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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. Results. Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion. The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183


Bone & Joint Open
Vol. 4, Issue 8 | Pages 628 - 635
22 Aug 2023
Hedlundh U Karlsson J Sernert N Haag L Movin T Papadogiannakis N Kartus J

Aims. A revision for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) has a major effect on the patient’s quality of life, including walking capacity. The objective of this case control study was to investigate the histological and ultrastructural changes to the gluteus medius tendon (GMED) in patients revised due to a PJI, and to compare it with revision THAs without infection performed using the same lateral approach. Methods. A group of eight patients revised due to a PJI with a previous lateral approach was compared with a group of 21 revised THAs without infection, performed using the same approach. The primary variables of the study were the fibril diameter, as seen in transmission electron microscopy (TEM), and the total degeneration score (TDS), as seen under the light microscope. An analysis of bacteriology, classification of infection, and antibiotic treatment was also performed. Results. Biopsy samples from the GMED from infected patients revealed a larger fibril diameter than control patients, as seen in the TEM (p < 0.001). Uninfected patients were slightly older and had their revisions performed significantly later than the infected patients. Histologically, samples from infected patients revealed significantly more vascularity (p < 0.001), the presence of glycosaminoglycans (p < 0.001), and a higher TDS (p = 0.003) than the control patients. The majority of patients had staphylococcal infections of various species. Conclusion. More histological degeneration in the GMED was found in patients undergoing THA revision surgery due to PJI than in patients undergoing THA revision surgery due to other reasons. Cite this article: Bone Jt Open 2023;4(8):628–635


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). Methods. The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions. Results. A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p<0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD. Conclusion. The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets. Cite this article: Bone Joint Res 2023;12(9):522–535


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1127 - 1133
1 Aug 2013
Lama P Le Maitre CL Dolan P Tarlton JF Harding IJ Adams MA

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127–33


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 Research
Vol. 5, Issue 9 | Pages 412 - 418
1 Sep 2016
Ye S Ju B Wang H Lee K

Objectives. Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Methods. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis. Results. The serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration. Conclusions. BMP-2 is anti-catabolic in human NP and AF cells, and its effects are partially mediated through provocation of the catabolic effect of IL-18. These findings indicate that BMP-2 may be a unique therapeutic option for prevention and reversal of disc degeneration. Cite this article: S. Ye, B. Ju, H. Wang, K-B. Lee. Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res 2016;5:412–418. DOI: 10.1302/2046-3758.59.BJR-2016-0032.R1


Bone & Joint Research
Vol. 10, Issue 8 | Pages 498 - 513
3 Aug 2021
Liu Z Lu C Shen P Chou S Shih C Chen J Tien YC

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513


Bone & Joint Research
Vol. 3, Issue 9 | Pages 273 - 279
1 Sep 2014
Vasiliadis ES Kaspiris A Grivas TB Khaldi L Lamprou M Pneumaticos SG Nikolopoulos K Korres DS Papadimitriou E

Objectives. The aim of this study was to examine whether asymmetric loading influences macrophage elastase (MMP12) expression in different parts of a rat tail intervertebral disc and growth plate and if MMP12 expression is correlated with the severity of the deformity. Methods. A wedge deformity between the ninth and tenth tail vertebrae was produced with an Ilizarov-type mini external fixator in 45 female Wistar rats, matched for their age and weight. Three groups were created according to the degree of deformity (10°, 30° and 50°). A total of 30 discs and vertebrae were evaluated immunohistochemically for immunolocalisation of MMP12 expression, and 15 discs were analysed by western blot and zymography in order to detect pro- and active MMP12. Results. No MMP12 expression was detected in the nucleus pulposus. Expression of MMP12 in the annulus progressively increased from group I to groups II and III, mainly at the concave side. Many growth plate chondrocytes expressed MMP12 in the control group, less in group I and rare in groups II and III. Changes in cell phenotype and reduction of cell number were observed, together with disorganisation of matrix microstructure similar to disc degeneration. ProMMP12 was detected at the area of 54 kDa and active MMP12 at 22 kDa. Conclusions. Expression of MMP12 after application of asymmetric loading in a rat tail increased in the intervertebral disc but decreased in the growth plate and correlated with the degree of the deformity and the side of the wedged disc. Cite this article: Bone Joint Res 2014;3:273–9


The Bone & Joint Journal
Vol. 98-B, Issue 11 | Pages 1505 - 1509
1 Nov 2016
Kong BY Kim SH Kim DH Joung HY Jang YH Oh JH

Aims. Our aim was to describe the atypical pattern of increased fatty degeneration in the infraspinatus muscle compared with the supraspinatus in patients with a massive rotator cuff tear. We also wished to describe the nerve conduction and electromyography findings in these patients. Patients and Methods. A cohort of patients undergoing surgery for a massive rotator cuff tear was identified and their clinical records obtained. Their MRI images were reviewed to ascertain the degree of retraction of the torn infraspinatus and supraspinatus muscles, and the degree of fatty degeneration in both muscles was recorded. Nerve conduction studies were also performed in those patients who showed more degeneration in the infraspinatus than in the supraspinatus. Results. Out of a total of 396 patients who underwent surgery for a massive rotator cuff tear between 2006 and 2015, 35 who had more severe fatty degeneration in the infraspinatus than in the supraspinatus were identified. There were 13 men and 22 women. Their mean age was 67.2 years (56 to 81). A total of 20 (57%) had grade 4 fatty degeneration as classified by Fuchs et al, in the infraspinatus. Patte grade 3 muscle retraction was seen in 25 patients (71%). In all, eight patients (23%) had abnormal nerve conduction studies. The mean retraction of the infraspinatus was 3.6 cm (2.1 to 4.8) in patients with more severe fatty degeneration in the infraspinatus, versus 3.0 cm (1.7 to 5.5) in those with more severe degeneration in the supraspinatus (p = 0.003). The retraction ratios were 0.98 (0.61 to 1.57) and 0.77 (0.38 to 1.92), respectively (p < 0.001). Conclusion. Fatty degeneration affecting the infraspinatus more than the supraspinatus may be, in the context of a massive rotator cuff tear, due to entrapment of the suprascapular nerve at the spinoglenoid notch. Cite this article: Bone Joint J 2016;98-B:1505–9


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 10 | Pages 1261 - 1270
1 Oct 2008
Hadjipavlou AG Tzermiadianos MN Bogduk N Zindrick MR

The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors


Bone & Joint Research
Vol. 5, Issue 6 | Pages 218 - 224
1 Jun 2016
Cheng N Guo A Cui Y

Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001


Bone & Joint Research
Vol. 9, Issue 10 | Pages 675 - 688
1 Oct 2020
Shao L Gou Y Fang J Hu Y Lian Q Zhang Y Wang Y Tian F Zhang L

Aims. Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1587 - 1593
1 Dec 2009
Oh JH Kim SH Kim JH Shin YH Yoon JP Oh CH

This study examined the role of vitamin D as a factor accounting for fatty degeneration and muscle function in the rotator cuff. There were 366 patients with disorders of the shoulder. A total of 228 patients had a full-thickness tear (group 1) and 138 patients had no tear (group 2). All underwent magnetic resonance arthrography and an isokinetic muscle performance test. The serum concentrations of vitamin D (25(OH)D. 3. ) were measured. In general, a lower serum level of vitamin D was related to higher fatty degeneration in the muscles of the cuff. Spearman’s correlation coefficients were 0.173 (p = 0.001), −0.181 (p = 0.001), and −0.117 (p = 0.026) for supraspinatus, infraspinatus and subscapularis, respectively. In group 1, multivariate linear regression analysis revealed that the serum level of vitamin D was an independent variable for fatty degeneration of the supraspinatus and infraspinatus. The serum vitamin D level has a significant negative correlation with the fatty degeneration of the cuff muscle and a positive correlation with isokinetic muscle torque


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 687 - 691
1 May 2005
Aihara T Takahashi K Ogasawara A Itadera E Ono Y Moriya H

We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra. Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term


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

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


We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration. There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration. Cite this article: Bone Joint J 2013;95-B:1239–43


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1298 - 1304
1 Oct 2012
Hughes SPF Freemont AJ Hukins DWL McGregor AH Roberts S

This article reviews the current knowledge of the intervertebral disc (IVD) and its association with low back pain (LBP). The normal IVD is a largely avascular and aneural structure with a high water content, its nutrients mainly diffusing through the end plates. IVD degeneration occurs when its cells die or become dysfunctional, notably in an acidic environment. In the process of degeneration, the IVD becomes dehydrated and vascularised, and there is an ingrowth of nerves. Although not universally the case, the altered physiology of the IVD is believed to precede or be associated with many clinical symptoms or conditions including low back and/or lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These include biological therapies and novel surgical techniques (such as total disc replacement), although many of these are still in their experimental phase. Central to developing further methods of treatment is the need for effective ways in which to assess patients and measure their outcomes. However, significant difficulties remain and it is therefore an appropriate time to be further investigating the scientific basis of and treatment of LBP


Bone & Joint 360
Vol. 3, Issue 2 | Pages 32 - 65
1 Apr 2014
Adams MA

This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 2 | Pages 289 - 294
1 Mar 2002
Phillips FM Reuben J Wetzel FT

Our study establishes a rabbit model of disc degeneration which requires neither a chemical nor physical injury to the disc. Disc degeneration similar to that seen in man was created at levels proximal (L4-L5) and caudal (L7-S1) to a simulated lumbar fusion and was studied for up to nine months after arthrodesis. Loss of the normal parallel arrangement of collagen bundles within the annular lamellae was observed in intervertebral discs adjacent to the fusion at three months. By six months there was further disorganisation as well as loss of distinction between the lamellae themselves. By nine months the structure of the disc had been replaced by disorganised fibrous tissue, and annular tears were seen. There was an initial cellular proliferative response followed by loss of chondrocytes and notochordal cells in the nucleus pulposus. Degeneration was accompanied by a decrease in the monomer size of proteoglycans. Narrowing of the disc space, endplate sclerosis and the formation of osteophytes at adjacent disc spaces were observed radiologically


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 3 | Pages 428 - 436
1 Apr 2001
Lovász G Park SH Ebramzadeh E Benya PD Llinás A Bellyei Á Luck JV Sarmiento A

To investigate the effect of instability on the remodelling of a minor articular surface offset, we created a 0.5 mm coronal step-off of the medial femoral condyle in 12 New Zealand white rabbits and transected the anterior cruciate ligament (ACL). A control group of 12 rabbits had only ACL resection and the opposite knee was used as the non-operated control. The osteoarthritic changes at 6, 12 and 24 weeks after surgery were evaluated histologically. In addition, changes in the immunological detection of 3-B-3(-) and 7-D-4 chondroitin-6-sulphate epitopes were determined because of the previous association of such changes with repair of cartilage and early osteoarthritis. In the instability/step-off group there was rapidly progressing focal degeneration of cartilage on the high side of the defect, not seen in previous step-off studies in stable knees. The rest of the femoral condyles and the tibial plateaux of the instability/step-off group had moderate osteoarthritis similar to that of the instability group. 3-B-3(-) was detectable in the early and the intermediate stages of osteoarthritis but no staining was seen in the severely damaged cartilage zones. Immunoreactivity with 7-D-4 increased as degeneration progressed. Our findings have shown that even a minor surface offset may induce rapid degeneration of cartilage when the stability of the knee is compromised


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 240 - 244
1 Mar 1999
Ishida Y Ohmori K Inoue H Suzuki K

We reviewed the radiographs of 325 unselected patients with defects in the pars interarticularis of L5 to study whether the incidence of vertebral slip in spondylolysis of L5 remained unchanged after the age of 20 years. MRI was also carried out on 111 of the patients to investigate the relationship between the shape of the transverse process of L5 and the degeneration of the discs adjacent to this level. The incidence of spondylolisthesis increased with age from 17% in the second decade to 51% in the sixth. The transverse process was significantly more slender in patients with less degeneration at L4/5 and advanced degeneration at L5/S1 than in patients with advanced degeneration at L4/5 and less degeneration at L5/S1. Vertebral slip secondary to an isthmic defect of L5 after the age of 20 years was confirmed and the adjacent disc degeneration was significantly related to the vertical thickness of the transverse process of L5


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 9 | Pages 1253 - 1258
1 Sep 2011
Alpantaki K Katonis P Hadjipavlou AG Spandidos DA Sourvinos G

It has been proposed that intervertebral disc degeneration might be caused by low-grade infection. The purpose of the present study was to assess the incidence of herpes viruses in intervertebral disc specimens from patients with lumbar disc herniation. A polymerase chain reaction based assay was applied to screen for the DNA of eight different herpes viruses in 16 patients and two controls. DNA of at least one herpes virus was detected in 13 specimens (81.25%). Herpes Simplex Virus type-1 (HSV-1) was the most frequently detected virus (56.25%), followed by Cytomegalovirus (CMV) (37.5%). In two patients, co-infection by both HSV-1 and CMV was detected. All samples, including the control specimens, were negative for Herpes Simplex Virus type-2, Varicella Zoster Virus, Epstein Barr Virus, Human Herpes Viruses 6, 7 and 8. The absence of an acute infection was confirmed both at the serological and mRNA level. To our knowledge this is the first unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease


The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 3 | Pages 369 - 373
1 May 1986
Gibson M Buckley J Mawhinney R Mulholland R Worthington B

The lumbar spines of 22 patients were examined for disc degeneration by magnetic resonance imaging (MRI) and by discography. The results from 50 intervertebral discs visualised by both techniques were independently assessed and graded on a five-point scale from normality to gross degeneration and then compared. In 44 discs the results agreed. Of the six discs which gave differing results, four discrepancies were due to observer error and two to incorrect placement of the discographic needle. MRI was shown to be more accurate than discography in the diagnosis of disc degeneration. It has several major advantages, which should make it the investigation of choice


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 726 - 736
1 May 2010
Hee HT Ismail HD Lim CT Goh JCH Wong HK

Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives . Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified. Methods . A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation. Results . Chronic cuff tears in nude rats resulted in a 30% to 40% decrease in muscle mass, a 23% reduction in production of muscle force, and an induction of genes that regulate atrophy, fibrosis, lipid accumulation, inflammation and macrophage recruitment. Marked large lipid droplet accumulation was also present. Conclusions . The extent of degenerative changes in nude rats was similar to what was observed in T-cell competent rats. T cells may not play an important role in regulating muscle degeneration following chronic muscle unloading. The general similarities between nude and T-cell competent rats suggest the nude rat is likely an appropriate preclinical model for the study of xenografts that have the potential to enhance the treatment of chronically torn rotator cuff muscles. Cite this article: Bone Joint Res 2014;3:262–72


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 4 | Pages 491 - 495
1 May 2001
Takahashi M Haro H Wakabayashi Y Kawa-uchi T Komori H Shinomiya K

It has been suggested that matrix metalloproteinase-3 (MMP-3, stromelysin-1) has an important role in the degeneration of intervertebral discs (IVDs). A human MMP-3 promoter 5A/6A polymorphism was reported to be involved in the regulation of MMP-3 gene expression. We suggest that IVD degeneration is associated with 5A/6A polymorphism. We studied 54 young and 49 elderly Japanese subjects. Degeneration of the lumbar discs was graded using MRI in the younger group and by radiography in the elderly. 5A/6A polymorphism was determined by polymerase-chain reaction-based assays. We found that the 5A5A and 5A6A genotype in the elderly was associated with a significantly larger number of degenerative IVDs than the 6A6A (p < 0.05), but there was no significant difference in the young. In the elderly, the IVD degenerative scores were also distributed more highly in the 5A5A and 5A6A genotypes (p = 0.0029). Our findings indicate that the 5A allele is a possible risk factor for the acceleration of degenerative changes in the lumbar disc in the elderly


Bone & Joint Research
Vol. 7, Issue 4 | Pages 274 - 281
1 Apr 2018
Collins KH Hart DA Seerattan RA Reimer RA Herzog W

Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 5 | Pages 678 - 682
1 Sep 1992
Osti O Vernon-Roberts B Moore R Fraser R

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 304 - 305
1 Mar 1999
Kumar A Bickerstaff DR Grimwood JS Suvarna SK

A 35-year-old man was seen with pain in the back of the knee. MRI showed a mass in the anterior cruciate ligament. Biopsy indicated mucoid degeneration. Arthroscopic resection of the ligament was carried out, with relief of symptoms


The Journal of Bone & Joint Surgery British Volume
Vol. 68-B, Issue 1 | Pages 36 - 41
1 Jan 1986
Adams M Dolan P Hutton W

One hundred and thirty-nine discs from cadaveric lumbar spines were injected with a mixture of radio-opaque fluid and dye. Discograms were taken and the discs were then sectioned in the sagittal plane. Examination of the sections revealed that injected fluid did not at first mix with the disc matrix but pushed it aside to form pools of injected fluid. The location of these pools, and hence the appearance of a discogram, depended on the stage of degeneration of the disc. It is concluded that useful clinical information can be obtained from discograms


The Journal of Bone & Joint Surgery British Volume
Vol. 71-B, Issue 3 | Pages 434 - 436
1 May 1989
Simpson A Creasy T Williamson D Wilson D Spivey J

An area of fibrous dysplasia of bone may undergo rapid enlargement which may be due to either cystic degeneration or malignant transformation. These complications may be clinically and radiologically indistinguishable and, unless both are borne in mind, incorrect management may follow. Magnetic resonance imaging was used in one of our cases and was the only imaging modality to demonstrate the true nature of the condition


The Journal of Bone & Joint Surgery British Volume
Vol. 65-B, Issue 4 | Pages 478 - 492
1 Aug 1983
Raji A Bowden R

Apart from preliminary notices of present work, previous reports of experimental and clinical trials of the effects of a high-peak pulsed electromagnetic field (PEMF) on degeneration and regeneration of peripheral nerves lacked statistical analysis. Therefore, we designed experiments with standardised operative, histological, cytological and morphometric techniques to assess the effect of PEMF on lesions of the common peroneal nerves in paired male rats matched for age, environmental conditions and level and type of lesion. One of two types of lesion was induced in the left common peroneal nerve: in 12 pairs of rats the nerve was crushed just above the knee and in the remaining 12 pairs the nerve was cut and immediately sutured at the same level. The right common peroneal nerve of each rat served as a control. Animals received 15 minutes of PEMF produced by a Diapulse machine or sham treatment daily for periods ranging from three and a half days to eight weeks after injury. Healthy nerves were unaffected, but after damage there were statistically significant differences between PEMF treated and sham treated rats. PEMF accelerated the recovery of injured limbs and the degeneration, regeneration and maturation of myelinated axons; epineural, perineural and intraneural fibrosis was reduced; and the luminal cross-sectional area of intraneural vessels increased after both types of lesion. Findings are discussed and the need for clinical trials is stressed


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 5 | Pages 740 - 744
1 Sep 1992
Jacobs J Rosenbaum D Hay R Gitelis S Black J

We present the case of a 65-year-old man who developed a malignant fibrous histiocytoma at the lesser trochanter five months after a cementless hip replacement. We have reviewed reports of similar cases and discuss them in terms of the possible mechanisms of sarcomatous degeneration and the latency of such changes


The Bone & Joint Journal
Vol. 102-B, Issue 6 | Pages 727 - 735
1 Jun 2020
Burger JA Dooley MS Kleeblad LJ Zuiderbaan HA Pearle AD

Aims

It remains controversial whether patellofemoral joint pathology is a contraindication to lateral unicompartmental knee arthroplasty (UKA). This study aimed to evaluate the effect of preoperative radiological degenerative changes and alignment on patient-reported outcome scores (PROMs) after lateral UKA. Secondarily, the influence of lateral UKA on the alignment of the patellofemoral joint was studied.

Methods

A consecutive series of patients who underwent robotic arm-assisted fixed-bearing lateral UKA with at least two-year follow-up were retrospectively reviewed. Radiological evaluation was conducted to obtain a Kellgren Lawrence (KL) grade, an Altman score, and alignment measurements for each knee. Postoperative PROMs were assessed using the Kujala (Anterior Knee Pain Scale) score, Knee Injury and Osteoarthritis Outcome Score Joint Replacement (KOOS JR), and satisfaction levels.


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 3 | Pages 431 - 435
1 May 1992
Osti O Fraser R

We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain


The Journal of Bone & Joint Surgery British Volume
Vol. 59-B, Issue 2 | Pages 236 - 240
1 May 1977
Green P

Thirty-three patients who had undergone anterior cervical fusion for degenerative disc disease were reviewed to determine the efficacy of the procedure. Only patients who were available for examination and who had undergone operation at least one year previously were included in the review. Nearly all had had arm pain and three-quarters neck pain. Diminished neck movement and neurological abnormalities in the arms had been frequent findings. Diagnosis from the clinical features and plain radiographs is described. Myelography was not used routinely and discography was not used at all. Indications for operation and surgical technique are described. Results show that pain in the neck and arm was relieved in a high proportion of cases and that the neurological abnormalities often recovered. It is concluded that this operation is safe and has a definite place in the relief of pain from cervical disc degeneration resistant to conservative treatment


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).


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

Aims

The complex relationship between acetabular component position and spinopelvic mobility in patients following total hip arthroplasty (THA) renders it difficult to optimize acetabular component positioning. Mobility of the normal lumbar spine during postural changes results in alterations in pelvic tilt (PT) to maintain the sagittal balance in each posture and, as a consequence, markedly changes the functional component anteversion (FCA). This study aimed to investigate the in vivo association of lumbar degenerative disc disease (DDD) with the PT angle and with FCA during postural changes in THA patients.

Methods

A total of 50 patients with unilateral THA underwent CT imaging for radiological evaluation of presence and severity of lumbar DDD. In all, 18 patients with lumbar DDD were compared to 32 patients without lumbar DDD. In vivo PT and FCA, and the magnitudes of changes (ΔPT; ΔFCA) during supine, standing, swing-phase, and stance-phase positions were measured using a validated dual fluoroscopic imaging system.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1187 - 1192
1 Sep 2012
Rakhra KS Lattanzio P Cárdenas-Blanco A Cameron IG Beaulé PE

Advanced MRI cartilage imaging such as T1-rho (T1ρ) for the diagnosis of early cartilage degradation prior to morpholgic radiological changes may provide prognostic information in the management of joint disease. This study aimed first to determine the normal T1ρ profile of cartilage within the hip, and secondly to identify any differences in T1ρ profile between the normal and symptomatic femoroacetabular impingement (FAI) hip. Ten patients with cam-type FAI (seven male and three female, mean age 35.9 years (28 to 48)) and ten control patients (four male and six female, mean age 30.6 years (22 to 35)) underwent 1.5T T1ρ MRI of a single hip. Mean T1ρ relaxation times for full thickness and each of the three equal cartilage thickness layers were calculated and compared between the groups. The mean T1ρ relaxation times for full cartilage thickness of control and FAI hips were similar (37.17 ms (sd 9.95) and 36.71 ms (sd 6.72), respectively). The control group demonstrated a T1ρ value trend, increasing from deep to superficial cartilage layers, with the middle third having significantly greater T1ρ relaxation values than the deepest third (p = 0.008). The FAI group demonstrated loss of this trend. The deepest third in the FAI group demonstrated greater T1ρ relaxation values than controls (p = 0.028).

These results suggest that 1.5T T1ρ MRI can detect acetabular hyaline cartilage changes in patients with FAI.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 5 | Pages 669 - 673
1 Jul 2004
Bock P Kristen K Kröner A Engel A

This study relates the extent of cartilage lesions within the first metatarsophalangeal joint to hallux valgus.

We prospectively examined 265 first metatarsophalangeal joints of 196 patients with a mean age of 54.2 years at operation for the existence of cartilage lesions.

Grade I lesions were found in 41 feet (15.5%), grade II in 82 (30.9%), grade III in 51 (19.3%), grade IV in 20 (7.5%). Only 71 (26.8%) showed no cartilage lesion. Cartilage lesions were found within the metatarsosesamoid and metatarsophalangeal compartments in 66 feet (34.0%), within the metatarsophalangeal compartment in 26 (13.4%) and within the metatarsosesamoid compartment in 102 (52.6%). A statistically significant correlation was found between the grade of cartilage lesion and the hallux valgus angle, both for the changes within the metatarsophalangeal and the metatarsosesamoid joints.


The Journal of Bone & Joint Surgery British Volume
Vol. 72-B, Issue 2 | Pages 275 - 276
1 Mar 1990
Bough B Thakore J Davies M Dowling F

The reproduction of symptoms on arthrography of the lumbar facet joint has been accepted as a screening procedure before localised spinal fusion. We studied the histology of 127 facet joints removed at operation from 84 patients, who had previously had facet arthrography. The specificity of the arthrographic results for degenerative joint disease was 75% but their sensitivity was only 59%. This gave a positive predictive value of 85%, but a negative predictive value of only 43%. We conclude that the production of symptoms during facet arthrography is of little value as a screening procedure.


The Journal of Bone & Joint Surgery British Volume
Vol. 41-B, Issue 2 | Pages 362 - 364
1 May 1959
Robertson DE


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 4 | Pages 589 - 594
1 Jul 1992
Edelson J Taitz C

We examined 200 scapular bones for signs of degenerative changes in the coraco-acromial arch. The slope and length of the acromion and the height of the arch were found to be most closely associated with degenerative change. These anatomical features are not significantly altered by current techniques of subacromial decompression.


The Journal of Bone & Joint Surgery British Volume
Vol. 63-B, Issue 2 | Pages 272 - 277
1 May 1981
Kikuchi S Macnab I Moreau P

There are many difficulties associated with the localisation of the symptomatic segment in patients presenting with cervicobrachial pain with no evidence of impaired conduction in the nerve root. Ancillary radiological investigations such as myelography, epidural phlebography, and epidural myelograms are of unreliable diagnostic value. However, discography can be of value if the technique described here is used. Infiltration of the cervical nerve root with local anaesthetic has also proved useful in the localisation of the symptomatic segment. The techniques used in cervical discography and infiltration of the nerve root are described and their reliability is assessed.


The Journal of Bone & Joint Surgery British Volume
Vol. 43-B, Issue 2 | Pages 387 - 393
1 May 1961
Berry RJ

A description is given of a mutation in the mouse which reduces the size of the nucleus pulposus in the intervertebral disc of the adults. The discs of these mice show greatly accelerated age changes. The consequences of a similar mutation in man are discussed.


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 5 | Pages 854 - 854
1 Sep 1996
LIVESLEY PJ


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 5 | Pages 854 - 854
1 Sep 1996
NOBLE J


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 2 | Pages 217 - 219
1 Mar 1996
Hubbard MJS

In a prospective randomised trial 76 knees with isolated degenerative changes in the medial femoral condyle of grades 3 or 4 were treated by either arthroscopic debridement (40) or washout (36).

All knees were followed up for at least one year and 58 for five years. The mean follow-up time was 4.5 years in the debridement group and 4.3 years in the washout group.

At one year 32 of the debridement group and five of the washout group were painfree and at five years 19 of a total of 32 survivors in the debridement group and three of the 26 in the washout group were also free from pain. The mean improvement in a modified Lysholm score was 28 for the debridement group at one year and 21 at five years. In the washout group it was only 5 at one year and 4 at five years.

For knees with lesions of the medial femoral condyle of grades 3 or 4, arthroscopic debridement appears to be the treatment of choice with over half the patients free from pain after five years.


The Journal of Bone & Joint Surgery British Volume
Vol. 53-B, Issue 2 | Pages 296 - 302
1 May 1971
van Creveld S Hoedemaeker PJ Kingma MJ Wagenvoort CA

1. Four joints of three young haemophiliacs who died in traffic accidents have been examined.

2. All patients had received prompt specific treatment for intra-articular and other haemorrhages.

3. Major macroscopic and histological changes were seen in the joints, but these changes were not quite so severe as those described before the days of specific treatment.

4. The possibilities of preventing articular changes and of minimising the effect of blood in the joints are discussed.


The Journal of Bone & Joint Surgery British Volume
Vol. 75-B, Issue 3 | Pages 381 - 385
1 May 1993
Jonsson B Stromqvist B

In a prospective, consecutive study we determined the frequency of common symptoms and signs in 300 patients with lumbar nerve-root compression syndromes. We compared 100 patients with disc herniation (mean age 43 years), 100 with lataral spinal stenosis (41 years) and 100 with central spinal stenosis (65 years), using a standard protocol of common signs and symptoms. The diagnoses were established by one or more of myelography, CT, MRI and nerve-root block, and all were confirmed at operation. The preoperative duration of symptoms was significantly shorter in patients with disc herniation. Pain at rest, at night, and on coughing was as common in lateral stenosis as in disc herniation, but regular consumption of analgesics was more common in patients with disc herniation. Positive straight-leg-raising tests were more common in disc herniation than in lateral stenosis and were uncommon in central stenosis. Motor disturbances were seen most often in central spinal stenosis, especially patellar reflex changes. Sensory disturbances were most common in patients with complete disc herniation.


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). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610


Bone & Joint Research
Vol. 13, Issue 9 | Pages 474 - 484
10 Sep 2024
Liu Y Li X Jiang L Ma J

Aims. Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods. Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results. We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion. This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT. Cite this article: Bone Joint Res 2024;13(9):474–484


Bone & Joint 360
Vol. 11, Issue 6 | Pages 34 - 36
1 Dec 2022

The December 2022 Spine Roundup. 360. looks at: Deep venous thrombosis prophylaxis protocol on a Level 1 trauma centre patient database; Non-specific spondylodiscitis: a new perspective for surgical treatment; Disc degeneration could be recovered after chemonucleolysis; Three-level anterior cervical discectomy and fusion versus corpectomy- anterior cervical discectomy and fusion “hybrid” procedures: how does the alignment look?; Rivaroxaban or enoxaparin for venous thromboembolism prophylaxis; Surgical site infection: when do we have to remove the implants?; Determination of a neurologic safe zone for bicortical S1 pedicle placement; Do you need to operate on unstable spine fractures in the elderly: outcomes and mortality; Degeneration to deformity: when does the patient need both?


The Bone & Joint Journal
Vol. 106-B, Issue 2 | Pages 195 - 202
1 Feb 2024
Jamshidi K Kargar Shooroki K Ammar W Mirzaei A

Aims. The epiphyseal approach to a chondroblastoma of the intercondylar notch of a child’s distal femur does not provide adequate exposure, thereby necessitating the removal of a substantial amount of unaffected bone to expose the lesion. In this study, we compared the functional outcomes, local recurrence, and surgical complications of treating a chondroblastoma of the distal femoral epiphysis by either an intercondylar or an epiphyseal approach. Methods. A total of 30 children with a chondroblastoma of the distal femur who had been treated by intraregional curettage and bone grafting were retrospectively reviewed. An intercondylar approach was used in 16 patients (group A) and an epiphyseal approach in 14 (group B). Limb function was assessed using the Musculoskeletal Tumor Society (MSTS) scoring system and Sailhan’s functional criteria. Results. At final follow-up, the mean MSTS score was 29.1 (SD 0.9) in group A and 26.7 (SD 1.5) in group B (p = 0.006). According to Sailhan’s criteria, the knee function was good and fair in 14 (87.5%) and two (12.5%) patients of group A, and eight (57.1%) and six (42.9%) patients of group B, respectively (p = 0.062). The lesion had recurred in one patient (6.2%) in group A and four patients (28.6%) in group B. Limb shortening > 1 cm was recorded in one patient (6.2%) from group A and six patients (42.8%) from group B. Joint degeneration was noted in one patient from group A and three patients from group B. Conclusion. An intercondylar approach to a chondroblastoma of the middle two-quarters of the distal femoral epiphysis results in better outcomes than a medial or lateral epiphyseal approach: specifically, better limb function, a lower rate of recurrence, and a lower rate of physeal damage and joint degeneration. Cite this article: Bone Joint J 2024;106-B(2):195–202


Bone & Joint Research
Vol. 11, Issue 11 | Pages 826 - 834
17 Nov 2022
Kawai T Nishitani K Okuzu Y Goto K Kuroda Y Kuriyama S Nakamura S Matsuda S

Aims. The preventive effects of bisphosphonates on articular cartilage in non-arthritic joints are unclear. This study aimed to investigate the effects of oral bisphosphonates on the rate of joint space narrowing in the non-arthritic hip. Methods. We retrospectively reviewed standing whole-leg radiographs from patients who underwent knee arthroplasties from 2012 to 2020 at our institute. Patients with previous hip surgery, Kellgren–Lawrence grade ≥ II hip osteoarthritis, hip dysplasia, or rheumatoid arthritis were excluded. The rate of hip joint space narrowing was measured in 398 patients (796 hips), and the effects of the use of bisphosphonates were examined using the multivariate regression model and the propensity score matching (1:2) model. Results. A total of 45 of 398 (11.3%) eligible patients were taking an oral bisphosphonate at the time of knee surgery, with a mean age of 75.8 years (SD 6.2) in bisphosphonate users and 75.7 years (SD 6.8) in non-users. The mean joint space narrowing rate was 0.04 mm/year (SD 0.11) in bisphosphonate users and 0.12 mm/year (SD 0.25) in non-users (p < 0.001). In the multivariate model, age (standardized coefficient = 0.0867, p = 0.016) and the use of a bisphosphonate (standardized coefficient = −0.182, p < 0.001) were associated with the joint space narrowing rate. After successfully matching 43 bisphosphonate users and 86 non-users, the joint narrowing rate was smaller in bisphosphonate users (p < 0.001). Conclusion. The use of bisphosphonates is associated with decreased joint degeneration in non-arthritic hips after knee arthroplasty. Bisphosphonates slow joint degeneration, thus maintaining the thickness of joint cartilage in the normal joint or during the early phase of osteoarthritis. Cite this article: Bone Joint Res 2022;11(11):826–834


Bone & Joint Research
Vol. 11, Issue 7 | Pages 453 - 464
20 Jul 2022
Wang H Shi Y He F Ye T Yu S Miao H Liu Q Zhang M

Aims. Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Methods. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis. Results. Abnormal adipogenesis, characterized by increased expression of CCAAT/enhancer-binding protein α (CEBPα), fatty acid binding protein 4 (FABP4), Perilipin1, Adiponectin (AdipoQ), and peroxisome proliferator-activated receptor γ (PPARγ), was enhanced in the degenerative cartilage of TMJ OA in UAC mice, accompanied by decreased expression of GDF11. After FFSS stimulation, there were fat droplets in the cytoplasm of cultured cells with increased expression of PPARγ, CEBPα, FABP4, Perilipin1, and AdipoQ and decreased expression of GDF11. Exogenous GDF11 inhibited increased lipid droplets and expression of AdipoQ, CEBPα, and FABP4 induced by FFSS stimulation. GDF11 did not affect the change in PPARγ expression under FFSS, but promoted its post-translational modification by small ubiquitin-related modifier (SUMOylation). Local injection of GDF11 alleviated TMJ OA-related cartilage degeneration and abnormal adipogenesis in UAC mice. Conclusion. Abnormal adipogenesis of chondrocytes and decreased GDF11 expression were observed in degenerative cartilage of TMJ OA. GDF11 supplementation effectively inhibits the adipogenesis of chondrocytes and thus alleviates TMJ condylar cartilage degeneration. GDF11 may inhibit the abnormal adipogenesis of chondrocytes by affecting the SUMOylation of PPARγ. Cite this article: Bone Joint Res 2022;11(7):453–464


Bone & Joint 360
Vol. 12, Issue 4 | Pages 30 - 32
1 Aug 2023

The August 2023 Spine Roundup360 looks at: Changes in paraspinal muscles correspond to the severity of degeneration in patients with lumbar stenosis; Steroid injections are not effective in the prevention of surgery for degenerative cervical myelopathy; A higher screw density is associated with fewer mechanical complications after surgery for adult spinal deformity; Methylprednisolone following minimally invasive lumbar decompression: a large prospective single-institution study; Occupancy rate of pedicle screw below 80% is a risk factor for upper instrumented vertebral fracture following adult spinal deformity surgery; Deterioration after surgery for degenerative cervical myelopathy: an observational study from the Canadian Spine Outcomes and Research Network


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. Results. A total of 144 discs were categorized as ‘positive’ and 174 discs as ‘negative’ by the results of provocation discography. The presence of defined facet tropism (OR 3.451, 95% CI 1.944 to 6.126) and higher Adams classification (OR 2.172, 95% CI 1.523 to 3.097) were important predictive parameters for discography-‘positive’ discs. FEM simulations showcased uneven stress distribution and significant disc displacement in tropism-affected discs, where loading exacerbated stress on facets with greater angles. During varied positions, notably increased stress and displacement were observed in discs with tropism compared to those with normal facet structure. Conclusion. Our findings indicate that facet tropism can contribute to disc herniation and changes in intradiscal pressure, potentially exacerbating disc degeneration due to altered force distribution and increased mechanical stress. Cite this article: Bone Joint Res 2024;13(9):452–461



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

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


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

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


Bone & Joint 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 Open
Vol. 5, Issue 9 | Pages 749 - 757
12 Sep 2024
Hajialiloo Sami S Kargar Shooroki K Ammar W Nahvizadeh S Mohammadi M Dehghani R Toloue B

Aims. The ulna is an extremely rare location for primary bone tumours of the elbow in paediatrics. Although several reconstruction options are available, the optimal reconstruction method is still unknown due to the rarity of proximal ulna tumours. In this study, we report the outcomes of osteoarticular ulna allograft for the reconstruction of proximal ulna tumours. Methods. Medical profiles of 13 patients, who between March 2004 and November 2021 underwent osteoarticular ulna allograft reconstruction after the resection of the proximal ulna tumour, were retrospectively reviewed. The outcomes were measured clinically by the assessment of elbow range of motion (ROM), stability, and function, and radiologically by the assessment of allograft-host junction union, recurrence, and joint degeneration. The elbow function was assessed objectively by the Musculoskeletal Tumor Society (MSTS) score and subjectively by the Toronto Extremity Salvage Score (TESS) and Mayo Elbow Performance Score (MEPS) questionnaire. Results. The mean follow-up of patients was 60.3 months (SD 28.5). The mean elbow flexion-extension ROM was 95.8° (SD 21). The mean MSTS of the patients was 84.4 (SD 8.2), the mean TESS was 83.8 (SD 6.7), and the mean MEPS was 79.2 (SD 11.5). All the patients had radiological union at the osteotomy site. Symptomatic osteoarthritic change was observed in three patients (23%), one of whom ended up with elbow joint fusion. Two patients (15.4%) had recurrence during the follow-up period. Surgical complications included two allograft fractures, two plate fractures, three medial instabilities, and two infections. Conclusion. Osteoarticular ulna allograft reconstruction provides acceptable functional outcomes. Despite a high rate of complications, it is still a valuable reconstruction method, particularly in skeletally immature patients who need their distal humerus physis for the rest of hand growth. Cite this article: Bone Jt Open 2024;5(9):749–757


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. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71


Bone & Joint Research
Vol. 11, Issue 7 | Pages 413 - 425
1 Jul 2022
Tu C Lai S Huang Z Cai G Zhao K Gao J Wu Z Zhong Z

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425


Bone & Joint Research
Vol. 10, Issue 3 | Pages 173 - 187
1 Mar 2021
Khury F Fuchs M Awan Malik H Leiprecht J Reichel H Faschingbauer M

Aims. To explore the clinical relevance of joint space width (JSW) narrowing on standardized-flexion (SF) radiographs in the assessment of cartilage degeneration in specific subregions seen on MRI sequences in knee osteoarthritis (OA) with neutral, valgus, and varus alignments, and potential planning of partial knee arthroplasty. Methods. We retrospectively reviewed 639 subjects, aged 45 to 79 years, in the Osteoarthritis Initiative (OAI) study, who had symptomatic knees with Kellgren and Lawrence grade 2 to 4. Knees were categorized as neutral, valgus, and varus knees by measuring hip-knee-angles on hip-knee-ankle radiographs. Femorotibial JSW was measured on posteroanterior SF radiographs using a special software. The femorotibial compartment was divided into 16 subregions, and MR-tomographic measurements of cartilage volume, thickness, and subchondral bone area were documented. Linear regression with adjustment for age, sex, body mass index, and Kellgren and Lawrence grade was used. Results. We studied 345 neutral, 87 valgus, and 207 varus knees. Radiological JSW narrowing was significantly (p < 0.01) associated with cartilage volume and thickness in medial femorotibial compartment in neutral (r = 0.78, odds ratio (OR) 2.33) and varus knees (r = 0.86, OR 1.92), and in lateral tibial subregions in valgus knees (r = 0.87, OR 3.71). A significant negative correlation was found between JSW narrowing and area of subchondral bone in external lateral tibial subregion in valgus knees (r = −0.65, p < 0.01) and in external medial tibial subregion in varus knees (r = −0.77, p < 0.01). No statistically significant correlation was found in anterior and posterior subregions. Conclusion. SF radiographs can be potentially used for initial detection of cartilage degeneration as assessed by MRI in medial and lateral but not in anterior or posterior subregions. Cite this article: Bone Joint Res 2021;10(3):173–187


The Bone & Joint Journal
Vol. 102-B, Issue 8 | Pages 981 - 996
1 Aug 2020
Yang Y Zhao H Chai Y Zhao D Duan L Wang H Zhu J Yang S Li C Chen S Chae S Song J Wang X Yu X

Aims. Whether to perform hybrid surgery (HS) in contrast to anterior cervical discectomy and fusion (ACDF) when treating patients with multilevel cervical disc degeneration remains a controversial subject. To resolve this we have undertaken a meta-analysis comparing the outcomes from HS with ACDF in this condition. Methods. Seven databases were searched for studies of HS and ACDF from inception of the study to 1 September 2019. Both random-effects and fixed-effects models were used to evaluate the overall effect of the C2-C7 range of motion (ROM), ROM of superior/inferior adjacent levels, adjacent segment degeneration (ASD), heterotopic ossification (HO), complications, neck disability index (NDI) score, visual analogue scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Odom’s criteria, blood loss, and operating and hospitalization time. To obtain more credible results contour-enhanced funnel plots, Egger’s and Begg’s tests, meta-regression, and sensitivity analyses were performed. Results. In total, 17 studies involving 861 patients were included in the analysis. HS was found to be superior to ACDF in maintaining C2-C7 ROM and ROM of superior/inferior adjacent levels, but HS did not reduce the incidence of associated level ASD. Also, HS did not cause a higher rate of HO than ACDF. The frequency of complications was similar between the two techniques. HS failed to achieve more favourable outcomes than ACDF using the NDI, VAS, JOA, and Odom’s scores. HS did not show any more advantages in operating or hospitalization time but did show reduction in blood loss. Conclusion. Although HS maintained cervical kinetics, it failed to reduce the incidence of ASD. This finding differs from previous reports. Moreover, patients did not show more benefits from HS with respect to symptom improvement, prevention of complications, and clinical outcomes. Cite this article: Bone Joint J 2020;102-B(8):981–996


The Bone & Joint Journal
Vol. 106-B, Issue 1 | Pages 86 - 92
1 Jan 2024
Scholte CHJ Dorleijn DMJ Krijvenaar DT van de Sande MAJ van Langevelde K

Aims. Due to its indolent clinical behaviour, the treatment paradigm of atypical cartilaginous tumours (ACTs) in the long bones is slowly shifting from intralesional resection (curettage) and local adjuvants, towards active surveillance through wait-and-scan follow-up. In this retrospective cohort study performed in a tertiary referral centre, we studied the natural behaviour of ACT lesions by active surveillance with MRI. Clinical symptoms were not considered in the surveillance programme. Methods. The aim of this study was to see whether active surveillance is safe regarding malignant degeneration and local progression. In total, 117 patients were evaluated with MRI assessing growth, cortical destruction, endosteal scalloping, periosteal reaction, relation to the cortex, and perilesional bone marrow oedema. Patients received up to six follow-up scans. Results. At the time of the first follow-up MRI, 8% of the lesions showed growth (n = 9), 86% remained stable (101), and 6% decreased in size (n = 7). During the third follow-up, with a mean follow-up time of 60 months (SD 23), 24 patients were scanned, of whom 13% had lesions that had grown and 13% lesions that had decreased in size. After 96 months (SD 37), at the sixth follow-up MRI, 100% of the lesions remained stable. None of the lesions showed malignant progression and although some lesions grew in size (mean 1 mm (SD 0.8)), no malignant progression occurred. Conclusion. We conclude that active surveillance with MRI is safe for ACTs in the long bones in the short- and mid-term follow-up. Cite this article: Bone Joint J 2024;106-B(1):86–92


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 394 - 400
1 Mar 2022
Lee KJ Kim YT Choi M Kim SH

Aims. The aim of this study was to compare the characteristics and outcomes of L-shaped and reverse L-shaped rotator cuff tears. Methods. A total of 82 shoulders (81 patients) after arthroscopic rotator cuff repair were retrospectively enrolled. The mean age of the patients was 62 years (SD 6), 33 shoulders (40.2%) were in male patients, and 57 shoulders (69.5%) were the right shoulder. Of these, 36 shoulders had an L-shaped tear (group L) and 46 had a reverse L-shaped tear (group RL). Both groups were compared regarding characteristics, pre- and postoperative pain, and functional outcomes. Muscle status was assessed by preoperative MRI, and re-tear rates by postoperative ultrasonography or MRI. Results. Patients in group RL were significantly older than in group L (p = 0.008), and group RL was significantly associated with female sex (odds ratio 2.5 (95% confidence interval 1.03 to 6.32); p = 0.041). Mean postoperative pain visual analogue scale (VAS) score was significantly greater (group L = 0.8 (SD 1.5), group RL = 1.7 (SD 2.2); p = 0.033) and mean postoperative American Shoulder and Elbow Surgeons (ASES) score was significantly lower in group RL than group L (group L = 91.4 (SD 13.1), group RL = 83.8 (SD 17.9); p = 0.028). However, postoperative mean VAS for pain and ASES score were not lower than the patient-acceptable symptom state scores. Mean retracted tear length was significantly larger in group L (group L = 24.6 mm (SD 6.5), group RL = 20.0 mm (SD 6.8); p = 0.003). Overall re-tear rate for 82 tears was 11.0% (nine shoulders), and re-tear rates in group L and RL were similar at 11.1% (four shoulders) and 10.9% (five shoulders), respectively (p = 1.000). No significant intergroup difference was found for fatty degeneration (FD) or muscle atrophy. Within group L, postoperative FD grades of supraspinatus and subscapularis worsened significantly (p = 0.034 and p = 0.008, respectively). Mean postoperative pain VAS (male = 1.2 (SD 1.8), female = 1.3 (SD 2.0)) and ASES scores (male = 88.7 (SD 15.5), female = 86.0 (SD 16.8)) were similar in male and female patients (p = 0.700 and p = 0.475, respectively). Regression analysis showed age was not a prognostic factor of postoperative pain VAS or ASES scores (p = 0.188 and p = 0.150, respectively). Conclusion. Older age and female sex were associated with reverse L-shaped tears. Although the postoperative functional outcomes of patients with reverse L-shaped tears were satisfactory, the clinical scores were poorer than those of patients with L-shaped tears. Surgeons should be aware of the differences in clinical outcome between L-shaped and reverse L-shaped rotator cuff tears. Cite this article: Bone Joint J 2022;104-B(3):394–400


The Bone & Joint Journal
Vol. 103-B, Issue 10 | Pages 1619 - 1626
1 Oct 2021
Bi M Zhou K Gan K Ding W Zhang T Ding S Li J

Aims. The aim of this study is to provide a detailed description of cases combining bridging patch repair with artificial ligament “internal brace” reinforcement to treat irreparable massive rotator cuff tears, and report the preliminary results. Methods. This is a retrospective review of patients with irreparable massive rotator cuff tears undergoing fascia lata autograft bridging repair with artificial ligament “internal brace” reinforcement technique between January 2017 and May 2018. Inclusion criteria were: patients treated arthroscopically for an incompletely reparable massive rotator cuff tear (dimension > 5 cm or two tendons fully torn), stage 0 to 4 supraspinatus fatty degeneration on MRI according to the Goutallier grading system, and an intact or reparable infraspinatus and/or subscapularis tendon of radiological classification Hamada 0 to 4. The surgical technique comprised two components: first, superior capsular reconstruction using an artificial ligament as an “internal brace” protective device for a fascia lata patch. The second was fascia lata autograft bridging repair for the torn supraspinatus. In all, 26 patients with a mean age 63.4 years (SD 6.2) were included. Results. All patients underwent more than two years of follow-up (mean 33.5 months (24 to 45)). All clinical scores were also improved at two-year follow-up (mean visual analogue scale 0.7 (SD 0.5) vs 6.1 (SD 1.2); p < 0.001; mean American Shoulder and Elbow Surgeons score 93.5 (SD 5.3) vs 42.5 (SD 10.8); p < 0.001; mean University of California, Los Angeles score, 31.7 (SD 3.7) vs 12.0 (SD 3.1); p < 0.001; and mean Constant-Murley score 88.7 (SD 3.5) vs 43.3 (SD 10.9); p < 0.001), and 24 of 26 fascia lata grafts were fully healed on MRI (92%). One patient had haematoma formation at the harvesting side of the fascia lata at two days postoperatively. Conclusion. The fascia lata autograft bridging repair combined with artificial ligament internal brace reinforcement technique achieved good functional outcomes, with a high rate of graft healing at two-year follow-up. Although the short-term results are promising, further studies with a greater number of patients would provide clearer results. Cite this article: Bone Joint J 2021;103-B(10):1619–1626


Objectives. Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb. Methods. The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin. Results. In total, 12 cases were found to have severe medial cartilage wear compared with the lateral cartilage. Immunofluorescence showed that the expression of Ob-Rb in the medial cartilage of the tibial plateau was high. High levels of leptin led to cell cycle arrest and inhibited autophagy. After overexpression of Ob-Rb, the physiological dose of leptin induced cell senescence in the chondrocytes. High doses of leptin inhibited autophagy by activating the mTOR signalling pathway. Blockade of the mTOR signalling pathway could restore autophagy and partially reverse senescence induced by leptin in chondrocytes. Conclusion. In summary, the present study demonstrated that high doses of leptin induce cell senescence by activating the mTOR pathway in chondrocytes from OA cartilage. Highly expressed Ob-Rb accelerates chondrocyte senescence by activating the leptin pathway in OA. Cite this article: X. Zhao, P. Huang, G. Li, L. Zhendong, G. Hu, Q. Xu. Activation of the leptin pathway by high expression of the long form of the leptin receptor (Ob-Rb) accelerates chondrocyte senescence in osteoarthritis. Bone Joint Res 2019;8:425–436. DOI: 10.1302/2046-3758.89.BJR-2018-0325.R2


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. Results. Surgical DMM with or without stereomicroscope led to decrease in the mean of weightbearing percentages (-20.64% vs -21.44%, p = 0.792) and paw withdrawal response thresholds (-21.35% vs -24.65%, p = 0.327) of the hind limbs. However, the coefficient of variation (CV) of weight-bearing percentages and paw withdrawal response thresholds in naked-eye group were significantly greater than that in the microscope group (19.82% vs 6.94%, p < 0.001; 21.85% vs 9.86%, p < 0.001). The gait analysis showed a similar pattern. Cartilage degeneration was observed in both DMM-surgery groups, evidenced by increased OARSI scores (summed score: 11.23 vs 11.43, p = 0.842), but the microscope group showed less variation in OARSI score than the naked-eye group (CV: 21.03% vs 32.44%; p = 0.032). Conclusion. Although surgical DMM aided by stereomicroscope is technically difficult, it produces a relatively more homogeneous OA model in terms of the discrete degree of pain behaviours and histopathological grading when compared with surgical DMM without stereomicroscope. Cite this article: Bone Joint Res 2022;11(8):518–527


Bone & Joint Research
Vol. 7, Issue 2 | Pages 157 - 165
1 Feb 2018
Sun Y Kiraly AJ Sun AR Cox M Mauerhan DR Hanley EN

Objectives. The objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01). Methods. Young Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs. Results. In addition to cartilage degeneration, osteophytes, subchondral bone advance, and BMLs increased with age. Subchondral bone advance was observed as early as six months, whereas BMLs and osteophytes were both observed mainly at 12 and 18 months. Fibrotic BMLs were found mostly underneath the degenerated cartilage on the medial side. In contrast, necrotic BMLs were found almost exclusively in the interspinous region. Orally administered CM-01 decreased all of these pathological changes and reduced the levels of MMP13 expression. Conclusion. Subchondral bone may play a role in cartilage degeneration. Subchondral bone changes are early events; formation of osteophytes and BMLs are later events in the OA disease process. Carolinas Molecule-01 is a promising small molecule candidate to be tested as an oral disease-modifying drug for human OA therapy. Cite this article: Y. Sun, A. J. Kiraly, A. R. Sun, M. Cox, D. R. Mauerhan, E. N. Hanley Jr. Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea pigs. Bone Joint Res 2018;7:157–165. DOI:10.1302/2046-3758.72.BJR-2017-0253


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1472 - 1478
1 Sep 2021
Shoji T Saka H Inoue T Kato Y Fujiwara Y Yamasaki T Yasunaga Y Adachi N

Aims. Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI. Methods. We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head. Results. There were 16 patients with postoperative OA progression. The T2 values of the centre to the anterolateral region of the acetabulum and femoral head in the OA progression cases were significantly higher than those in patients without OA progression. The preoperative T2 values in those regions were positively correlated with the narrowed joint space width. The receiver operating characteristic analysis revealed that the T2 value of the central portion in the acetabulum provided excellent discrimination, with OA progression patients having an area under the curve of 0.858. Furthermore, logistic regression analysis showed T2 values of the centre to the acetabulum’s anterolateral portion as independent predictors of subsequent OA progression (p < 0.001). Conclusion. This was the first study to evaluate the relationship between intra-articular degeneration using T2 mapping MRI and postoperative OA progression. Our findings suggest that preoperative T2 values of the hip can be better prognostic factors for OA progression than radiological measures following RAO. Cite this article: Bone Joint J 2021;103-B(9):1472–1478


The Bone & Joint Journal
Vol. 103-B, Issue 4 | Pages 725 - 733
1 Apr 2021
Lai MKL Cheung PWH Samartzis D Karppinen J Cheung KMC Cheung JPY

Aims. The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. Methods. This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate. Results. Axial AP vertebral canal diameter (p < 0.001), interpedicular distance (p < 0.001), AP dural sac diameter (p < 0.001), lamina angle (p < 0.001), and sagittal mid-vertebral body height (p < 0.001) were significantly different between those identified as having DSS and controls. Narrower interpedicular distance (OR 0.745 (95% CI 0.618 to 0.900); p = 0.002) and AP dural sac diameter (OR 0.506 (95% CI 0.400 to 0.641); p < 0.001) were associated with DSS. Lamina angle (OR 1.127 (95% CI 1.045 to 1.214); p = 0.002) and right facet joint angulation (OR 0.022 (95% CI 0.002 to 0.247); p = 0.002) were also associated with DSS. No association was observed between disc parameters and DSS. Conclusion. From this large-scale cohort, the canal size is found to be independent of body stature. Other than spinal canal dimensions, abnormal orientations of lamina angle and facet joint angulation may also be a result of developmental variations, leading to increased likelihood of DSS. Other skeletal parameters are spared. There was no relationship between DSS and soft tissue changes of the spinal column, which suggests that DSS is a unique result of bony maldevelopment. These findings require validation in other ethnicities and populations. Level of Evidence: I (diagnostic study). Cite this article: Bone Joint J 2021;103-B(4):725–733


Bone & Joint Research
Vol. 9, Issue 12 | Pages 857 - 869
1 Dec 2020
Slullitel PA Coutu D Buttaro MA Beaule PE Grammatopoulos G

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article: Bone Joint Res 2020;9(12):857–869


Bone & Joint Open
Vol. 2, Issue 11 | Pages 988 - 996
26 Nov 2021
Mohtajeb M Cibere J Mony M Zhang H Sullivan E Hunt MA Wilson DR

Aims. Cam and pincer morphologies are potential precursors to hip osteoarthritis and important contributors to non-arthritic hip pain. However, only some hips with these pathomorphologies develop symptoms and joint degeneration, and it is not clear why. Anterior impingement between the femoral head-neck contour and acetabular rim in positions of hip flexion combined with rotation is a proposed pathomechanism in these hips, but this has not been studied in active postures. Our aim was to assess the anterior impingement pathomechanism in both active and passive postures with high hip flexion that are thought to provoke impingement. Methods. We recruited nine participants with cam and/or pincer morphologies and with pain, 13 participants with cam and/or pincer morphologies and without pain, and 11 controls from a population-based cohort. We scanned hips in active squatting and passive sitting flexion, adduction, and internal rotation using open MRI and quantified anterior femoroacetabular clearance using the β angle. Results. In squatting, we found significantly decreased anterior femoroacetabular clearance in painful hips with cam and/or pincer morphologies (mean -11.3° (SD 19.2°)) compared to pain-free hips with cam and/or pincer morphologies (mean 8.5° (SD 14.6°); p = 0.022) and controls (mean 18.6° (SD 8.5°); p < 0.001). In sitting flexion, adduction, and internal rotation, we found significantly decreased anterior clearance in both painful (mean -15.2° (SD 15.3°); p = 0.002) and painfree hips (mean -4.7° (SD 13°); p = 0.010) with cam and/pincer morphologies compared to the controls (mean 7.1° (SD 5.9°)). Conclusion. Our results support the anterior femoroacetabular impingement pathomechanism in hips with cam and/or pincer morphologies and highlight the effect of posture on this pathomechanism. Cite this article: Bone Jt Open 2021;2(11):988–996


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 12 | Pages 1602 - 1607
1 Dec 2007
Beard DJ Pandit H Ostlere S Jenkins C Dodd CAF Murray DW

Anterior knee pain and/or radiological evidence of degeneration of the patellofemoral joint are considered to be contraindications to unicompartmental knee replacement. The aim of this study was to determine whether this is the case. Between January 2000 and September 2003, in 100 knees (91 patients) in which Oxford unicompartmental knee replacements were undertaken for anteromedial osteoarthritis, pre-operative anterior knee pain and the radiological status of the patellofemoral joint were defined using the Altman and Ahlback systems. Outcome was evaluated at two years with the Oxford knee score and the American Knee Society score. Pre-operatively 54 knees (54%) had anterior knee pain. The clinical outcome was independent of the presence or absence of pre-operative anterior knee pain. Degenerative changes of the patellofemoral joint were seen in 54 patients (54%) on the skyline radiographs, including ten knees (10%) with joint space obliteration. Patients with medial patellofemoral degeneration had a similar outcome to those without. For some outcome measures patients with lateral patellofemoral degeneration had a worse score than those without, but these patients still had a good outcome, with a mean Oxford knee score of 37.6 (SD 9.5). These results show that neither anterior knee pain nor radiologically-demonstrated medial patellofemoral joint degeneration should be considered a contraindication to Oxford unicompartmental knee replacement. With lateral patellofemoral degeneration the situation is less well defined and caution should be observed


Bone & Joint Research
Vol. 9, Issue 5 | Pages 225 - 235
1 May 2020
Peng X Zhang C Bao J Zhu L Shi R Xie Z Wang F Wang K Wu X

Aims. Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Methods. Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds. Results. The expression of A20 was upregulated in degenerate human intervertebral discs. The A20 levels of NPCs in TNF-α inflammatory microenvironments were dramatically higher than those of the control group. TNF-α significantly decreased cell proliferation potency but increased senescence-associated beta-galactosidase (SA-β-Gal) activity, the expression of senescence-associated proteins, the synthesis of extracellular matrix, and G1 cycle arrest. The senescence indicators and NF-κB/p65 expression of A20 downregulated group treated with TNF-α were significantly upregulated compared to TNF-α-treated normal NPCs. Conclusion. A20 has a self-protective effect on the senescence of NPCs induced by TNF-α. The downregulation of A20 in NPCs exacerbated the senescence of NPCs induced by TNF-α. Cite this article:Bone Joint Res. 2020;9(5):225–235


Bone & Joint Open
Vol. 2, Issue 12 | Pages 1057 - 1061
1 Dec 2021
Ahmad SS Weinrich L Giebel GM Beyer MR Stöckle U Konrads C

Aims. The aim of this study was to determine the association between knee alignment and the vertical orientation of the femoral neck in relation to the floor. This could be clinically important because changes of femoral neck orientation might alter chondral joint contact zones and joint reaction forces, potentially inducing problems like pain in pre-existing chondral degeneration. Further, the femoral neck orientation influences the ischiofemoral space and a small ischiofemoral distance can lead to impingement. We hypothesized that a valgus knee alignment is associated with a more vertical orientation of the femoral neck in standing position, compared to a varus knee. We further hypothesized that realignment surgery around the knee alters the vertical orientation of the femoral neck. Methods. Long-leg standing radiographs of patients undergoing realignment surgery around the knee were used. The hip-knee-ankle angle (HKA) and the vertical orientation of the femoral neck in relation to the floor were measured, prior to surgery and after osteotomy-site-union. Linear regression was performed to determine the influence of knee alignment on the vertical orientation of the femoral neck. Results. The cohort included 147 patients who underwent knee realignment-surgery. The mean age was 51.5 years (SD 11). Overall, 106 patients underwent a valgisation-osteotomy, while 41 underwent varisation osteotomy. There was a significant association between the orientation of the knee and the coronal neck-orientation. In the varus group, the median orientation of the femoral neck was 46.5° (interquartile range (IQR) 49.7° to 50.0°), while in the valgus group, the orientation was 52.0° (IQR 46.5° to 56.7°; p < 0.001). Linear regression analysis revealed that HKA demonstrated a direct influence on the coronal neck-orientation (β = 0.5 (95% confidence interval (CI) 0.2 to 0.7); p = 0.002). Linear regression also showed that realignment surgery was associated with a significant influence on the change in the coronal femoral neck orientation (β = 5.6 (95% CI 1.5 to 9.8); p = 0.008). Conclusion. Varus or valgus knee alignment is associated with either a more horizontal or a more vertical femoral neck orientation in standing position, respectively. Subsequently, osteotomies around the knee alter the vertical orientation of the femoral neck. These aspects are of importance when planning osteotomies around the knee in order to appreciate the effects on the adjacent hip joint. The concept may be of even more relevance in dysplastic hips. Cite this article: Bone Jt Open 2021;2(12):1057–1061


The Bone & Joint Journal
Vol. 98-B, Issue 6 | Pages 829 - 833
1 Jun 2016
Hou Y Nie L Pan X Si M Han Y Li J Zhang H

Aims. In order to evaluate the effectiveness of the Mobi-C implant in cervical disc degeneration, a randomised study was conducted, comparing the Mobi-C prosthesis arthroplasty with anterior cervical disc fusion (ACDF) in patients with single level cervical spondylosis. Patients and Methods. From January 2008 to July 2009, 99 patients were enrolled and randomly divided into two groups, those having a Mobi-C implant (n = 51; 30 men, 21 women) and those undergoing ACDF (n = 48; 28 men, 20 women).The patients were followed up for five years, with the primary outcomes being the Japanese Orthopaedic Association score, visual analogue scale for pain and the incidence of further surgery. The secondary outcomes were the Neck Disability Index and range of movement (ROM) of the treated segment. Results. The incidence of further surgery was found to be statistically significant between the two groups (p = 0.49), with seven ACDF patients requiring further surgery and only one Mobi-C patient requiring re-operation. There were significant differences (p < 0.001) between the two groups in the ROM of the treated segment. However, both Mobi-C surgery and ACDF surgery were effective in improving the patient’s clinical symptoms. Take home message: Mobi-C implant surgery is a safe alternative to ACDF surgery in cervical disc degeneration. Cite this article: Bone Joint J 2016;98-B:829–3


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Methods

Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.


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 3 | Pages 199 - 201
7 Mar 2023
Brzeszczyńska J Brzeszczyński F

Cite this article: Bone Joint Res 2023;12(3):199–201.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 154 - 161
1 Feb 2019
Cheung PWH Fong HK Wong CS Cheung JPY

Aims. The aim of this study was to determine the influence of developmental spinal stenosis (DSS) on the risk of re-operation at an adjacent level. Patients and Methods. This was a retrospective study of 235 consecutive patients who had undergone decompression-only surgery for lumbar spinal stenosis and had a minimum five-year follow-up. There were 106 female patients (45.1%) and 129 male patients (54.9%), with a mean age at surgery of 66.8 years (. sd. 11.3). We excluded those with adult deformity and spondylolisthesis. Presenting symptoms, levels operated on initially and at re-operation were studied. MRI measurements included the anteroposterior diameter of the bony spinal canal, the degree of disc degeneration, and the thickness of the ligamentum flavum. DSS was defined by comparative measurements of the bony spinal canal. Risk factors for re-operation at the adjacent level were determined and included in a multivariate stepwise logistic regression for prediction modelling. Odds ratios (ORs) with 95% confidence intervals were calculated. Results. Of the 235 patients, 21.7% required re-operation at an adjacent segment. Re-operation at an adjacent segment was associated with DSS (p = 0.026), the number of levels decompressed (p = 0.008), and age at surgery (p = 0.013). Multivariate regression model (p < 0.001) controlled for other confounders showed that DSS was a significant predictor of re-operation at an adjacent segment, with an adjusted OR of 3.93. Conclusion. Patients with DSS who have undergone lumbar spinal decompression are 3.9 times more likely to undergo future surgery at an adjacent level. This is a poor prognostic indicator that can be identified prior to index decompression surgery


Bone & Joint Open
Vol. 4, Issue 5 | Pages 329 - 337
8 May 2023
Khan AQ Chowdhry M Sherwani MKA McPherson EJ

Aims

Total hip arthroplasty (THA) is considered the preferred treatment for displaced proximal femoral neck fractures. However, in many countries this option is economically unviable. To improve outcomes in financially disadvantaged populations, we studied the technique of concomitant valgus hip osteotomy and operative fixation (VOOF). This prospective serial study compares two treatment groups: VOOF versus operative fixation alone with cannulated compression screws (CCSs).

Methods

In the first series, 98 hip fixation procedures were performed using CCS. After fluoroscopic reduction of the fracture, three CCSs were placed. In the second series, 105 VOOF procedures were performed using a closing wedge intertrochanteric osteotomy with a compression lag screw and lateral femoral plate. The alignment goal was to create a modified Pauwel’s fracture angle of 30°. After fluoroscopic reduction of fracture, lag screw was placed to achieve the calculated correction angle, followed by inter-trochanteric osteotomy and placement of barrel plate. Patients were followed for a minimum of two years.


The Bone & Joint Journal
Vol. 101-B, Issue 11 | Pages 1356 - 1361
1 Nov 2019
Chalmers BP Mehrotra KG Sierra RJ Pagnano MW Taunton MJ Abdel MP

Aims. Knee osteonecrosis in advanced stages may lead to joint degeneration. Total knee arthroplasty (TKA) for osteonecrosis has traditionally been associated with suboptimal results. We analyzed outcomes of contemporary TKAs for osteonecrosis, with particular emphasis on: survivorship free from aseptic loosening, any revision, and any reoperation plus the clinical outcomes, complications, and radiological results. Patients and Methods. In total, 156 patients undergoing 167 primary TKAs performed for osteonecrosis between 2004 and 2014 at a single institution were reviewed. The mean age at index TKA was 61 years (14 to 93) and the mean body mass index (BMI) was 30 kg/m. 2. (18 to 51) The mean follow-up was six years (2 to 12). A total of 110 TKAs (66%) were performed for primary osteonecrosis and 57 TKAs (34%) for secondary osteonecrosis. Overall, 15 TKAs (9%) had tibial stems, while 12 TKAs (7%) had femoral stems. Posterior-stabilized designs were used in 147 TKAs (88%) of TKAs. Bivariate Cox regression analysis was conducted to identify risk factors for revision and reoperation. Results. Survivorship free from aseptic loosening, any revision, and any reoperation at ten years was 97% (95% confidence interval (CI) 93 to 100), 93% (95% CI 85 to 100), and 82% (95% CI 69 to 93), respectively. No factors, including age, sex, BMI, primary versus secondary osteonecrosis, stem utilization, and constraint, were identified as risk factors for reoperation. Four TKAs (2%) underwent revision, most commonly for tibial aseptic loosening (n = 2). Excluding revisions and reoperations, there was a total of 11 complications (7%), with the most common being a manipulation under anaesthesia (six TKAs, 4%). Mean Knee Society Scores (Knee component) significantly improved from 57 (32 to 87) preoperatively to 91 (49 to 100) postoperatively (p < 0.001). No unrevised TKAs had complete radiolucent lines or radiological evidence of loosening. Conclusion. Contemporary cemented TKAs with selective stem utilization for osteonecrosis resulted in durable survivorship, a low complication rate, and reliable improvement in clinical outcomes. Cite this article: Bone Joint J 2019;101-B:1356–1361


The Bone & Joint Journal
Vol. 100-B, Issue 4 | Pages 450 - 454
1 Apr 2018
Chalmers BP Mehrotra KG Sierra RJ Pagnano MW Taunton MJ Abdel MP

Aims. Primary (or spontaneous) and secondary osteonecrosis of the knee can lead to severe joint degeneration, for which either total or unicompartmental arthroplasty may be considered. However, there are limited studies analyzing outcomes of unicompartmental knee arthroplasties (UKAs) for osteonecrosis involving an isolated compartment of the knee. The aims of this study were to analyze outcomes of UKAs for osteonecrosis with specific focus on 1) survivorship free of any revision or reoperation, 2) risk factors for failure, 3) clinical outcomes, and 4) complications. Patients and Methods. A total of 45 patients underwent 46 UKAs for knee osteonecrosis between 2002 and 2014 at our institution (The Mayo Clinic, Rochester, Minnesota). Twenty patients (44%) were female; the mean age of the patients was 66 years, and mean body mass index (BMI) was 31 kg/m. 2. Of the 46 UKAs, 44 (96%) were medial UKAs, and 35 (76%) were fixed-bearing design. Mean mechanical axis postoperatively was 1.5° varus (0° to 5° varus); 41 UKAs (89%) were performed for primary osteonecrosis. Mean follow-up was five years (2 to 12). Results. Survivorship free of any revision in the cohort was 89% (95% CI 77 to 99) and 76% (95% CI 53 to 99) at five and ten years, respectively. In patients undergoing UKA for primary osteonecrosis survivorship free of any revision was 93% (95% CI 83 to 100)at both five and ten years. Secondary osteonecrosis was a significant risk factor for poorer survivorship free of any revision or reoperation (hazard ratio 7.7, p = 0.03). Three medial UKAs (6.5%) were converted to total knee arthroplasties (TKAs): two for lateral compartment degeneration and one for development of lateral osteonecrosis. No implants were revised for loosening, fracture, or wear. Knee Society scores improved from a mean of 60 (44 to 72) preoperatively to a mean of 94 postoperatively (82 to 100) (p < 0.001). There were no surgical complications. Conclusion. When done for primary osteonecrosis of the knee, UKA resulted in reliable clinical improvement, minimal complications, and durable estimated implant survivorship free of revision at ten years. UKA done for secondary osteonecrosis was substantially less durable at mid-term follow-up. Progression of knee degeneration, rather than implant failure or loosening, was most common indication for conversion to TKA. Cite this article: Bone Joint J 2018;100-B:450–4


Bone & Joint Research
Vol. 5, Issue 12 | Pages 602 - 609
1 Dec 2016
Muto T Kokubu T Mifune Y Inui A Sakata R Harada Y Takase F Kurosaka M

Objectives. Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Methods. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed. Results. Exposure to TA significantly decreased cell viability and changed the cell morphology; these effects were prevented by the simultaneous administration of PRP. Compared with the control group, expression levels of inflammatory genes and reactive oxygen species production were reduced in the TA, PRP, and TA+PRP groups. PRP significantly decreased the expression levels of degenerative marker genes. Conclusions. The combination of TA plus PRP exerts anti-inflammatory and anti-degenerative effects on rotator cuff-derived cells stimulated by IL-1ß. This combination has the potential to relieve the symptoms of rotator cuff injury. Cite this article: T. Muto, T. Kokubu, Y. Mifune, A. Inui, R. Sakata, Y. Harada, F. Takase, M. Kurosaka. Effects of platelet-rich plasma and triamcinolone acetonide on interleukin-1ß-stimulated human rotator cuff-derived cells. Bone Joint Res 2016;5:602–609. DOI: 10.1302/2046-3758.512.2000582


The Bone & Joint Journal
Vol. 104-B, Issue 12 | Pages 1343 - 1351
1 Dec 2022
Karlsson T Försth P Skorpil M Pazarlis K Öhagen P Michaëlsson K Sandén B

Aims

The aims of this study were first, to determine if adding fusion to a decompression of the lumbar spine for spinal stenosis decreases the rate of radiological restenosis and/or proximal adjacent level stenosis two years after surgery, and second, to evaluate the change in vertebral slip two years after surgery with and without fusion.

Methods

The Swedish Spinal Stenosis Study (SSSS) was conducted between 2006 and 2012 at five public and two private hospitals. Six centres participated in this two-year MRI follow-up. We randomized 222 patients with central lumbar spinal stenosis at one or two adjacent levels into two groups, decompression alone and decompression with fusion. The presence or absence of a preoperative spondylolisthesis was noted. A new stenosis on two-year MRI was used as the primary outcome, defined as a dural sac cross-sectional area ≤ 75 mm2 at the operated level (restenosis) and/or at the level above (proximal adjacent level stenosis).


The Bone & Joint Journal
Vol. 96-B, Issue 12 | Pages 1618 - 1622
1 Dec 2014
von Roth P Abdel MP Wauer F Winkler T Wassilew G Diederichs G Perka C

Intact abductors of the hip play a crucial role in preventing limping and are known to be damaged through the direct lateral approach. The extent of trauma to the abductors after revision total hip replacement (THR) is unknown. The aim of this prospective study was to compare the pre- and post-operative status of the gluteus medius muscle after revision THR. We prospectively compared changes in the muscle and limping in 30 patients who were awaiting aseptic revision THR and 15 patients undergoing primary THR. The direct lateral approach as described by Hardinge was used for all patients. MRI scans of the gluteus medius and functional analyses were recorded pre-operatively and six months post-operatively. The overall mean fatty degeneration of the gluteus medius increased from 35.8% (1.1 to 98.8) pre-operatively to 41% (1.5 to 99.8) after multiple revision THRs (p = 0.03). There was a similar pattern after primary THR, but with considerably less muscle damage (p = 0.001), indicating progressive muscle damage. Despite an increased incidence of a positive Trendelenburg sign following revision surgery (p = 0.03) there was no relationship between the cumulative fatty degeneration in the gluteus medius and a positive Trendelenburg sign (p = 0.26). The changes associated with other surgical approaches to the hip warrant investigation. Cite this article: Bone Joint J 2014;96-B:1618–22


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 Open
Vol. 5, Issue 7 | Pages 612 - 620
19 Jul 2024
Bada ES Gardner AC Ahuja S Beard DJ Window P Foster NE

Aims

People with severe, persistent low back pain (LBP) may be offered lumbar spine fusion surgery if they have had insufficient benefit from recommended non-surgical treatments. However, National Institute for Health and Care Excellence (NICE) 2016 guidelines recommended not offering spinal fusion surgery for adults with LBP, except as part of a randomized clinical trial. This survey aims to describe UK clinicians’ views about the suitability of patients for such a future trial, along with their views regarding equipoise for randomizing patients in a future clinical trial comparing lumbar spine fusion surgery to best conservative care (BCC; the FORENSIC-UK trial).

Methods

An online cross-sectional survey was piloted by the multidisciplinary research team, then shared with clinical professional groups in the UK who are involved in the management of adults with severe, persistent LBP. The survey had seven sections that covered the demographic details of the clinician, five hypothetical case vignettes of patients with varying presentations, a series of questions regarding the preferred management, and whether or not each clinician would be willing to recruit the example patients into future clinical trials.


The Bone & Joint Journal
Vol. 102-B, Issue 4 | Pages 513 - 518
1 Apr 2020
Hershkovich O D’Souza A Rushton PRP Onosi IS Yoon WW Grevitt MP

Aims. Significant correction of an adolescent idiopathic scoliosis in the coronal plane through a posterior approach is associated with hypokyphosis. Factors such as the magnitude of the preoperative coronal curve, the use of hooks, number of levels fused, preoperative kyphosis, screw density, and rod type have all been implicated. Maintaining the normal thoracic kyphosis is important as hypokyphosis is associated with proximal junctional failure (PJF) and early onset degeneration of the spine. The aim of this study was to determine if coronal correction per se was the most relevant factor in generating hypokyphosis. Methods. A total of 95 patients (87% female) with a median age of 14 years were included in our study. Pre- and postoperative radiographs were measured and the operative data including upper instrumented vertebra (UIV), lower instrumented vertebra (LIV), metal density, and thoracic flexibility noted. Further analysis of the post-surgical coronal outcome (group 1 < 60% correction and group 2 ≥ 60%) were studied for their association with the postoperative kyphosis in the sagittal plane using univariate and multivariate logistic regression. Results. Of the 95 patients, 71.6% (68) had a thoracic correction of > 60%. Most (97.8%) had metal density < 80%, while thoracic flexibility > 50% was found in 30.5% (29). Preoperative hypokyphosis (< 20°) was present in 25.3%. A postoperative thoracic hypokyphosis was four times more likely to occur in patients with thoracic correction ≥ 60% (odds ratio (OR) 4.08; p = 0.005), after adjusting for confounding variables. This association was not affected by metal density, thoracic flexibility, LIV, UIV, age, or sex. Conclusion. Our study supports the ‘essential lordosis’ hypothesis of Roaf and Dickson, i.e. with a greater ability to translate the apical vertebra towards the midline, there is a commensurate lengthening of the anterior column due to the vertebral wedging. Cite this article: Bone Joint J 2020;102-B(4):513–518


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.


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 9 | Pages 1183 - 1186
1 Sep 2006
Quinlan JF Duke D Eustace S

Bertolotti’s syndrome is characterised by anomalous enlargement of the transverse process(es) of the most caudal lumbar vertebra which may articulate or fuse with the sacrum or ilium and cause isolated L4/5 disc disease. We analysed the elective MR scans of the lumbosacral spine of 769 consecutive patients with low back pain taken between July 2003 and November 2004. Of these 568 showed disc degeneration. Bertolotti’s syndrome was present in 35 patients with a mean age of 32.7 years (15 to 60). This was a younger age than that of patients with multiple disc degeneration, single-level disease and isolated disc degeneration at the L4/5 level (p ≤ 0.05). The overall incidence of Bertolotti’s syndrome in our study was 4.6% (35 of 769). It was present in 11.4% (20 patients) of the under-30 age group. Our findings suggest that Bertolotti’s syndrome must form part of a list of differential diagnoses in the investigation of low back pain in young people


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.


The Bone & Joint Journal
Vol. 105-B, Issue 7 | Pages 735 - 742
1 Jul 2023
Andronic O Germann C Jud L Zingg PO

Aims

This study reports mid-term outcomes after periacetabular osteotomy (PAO) exclusively in a borderline hip dysplasia (BHD) population to provide a contrast to published outcomes for arthroscopic surgery of the hip in BHD.

Methods

We identified 42 hips in 40 patients treated between January 2009 and January 2016 with BHD defined as a lateral centre-edge angle (LCEA) of ≥ 18° but < 25°. A minimum five-year follow-up was available. Patient-reported outcomes (PROMs) including Tegner score, subjective hip value (SHV), modified Harris Hip Score (mHHS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were assessed. The following morphological parameters were evaluated: LCEA, acetabular index (AI), α angle, Tönnis staging, acetabular retroversion, femoral version, femoroepiphyseal acetabular roof index (FEAR), iliocapsularis to rectus femoris ratio (IC/RF), and labral and ligamentum teres (LT) pathology.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.