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The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 66 - 71
1 Jan 2007
Suh KT Lee SS Kim SJ Kim YK Lee JS

The scoliosis observed in chickens after pinealectomy resembles that seen in humans with an adolescent idiopathic scoliosis, suggesting that melatonin deficiency may be responsible. However, to date there have been no studies of pineal gland glucose metabolism in patients with adolescent idiopathic scoliosis that might support this hypothesis. We examined the excretion of urinary 6-sulfatoxyl-melatonin as well as the glucose metabolism of the pineal gland in 14 patients with an adolescent idiopathic scoliosis and compared them with those of 13 gender-matched healthy controls using F-18 fluorodeoxyglucose brain positron emission tomography. There was no significant difference in the level of urinary 6-sulfatoxyl-melatonin or pineal gland metabolism between the study and the control group. We conclude that permanent melatonin deficiency is not a causative factor in the aetiology of adolescent idiopathic scoliosis


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_4 | Pages 16 - 16
1 Feb 2014
Juroskova V Fulford J Barker AR Meakin JR
Full Access

Purpose of the study. To assess the ability of magnetic resonance spectroscopy (MRS) to detect changes in spinal muscle metabolism after a 4-week exercise intervention. Background. Spinal muscle atrophy is associated with back pain and exercise interventions have been shown to reduce pain and improve function. It is not always clear, however, whether improvements are due to enhanced muscle performance or occur for other reasons (e.g. psychological, neurological). MRS can be used to measure muscle metabolism and could therefore be useful for assessing the mechanisms by which exercise improves function in back pain patients. Methods. Eleven healthy participants took part in a 4-week exercise intervention to strengthen the spinal muscles. Before and after the intervention, the participants underwent an assessment that included using MRS to monitor the phosphocreatine levels in the spinal muscles around the level of L3L4 whilst they performed a modified Biering-Sorensen test to fatigue. Results. Relative to the pre-intervention assessment, the post-intervention endurance time significantly increased (mean=20 s, 95% CI 7–34 s, p=0.01). The phosphocreatine depletion, taken at an equivalent time point in both assessments, significantly decreased (mean=12%, 95% CI 5–19%, p=0.006). Even at the point of the fatigue, the phosphocreatine depletion was lower post-intervention (mean=8%, 95%CI 1–15%, p=0.045). Conclusion. MRS can be used to detect changes in the metabolism of the spinal muscles after a 4-week exercise intervention


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_4 | Pages 18 - 18
1 Feb 2014
Lama P Claireaux H Flower L Harding∗ I Dolan P Adams M
Full Access

Introduction

Physical disruption of the extracellular matrix influences the mechanical and chemical environment of intervertebral disc cells. We hypothesise that this can explain degenerative changes such as focal proteoglycan loss, impaired cell-matrix binding, cell clustering, and increased activity of matrix-degrading enzymes.

Methods

Disc tissue samples were removed surgically from 11 patients (aged 34–75 yrs) who had a painful but non-herniated disc. Each sample was divided into a pair of specimens (approximately 5mm3), which were cultured at 37°C under 5% CO2. One of each pair was allowed to swell, while the other was restrained by a perspex ring. Live-cell imaging was performed with a wide field microscope for 36 hrs. Specimens were then sectioned at 5 and 30 μm for histology and immunofluorescence using a confocal microscope. Antibodies were used to recognise free integrin receptor α5β1, matrix metalloprotease MMP-1, and denatured collagen types I-III. Proteoglycan content of the medium, analysed using the colorimetric DMMB assay, was used to assess tissue swelling and GAG loss. Constrained/unconstrained results were compared using matched-pair t-tests.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_1 | Pages 2 - 2
23 Jan 2023
Newton Ede M Pearson MJ Philp AM Cooke ME Nicholson T Grover LM Jones SW
Full Access

To determine whether spinal facet osteoblasts at the curve apex display a different phenotype to osteoblasts from outside the curve in patients with adolescent idiopathic scoliosis (AIS). Intrinsic differences in the phenotype of spinal facet bone tissue and in spinal osteoblasts have been implicated in the pathogenesis of AIS. However, no study has compared the phenotype of facet osteoblasts at the curve apex with the facet osteoblasts from outside the curve in patients with AIS. Facet bone tissue was collected from three sites, the concave and convex side at the curve apex and from outside the curve from three female patients with AIS (aged 13–16 years). Micro-CT analysis was used to determine the density and trabecular structure. Osteoblasts were then cultured from the sampled bone. Osteoblast phenotype was investigated by assessing cellular proliferation (MTS assay), cellular metabolism (alkaline phosphatase and Seahorse Analyser), bone nodule mineralisation (Alizarin red assay), and the mRNA expression of Wnt signalling genes (quantitative RT-PCR). Convex bone showed greater bone mineral density and trabecular thickness than did concave bone. The convex side of the curve apex exhibited a significantly higher proliferative and metabolic phenotype and a greater capacity to form mineralised bone nodules than did concave osteoblasts. mRNA expression of SKP2 was significantly greater in both concave and convex osteoblasts than in non-curve osteoblasts. The expression of SFRP1 was significantly downregulated in convex osteoblasts compared with either concave or non-curve. Intrinsic differences that affect osteoblast function are exhibited by spinal facet osteoblasts at the curve apex in patients with AIS


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 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 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.


The Bone & Joint Journal
Vol. 103-B, Issue 8 | Pages 1400 - 1404
1 Aug 2021
Sim FCJ Birley E Khan AL Loughenbury PR Millner P

Aims

The aim of this study was to determine whether there is an increased prevalence of scoliosis in patients who have suffered from a haematopoietic malignancy in childhood.

Methods

Patients with a history of lymphoma or leukaemia with a current age between 12 and 25 years were identified from the regional paediatric oncology database. The medical records and radiological findings were reviewed, and any spinal deformity identified. The treatment of the malignancy and the spinal deformity, if any, was noted.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXVII | Pages 17 - 17
1 Jun 2012
Yeung H Lam T Liu Z Tam E Sun G Lee K Qiu Y Cheng J
Full Access

Introduction. Despite extensive research, the cause of adolescent idiopathic scoliosis (AIS) is still largely unclear. Girls with AIS tend to be taller and leaner, and have a lower body-mass index (BMI) and lower bone mass, than do healthy girls. Recent MRI studies have shown the presence of relative anterior spinal overgrowth in girls with AIS. The lower bone mineral status and BMI could be related to dysfunctional central regulation pathway of growth, bodyweight, and bone metabolism. Following several interesting reports on the role of leptin in regulation of the above pathway in animals and human beings, our recent study has shown a low leptin concentration in girls with AIS girls compared with healthy adolescents. This finding leads to our new hypothesis that abnormal leptin bioavailability could be associated with the lower bodyweight, lower bone mineral density, and relatively disproportional endochondral skeletal growth in AIS. This study aimed to investigate the leptin bioavailability in girls with AIS. Methods. 53 girls with AIS and 27 healthy girls (aged 11–16 years) were recruited in this preliminary study. Clinical and anthropometric data were obtained. Blood samples were obtained for ELISA of leptin and soluble leptin receptor (sOB-R). Independent Student's t test and multivariate regression were used in group comparison. Results. The AIS group had significantly lower BMI and longer arm span than did controls. Additionally, girls with AIS had significantly higher soluble leptin receptor concentrations (22·1 ng/mL [□}6·9] vs 17·8 ng/mL [4·4]; p<0·01). However, the leptin concentration (7·6 ng/mL [□}5·3] vs 8·7 ng/mL [□}6·0]) and the leptin/sOB-R ratio (0·38 [□}0·28] vs 0·56 [□}0·47]) were similar to that of the controls. In girls with AIS, the leptin, sOB-R, and the leptin/sOB-R ratio correlated well with bodyweight and BMI. After adjustment for BMI, sOB-R in girls with AIS was significantly higher than in controls (r=0·37, p=0·042). Conclusions. This preliminary report showed that the soluble leptin receptor could be abnormal in girls with AIS. Leptin and sOB-R are related to bodyweight. sOB-R is a major modulator of leptin concentration in circulation, the abnormality of which may lead to the retention of leptin in the circulation and thus abnormal regulatory effect. In this study, girls with AIS had lower BMI and longer arm span, which may reflect the possible change resulting from abnormal leptin bioavailability. Further longitudinal study with larger sample size would be useful to help to understand the long-term effect of the low leptin and high sOB-R in girls with AIS on their bodyweight and skeletal development. It is also noteworthy to study the mechanism of increased sOB-R in AIS


The Bone & Joint Journal
Vol. 102-B, Issue 12 | Pages 1717 - 1722
1 Dec 2020
Kang T Park SY Lee JS Lee SH Park JH Suh SW

Aims

As the population ages and the surgical complexity of lumbar spinal surgery increases, the preoperative stratification of risk becomes increasingly important. Understanding the risks is an important factor in decision-making and optimizing the preoperative condition of the patient. Our aim was to determine whether the modified five-item frailty index (mFI-5) and nutritional parameters could be used to predict postoperative complications in patients undergoing simple or complex lumbar spinal fusion.

Methods

We retrospectively reviewed 584 patients who had undergone lumbar spinal fusion for degenerative lumbar spinal disease. The 'simple' group (SG) consisted of patients who had undergone one- or two-level posterior lumbar fusion. The 'complex' group (CG) consisted of patients who had undergone fusion over three or more levels, or combined anterior and posterior surgery. On admission, the mFI-5 was calculated and nutritional parameters collected.


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 Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1093 - 1098
1 Aug 2016
Park S Kim HJ Ko BG Chung JW Kim SH Park SH Lee MH Yeom JS

Aims

The purpose of this study was to investigate the prevalence of sarcopenia and to examine its impact on patients with degenerative lumbar spinal stenosis (DLSS).

Patients and Methods

This case-control study included two groups: one group consisting of patients with DLSS and a second group of control subjects without low back or neck pain and related leg pain. Five control cases were randomly selected and matched by age and gender (n = 77 cases and n = 385 controls) for each DLSS case. Appendicular muscle mass, hand-grip strength, sit-to-stand test, timed up and go (TUG) test, and clinical outcomes, including the Oswestry Disability Index (ODI) scores and the EuroQol EQ-5D were compared between the two groups.


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. 92-B, Issue 8 | Pages 1118 - 1122
1 Aug 2010
Lee JS Suh KT Eun IS

Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes.

These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.


Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc.

Cite this article: Bone Joint Res 2013;2:169–78.