Aims

The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model.

Abstract

Aims

To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD_SV) for alleviation of the progression of osteoarthritis (OA) in rabbits through modulation of the peroxisome proliferator-activated receptor (PPARγ).

Aims

Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture.

Background

Medical advances and an ageing population mean that more people than ever rely on artificial joints. In the past years, shoulder joint replacement has developed rapidly and the numbers of shoulder prostheses implanted increased dramatically. Wear is one of the main contributors to the failure of shoulder implants. It is therefore important to measure the wear properties of the articulating surfaces within the joint in vitro. Investigation of wear characteristics through a comprehensive range of motion using a sophisticated shoulder simulator would reveal the durability of the material, the performance of component design and the safety analyses of prostheses. The purpose of the work was to develop and validate a multi-station shoulder simulator, which could accurately simulate physiological gleno-humeral forces and displacements during activities of daily living.

Aims

The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA).

Purpose

The aim of this study was to compare the accuracy of limb alignment and component positioning after total knee arthroplasty(TKA) performed using fixed or individual distal femoral valgus correction angle(VCA)in valgus knees.

Purpose

Recently many authors have questioned the role of tourniquets in primary knee arthroplasty (TKA). Meanwhile, whether the use of an intra-articular wound drainage is an advance over the lack of a drain in TKA is controversial in the literature. This study aimed to investigate the efficacy and safety of drainage or not in TKA without a tourniquet.

Purpose

There is controversial whether synovectomy must be done in primary total knee arthroplasty (TKA). The objectivity of the study was to compare the effect of synovectomy on inflammation and clinical outcomes after surgical treatment of knee osteoarthritis.

Purpose

Previous studies have demonstrated pronounced reduction of sleep quality following major surgery, which may affect postoperative pain and early recovery. This prospective, randomized, controlled trial was designed to evaluate the effect of zolpidem on sleep quality in fast-track total knee arthroplasty (TKA).

Summary Statement

DNA damage induced by systemic drugs or local γ-irradiation drives disc degeneration and DNA repair ability is extremely important to help prevent bad effects of genotoxins (DNA damage inducing agents) on disc.

Introduction

Different subclinical neurological dysfunction has been reported in adolescent idiopathic scoliosis (AIS), including poor postural control and asymmetric otolith vestibulo-ocular responses when compared with normal controls. The objective of this pilot study is to establish whether abnormal MRI morphoanatomical changes arise in the CNS (brain and vestibular system), among left-thoracic versus right-thoracic AIS when compared with normal adolescent controls, with use of advanced computerised statistical morphometry techniques.

Observation of sub-clinical neurological abnormalities has led to the proposal of a neuro-developmental etiologic model for AIS. Our research group have demonstrated longer latency in somatosensory–evoked potential (SSEP) and impaired balance control in AIS subjects. A previous pilot study compared the regional brain volume between right thoracic AIS subjects and normal controls. Significant regional brain differences were found relating to corpus callosum, premotor cortex, proprioceptive and visual centers. Most of these regions involved the brain unilaterally, indicating there might be abnormal asymmetrical development in the brain in right thoracic AIS. In this pilot study, we investigated whether similar changes are present in left thoracic AIS patients who differ from matched control subjects. Nine AIS female patients with atypical left thoracic AIS (mean age 14.8, mean Cobb angle 19°) and 11 matched controls as well as 20 right thoracic AIS (mean Cobb angle 33.8°) and 17 matched controls, underwent three-dimensional isotropic magnetization prepared rapid acquisition gradient echo (3D_MPRAGE) magnetic resonance (MR) imaging of the brain. Fully automatic morphometric analysis was used to analyse the MR images; it included brain-tissue classification into grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). and non-linear registration to a template brain. Tissue densities were compared between AIS subjects and controls. There was no significant difference between AIS subjects and normal controls when comparing absolute and relative (i.e. brain-size adjusted) volumes of grey and white matter. Using voxel-based morphometry, significant group differences (controls > left AIS) were found in the density of WM in the genu of the corpus callosum, the left internal capsule (anterior arm) and WM underlying the orbitofrontal cortex of the left hemisphere. The above differences were not observed in the right AIS group. This first controlled study of regional tissue density showed that corpus callosum, which is the major commissural fiber tract, was different in the atypical left thoracic scoliosis while significant regional brain changes have not yet been found in those with typical right thoracic scoliosis. Further investigation is warranted to see whether the above discrepancy is related to laterality of the scoliotic curves and infratentorial neuroanatomical abnormalities. A larger sample and a longitudinal study is required to establish whether the brain abnormalities are predictive of curve progression.

Introduction: Observation of sub-clinical neurological abnormalities has led to the proposal of a neuro-developmental etiologic model for adolescent idiopathic scoliosis (AIS). We have previously demonstrated prolonged latency in somatosensory evoked potentials (SSEP) and impaired balance control in subjects with AIS. Furthermore we have compared regional brain volumes in right thoracic AIS subjects and normal controls. Significant neuro-anatomic regional differences were observed in the corpus callosum, premotor cortex, proprioceptive and visual centers of the AIS subjects compared to control subjects. Most of these regional differences involved the brain unilaterally, indicating there may be abnormal asymmetrical development in the brain of subjects with right thoracic AIS.

Methods: Following ethical committee approval a total of 29 subjects with AIS were recruited. Patients with congenital, neuromuscular or syndromic scoliosis were excluded from the study. Twenty-eight age- and sex-matched controls were recruited from local schools. All recruits underwent three-dimensional isotropic magnetization prepared rapid acquisition gradient echo (3D_MPRAGE) magnetic resonance (MR) imaging of the brain. Modern morphometric analyses of the MR images were carried out including classification of tissue into grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Tissue densities were compared between AIS subjects and controls. Comparisons were made between those subjects with left thoracic AIS (n=9) and age and sex-matched controls (n=11) and those subjects with right thoracic AIS (n=20) and age and sex-matched controls (n=17).

Results: For subjects with left thoracic curves the mean Cobb angle was 19 degrees. For subjects with right thoracic curves the mean Cobb angle was 33.8 degrees There was no significant differences observed between AIS subjects and normal controls when comparing both absolute and relative (i.e. adjusted for brain size) volumes of GM and WM. However voxel-based morphometric analysis identified significant differences in the density of WM in the genu of the corpus callosum, the left internal capsule and WM underlying the left orbitofrontal cortex when comparing those subjects with left thoracic scoliosis to controls. The above differences were not not observed when those subjects with right thoracic scoliosis were compared to controls..

Discussion: This controlled study of regional brain tissue density has demonstrated important differences in the corpus callosum, the left internal capsule and the left orbitofrontal cortex when the brain of those subjects with left thoracic scoliosis is compared to age and sex matched controls. In this study significant regional brain differences have not been identified in those subjects with right thoracic scoliosis. Further studies are warranted to ascertain whether these morphologial differences in the brain are linked with the etiopathogenisis of left sided thoracic scoliosis. A larger sample and a longitudinal study are required to establish whether brain abnormalities are predictive of curve progression.

Introduction: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, which appears to be caused by a melatonin signalling dysfunction proved recently in osteoblasts. This pathology occurs and progresses during the time of pre-puberty and puberty growth. This period is known to be under the hormonal control and coincides with many biological changes related to the secretion of estrogens, of which estradiol (E2) is the most active. The female prevalence of AIS disease is clearly evident. Indeed, in Quebec the spine deformities considered clinically significant (at least 11° of deformity) are found in a girl:boy ratio of approximately 2:1 for reduced scoliosis, and this ratio increases to 10:1 for scoliosis of more than 30o of deformation. However, the reason for this female prevalence as well as the role of estrogens and estrogen receptors in AIS is not clear despite the fact that these hormones are known for their impact on bone and bone growth, including the spine.

The purpose of the present study was to investigate the role of E2 on the responsiveness of the AIS cells to the melatonin, to determine the expression of estrogens receptors (ERα and ERβ) in AIS tissues and to clarify the impact of estrogen receptor gene polymorphisms in the pathogenesis of AIS.

Methodology: The effects of oestrogen on the AIS osteoblasts (n=10) response to the melatonin was determined by measuring the reduction of forskolin-induced cAMP accumulation. The forskolin treated osteoblasts were incubated in the presence of increasing amounts of melatonin (10–11 to 10-5 M) with or without physiological concentrations (10-10 M) of 17-β-estradiol for 16 hours, and the intracellular cAMP measured by radio-immunoassay using Biotrak Kit. Using RT-PCR, we determined ERα and ERβ mRNA expression in osteoblasts from AIS patients (n=14). Polymorphisms of the first intron of the ERα gene, which contains the XbaI and PvuII polymorphisms, were investigated by PCR following digestion with restriction enzyme and using the genomic DNA from lymphocytes isolated from scoliotic patients (n=33). Using the restriction enzymes XbaI and PvuII, the allelic variants XX, Xx, xx, PP, Pp, and pp were identified in 33 AIS patients (uppercase letters represent absence, and lowercase letters represent presence of restriction sites).

Results: The intracellular level of cAMP was significantly increased (p< 0.01) in the presence of a physiological concentration of 17-β-estradiol (10-10 M) when compared to the level observed in the presence of melatonin alone (10-9 M) (melatonin + estradiol: 109.46 ± 20.07; melatonin 76.09 ± 12.32 (mean ± SD)). As previously described by Dr Moreau’s team, the same pattern (three type of response to melatonin) takes place in the presence of 17-β-estradiol. We observed the loss of ERβ gene expression in 8/ 14 AIS patients contrasting with ERα gene expression that was found in all AIS patients. The XbaI and PvuII polymorphisms were found in 70% (23/33) and 80% (26/33) of the cases respectively. Of the 33 cases, 21 presented both digestion sites, 24 presented PvuII digestion site (6 homozygote, 18 heterozygote) and 23 (8 homozygote, 15 heterozygote) presented XbaI digestion site. The allelic variants were found as follows: XX: n=8, Xx: n=15, xx: n=8, PP: n=6, Pp: n=18 and pp: n=6. Classified by their location in the spine, seven right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and nine right thoracic-left lumbar were found among the patients presenting PvuII positive polymorphism. Among the patients with XbaI positive polymorphism, six right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and eight right thoracic left lumbar were found.

Conclusion: These results show the antagonistic effects of the 17-β-estradiol on AIS osteoblasts response to the melatonin. Thus estrogens interference with melatonin signalling activity would act as a triggering or aggravating factor in the pathogenesis of AIS. At the molecular level, it is possible that estrogens attenuate the response of AIS cells to melatonin through the desensitization of melatonin receptors. The loss of ERβ expression in a significant number of AIS patients appears to be important for the change of the ERα/ERβ receptors ratio that consequently may perhaps alter estrogens signalling pathways. The XbaI and PvuII polymorphisms are present in a significant number of AIS patients but this was not dependant of the curve pattern. These results clearly support the interplays and crosstalk between estrogens and melatonin signalling pathways in AIS aetiopathogenesis.

Supported by the Fondation Yves Cotrel, Institut de France

Purpose: Recently, we highlighted a dysfunction in the melatonin signalling pathway in the osteoblasts from adolescent idiopathic scoliosis patients (AIS). The objective of this project is to verify if in the cells coming from the SIA patients, estrogens interfere with melatonin signalling pathways and to identify mechanisms through which these effects are carried out.

Methods: The effects of estrogens on the melatonin signalling pathway, in osteoblasts from AIS patients (n=7), were determined by measuring the capacity of the Gi proteins to inhibit the accumulation of cAMP. The osteoblasts were incubated in the presence of increasing amounts of melatonin (10–11 to 10–5 M) with or without 17-& #946;-estradiol in physiological concentrations (10–10 M) (n=7). Moreover, coimmunoprecipitations using anti-phosphoserine antibodies were carried out and then followed with a Western blot in order to detect melatonin receptors (MT1 and MT2).

Results: The intracellular level of cAMP is higher in the presence of a physiological concentration of 17-& #946;-estradiol among scoliotic patients compared to the level observed in the presence of melatonin alone. Moreover, the preliminary results of the coimmunoprecipitations seem to show an increase in the phosphorylation of proteins interacting with MT1 and MT2 receptors. The precise nature of these proteins remains to be identified.

Conclusions: These results seem to show the antagonistic effects of the 17-& #946;-estradiol on the melatonin signalling pathway in the osteoblasts from AIS patients. However, more cAMP dosages in the presence and absence of 17-& #946;-estradiol are underway so as to increase the number of patients. The results of this study could contribute to the development of the first molecular screening tests as well as the development of new therapeutic approaches.