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The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 4 | Pages 555 - 559
1 Apr 2010
Deguchi M Shinjo R Yoshioka Y Seki H

The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p < 0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker


The Journal of Bone & Joint Surgery British Volume
Vol. 85-B, Issue 8 | Pages 1151 - 1154
1 Nov 2003
Sugimori K Kawaguchi Y Morita M Kitajima I Kimura T

We measured the serum concentration of C-reactive protein (CRP) by a high-sensitive method in patients with lumbar disc herniation. There were 48 patients in the study group and 53 normal controls. The level and type of herniation were evaluated. The clinical data including the neurological findings, the angle of straight leg raising and post-operative recovery as measured by the Japanese Orthopaedic Association (JOA) score, were recorded. The high-sensitive CRP (hs-CRP) was measured by an ultrasensitive latex-enhanced immunoassay. The mean hs-CRP concentration was 0.056 ± 0.076 mg/dl in the patient group and 0.017 ± 0.021 mg/dl in the control group. The difference was statistically significant (p = 0.006). There was no other correlation between the hs-CRP concentration and the level and type of herniation, or the pre-operative clinical data. A positive correlation was found between the concentration of hs-CRP before operation and the JOA score after. Those with a higher concentration of hs-CRP before operation showed a poorer recovery after. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to impingement of the nerve root caused by disc herniation and might be a predictor of recovery after operation


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

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


The Bone & Joint Journal
Vol. 97-B, Issue 1 | Pages 89 - 93
1 Jan 2015
Maier GS Seeger JB Horas K Roth KE Kurth AA Maus U

Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, . sd. 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, . sd. 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women. Cite this article: Bone Joint J 2015;97-B:89–93


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 7 | Pages 949 - 954
1 Jul 2011
Bisseling P Zeilstra DJ Hol AM van Susante JLC

The purpose of this study was to evaluate whether concerns about the release of metal ions in metal-on-metal total hip replacements (THR) should be extended to patients with metal-bearing total disc replacements (TDR). Cobalt and chromium levels in whole blood and serum were measured in ten patients with a single-level TDR after a mean follow-up of 34.5 months (13 to 61) using inductively-coupled plasma mass spectrometry. These metal ion levels were compared with pre-operative control levels in 81 patients and with metal ion levels 12 months after metal-on-metal THR (n = 21) and resurfacing hip replacement (n = 36). Flexion-extension radiographs were used to verify movement of the TDR. Cobalt levels in whole blood and serum were significantly lower in the TDR group than in either the THR (p = 0.007) or the resurfacing group (p < 0.001). Both chromium levels were also significantly lower after TDR versus hip resurfacing (p < 0.001), whereas compared with THR this difference was only significant for serum levels (p = 0.008). All metal ion levels in the THR and resurfacing groups were significantly higher than in the control group (p < 0.001). In the TDR group only cobalt in whole blood appeared to be significantly higher (p < 0.001). The median range of movement of the TDR was 15.5° (10° to 22°). These results suggest that there is minimal cause for concern about high metal ion concentrations after TDR, as the levels appear to be only moderately elevated. However, spinal surgeons using a metal-on-metal TDR should still be aware of concerns expressed in the hip replacement literature about toxicity from elevated metal ion levels, and inform their patients appropriately


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.


The Bone & Joint Journal
Vol. 105-B, Issue 4 | Pages 439 - 448
15 Mar 2023
Hong H Pan X Song J Fang N Yang R Xiang L Wang X Huang C

Aims

The prevalence of scoliosis is not known in patients with idiopathic short stature, and the impact of treatment with recombinant human growth hormone on those with scoliosis remains controversial. We investigated the prevalence of scoliosis radiologically in children with idiopathic short stature, and the impact of treatment with growth hormone in a cross-sectional and retrospective cohort study.

Methods

A total of 2,053 children with idiopathic short stature and 4,106 age- and sex-matched (1:2) children without short stature with available whole-spine radiographs were enrolled in the cross-sectional study. Among them, 1,056 with idiopathic short stature and 790 controls who had radiographs more than twice were recruited to assess the development and progression of scoliosis, and the need for bracing and surgery.


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.


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

Aims

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

Methods

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


Bone & Joint Research
Vol. 12, Issue 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.


The Bone & Joint Journal
Vol. 99-B, Issue 1 | Pages 116 - 121
1 Jan 2017
Bajada S Ved A Dudhniwala AG Ahuja S

Aims. Rates of mortality as high as 25% to 30% have been described following fractures of the odontoid in the elderly population. The aim of this study was to examine whether easily identifiable variables present on admission are associated with mortality. . Patients and Methods. A consecutive series of 83 elderly patients with a fracture of the odontoid following a low-impact injury was identified retrospectively. Data that were collected included demographics, past medical history and the results of blood tests on admission. Radiological investigations were used to assess the Anderson and D’Alonzo classification and displacement of the fracture. The mean age was 82.9 years (65 to 101). Most patients (66; 79.5%) had a type 2 fracture. An associated neurological deficit was present in 11 (13.3%). All were treated conservatively; 80 (96.4%) with a hard collar and three (3.6%) with halo vest immobilisation. Results. The rate of mortality was 16% (13 patients) at 30 days and 24% (20 patients) at one year after injury. A low serum level of haemoglobin and the presence of a neurological deficit on admission were independent predicators of mortality at 30 days on binary logistic regression analysis. A, low level of haemoglobin, admission from an institution, a neurological deficit and type 3 fractures were independent predictors of mortality at one year. . Conclusion. We suggest that these easily identifiable predictors present on admission can be used to identify patients at high risk and guide management by a multidisciplinary team. Cite this article: Bone Joint J 2017;99-B:116–21


Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.


The Journal of Bone & Joint Surgery British Volume
Vol. 84-B, Issue 7 | Pages 1036 - 1039
1 Sep 2002
Tai CC Want S Quraishi NA Batten J Kalra M Hughes SPF

Antibiotics are often administrated prophylactically in spinal procedures to reduce the risk of infection of the disc space. It is still not known which antibiotics are able to penetrate the intervertebral disc effectively. In a prospective, randomised, double-blind clinical study, we examined the penetration of the intervertebral discs of two commonly used antibiotics, cefuroxime and gentamicin. The patients, randomised into two groups, received either 1.5 g of cefuroxime or 5 mg/kg of gentamicin prophylactically two hours before their intervertebral discs were removed. A specimen of blood, from which serum antibiotic levels were determined, was obtained at the time of discectomy. Therapeutic levels of antibiotic were detectable in the intervertebral discs of the ten patients who received gentamicin. Only two of the ten patients (20%) who received cefuroxime had a quantifiable level of antibiotic in their discs although therapeutic serum levels of cefuroxime were found in all ten patients. Our results show that cefuroxime does not diffuse into human intervertebral discs as readily as gentamicin. It is possible that the charge due to ionisable groups on the antibiotics can influence the penetration of the antibiotics. We therefore recommend the use of gentamicin in a single prophylactic dose for all spinal procedures in order to reduce the risk of discitis


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.


Bone & Joint Open
Vol. 1, Issue 7 | Pages 405 - 414
15 Jul 2020
Abdelaal A Munigangaiah S Trivedi J Davidson N

Aims

Magnetically controlled growing rods (MCGR) have been gaining popularity in the management of early-onset scoliosis (EOS) over the past decade. We present our experience with the first 44 MCGR consecutive cases treated at our institution.

Methods

This is a retrospective review of consecutive cases of MCGR performed in our institution between 2012 and 2018. This cohort consisted of 44 children (25 females and 19 males), with a mean age of 7.9 years (3.7 to 13.6). There were 41 primary cases and three revisions from other rod systems. The majority (38 children) had dual rods. The group represents a mixed aetiology including idiopathic (20), neuromuscular (13), syndromic (9), and congenital (2). The mean follow-up was 4.1 years, with a minimum of two years. Nine children graduated to definitive fusion. We evaluated radiological parameters of deformity correction (Cobb angle), and spinal growth (T1-T12 and T1-S1 heights), as well as complications during the course of treatment.


The Bone & Joint Journal
Vol. 101-B, Issue 5 | Pages 621 - 624
1 May 2019
Pumberger M Bürger J Strube P Akgün D Putzier M

Aims

During revision procedures for aseptic reasons, there remains a suspicion that failure may have been the result of an undetected subclinical infection. However, there is little evidence available in the literature about unexpected positive results in presumed aseptic revision spine surgery. The aims of our study were to estimate the prevalence of unexpected positive culture using sonication and to evaluate clinical characteristics of these patients.

Patients and Methods

All patients who underwent a revision surgery after instrumented spinal surgery at our institution between July 2014 and August 2016 with spinal implants submitted for sonication were retrospectively analyzed. Only revisions presumed as aseptic are included in the study. During the study period, 204 spinal revisions were performed for diagnoses other than infection. In 38 cases, sonication cultures were not obtained, leaving a study cohort of 166 cases. The mean age of the cohort was 61.5 years (sd 20.4) and there were 104 female patients


The Bone & Joint Journal
Vol. 101-B, Issue 1 | Pages 75 - 82
1 Jan 2019
Kim J Lee SY Jung JH Kim SW Oh J Park MS Chang H Kim T

Aims

The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation.

Patients and Methods

A total of 134 haemodialyzed patients aged more than 50 years who underwent surgical treatment for pyogenic spondylodiscitis were included in the study. Their mean age was 66.4 years (50 to 83); 66 were male (49.3%) and 68 were female (50.7%). They were divided into two groups according to whether spinal instrumentation was used or not. Propensity score matching was used to attenuate the potential selection bias. The outcome of treatment was compared between these two groups.


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 253 - 259
1 Mar 2019
Shafafy R Valsamis EM Luck J Dimock R Rampersad S Kieffer W Morassi GL Elsayed S

Aims

Fracture of the odontoid process (OP) in the elderly is associated with mortality rates similar to those of hip fracture. The aim of this study was to identify variables that predict mortality in patients with a fracture of the OP, and to assess whether established hip fracture scoring systems such as the Nottingham Hip Fracture Score (NHFS) or Sernbo Score might also be used as predictors of mortality in these patients.

Patients and Methods

We conducted a retrospective review of patients aged 65 and over with an acute fracture of the OP from two hospitals. Data collected included demographics, medical history, residence, mobility status, admission blood tests, abbreviated mental test score, presence of other injuries, and head injury. All patients were treated in a semi-rigid cervical orthosis. Univariate and multivariate analysis were undertaken to identify predictors of mortality at 30 days and one year. A total of 82 patients were identified. There were 32 men and 50 women with a mean age of 83.7 years (67 to 100).


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 1 | Pages 13 - 18
1 Jan 1998
Ransford AO Morley T Edgar MA Webb P Passuti N Chopin D Morin C Michel F Garin C Pries D

We have evaluated the use of a synthetic porous ceramic (Triosite) as a substitute for bone graft in posterior spinal fusion for idiopathic scoliosis. In a prospective, randomised study 341 patients at five hospitals in the UK and France were randomly allocated either to autograft from the iliac crest or rib segments (171) or to receive Triosite blocks (170). All patients were assessed after operation and at 3, 6, 12 and 18 months. The two groups were similar with regard to all demographic and baseline variables, but the 184 treated in France (54%) had Cotrel-Dubouset instrumentation and the 157 treated in the UK usually had Harrington-Luque implants. In the Triosite group the average Cobb angle of the upper curve was 56°, corrected to 24° (57%). At 18 months, the average was 26° (3% loss). In the autograft group the average preoperative upper curve of 53° was corrected to 21° (60%). At 18 months the mean curve was 25° (8% loss). Pain levels after operation were similar in the two groups, being mild in most cases. In the Triosite group only three patients had problems of wound healing, but in the autograft group, 14 patients had delayed healing, infection or haematoma in the spinal wound. In addition, 15 autograft patients had pain at the donor site at three months. Seven had infections, two had haematoma and four had delayed healing. The haematological and serum biochemistry results showed no abnormal trends and no significant differences between the groups. There were no adverse events related to the graft material and no evidence of allergenicity. Our results suggest that Triosite synthetic porous ceramic is a safe and effective substitute for autograft in these patients. Histological findings on biopsy indicate that Triosite provides a favourable scaffolding for the formation of new bone and is gradually incorporated into the fusion mass


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.