of osteoarthritis (OA) and Kashin-Beck disease (KBD) remain largely unknown. Our study aimed to address this by conducting a comparative analysis of the metabolic profiles present in the cartilage of KBD and OA. Methods. Cartilage samples from patients with KBD (n = 10) and patients with OA (n = 10) were collected during total knee arthroplasty surgery. An untargeted metabolomics approach using liquid chromatography coupled with mass spectrometry (LC-MS) was conducted to investigate the metabolomics profiles of KBD and OA. LC-MS raw data files were converted into mzXML format and then processed by the XCMS, CAMERA, and metaX toolbox implemented with R software. The online Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to annotate the metabolites by matching the exact molecular mass data of samples with those from the database. Results. A total of 807 ion features were identified for KBD and OA, including 577 positive (240 for upregulated and 337 for downregulated) and 230 negative (107 for upregulated and 123 for downregulated) ions. After annotation, LC-MS identified significant expressions of ten upregulated and eight downregulated second-level metabolites, and 183 upregulated and 162 downregulated first-level metabolites between KBD and OA. We identified differentially expressed second-level metabolites that are highly associated with cartilage damage, including dimethyl sulfoxide, uric acid, and betaine. These metabolites exist in sulphur metabolism, purine metabolism, and glycine, serine, and threonine metabolism. Conclusion. This comprehensive comparative analysis of metabolism in OA and KBD cartilage provides new evidence of differences in the pathogenetic mechanisms underlying cartilage damage in these two conditions. Cite this article: Bone Joint Res 2024;13(7):362–371


Bone & Joint Research
Vol. 13, Issue 9 | Pages 513 - 524
19 Sep 2024
Kalsoum R Minns Lowe CJ Gilbert S McCaskie AW Snow M Wright K Bruce G Mason DJ Watt FE

Aims. To explore key stakeholder views around feasibility and acceptability of trials seeking to prevent post-traumatic osteoarthritis (PTOA) following knee injury, and provide guidance for next steps in PTOA trial design. Methods. Healthcare professionals, clinicians, and/or researchers (HCP/Rs) were surveyed, and the data were presented at a congress workshop. A second and related survey was then developed for people with joint damage caused by knee injury and/or osteoarthritis (PJDs), who were approached by a UK Charity newsletter or Oxford involvement registry. Anonymized data were collected and analyzed in Qualtrics. Results. Survey responses (n = 19 HCP/Rs, 39 PJDs) supported studies testing pharmacological agents preventing PTOA. All HCP/Rs and 30/31 (97%) PJDs supported the development of new treatments that improved or delayed knee symptoms and damage to knee structure. PJDs thought that improving structural knee damage was more important than knee symptoms. Both groups found studies more acceptable as expected future benefit and risk of PTOA increased. All drug delivery routes were acceptable. Workshop participants (around n = 60) reflected survey views. Discussions suggested that stratifying using molecular testing for likely drug response appeared to be more acceptable than using characteristics such as sex, age, and BMI. Conclusion. Our findings supported PTOA drug intervention studies, including situations where there is low risk of disease, no expected benefit of treatment, and frequent treatment administration. PJDs appeared less risk-averse than HCP/Rs. This work reinforces the benefits of consensus and involvement work in the co-creation of PTOA drug trial design. Involvement of key stakeholders, such as PJDs with different risks of OA and regulatory representatives, are critical for trial design success. Cite this article: Bone Joint Res 2024;13(9):513–524


Bone & Joint Open
Vol. 5, Issue 6 | Pages 514 - 523
24 Jun 2024
Fishley W Nandra R Carluke I Partington PF Reed MR Kramer DJ Wilson MJ Hubble MJW Howell JR Whitehouse SL Petheram TG Kassam AM

Aims. In metal-on-metal (MoM) hip arthroplasties and resurfacings, mechanically induced corrosion can lead to elevated serum metal ions, a local inflammatory response, and formation of pseudotumours, ultimately requiring revision. The size and diametral clearance of anatomical (ADM) and modular (MDM) dual-mobility polyethylene bearings match those of Birmingham hip MoM components. If the acetabular component is satisfactorily positioned, well integrated into the bone, and has no surface damage, this presents the opportunity for revision with exchange of the metal head for ADM/MDM polyethylene bearings without removal of the acetabular component. Methods. Between 2012 and 2020, across two centres, 94 patients underwent revision of Birmingham MoM hip arthroplasties or resurfacings. Mean age was 65.5 years (33 to 87). In 53 patients (56.4%), the acetabular component was retained and dual-mobility bearings were used (DM); in 41 (43.6%) the acetabulum was revised (AR). Patients underwent follow-up of minimum two-years (mean 4.6 (2.1 to 8.5) years). Results. In the DM group, two (3.8%) patients underwent further surgery: one (1.9%) for dislocation and one (1.9%) for infection. In the AR group, four (9.8%) underwent further procedures: two (4.9%) for loosening of the acetabular component and two (4.9%) following dislocations. There were no other dislocations in either group. In the DM group, operating time (68.4 vs 101.5 mins, p < 0.001), postoperative drop in haemoglobin (16.6 vs 27.8 g/L, p < 0.001), and length of stay (1.8 vs 2.4 days, p < 0.001) were significantly lower. There was a significant reduction in serum metal ions postoperatively in both groups (p < 0.001), although there was no difference between groups for this reduction (p = 0.674 (cobalt); p = 0.186 (chromium)). Conclusion. In selected patients with Birmingham MoM hips, where the acetabular component is well-fixed and in a satisfactory position with no surface damage, the metal head can be exchanged for polyethylene ADM/MDM bearings with retention of the acetabular prosthesis. This presents significant benefits, with a shorter procedure and a lower risk of complications. Cite this article: Bone Jt Open 2024;5(6):514–523


Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. Methods. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD. Results. A correlation between DDIT4 expression levels and disc degeneration was shown with human nucleus pulposus and needle-punctured rat disc specimens. We confirmed that DDIT4 was responsible for activating the ROS-TXNIP-NLRP3 axis during oxidative stress-induced pyroptosis in rat nucleus pulposus in vitro. Mitochondria were damaged during oxidative stress, and DDIT4 contributed to mitochondrial damage and ROS production. In addition, siDDIT4@G5-P-HA hydrogels showed good delivery activity of siDDIT4 to NPCs. In vitro studies illustrated the potential of the siDDIT4@G5-P-HA hydrogel for alleviating IVDD in rats. Conclusion. DDIT4 is a key player in mediating pyroptosis and IVDD in NPCs through the ROS-TXNIP-NLRP3 axis. Additionally, siDDIT4@G5-P-HA hydrogel has been found to relieve IVDD in rats. Our research offers an innovative treatment option for IVDD. Cite this article: Bone Joint Res 2024;13(5):247–260


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


Aims. This study investigated vancomycin-microbubbles (Vm-MBs) and meropenem (Mp)-MBs with ultrasound-targeted microbubble destruction (UTMD) to disrupt biofilms and improve bactericidal efficiency, providing a new and promising strategy for the treatment of device-related infections (DRIs). Methods. A film hydration method was used to prepare Vm-MBs and Mp-MBs and examine their characterization. Biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were treated with different groups. Biofilm biomass differences were determined by staining. Thickness and bacterial viability were observed with confocal laser scanning microscope (CLSM). Colony counts were determined by plate-counting. Scanning electron microscopy (SEM) observed bacterial morphology. Results. The Vm-MBs and Mp-MBs met the experimental requirements. The biofilm biomass in the Vm, Vm-MBs, UTMD, and Vm-MBs + UTMD groups was significantly lower than in the control group. MRSA and E. coli biofilms were most notably damaged in the Vm-MBs + UTMD group and Mp-MBs + UTMD group, respectively, with mean 21.55% (SD 0.08) and 19.73% (SD 1.25) remaining in the biofilm biomass. Vm-MBs + UTMD significantly reduced biofilm thickness and bacterial viability (p = 0.005 and p < 0.0001, respectively). Mp-MBs + UTMD could significantly decrease biofilm thickness and bacterial viability (allp < 0.001). Plate-counting method showed that the numbers of MRSA and E. coli bacterial colonies were significantly lower in the Vm-MBs + UTMD group and the Mp, Mp-MBs, UTMD, Mp-MBs + UTMD groups compared to the control group (p = 0.031). SEM showed that the morphology and structure of MRSA and E. coli were significantly damaged in the Vm-MBs + UTMD and Mp-MBs + UTMD groups. Conclusion. Vm-MBs or Mp-MBs combined with UTMD can effectively disrupt biofilms and protectively release antibiotics under ultrasound mediation, significantly reducing bacterial viability and improving the bactericidal effect of antibiotics. Cite this article: Bone Joint Res 2024;13(9):441–451


Bone & Joint Research
Vol. 13, Issue 7 | Pages 342 - 352
9 Jul 2024
Cheng J Jhan S Chen P Hsu S Wang C Moya D Wu Y Huang C Chou W Wu K

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352


Bone & Joint Research
Vol. 13, Issue 5 | Pages 214 - 225
3 May 2024
Groven RVM Kuik C Greven J Mert Ü Bouwman FG Poeze M Blokhuis TJ Huber-Lang M Hildebrand F Cillero-Pastor B van Griensven M

Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225


Bone & Joint Open
Vol. 2, Issue 11 | Pages 1004 - 1016
26 Nov 2021
Wight CM Whyne CM Bogoch ER Zdero R Chapman RM van Citters DW Walsh WR Schemitsch E

Aims. This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads. Methods. In all, six 28 mm and six 36 mm titanium stem-cobalt chrome head pairs with polyethylene sockets were tested in a novel instrumented hip simulator. Samples were tested using simulated gait data with incremental increasing loads to determine corrosion onset load and electrochemical activity. Half of each head size group were then cycled with simulated gait and the other half with gait compression only. Damage was measured by area and maximum linear wear depth. Results. Overall, 36 mm heads had lower corrosion onset load (p = 0.009) and change in open circuit potential (OCP) during simulated gait with (p = 0.006) and without joint movement (p = 0.004). Discontinuing gait’s joint movement decreased corrosion currents (p = 0.042); however, wear testing showed no significant effect of joint movement on taper damage. In addition, 36 mm heads had greater corrosion area (p = 0.050), but no significant difference was found for maximum linear wear depth (p = 0.155). Conclusion. Larger heads are more susceptible to taper corrosion; however, not due to frictional torque as hypothesized. An alternative hypothesis of taper flexural rigidity differential is proposed. Further studies are necessary to investigate the clinical significance and underlying mechanism of this finding. Cite this article: Bone Jt Open 2021;2(11):1004–1016


Bone & Joint Research
Vol. 12, Issue 4 | Pages 259 - 273
6 Apr 2023
Lu R Wang Y Qu Y Wang S Peng C You H Zhu W Chen A

Aims. Osteoarthritis (OA) is a prevalent joint disorder with inflammatory response and cartilage deterioration as its main features. Dihydrocaffeic acid (DHCA), a bioactive component extracted from natural plant (gynura bicolor), has demonstrated anti-inflammatory properties in various diseases. We aimed to explore the chondroprotective effect of DHCA on OA and its potential mechanism. Methods. In vitro, interleukin-1 beta (IL-1β) was used to establish the mice OA chondrocytes. Cell counting kit-8 evaluated chondrocyte viability. Western blotting analyzed the expression levels of collagen II, aggrecan, SOX9, inducible nitric oxide synthase (iNOS), IL-6, matrix metalloproteinases (MMPs: MMP1, MMP3, and MMP13), and signalling molecules associated with nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Immunofluorescence analysis assessed the expression of aggrecan, collagen II, MMP13, and p-P65. In vivo, a destabilized medial meniscus (DMM) surgery was used to induce mice OA knee joints. After injection of DHCA or a vehicle into the injured joints, histological staining gauged the severity of cartilage damage. Results. DHCA prevented iNOS and IL-6 from being upregulated by IL-1β. Moreover, the IL-1β-induced upregulation of MMPs could be inhibited by DHCA. Additionally, the administration of DHCA counteracted IL-1β-induced downregulation of aggrecan, collagen II, and SOX9. DHCA protected articular cartilage by blocking the NF-κB and MAPK pathways. Furthermore, DHCA mitigated the destruction of articular cartilage in vivo. Conclusion. We present evidence that DHCA alleviates inflammation and cartilage degradation in OA chondrocytes via suppressing the NF-κB and MAPK pathways, indicating that DHCA may be a potential agent for OA treatment. Cite this article: Bone Joint Res 2023;12(4):259–273


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

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


Bone & Joint Research
Vol. 13, Issue 10 | Pages 546 - 558
4 Oct 2024
Li Y Wuermanbieke S Wang F Mu W Ji B Guo X Zou C Chen Y Zhang X Cao L

Aims. The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. Methods. A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated. Results. Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion. IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use. Cite this article: Bone Joint Res 2024;13(10):546–558


Bone & Joint Research
Vol. 13, Issue 6 | Pages 272 - 278
5 Jun 2024
Niki Y Huber G Behzadi K Morlock MM

Aims. Periprosthetic fracture and implant loosening are two of the major reasons for revision surgery of cementless implants. Optimal implant fixation with minimal bone damage is challenging in this procedure. This pilot study investigates whether vibratory implant insertion is gentler compared to consecutive single blows for acetabular component implantation in a surrogate polyurethane (PU) model. Methods. Acetabular components (cups) were implanted into 1 mm nominal under-sized cavities in PU foams (15 and 30 per cubic foot (PCF)) using a vibratory implant insertion device and an automated impaction device for single blows. The impaction force, remaining polar gap, and lever-out moment were measured and compared between the impaction methods. Results. Impaction force was reduced by 89% and 53% for vibratory insertion in 15 and 30 PCF foams, respectively. Both methods positioned the component with polar gaps under 2 mm in 15 PCF foam. However, in 30 PCF foam, the vibratory insertion resulted in a clinically undesirable polar gap of over 2 mm. A higher lever-out moment was achieved with the consecutive single blow insertion by 42% in 15 PCF and 2.7 times higher in 30 PCF foam. Conclusion. Vibratory implant insertion may lower periprosthetic fracture risk by reducing impaction forces, particularly in low-quality bone. Achieving implant seating using vibratory insertion requires adjustment of the nominal press-fit, especially in denser bone. Further preclinical testing on real bone tissue is necessary to assess whether its viscoelasticity in combination with an adjusted press-fit can compensate for the reduced primary stability after vibratory insertion observed in this study. Cite this article: Bone Joint Res 2024;13(6):272–278


Bone & Joint Open
Vol. 3, Issue 10 | Pages 804 - 814
13 Oct 2022
Grammatopoulos G Laboudie P Fischman D Ojaghi R Finless A Beaulé PE

Aims. The primary aim of this study was to determine the ten-year outcome following surgical treatment for femoroacetabular impingement (FAI). We assessed whether the evolution of practice from open to arthroscopic techniques influenced outcomes and tested whether any patient, radiological, or surgical factors were associated with outcome. Methods. Prospectively collected data of a consecutive single-surgeon cohort, operated for FAI between January 2005 and January 2015, were retrospectively studied. The cohort comprised 393 hips (365 patients; 71% male (n = 278)), with a mean age of 34.5 years (SD 10.0). Over the study period, techniques evolved from open surgical dislocation (n = 94) to a combined arthroscopy-Hueter technique (HA + Hueter; n = 61) to a pure arthroscopic technique (HA; n = 238). Outcome measures of interest included modes of failures, complications, reoperation, and patient-reported outcome measures (PROMs). Demographic, radiological, and surgical factors were tested for possible association with outcome. Results. At a mean follow-up of 7.5 years (SD 2.5), there were 43 failures in 38 hips (9.7%), with 35 hips (8.9%) having one failure mode, one hip (0.25%) having two failure modes, and two hips (0.5%) having three failure modes. The five- and ten-year hip joint preservation rates were 94.1% (SD 1.2%; 95% confidence interval (CI) 91.8 to 96.4) and 90.4% (SD 1.7%; 95% CI 87.1 to 93.7), respectively. Inferior survivorship was detected in the surgical dislocation group. Age at surgery, Tönnis grade, cartilage damage, and absence of rim-trimming were associated with improved preservation rates. Only Tönnis grade was an independent predictor of hip preservation. All PROMs improved postoperatively. Factors associated with improvement in PROMs included higher lateral centre-edge and α angles, and lower retroversion index and BMI. Conclusion. FAI surgery provides lasting improvement in function and a joint preservation rate of 90.4% at ten years. The evolution of practice was not associated with inferior outcome. Since degree of arthritis is the primary predictor of outcome, improved awareness and screening may lead to prompt intervention and better outcomes. Cite this article: Bone Jt Open 2022;3(10):804–814


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

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


Bone & Joint Open
Vol. 5, Issue 4 | Pages 343 - 349
22 Apr 2024
Franssen M Achten J Appelbe D Costa ML Dutton S Mason J Gould J Gray A Rangan A Sheehan W Singh H Gwilym SE

Aims. Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods. The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion. The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England – Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024. Cite this article: Bone Jt Open 2024;5(4):343–349


Bone & Joint Research
Vol. 11, Issue 12 | Pages 881 - 889
1 Dec 2022
Gómez-Barrena E Padilla-Eguiluz N López-Marfil M Ruiz de la Reina R

Aims. Successful cell therapy in hip osteonecrosis (ON) may help to avoid ON progression or total hip arthroplasty (THA), but the achieved bone regeneration is unclear. The aim of this study was to evaluate amount and location of bone regeneration obtained after surgical injection of expanded autologous mesenchymal stromal cells from the bone marrow (BM-hMSCs). Methods. A total of 20 patients with small and medium-size symptomatic stage II femoral head ON treated with 140 million BM-hMSCs through percutaneous forage in the EudraCT 2012-002010-39 clinical trial were retrospectively evaluated through preoperative and postoperative (three and 12 months) MRI. Then, 3D reconstruction of the original lesion and the observed postoperative residual damage after bone regeneration were analyzed and compared per group based on treatment efficacy. Results. The mean preoperative lesion volume was 18.7% (SD 10.2%) of the femoral head. This reduced to 11.6% (SD 7.5%) after three months (p = 0.015) and 3.7% (SD 3%) after one year (p < 0.001). Bone regeneration in healed cases represented a mean 81.2% (SD 13.8%) of the initial lesion volume at one year. Non-healed cases (n = 1 stage progression; n = 3 THAs) still showed bone regeneration but this did not effectively decrease the ON volume. A lesion size under mean 10% (SD 6%) of the femoral head at three months predicted no ON stage progression at one year. Regeneration in the lateral femoral head (C2 under Japanese Investigation Committee (JCI) classification) and in the central and posterior regions of the head was predominant in cases without ON progression. Conclusion. Bone regeneration was observed in osteonecrotic femoral heads three months after expanded autologous BM-hMSC injection, and the volume and location of regeneration indicated the success of the therapy. Cite this article: Bone Joint Res 2022;11(12):881–889


Bone & Joint Open
Vol. 3, Issue 9 | Pages 666 - 673
1 Sep 2022
Blümel S Leunig M Manner H Tannast M Stetzelberger VM Ganz R

Aims. Avascular femoral head necrosis in the context of gymnastics is a rare but serious complication, appearing similar to Perthes’ disease but occurring later during adolescence. Based on 3D CT animations, we propose repetitive impact between the main supplying vessels on the posterolateral femoral neck and the posterior acetabular wall in hyperextension and external rotation as a possible cause of direct vascular damage, and subsequent femoral head necrosis in three adolescent female gymnasts we are reporting on. Methods. Outcome of hip-preserving head reduction osteotomy combined with periacetabular osteotomy was good in one and moderate in the other up to three years after surgery; based on the pronounced hip destruction, the third received initially a total hip arthroplasty. Results. The described pathology is quite devastating, and extensive joint preserving surgery (which has been shown successful in Perthes’ cases) was less successful in this patient cohort. Conclusion. Supraselective angiography may be helpful to improve pathomechanical understanding and surgical decision making. Cite this article: Bone Jt Open 2022;3(9):666–673


Bone & Joint Research
Vol. 9, Issue 10 | Pages 731 - 741
28 Oct 2020
He Z Nie P Lu J Ling Y Guo J Zhang B Hu J Liao J Gu J Dai B Feng Z

Aims. Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion. Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741


Bone & Joint Research
Vol. 8, Issue 10 | Pages 495 - 501
1 Oct 2019
Hampp EL Sodhi N Scholl L Deren ME Yenna Z Westrich G Mont MA

Objectives. The use of the haptically bounded saw blades in robotic-assisted total knee arthroplasty (RTKA) can potentially help to limit surrounding soft-tissue injuries. However, there are limited data characterizing these injuries for cruciate-retaining (CR) TKA with the use of this technique. The objective of this cadaver study was to compare the extent of soft-tissue damage sustained through a robotic-assisted, haptically guided TKA (RATKA) versus a manual TKA (MTKA) approach. Methods. A total of 12 fresh-frozen pelvis-to-toe cadaver specimens were included. Four surgeons each prepared three RATKA and three MTKA specimens for cruciate-retaining TKAs. A RATKA was performed on one knee and a MTKA on the other. Postoperatively, two additional surgeons assessed and graded damage to 14 key anatomical structures in a blinded manner. Kruskal–Wallis hypothesis tests were performed to assess statistical differences in soft-tissue damage between RATKA and MTKA cases. Results. Significantly less damage occurred to the PCLs in the RATKA versus the MTKA specimens (p < 0.001). RATKA specimens had non-significantly less damage to the deep medial collateral ligaments (p = 0.149), iliotibial bands (p = 0.580), poplitei (p = 0.248), and patellar ligaments (p = 0.317). The remaining anatomical structures had minimal soft-tissue damage in all MTKA and RATKA specimens. Conclusion. The results of this study indicate that less soft-tissue damage may occur when utilizing RATKA compared with MTKA. These findings are likely due to the enhanced preoperative planning with the robotic software, the real-time intraoperative feedback, and the haptically bounded saw blade, all of which may help protect the surrounding soft tissues and ligaments. Cite this article: Bone Joint Res 2019;8:495–501


Bone & Joint Research
Vol. 9, Issue 6 | Pages 322 - 332
1 Jun 2020
Zhao H Yeersheng R Kang X Xia Y Kang P Wang W

Aims. The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods. This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results. The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion. Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332


Bone & Joint Research
Vol. 10, Issue 1 | Pages 10 - 21
1 Jan 2021
Zong Z Zhang X Yang Z Yuan W Huang J Lin W Chen T Yu J Chen J Cui L Li G Wei B Lin S

Aims. Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model. Methods. Mesenchymal stem cells (MSCs) were isolated from ageing patients and preconditioned with chondrogenic differentiation medium, followed by normal growth medium. Cellular assays including Bromodeoxyuridine / 5-bromo-2'-deoxyuridine (BrdU), quantitative polymerase chain reaction (q-PCR), β-Gal, Rosette forming, and histological staining were compared in the manipulated human mesenchymal stem cells (hM-MSCs) and their controls. The anterior cruciate ligament transection (ACLT) rabbit models were locally injected with two millions, four millions, or eight millions of hM-MSCs or phosphate-buffered saline (PBS). Osteoarthritis Research Society International (OARSI) scoring was performed to measure the pathological changes in the affected joints after staining. Micro-CT analysis was conducted to determine the microstructural changes in subchondral bone. Results. Stepwise preconditioning approach significantly enhanced the proliferation and chondrogenic potential of ageing hMSCs at early passage. Interestingly, remarkably lower immunogenicity and senescence was also found in hM-MSCs. Data from animal studies showed cartilage damage was retarded and subchondral bone remodelling was prevented by the treatment of preconditioned MSCs. The therapeutic effect depended on the number of cells applied to animals, with the best effect observed when treated with eight millions of hM-MSCs. Conclusion. This study demonstrated a reliable and feasible stepwise preconditioning strategy to improve the safety and efficacy of ageing MSCs for the prevention of OA development. Cite this article: Bone Joint Res 2021;10(1):10–21


Bone & Joint Research
Vol. 6, Issue 5 | Pages 345 - 350
1 May 2017
Di Laura A Hothi H Henckel J Swiatkowska I Liow MHL Kwon Y Skinner JA Hart AJ

Objectives. The use of ceramic femoral heads in total hip arthroplasty (THA) has increased due to their proven low bearing wear characteristics. Ceramic femoral heads are also thought to reduce wear and corrosion at the head-stem junction with titanium (Ti) stems when compared with metal heads. We sought to evaluate taper damage of ceramic compared with metal heads when paired with cobalt chromium (CoCr) alloy stems in a single stem design. Methods. This retrieval study involved 48 total hip arthroplasties (THAs) with CoCr V40 trunnions paired with either CoCr (n = 21) or ceramic (n = 27) heads. The taper junction of all hips was evaluated for fretting/corrosion damage and volumetric material loss using a roundness-measuring machine. We used linear regression analysis to investigate taper damage differences after adjusting for potential confounding variables. Results. We measured median taper material loss rates of 0.210 mm. 3. /year (0.030 to 0.448) for the metal head group and 0.084 mm. 3. /year (0.059 to 0.108) for the ceramic group. The difference was not significant (p = 0.58). Moreover, no significant correlation between material loss and implant or patient factors (p > 0.05) was found. Conclusions. Metal heads did not increase taper damage on CoCr trunnions compared with ceramic heads from the same hip design. The amount of material released at the taper junctions was very low when compared with available data regarding CoCr/Ti coupling in metal-on-metal bearings. Cite this article: A. Di Laura, H. Hothi, J. Henckel, I. Swiatkowska, M. H. L. Liow, Y-M. Kwon, J. A. Skinner, A. J. Hart. Retrieval analysis of metal and ceramic femoral heads on a single CoCr stem design. Bone Joint Res 2017;6:–350. DOI: 10.1302/2046-3758.65.BJR-2016-0325.R1


Bone & Joint Research
Vol. 5, Issue 10 | Pages 461 - 469
1 Oct 2016
Liu YK Deng XX Yang H

Objectives. The cytotoxicity induced by cobalt ions (Co. 2+. ) and cobalt nanoparticles (Co-NPs) which released following the insertion of a total hip prosthesis, has been reported. However, little is known about the underlying mechanisms. In this study, we investigate the toxic effect of Co. 2+. and Co-NPs on liver cells, and explain further the potential mechanisms. Methods. Co-NPs were characterised for size, shape, elemental analysis, and hydrodynamic diameter, and were assessed by Transmission Electron Microscope, Scanning Electron Microscope, Energy Dispersive X-ray Spectroscopy and Dynamic Light Scattering. BRL-3A cells were used in this study. Cytotoxicity was evaluated by MTT and lactate dehydrogenase release assay. In order to clarify the potential mechanisms, reactive oxygen species, Bax/Bcl-2 mRNA expression, IL-8 mRNA expression and DNA damage were assessed on BRL-3A cells after Co. 2+. or Co-NPs treatment. Results. Results showed cytotoxic effects of Co. 2+. and Co-NPs were dependent upon time and dosage, and the cytotoxicity of Co-NPs was greater than that of Co. 2+. In addition, Co-NPs elicited a significant (p < 0.05) reduction in cell viability with a concomitant increase in lactic dehydrogenase release, reactive oxygen species generation, IL-8 mRNA expression, Bax/Bcl-2 mRNA expression and DNA damage after 24 hours of exposure. Conclusion. Co-NPs induced greater cytotoxicity and genotoxicity in BRL-3A cells than Co. 2+. Cell membrane damage, oxidative stress, immune inflammation and DNA damage may play an important role in the effects of Co-NPs on liver cells. Cite this article: Y. K. Liu, X. X. Deng, H.L. Yang. Cytotoxicity and genotoxicity in liver cells induced by cobalt nanoparticles and ions. Bone Joint Res 2016;5:461–469. DOI: 10.1302/2046-3758.510.BJR-2016-0016.R1


Bone & Joint Research
Vol. 8, Issue 2 | Pages 101 - 106
1 Feb 2019
Filardo G Petretta M Cavallo C Roseti L Durante S Albisinni U Grigolo B

Objectives. Meniscal injuries are often associated with an active lifestyle. The damage of meniscal tissue puts young patients at higher risk of undergoing meniscal surgery and, therefore, at higher risk of osteoarthritis. In this study, we undertook proof-of-concept research to develop a cellularized human meniscus by using 3D bioprinting technology. Methods. A 3D model of bioengineered medial meniscus tissue was created, based on MRI scans of a human volunteer. The Digital Imaging and Communications in Medicine (DICOM) data from these MRI scans were processed using dedicated software, in order to obtain an STL model of the structure. The chosen 3D Discovery printing tool was a microvalve-based inkjet printhead. Primary mesenchymal stem cells (MSCs) were isolated from bone marrow and embedded in a collagen-based bio-ink before printing. LIVE/DEAD assay was performed on realized cell-laden constructs carrying MSCs in order to evaluate cell distribution and viability. Results. This study involved the realization of a human cell-laden collagen meniscus using 3D bioprinting. The meniscus prototype showed the biological potential of this technology to provide an anatomically shaped, patient-specific construct with viable cells on a biocompatible material. Conclusion. This paper reports the preliminary findings of the production of a custom-made, cell-laden, collagen-based human meniscus. The prototype described could act as the starting point for future developments of this collagen-based, tissue-engineered structure, which could aid the optimization of implants designed to replace damaged menisci. Cite this article: G. Filardo, M. Petretta, C. Cavallo, L. Roseti, S. Durante, U. Albisinni, B. Grigolo. Patient-specific meniscus prototype based on 3D bioprinting of human cell-laden scaffold. Bone Joint Res 2019;8:101–106. DOI: 10.1302/2046-3758.82.BJR-2018-0134.R1


Bone & Joint Research
Vol. 6, Issue 3 | Pages 162 - 171
1 Mar 2017
Walker JA Ewald TJ Lewallen E Van Wijnen A Hanssen AD Morrey BF Morrey ME Abdel MP Sanchez-Sotelo J

Objectives. Sustained intra-articular delivery of pharmacological agents is an attractive modality but requires use of a safe carrier that would not induce cartilage damage or fibrosis. Collagen scaffolds are widely available and could be used intra-articularly, but no investigation has looked at the safety of collagen scaffolds within synovial joints. The aim of this study was to determine the safety of collagen scaffold implantation in a validated in vivo animal model of knee arthrofibrosis. Materials and Methods. A total of 96 rabbits were randomly and equally assigned to four different groups: arthrotomy alone; arthrotomy and collagen scaffold placement; contracture surgery; and contracture surgery and collagen scaffold placement. Animals were killed in equal numbers at 72 hours, two weeks, eight weeks, and 24 weeks. Joint contracture was measured, and cartilage and synovial samples underwent histological analysis. Results. Animals that underwent arthrotomy had equivalent joint contractures regardless of scaffold implantation (-13.9° versus -10.9°, equivalence limit 15°). Animals that underwent surgery to induce contracture did not demonstrate equivalent joint contractures with (41.8°) or without (53.9°) collagen scaffold implantation. Chondral damage occurred in similar rates with (11 of 48) and without (nine of 48) scaffold implantation. No significant difference in synovitis was noted between groups. Absorption of the collagen scaffold occurred within eight weeks in all animals. Conclusion. Our data suggest that intra-articular implantation of a collagen sponge does not induce synovitis or cartilage damage. Implantation in a native joint does not seem to induce contracture. Implantation of the collagen sponge in a rabbit knee model of contracture may decrease the severity of the contracture. Cite this article: J. A. Walker, T. J. Ewald, E. Lewallen, A. Van Wijnen, A. D. Hanssen, B. F. Morrey, M. E. Morrey, M. P. Abdel, J. Sanchez-Sotelo. Intra-articular implantation of collagen scaffold carriers is safe in both native and arthrofibrotic rabbit knee joints. Bone Joint Res 2016;6:162–171. DOI: 10.1302/2046-3758.63.BJR-2016-0193


Bone & Joint Research
Vol. 9, Issue 2 | Pages 60 - 70
1 Feb 2020
Li Z Arioka M Liu Y Aghvami M Tulu S Brunski JB Helms JA

Aims. Surgeons and most engineers believe that bone compaction improves implant primary stability without causing undue damage to the bone itself. In this study, we developed a murine distal femoral implant model and tested this dogma. Methods. Each mouse received two femoral implants, one placed into a site prepared by drilling and the other into the contralateral site prepared by drilling followed by stepwise condensation. Results. Condensation significantly increased peri-implant bone density but it also produced higher strains at the interface between the bone and implant, which led to significantly more bone microdamage. Despite increased peri-implant bone density, condensation did not improve implant primary stability as measured by an in vivo lateral stability test. Ultimately, the condensed bone underwent resorption, which delayed the onset of new bone formation around the implant. Conclusion. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability or to new peri-implant bone formation. Cite this article:Bone Joint Res. 2020;9(2):60–70


Bone & Joint Research
Vol. 9, Issue 4 | Pages 192 - 199
1 Apr 2020
Pijls BG Sanders IMJG Kujiper EJ Nelissen RGHH

Aims. Induction heating is a noninvasive, nonantibiotic treatment modality that can potentially be used to cause thermal damage to the bacterial biofilm on the metal implant surface. The purpose of this study was to determine the effectiveness of induction heating on killing Staphylococcus epidermidis from biofilm and to determine the possible synergistic effect of induction heating and antibiotics. Methods. S. epidermidis biofilms were grown on titanium alloy (Ti6Al4V) coupons for 24 hours (young biofilm) and seven days (mature biofilm). These coupons with biofilm were heated to temperatures of 50°C, 55°C, 60°C, 65°C, 70°C, 80°C, and 90°C for 3.5 minutes and subsequently exposed to vancomycin and rifampicin at clinically relevant concentrations. Results. For the young biofilm, total eradication was observed at 65°C or higher for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. For the mature biofilm, total eradication was observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 10 mg/l and rifampicin 1 mg/l. Total eradication was also observed at 60°C for 3.5 minutes followed by 24 hours of vancomycin 1 mg/l and rifampicin 1 mg/l followed by another thermal shock of 60°C for 3.5 minutes (two thermal shocks). Conclusion. Induction heating of Ti6Al4V coupons is effective in reducing bacterial load in vitro for S. epidermidis biofilms. Induction heating and antibiotics have a synergistic effect resulting in total eradication of the biofilm at 60°C or higher for clinically relevant concentrations of vancomycin and rifampicin. Cite this article:Bone Joint Res. 2020;9(4):192–199


Bone & Joint Research
Vol. 12, Issue 8 | Pages 497 - 503
16 Aug 2023
Lee J Koh Y Kim PS Park J Kang K

Aims

Focal knee arthroplasty is an attractive alternative to knee arthroplasty for young patients because it allows preservation of a large amount of bone for potential revisions. However, the mechanical behaviour of cartilage has not yet been investigated because it is challenging to evaluate in vivo contact areas, pressure, and deformations from metal implants. Therefore, this study aimed to determine the contact pressure in the tibiofemoral joint with a focal knee arthroplasty using a finite element model.

Methods

The mechanical behaviour of the cartilage surrounding a metal implant was evaluated using finite element analysis. We modelled focal knee arthroplasty with placement flush, 0.5 mm deep, or protruding 0.5 mm with regard to the level of the surrounding cartilage. We compared contact stress and pressure for bone, implant, and cartilage under static loading conditions.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 58 - 71
17 Jan 2023
Dagneaux L Limberg AK Owen AR Bettencourt JW Dudakovic A Bayram B Gades NM Sanchez-Sotelo J Berry DJ van Wijnen A Morrey ME Abdel MP

Aims

As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA).

Methods

Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections.


Bone & Joint Research
Vol. 7, Issue 2 | Pages 196 - 204
1 Feb 2018
Krull A Morlock MM Bishop NE

Objectives. Taper junctions between modular hip arthroplasty femoral heads and stems fail by wear or corrosion which can be caused by relative motion at their interface. Increasing the assembly force can reduce relative motion and corrosion but may also damage surrounding tissues. The purpose of this study was to determine the effects of increasing the impaction energy and the stiffness of the impactor tool on the stability of the taper junction and on the forces transmitted through the patient’s surrounding tissues. Methods. A commercially available impaction tool was modified to assemble components in the laboratory using impactor tips with varying stiffness at different applied energy levels. Springs were mounted below the modular components to represent the patient. The pull-off force of the head from the stem was measured to assess stability, and the displacement of the springs was measured to assess the force transmitted to the patient’s tissues. Results. The pull-off force of the head increased as the stiffness of the impactor tip increased but without increasing the force transmitted through the springs (patient). Increasing the impaction energy increased the pull-off force but also increased the force transmitted through the springs. Conclusions. To limit wear and corrosion, manufacturers should maximize the stiffness of the impactor tool but without damaging the surface of the head. This strategy will maximize the stability of the head on the stem for a given applied energy, without influencing the force transmitted through the patient’s tissues. Current impactor designs already appear to approach this limit. Increasing the applied energy (which is dependent on the mass of the hammer and square of the contact speed) increases the stability of the modular connection but proportionally increases the force transmitted through the patient’s tissues, as well as to the surface of the head, and should be restricted to safe levels. Cite this article: A. Krull, M. M. Morlock, N. E. Bishop. Maximizing the fixation strength of modular components by impaction without tissue damage. Bone Joint Res 2018;7:196–204. DOI: 10.1302/2046-3758.72.BJR-2017-0078.R2


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 347 - 355
15 Mar 2023
Birch NC Cheung JPY Takenaka S El Masri WS

Initial treatment of traumatic spinal cord injury remains as controversial in 2023 as it was in the early 19th century, when Sir Astley Cooper and Sir Charles Bell debated the merits or otherwise of surgery to relieve cord compression. There has been a lack of high-class evidence for early surgery, despite which expeditious intervention has become the surgical norm. This evidence deficit has been progressively addressed in the last decade and more modern statistical methods have been used to clarify some of the issues, which is demonstrated by the results of the SCI-POEM trial. However, there has never been a properly conducted trial of surgery versus active conservative care. As a result, it is still not known whether early surgery or active physiological management of the unstable injured spinal cord offers the better chance for recovery. Surgeons who care for patients with traumatic spinal cord injuries in the acute setting should be aware of the arguments on all sides of the debate, a summary of which this annotation presents.

Cite this article: Bone Joint J 2023;105-B(4):347–355.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 785 - 792
19 Sep 2024
Clement RGE Wong SJ Hall A Howie SEM Simpson AHRW

Aims

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

Methods

All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome.


Bone & Joint Research
Vol. 12, Issue 4 | Pages 274 - 284
11 Apr 2023
Du X Jiang Z Fang G Liu R Wen X Wu Y Hu S Zhang Z

Aims

This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA).

Methods

Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 397 - 411
3 Jul 2023
Ruan X Gu J Chen M Zhao F Aili M Zhang D

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Research
Vol. 13, Issue 11 | Pages 659 - 672
20 Nov 2024
Mo H Sun K Hou Y Ruan Z He Z Liu H Li L Wang Z Guo F

Aims

Osteoarthritis (OA) is a common degenerative disease. PA28γ is a member of the 11S proteasome activator and is involved in the regulation of several important cellular processes, including cell proliferation, apoptosis, and inflammation. This study aimed to explore the role of PA28γ in the occurrence and development of OA and its potential mechanism.

Methods

A total of 120 newborn male mice were employed for the isolation and culture of primary chondrocytes. OA-related indicators such as anabolism, catabolism, inflammation, and apoptosis were detected. Effects and related mechanisms of PA28γ in chondrocyte endoplasmic reticulum (ER) stress were studied using western blotting, real-time polymerase chain reaction (PCR), and immunofluorescence. The OA mouse model was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity of 15 12-week-old male mice to reduce the expression of PA28γ. The degree of cartilage destruction was evaluated by haematoxylin and eosin (HE) staining, safranin O/fast green staining, toluidine blue staining, and immunohistochemistry.


Bone & Joint Open
Vol. 4, Issue 3 | Pages 210 - 218
28 Mar 2023
Searle HKC Rahman A Desai AP Mellon SJ Murray DW

Aims

To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics.

Methods

Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSWL) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 110 - 123
7 Mar 2024
Xu J Ruan Z Guo Z Hou L Wang G Zheng Z Zhang X Liu H Sun K Guo F

Aims

Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear.

Methods

In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression.


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.


The Bone & Joint Journal
Vol. 105-B, Issue 5 | Pages 471 - 473
1 May 2023
Peterson N Perry DC

Salter-Harris II fractures of the distal tibia affect children frequently, and when they are displaced present a treatment dilemma. Treatment primarily aims to restore alignment and prevent premature physeal closure, as this can lead to angular deformity, limb length difference, or both. Current literature is of poor methodological quality and is contradictory as to whether conservative or surgical management is superior in avoiding complications and adverse outcomes. A state of clinical equipoise exists regarding whether displaced distal tibial Salter-Harris II fractures in children should be treated with surgery to achieve anatomical reduction, or whether cast treatment alone will lead to a satisfactory outcome. Systematic review and meta-analysis has concluded that high-quality prospective multicentre research is needed to answer this question. The Outcomes of Displaced Distal tibial fractures: Surgery Or Casts in KidS (ODD SOCKS) trial, funded by the National Institute for Health and Care Research, aims to provide this high-quality research in order to answer this question, which has been identified as a top-five research priority by the British Society for Children’s Orthopaedic Surgery.

Cite this article: Bone Joint J 2023;105-B(5):471–473.


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.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

Methods

Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims

Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods

HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.


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.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 193 - 200
23 Apr 2024
Reynolds A Doyle R Boughton O Cobb J Muirhead-Allwood S Jeffers J

Aims

Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.

Methods

Posterior approach THAs were carried out on three cadavers by an expert orthopaedic surgeon. An instrumented mallet and introducer were used to insert cementless acetabular cups. The motion of the mallet, relative to the introducer, was analyzed for a total of 110 strikes split into low-, medium-, and high-effort strikes. Three parameters were extracted from these data: strike vector, strike offset, and mallet face alignment.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1100 - 1110
1 Oct 2024
Arenas-Miquelez A Barco R Cabo Cabo FJ Hachem A

Bone defects are frequently observed in anterior shoulder instability. Over the last decade, knowledge of the association of bone loss with increased failure rates of soft-tissue repair has shifted the surgical management of chronic shoulder instability. On the glenoid side, there is no controversy about the critical glenoid bone loss being 20%. However, poor outcomes have been described even with a subcritical glenoid bone defect as low as 13.5%. On the humeral side, the Hill-Sachs lesion should be evaluated concomitantly with the glenoid defect as the two sides of the same bipolar lesion which interact in the instability process, as described by the glenoid track concept. We advocate adding remplissage to every Bankart repair in patients with a Hill-Sachs lesion, regardless of the glenoid bone loss. When critical or subcritical glenoid bone loss occurs in active patients (> 15%) or bipolar off-track lesions, we should consider anterior glenoid bone reconstructions. The techniques have evolved significantly over the last two decades, moving from open procedures to arthroscopic, and from screw fixation to metal-free fixation. The new arthroscopic techniques of glenoid bone reconstruction procedures allow precise positioning of the graft, identification, and treatment of concomitant injuries with low morbidity and faster recovery. Given the problems associated with bone resorption and metal hardware protrusion, the new metal-free techniques for Latarjet or free bone block procedures seem a good solution to avoid these complications, although no long-term data are yet available.

Cite this article: Bone Joint J 2024;106-B(10):1100–1110.


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.


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.


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.


Bone & Joint Open
Vol. 4, Issue 1 | Pages 13 - 18
5 Jan 2023
Walgrave S Oussedik S

Abstract

Robotic-assisted total knee arthroplasty (TKA) has proven higher accuracy, fewer alignment outliers, and improved short-term clinical outcomes when compared to conventional TKA. However, evidence of cost-effectiveness and individual superiority of one system over another is the subject of further research. Despite its growing adoption rate, published results are still limited and comparative studies are scarce. This review compares characteristics and performance of five currently available systems, focusing on the information and feedback each system provides to the surgeon, what the systems allow the surgeon to modify during the operation, and how each system then aids execution of the surgical plan.

Cite this article: Bone Jt Open 2023;4(1):13–18.


Aims

Osteochondral lesions of the talus (OLT) are a common cause of disability and chronic ankle pain. Many operative treatment strategies have been introduced; however, they have their own disadvantages. Recently lesion repair using autologous cartilage chip has emerged therefore we investigated the efficacy of particulated autologous cartilage transplantation (PACT) in OLT.

Methods

We retrospectively analyzed 32 consecutive symptomatic patients with OLT who underwent PACT with minimum one-year follow-up. Standard preoperative radiography and MRI were performed for all patients. Follow-up second-look arthroscopy or MRI was performed with patient consent approximately one-year postoperatively. Magnetic resonance Observation of Cartilage Repair Tissue (MOCART) score and International Cartilage Repair Society (ICRS) grades were used to evaluate the quality of the regenerated cartilage. Clinical outcomes were assessed using the pain visual analogue scale (VAS), Foot Function Index (FFI), and Foot Ankle Outcome Scale (FAOS).


Aims

Arthroscopic microfracture is a conventional form of treatment for patients with osteochondritis of the talus, involving an area of < 1.5 cm2. However, some patients have persistent pain and limitation of movement in the early postoperative period. No studies have investigated the combined treatment of microfracture and shortwave treatment in these patients. The aim of this prospective single-centre, randomized, double-blind, placebo-controlled trial was to compare the outcome in patients treated with arthroscopic microfracture combined with radial extracorporeal shockwave therapy (rESWT) and arthroscopic microfracture alone, in patients with ostechondritis of the talus.

Methods

Patients were randomly enrolled into two groups. At three weeks postoperatively, the rESWT group was given shockwave treatment, once every other day, for five treatments. In the control group the head of the device which delivered the treatment had no energy output. The two groups were evaluated before surgery and at six weeks and three, six and 12 months postoperatively. The primary outcome measure was the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale. Secondary outcome measures included a visual analogue scale (VAS) score for pain and the area of bone marrow oedema of the talus as identified on sagittal fat suppression sequence MRI scans.


Bone & Joint Open
Vol. 5, Issue 1 | Pages 28 - 36
18 Jan 2024
Selmene MA Moreau PE Zaraa M Upex P Jouffroy P Riouallon G

Aims

Post-traumatic periprosthetic acetabular fractures are rare but serious. Few studies carried out on small cohorts have reported them in the literature. The aim of this work is to describe the specific characteristics of post-traumatic periprosthetic acetabular fractures, and the outcome of their surgical treatment in terms of function and complications.

Methods

Patients with this type of fracture were identified retrospectively over a period of six years (January 2016 to December 2021). The following data were collected: demographic characteristics, date of insertion of the prosthesis, details of the intervention, date of the trauma, characteristics of the fracture, and type of treatment. Functional results were assessed with the Harris Hip Score (HHS). Data concerning complications of treatment were collected.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 768 - 775
18 Sep 2024
Chen K Dong X Lu Y Zhang J Liu X Jia L Guo Y Chen X

Aims

Surgical approaches to cervical ossification of the posterior longitudinal ligament (OPLL) remain controversial. The purpose of the present study was to analyze and compare the long-term neurological recovery following anterior decompression with fusion (ADF) and posterior laminectomy and fusion with bone graft and internal fixation (PLF) based on > ten-year follow-up outcomes in a single centre.

Methods

Included in this retrospective cohort study were 48 patients (12 females; mean age 55.79 years (SD 8.94)) who were diagnosed with cervical OPLL, received treatment in our centre, and were followed up for 10.22 to 15.25 years. Of them, 24 patients (six females; mean age 52.88 years (SD 8.79)) received ADF, and the other 24 patients (five females; mean age 56.25 years (SD 9.44)) received PLF. Clinical data including age, sex, and the OPLL canal-occupying ratio were analyzed and compared. The primary outcome was Japanese Orthopaedic Association (JOA) score, and the secondary outcome was visual analogue scale neck pain.


Bone & Joint Open
Vol. 4, Issue 7 | Pages 523 - 531
11 Jul 2023
Passaplan C Hanauer M Gautier L Stetzelberger VM Schwab JM Tannast M Gautier E

Aims

Hyaline cartilage has a low capacity for regeneration. Untreated osteochondral lesions of the femoral head can lead to progressive and symptomatic osteoarthritis of the hip. The purpose of this study is to analyze the clinical and radiological long-term outcome of patients treated with osteochondral autograft transfer. To our knowledge, this study represents a series of osteochondral autograft transfer of the hip with the longest follow-up.

Methods

We retrospectively evaluated 11 hips in 11 patients who underwent osteochondral autograft transfer in our institution between 1996 and 2012. The mean age at the time of surgery was 28.6 years (8 to 45). Outcome measurement included standardized scores and conventional radiographs. Kaplan-Meier survival curve was used to determine the failure of the procedures, with conversion to total hip arthroplasty (THA) defined as the endpoint.


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.


Bone & Joint Open
Vol. 5, Issue 5 | Pages 385 - 393
13 May 2024
Jamshidi K Toloue Ghamari B Ammar W Mirzaei A

Aims

Ilium is the most common site of pelvic Ewing’s sarcoma (ES). Resection of the ilium and iliosacral joint causes pelvic disruption. However, the outcomes of resection and reconstruction are not well described. In this study, we report patients’ outcomes after resection of the ilium and iliosacral ES and reconstruction with a tibial strut allograft.

Methods

Medical files of 43 patients with ilium and iliosacral ES who underwent surgical resection and reconstruction with a tibial strut allograft between January 2010 and October 2021 were reviewed. The lesions were classified into four resection zones: I1, I2, I3, and I4, based on the extent of resection. Functional outcomes, oncological outcomes, and surgical complications for each resection zone were of interest. Functional outcomes were assessed using a Musculoskeletal Tumor Society (MSTS) score and Toronto Extremity Salvage Score (TESS).


Bone & Joint Open
Vol. 5, Issue 11 | Pages 992 - 998
6 Nov 2024
Wignadasan W Magan A Kayani B Fontalis A Chambers A Rajput V Haddad FS

Aims

While residual fixed flexion deformity (FFD) in unicompartmental knee arthroplasty (UKA) has been associated with worse functional outcomes, limited evidence exists regarding FFD changes. The objective of this study was to quantify FFD changes in patients with medial unicompartmental knee arthritis undergoing UKA, and investigate any correlation with clinical outcomes.

Methods

This study included 136 patients undergoing robotic arm-assisted medial UKA between January 2018 and December 2022. The study included 75 males (55.1%) and 61 (44.9%) females, with a mean age of 67.1 years (45 to 90). Patients were divided into three study groups based on the degree of preoperative FFD: ≤ 5°, 5° to ≤ 10°, and > 10°. Intraoperative optical motion capture technology was used to assess pre- and postoperative FFD. Clinical FFD was measured pre- and postoperatively at six weeks and one year following surgery. Preoperative and one-year postoperative Oxford Knee Scores (OKS) were collected.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

Aims

Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease.

Methods

We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

Aims

Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model.

Methods

A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM+) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM+ using immunohistochemistry and immunofluorescence.


Bone & Joint Research
Vol. 13, Issue 9 | Pages 452 - 461
5 Sep 2024
Lee JY Lee HI Lee S Kim NH

Aims

The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM).

Methods

Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 536 - 545
8 Sep 2023
Luo P Yuan Q Yang M Wan X Xu P

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.


The Bone & Joint Journal
Vol. 106-B, Issue 5 Supple B | Pages 59 - 65
1 May 2024
Liu WKT Cheung A Fu H Chan PK Chiu KY

Aims

Isolated acetabular liner exchange with a highly crosslinked polyethylene (HXLPE) component is an option to address polyethylene wear and osteolysis following total hip arthroplasty (THA) in the presence of a well-fixed acetabular shell. The liner can be fixed either with the original locking mechanism or by being cemented within the acetabular component. Whether the method used for fixation of the HXLPE liner has any bearing on the long-term outcomes is still unclear.

Methods

Data were retrieved for all patients who underwent isolated acetabular component liner exchange surgery with a HXLPE component in our institute between August 2000 and January 2015. Patients were classified according to the fixation method used (original locking mechanism (n = 36) or cemented (n = 50)). Survival and revision rates were compared. A total of 86 revisions were performed and the mean duration of follow-up was 13 years.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 739 - 750
4 Oct 2022
Shu L Abe N Li S Sugita N

Aims

To fully quantify the effect of posterior tibial slope (PTS) angles on joint kinematics and contact mechanics of intact and anterior cruciate ligament-deficient (ACLD) knees during the gait cycle.

Methods

In this controlled laboratory study, we developed an original multiscale subject-specific finite element musculoskeletal framework model and integrated it with the tibiofemoral and patellofemoral joints with high-fidelity joint motion representations, to investigate the effects of 2.5° increases in PTS angles on joint dynamics and contact mechanics during the gait cycle.


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.


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.


Bone & Joint Research
Vol. 12, Issue 12 | Pages 702 - 711
1 Dec 2023
Xue Y Zhou L Wang J

Aims

Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Methods

First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) was used to verify the effectiveness of markers.


Bone & Joint Open
Vol. 4, Issue 1 | Pages 19 - 26
13 Jan 2023
Nishida K Nasu Y Hashizume K Okita S Nakahara R Saito T Ozaki T Inoue H

Aims

There are concerns regarding complications and longevity of total elbow arthroplasty (TEA) in young patients, and the few previous publications are mainly limited to reports on linked elbow devices. We investigated the clinical outcome of unlinked TEA for patients aged less than 50 years with rheumatoid arthritis (RA).

Methods

We retrospectively reviewed the records of 26 elbows of 21 patients with RA who were aged less than 50 years who underwent primary TEA with an unlinked elbow prosthesis. The mean patient age was 46 years (35 to 49), and the mean follow-up period was 13.6 years (6 to 27). Outcome measures included pain, range of motion, Mayo Elbow Performance Score (MEPS), radiological evaluation for radiolucent line and loosening, complications, and revision surgery with or without implant removal.


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

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 411 - 426
28 Aug 2024
Liu D Wang K Wang J Cao F Tao L

Aims

This study explored the shared genetic traits and molecular interactions between postmenopausal osteoporosis (POMP) and sarcopenia, both of which substantially degrade elderly health and quality of life. We hypothesized that these motor system diseases overlap in pathophysiology and regulatory mechanisms.

Methods

We analyzed microarray data from the Gene Expression Omnibus (GEO) database using weighted gene co-expression network analysis (WGCNA), machine learning, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to identify common genetic factors between POMP and sarcopenia. Further validation was done via differential gene expression in a new cohort. Single-cell analysis identified high expression cell subsets, with mononuclear macrophages in osteoporosis and muscle stem cells in sarcopenia, among others. A competitive endogenous RNA network suggested regulatory elements for these genes.


Bone & Joint Research
Vol. 11, Issue 9 | Pages 629 - 638
1 Sep 2022
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Aims

Here we used a mature seven-day biofilm model of Staphylococcus aureus, exposed to antibiotics up to an additional seven days, to establish the effectiveness of either mechanical cleaning or antibiotics or non-contact induction heating, and which combinations could eradicate S. aureus in mature biofilms.

Methods

Mature biofilms of S. aureus (ATCC 29213) were grown on titanium alloy (Ti6Al4V) coupons for seven days and were subjected to the following treatments or their combinations: antibiotics, mechanical cleaning, or heat shock by induction heating of 60°C for one minute. Experiments were repeated at least five times.


The Bone & Joint Journal
Vol. 105-B, Issue 3 | Pages 227 - 229
1 Mar 2023
Theologis T Brady MA Hartshorn S Faust SN Offiah AC

Acute bone and joint infections in children are serious, and misdiagnosis can threaten limb and life. Most young children who present acutely with pain, limping, and/or loss of function have transient synovitis, which will resolve spontaneously within a few days. A minority will have a bone or joint infection. Clinicians are faced with a diagnostic challenge: children with transient synovitis can safely be sent home, but children with bone and joint infection require urgent treatment to avoid complications. Clinicians often respond to this challenge by using a series of rudimentary decision support tools, based on clinical, haematological, and biochemical parameters, to differentiate childhood osteoarticular infection from other diagnoses. However, these tools were developed without methodological expertise in diagnostic accuracy and do not consider the importance of imaging (ultrasound scan and MRI). There is wide variation in clinical practice with regard to the indications, choice, sequence, and timing of imaging. This variation is most likely due to the lack of evidence concerning the role of imaging in acute bone and joint infection in children. We describe the first steps of a large UK multicentre study, funded by the National Institute for Health Research, which seeks to integrate definitively the role of imaging into a decision support tool, developed with the assistance of individuals with expertise in the development of clinical prediction tools.

Cite this article: Bone Joint J 2023;105-B(3):227–229.


Bone & Joint Open
Vol. 4, Issue 4 | Pages 219 - 225
1 Apr 2023
Wachtel N Meyer E Volkmer E Knie N Lukas B Giunta R Demmer W

Aims

Wrist arthroscopy is a standard procedure in hand surgery for diagnosis and treatment of wrist injuries. Even though not generally recommended for similar procedures, general administration of perioperative antibiotic prophylaxis (PAP) is still widely used in wrist arthroscopy.

Methods

A clinical ambispective dual-centre study was performed to determine whether PAP reduces postoperative infection rates after soft tissue-only wrist arthroscopies. Retrospective and prospective data was collected at two hospitals with departments specialized in hand surgery. During the study period, 464 wrist arthroscopies were performed, of these 178 soft-tissue-only interventions met the study criteria and were included. Signs of postoperative infection and possible adverse drug effects (ADEs) of PAP were monitored. Additionally, risk factors for surgical site infection (SSIs), such as diabetes mellitus and BMI, were obtained.


Bone & Joint Open
Vol. 5, Issue 5 | Pages 394 - 400
15 May 2024
Nishi M Atsumi T Yoshikawa Y Okano I Nakanishi R Watanabe M Usui Y Kudo Y

Aims

The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs.

Methods

Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)).


Bone & Joint Open
Vol. 5, Issue 9 | Pages 793 - 799
20 Sep 2024
Cederqvist S Flinkkilä T Tuominen A Sormaala M Ylinen J Kautiainen H Sirniö K Pamilo K Kiviranta I Paloneva J

Aims

Rotator cuff disease (RCD) can considerably decrease quality of life. Here, we investigated whether health-related quality of life (HRQoL) influences the need for surgery in patients with RCD.

Methods

We performed an analysis of 417 patients with symptomatic RCD who were recruited from two hospitals between June 2008 and December 2014 to be randomized to receive non-surgical or surgical treatment. After a three-month rehabilitation period, 36-Item Short-Form Health Survey questionnaire (SF-36), shoulder pain (visual analogue scale (VAS)), and shoulder function (Constant-Murley score) data were available from 191 still-symptomatic patients who were eligible for surgery. A control group was formed from 87 excluded patients who were no longer eligible for surgery due to relief of symptoms.


Bone & Joint Open
Vol. 3, Issue 11 | Pages 907 - 912
23 Nov 2022
Hurley RJ McCabe FJ Turley L Maguire D Lucey J Hurson CJ

Aims

The use of fluoroscopy in orthopaedic surgery creates risk of radiation exposure to surgeons. Appropriate personal protective equipment (PPE) can help mitigate this. The primary aim of this study was to assess if current radiation protection in orthopaedic trauma is safe. The secondary aims were to describe normative data of radiation exposure during common orthopaedic procedures, evaluate ways to improve any deficits in protection, and validate the use of electronic personal dosimeters (EPDs) in assessing radiation dose in orthopaedic surgery.

Methods

Radiation exposure to surgeons during common orthopaedic trauma operations was prospectively assessed using EPDs and thermoluminescent dosimeters (TLDs). Normative data for each operation type were calculated and compared to recommended guidelines.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 795 - 800
1 Jul 2023
Parsons N Achten J Costa ML

Aims

To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial.

Methods

The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded.


Bone & Joint Open
Vol. 5, Issue 11 | Pages 984 - 991
6 Nov 2024
Molloy T Gompels B McDonnell S

Aims

This Delphi study assessed the challenges of diagnosing soft-tissue knee injuries (STKIs) in acute settings among orthopaedic healthcare stakeholders.

Methods

This modified e-Delphi study consisted of three rounds and involved 32 orthopaedic healthcare stakeholders, including physiotherapists, emergency nurse practitioners, sports medicine physicians, radiologists, orthopaedic registrars, and orthopaedic consultants. The perceived importance of diagnostic components relevant to STKIs included patient and external risk factors, clinical signs and symptoms, special clinical tests, and diagnostic imaging methods. Each round required scoring and ranking various items on a ten-point Likert scale. The items were refined as each round progressed. The study produced rankings of perceived importance across the various diagnostic components.


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.


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 cm2) 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.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 879 - 885
14 Oct 2024
Moore J van de Graaf VA Wood JA Humburg P Colyn W Bellemans J Chen DB MacDessi SJ

Aims

This study examined windswept deformity (WSD) of the knee, comparing prevalence and contributing factors in healthy and osteoarthritic (OA) cohorts.

Methods

A case-control radiological study was undertaken comparing 500 healthy knees (250 adults) with a consecutive sample of 710 OA knees (355 adults) undergoing bilateral total knee arthroplasty. The mechanical hip-knee-ankle angle (mHKA), medial proximal tibial angle (MPTA), and lateral distal femoral angle (LDFA) were determined for each knee, and the arithmetic hip-knee-ankle angle (aHKA), joint line obliquity, and Coronal Plane Alignment of the Knee (CPAK) types were calculated. WSD was defined as a varus mHKA of < -2° in one limb and a valgus mHKA of > 2° in the contralateral limb. The primary outcome was the proportional difference in WSD prevalence between healthy and OA groups. Secondary outcomes were the proportional difference in WSD prevalence between constitutional varus and valgus CPAK types, and to explore associations between predefined variables and WSD within the OA group.


The Bone & Joint Journal
Vol. 106-B, Issue 6 | Pages 582 - 588
1 Jun 2024
Bertram W Howells N White SP Sanderson E Wylde V Lenguerrand E Gooberman-Hill R Bruce J

Aims

The aim of this study was to describe the prevalence and patterns of neuropathic pain over one year in a cohort of patients with chronic post-surgical pain at three months following total knee arthroplasty (TKA).

Methods

Between 2016 and 2019, 363 patients with troublesome pain, defined as a score of ≤ 14 on the Oxford Knee Score pain subscale, three months after TKA from eight UK NHS hospitals, were recruited into the Support and Treatment After Replacement (STAR) clinical trial. Self-reported neuropathic pain and postoperative pain was assessed at three, nine, and 15 months after surgery using the painDETECT and Douleur Neuropathique 4 (DN4) questionnaires collected by postal survey.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 423 - 432
6 Jul 2023
Xie H Wang N He H Yang Z Wu J Yang T Wang Y

Aims

Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

Methods

PubMed, Embase, and Cochrane Library were systematically searched to retrieve relevant articles published before 15 November 2022. Studies focusing on the correlation between selenium and BMD, OP, or fracture were included. Effect sizes included regression coefficient (β), weighted mean difference (WMD), and odds ratio (OR). According to heterogeneity, the fixed-effect or random-effect model was used to assess the association between selenium and bone health.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 393 - 398
25 May 2023
Roof MA Lygrisse K Shichman I Marwin SE Meftah M Schwarzkopf R

Aims

Revision total knee arthroplasty (rTKA) is a technically challenging and costly procedure. It is well-documented that primary TKA (pTKA) have better survivorship than rTKA; however, we were unable to identify any studies explicitly investigating previous rTKA as a risk factor for failure following rTKA. The purpose of this study is to compare the outcomes following rTKA between patients undergoing index rTKA and those who had been previously revised.

Methods

This retrospective, observational study reviewed patients who underwent unilateral, aseptic rTKA at an academic orthopaedic speciality hospital between June 2011 and April 2020 with > one-year of follow-up. Patients were dichotomized based on whether this was their first revision procedure or not. Patient demographics, surgical factors, postoperative outcomes, and re-revision rates were compared between the groups.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 202 - 211
7 Mar 2023
Bai Z Shou Z Hu K Yu J Meng H Chen C

Aims

This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect.

Methods

This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 636 - 643
10 Oct 2023
Hamilton V Sheikh S Szczepanska A Maskell N Hamilton F Reid JP Bzdek BR Murray JRD

Aims

Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.

Methods

The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures.


Bone & Joint Research
Vol. 11, Issue 7 | Pages 484 - 493
13 Jul 2022
Hayer S Niederreiter B Kalkgruber M Wanic K Maißner J Smolen JS Aletaha D Blüml S Redlich K

Aims

Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss.

Methods

Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old IL1-/-IL6-/-hTNFtg in comparison to IL1-/-hTNFtg, IL6-/-hTNFtg, and hTNFtg mice. µCT bone analysis of single deficient and wild-type mice was also performed.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 321 - 331
3 Jul 2024
Naito T Yamanaka Y Tokuda K Sato N Tajima T Tsukamoto M Suzuki H Kawasaki M Nakamura E Sakai A

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods

Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.


Bone & Joint Research
Vol. 12, Issue 2 | Pages 121 - 132
1 Feb 2023
Mo H Wang Z He Z Wan J Lu R Wang C Chen A Cheng P

Aims

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

Methods

After inhibiting Peli1 expression in chondrocytes with small interfering RNA (siRNA), interleukin (IL)-1β was used to simulate inflammation, and OA-related indicators such as synthesis, decomposition, inflammation, and apoptosis were detected. Toll-like receptor (TLR) and nuclear factor-kappa B (NF-κB) signalling pathway were detected. After inhibiting the expression of Peli1 in macrophages Raw 264.7 with siRNA and intervening with lipopolysaccharide (LPS), the polarization index of macrophages was detected, and the supernatant of macrophage medium was extracted as conditioned medium to act on chondrocytes and detect the apoptosis index. The OA model of mice was established by destabilized medial meniscus (DMM) surgery, and adenovirus was injected into the knee cavity to reduce the expression of Peli1. The degree of cartilage destruction and synovitis were evaluated by haematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, and immunohistochemistry.


Bone & Joint Research
Vol. 11, Issue 8 | Pages 518 - 527
17 Aug 2022
Hu W Lin J Wei J Yang Y Fu K Zhu T Zhu H Zheng X

Aims

To evaluate inducing osteoarthritis (OA) by surgical destabilization of the medial meniscus (DMM) in mice with and without a stereomicroscope.

Methods

Based on sample size calculation, 70 male C57BL/6 mice were randomly assigned to three surgery groups: DMM aided by a stereomicroscope; DMM by naked eye; or sham surgery. The group information was blinded to researchers. Mice underwent static weightbearing, von Frey test, and gait analysis at two-week intervals from eight to 16 weeks after surgery. Histological grade of OA was determined with the Osteoarthritis Research Society International (OARSI) scoring system.


Bone & Joint Research
Vol. 13, Issue 5 | Pages 237 - 246
17 May 2024
Cheng B Wu C Wei W Niu H Wen Y Li C Chen P Chang H Yang Z Zhang F

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Methods

Peripheral blood samples were collected from KBD patients at baseline of chondroitin sulphate treatment. Methylation profiles were generated using reduced representation bisulphite sequencing (RRBS) from peripheral blood. Differentially methylated regions (DMRs) were identified using MethylKit, while DMR-related genes were defined as those annotated to the gene body or 2.2-kilobase upstream regions of DMRs. Selected DMR-related genes were further validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to assess expression levels. Tensor composition analysis was performed to identify cell-specific differential DNA methylation from bulk tissue.


Bone & Joint Open
Vol. 5, Issue 1 | Pages 69 - 77
25 Jan 2024
Achten J Appelbe D Spoors L Peckham N Kandiyali R Mason J Ferguson D Wright J Wilson N Preston J Moscrop A Costa M Perry DC

Aims

The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial.

Methods

Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment.