Dataset Information

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis.

ABSTRACT: Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control with vehicle (CON/VEH; n = 20), (2) control with MIN (CON/MIN; n = 20), (3) TR with vehicle (TR/VEH; n = 30), or (4) TR with MIN (TR/MIN; n = 30). MIN (0.01 mg/kg/week) and vehicle were administered intraperitoneally to their respective groups. TR was performed at age 4 weeks, and the mice were sacrificed at age 9 weeks. Body weights, spine radiographs, femoral bone mineral density (BMD), serum bone marker levels, and histomorphometry of the cancellous bone of the thoracic vertebrae were analyzed. TR significantly reduced weight gain in the TR/VEH group relative to the CON/VEH group. TR also induced osteoporosis with accelerated bone resorption, as indicated by decreases in femoral BMDs and thoracic cancellous bone volume and increases in serum bone resorption marker levels and histomorphometric resorption parameters in the TR/VEH group. MIN partially improved body weight gain and improved poor bone structure relative to the TR/VEH group by suppressing high bone resorption in the TR/MIN mice. MIN significantly reduced the curve magnitudes, as indicated by a 43% lower curve magnitude in the TR/MIN mice than in the TR/VEH mice (17.9 ± 8.9° vs. 31.5 ± 13.1°; p< 0.001). The administration of MIN increased bone mass and reduced the severity of scoliosis in the TR mice. MIN was suggested as a possible inhibitor of scoliosis development.

SUBMITTER: Tanabe H

PROVIDER: S-EPMC6107151 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis.

Tanabe Hironori H Aota Yoichi Y Yamaguchi Yasuteru Y Kaneko Kanichiro K Imai Sousuke S Takahashi Masaki M Taguri Masataka M Saito Tomoyuki T

PloS one 20180823 8

Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control wi ...[more]

PMID: 30138335

Similar Datasets

Project description:There is no consensus on the definition of a structural proximal thoracic curve (PTC) and the indications for fusion. As such, we assessed a single institute's experience in the management of large PTCs (>35 degrees) in patients with adolescent idiopathic scoliosis (AIS) who were either fused or not fused. A retrospective radiographic analyses of 30 consecutive AIS patients with double thoracic curves who underwent PSF with a minimum of 2 years' follow-up were included for review. The patients were divided into two groups: group 1 (n = 15 patients) with fusion extended up to T2 or T3 and group 2 (n = 15) with fusion limited to T5 or below. Shoulder balance was assessed according to clavicular angle, first-rib difference, and radiographic shoulder height difference (SHD). PTCs were defined based on a Cobb angle of >35, the presence of apical rotation, and a positive T1 tilt. The decision to fuse the PTC was based on curve magnitude only, with those between 35 and 45 degrees undergoing a selective fusion of the main thoracic curve (MTC), with both curves fused if the PTC was more than 45 degrees. In group 1, there were eight females and seven males. Their ages ranged between 12 and 33 years, with a mean of 16.2 ± 5.5 years. Postoperatively, the mean PTC correction was 45.6%, which statistically differed from preoperative status (p = 0.001). No statistical difference was noted in T1 tilt and the first-rib difference from preoperative to postoperative follow-up (p > 0.05). However, the clavicular angle and SHD were increased significantly at the immediate postoperative interval (p < 0.05) but demonstrated no significant changes between the initial and the last follow-up values (p > 0.05). Group 2 consisted of one male and 14 females. The mean age was 16.4 ± 4 years (range: 11 to 28 years). The mean spontaneous PTC correction was 28.3% and remained essentially unchanged at the end of the follow-up. The improvement in the curve from preoperative status was highly statistically significant (p = 0.001). All radiographic shoulder parameters exhibited a significant increase in the immediate postoperative period and at last follow-up, and shoulder balance improvement was not noted on follow-up. Although both groups were not statistically similar with regards to the preoperative PTC, AVR, apical vertebral translation, and shoulder parameters, no significant difference could be found in PTC or shoulder parameters between both groups at last follow-up (p > 0.05). Our study illustrates important observations that should be considered in defining the PTC for fusion consideration. Spontaneous correction of the PTC occurs in structural curves greater than 35 degrees and less than 45 degrees, and this correction is maintained over time. Despite that correction, radiographic shoulder parameters are expected to slightly increase. Nonfusion strategy may be appropriate for PTCs between 35 and 45 degrees. After fusion of both the MTC and the PTC, the radiographic shoulder parameters did not significantly differ. Preoperative radiographic shoulder parameters are not predictive of postoperative shoulder imbalance.

Project description:INTRODUCTION:Altered trunk shape and body alignment in Lenke 1 thoracic adolescent idiopathic scoliosis (AIS) may affect the body's balance control during activities. The current study aimed to identify the effects of Lenke 1 thoracic AIS on the balance control during level walking in terms of the inclination angles (IA) of the center of mass (COM) relative to the center of pressure (COP), the rate of change of IA (RCIA), and the jerk index of IA. The association between the Cobb angle, IA and RCIA was also evaluated. MATERIALS AND METHODS:Sixteen adolescents with AIS (age: 14.0±1.8 years, height: 154.8±4.7 cm, mass: 42.0±7.5 kg) and sixteen healthy controls (age: 14.4±2.0 years, height: 158.4±6.2 cm, body mass: 48.6±8.9 kg) performed level walking in a gait laboratory. The kinematic and ground reaction force data were measured for both concave-side and convex-side limb cycles, and used to calculate the IA and RCIA, the jerk index of IA, and the temporal-spatial parameters. Correlations between the Cobb angle, IA and RCIA were quantified using Pearson's correlation coefficients (r). RESULTS:The patients showed less smooth COM-COP motion with increased jerk index of IA in the sagittal plane during single limb support (SLS) of the concave-limb (p = 0.05) and in the frontal plane during double limb support (DLS) (p < 0.05). The patients also showed significantly increased posterior RCIA on both the concave and convex side during initial (p = 0.04, p = 0.03) and terminal (p = 0.04, p = 0.03) DLS when compared to healthy controls. In the frontal plane, the patients walking on the concave-side limb showed decreased IA over SLS (p = 0.01), and at contralateral toe-off (p<0.01) and contralateral heel-strike (p = 0.02), but increased mean IA magnitude over terminal DLS (p = 0.01). The frontal IA at contralateral toe-off and SLS for AIS-A showed a moderate to strong correlation with Cobb angles (r = -0.46 and -0.61), and the sagittal RCIA over the initial DLS for AIS-A also showed a significant, strong correlation with Cobb angles (r = -0.50). CONCLUSIONS:The patients with Lenke 1 thoracic scoliosis in the current study showed altered and jerkier COM-COP control during level walking when compared to healthy controls. During DLS, the patients increased the posterior RCIA in the sagittal plane with increased IA jerk index in the frontal plane for both the concave- and the convex-side limb, indicating their difficulty in maintaining a smooth transfer of the body weight. During SLS of the concave-side limb, the patients adopted a conservative COM-COP control strategy, as indicated by a decreased IA in the frontal plane, but showed a jerky COM-COP control in the sagittal plane. The COM-COP control of the patients was associated with the severity of the spinal deformity. The current results suggest that this patient group should be monitored for signs of an increased risk of loss of balance during weight transfer on the concave-side limb.

Project description:ObjectiveLow bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover.MethodsA total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X-ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < -1, and the normal (NOR) group if the Z score ≥ -1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low-quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta-diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The "Random forest" was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD.ResultsThe serum β-CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia-Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia-Shigella was negatively correlated with femur BMD and positively correlated with serum β-CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups.ConclusionThe alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

Dataset Information

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis.

Publications

Minodronate treatment improves low bone mass and reduces progressive thoracic scoliosis in a mouse model of adolescent idiopathic scoliosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets