Defining the bone morphometry, micro-architecture and volumetric density profile in osteopenic vs non-osteopenic adolescent idiopathic scoliosis.

PURPOSE: Osteopenia has been widely reported in about 30 % of girls with adolescent idiopathic scoliosis (AIS). However, the bone quality profile of the 70 % non-osteopenic AIS defined by areal bone mineral density (BMD) with conventional dual-energy X-ray absorptiometry (DXA) has not been adequately studied. Our purpose was to verify whether abnormal volumetric BMD (vBMD) and bone structure (morphometry and micro-architecture) also existed in the non-osteopenic AIS when compared with matched controls using both DXA and high-resolution peripheral computed tomography (HR-pQCT). METHODS: This was a case-control cross-sectional study. 257 AIS girls with a mean age of 12.7 (SD = 0.8) years old and 187 age- and gender-matched normal controls with an average age of 12.9 (SD = 0.5) years old were included. Areal BMD (aBMD) and bone quality were measured with standard DXA and HR-pQCT, respectively. The parameters of HR-pQCT could be categorized as bone morphometry, vBMD and bone micro-architecture. The results were compared between the osteopenic AIS and osteopenic control, and between the non-osteopenic AIS and non-osteopenic control. RESULTS: In addition to the lower aBMD and vBMD, osteopenic AIS showed significantly greater cortical perimeter and trabecular area than the osteopenic control even after adjustments of age (P < 0.05). Non-osteopenic AIS also showed significantly lower aBMD together with lower cortical area, thickness and vBMD than the non-osteopenic control (P < 0.05). After adjustments of age, cortical area and vBMD, and trabecular number and separation continued to show statistical significance (P < 0.05). Both the osteopenic and non-osteopenic AIS subgroups revealed significant abnormal bone quality parameters from that in the control group after adjustments of age and aBMD with multi-linear regression analysis (P < 0.05). CONCLUSIONS: The present study specifically defined the abnormal profile of bone quality in the osteopenic and non-osteopenic AIS for the first time. Both the osteopenic and non-osteopenic AIS were likely to have relatively lower bone mineral status and abnormal bone morphometry, micro-architecture and volumetric density profile compared with their normal matched controls. The observed abnormalities were suggestive of decreased endocortical bone apposition or active endocortical resorption that could affect the mechanical bone strength in AIS. The underlying pathomechanism might be attributed to abnormal bone modeling/remodeling that could be associated with the etiopathogenesis of AIS.

A Critical Comparison Between Two Scanning Protocols of High-Resolution Peripheral Quantitative Computed Tomography at the Distal Radius in Adolescents.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a unique technology for assessing bone mineral density and bone microarchitecture. Currently, no universally accepted protocol for selecting the region of interest (ROI) at the distal radius has been established for growing subjects. This study aimed (1) to investigate the differences in HR-pQCT measurements of 2 different ROI protocols applied to the distal radius of healthy adolescents and (2) to identify the least common area of ROI (the least common ROI) between the protocols. Twenty-six boys and 26 girls aged between 13 and 16 yr old were recruited. Nondominant distal radius was scanned by 2 HR-pQCT protocols, namely, the "5-mm protocol," where the distal end of ROI started at 5 mm proximal to a reference line, and the "4% protocol," where the ROI started at 4% of the ulnar length proximal to another reference line. The least common ROI between the 2 protocols was identified and the slice numbering within the common ROI was determined. Bland-Altman plots were used to check the agreement of the least common ROIs between the 2 protocols. Paired t-test and Wilcoxon signed-rank test were used for analysis. In boys, significant differences between protocols were found in most parameters with the maximum difference observed in the cortical area (25.0%, p < 0.001). In girls, differences were observed only for total volumetric bone mineral density (3.6%, p = 0.032). The number of slices in the least common ROI was 66 (60.0%) and 57 (51.8%) in boys and girls, respectively. Good agreements on all HR-pQCT parameters from the least common ROI between the 2 protocols were found. Significant differences in bone parameters were noted between the 2 protocols. When comparing the 2 protocols, observed gender differences could reflect the differences in skeletal growth at the peripubertal period between genders. Least common ROI could be useful for cross-center comparisons and when merging datasets from different centers.

Initial Cobb angle reduction velocity following bracing as a new predictor for curve progression in adolescent idiopathic scoliosis.

PURPOSE: The initial correction rate (ICR) has been widely used as a predictor for curve progression in adolescent idiopathic scoliosis (AIS) undergoing bracing treatment. We proposed a new parameter, the initial Cobb angle reduction velocity (ARV), for prediction of curve progression. The purpose of this study was to identify whether the initial ARV was a more effective predictor than ICR for curve progression in AIS patients undergoing brace treatment, and to evaluate the ideal cut-off point of initial ARV for prediction of curve progression. METHODS: This was a retrospective cohort study on AIS girls receiving standardized bracing treatment regularly followed up every 3-6 months. Standardized SRS criteria for bracing study were utilized in the case selection. The demographic data, maturity status and Cobb angle of each visit were recorded. The initial ARV and ICR were identified. Patients were divided into progressive (≥6°) and non-progressive (<6°) groups based on their final bracing outcome. Differences between two groups were identified and logistic regression analysis was applied to compare the predictive values of initial ARV and ICR for curve progression during bracing treatment. RESULTS: Seventy-six patients were included in the non-progressive group and 19 in the progressive group. Significant differences between non-progressive and progressive groups were found in terms of initial ARV (12.8 ± 21.4°/year vs -5.4 ± 15.2°/year, P = 0.001) and ICR (12.1 ± 20.7 % vs -5.8 ± 18.0 %, P = 0.001). The logistic regression analysis revealed that age at initial visit (OR 1.742, P = 0.043) and initial ARV (OR 1.057, P = 0.002) had higher predictive values than ICR (P = 0.601) for curve progression in braced AIS girls. The ideal cut-off point of initial ARV was 10°/year (OR 8.959, P = 0.005) for the prediction of curve progression. CONCLUSIONS: The initial Cobb angle reduction velocity serves as a better predictor for curve progression than initial correction rate in braced AIS patients with follow-up interval of 3-6 months. At the second visit following bracing prescription, those AIS patients with reduction velocity in Cobb angle lower than 10°/year have significantly higher risk of curve progression.

A prospective randomized controlled study on the treatment outcome of SpineCor brace versus rigid brace for adolescent idiopathic scoliosis with follow-up according to the SRS standardized criteria.

PURPOSE: SpineCor is a relatively innovative brace for non-operative treatment of adolescent idiopathic scoliosis (AIS). However, the effectiveness of SpineCor still remains controversial. The objective of the current study was to compare the treatment outcomes of SpineCor brace with that of rigid brace following the standardized Scoliosis Research Society (SRS) criteria on AIS brace study. METHODS: Females subjects with AIS and aged 10-14 were randomly allocated into two groups undergoing treatment of SpineCor (S Group, n = 20) or rigid brace (R Group, n = 18). During SpineCor treatment, patients who had curve progression of >5° would be required to switch to rigid brace treatment. The effectiveness of the two brace treatments was assessed using the SRS standardized criteria. RESULTS: Before skeletal maturity, 7 (35.0%) patients in the S Group and 1 (5.6%) patient in the R Group had curve progression >5° (P = 0.026). At skeletal maturity, 5 of the 7 (71.4%) patients who failed with SpineCor bracing showed control from further progression by changing to rigid bracing. At the latest follow-up with a mean duration of 45.1 months after skeletally maturity, 29.4% of patients who were successfully treated by rigid brace showed further curve progression beyond skeletal maturity, versus 38.5% of patients in the SpineCor group (P > 0.05). For both groups, the primary curves were slightly improved at the time of brace weaning, but additionally increased at the latest follow-up, with a rate of 1.5° per year for post-maturity progression. CONCLUSIONS: Curve progression rate was found to be significantly higher in the SpineCor group when compared with the rigid brace group. Changing to rigid bracing could control further curve progression for majority of patients who previously failed with SpineCor bracing. For both SpineCor and rigid brace treatments, 30-40% of patients who were originally successfully treated by bracing would exhibit further curve progression beyond skeletal maturity. The post-maturity progression rate was found to be 1.5° per year in the current study, which was relatively greater than those reported before.

Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis.

Introduction: Adolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case-control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS. Methods: The study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle <6°). Clinical and radiological assessments were conducted on each group. Results: Cobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p < 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011). Discussion: Patients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression.

Persistent low-normal bone mineral density in adolescent idiopathic scoliosis with different curve severity: A longitudinal study from presentation to beyond skeletal maturity and peak bone mass.

OBJECTIVES: Low bone mineral status has been reported in patients first presented with adolescent idiopathic scoliosis (AIS). We aimed to study whether low-normal bone mineral density (BMD) is persistent among AIS girls during puberty and at peak bone mass, and whether if such persistence is associated with curve severity and differed from healthy controls. METHOD: This prospective longitudinal study comprised 550 AIS girls and 194 healthy control subjects followed from 1997 till 2016. Low-normal BMD was defined as z-standardized bone mineral density (z-BMD) of bilateral femoral neck ≤ -1. Markov Chain 2-stages analysis was conducted to investigate the low-normal BMD transition rate. Linear mixed-effects model and Bland-Altman plot were used to investigate whether low-normal BMD is persistent among a subgroup of AIS patients that reached peak bone mass. RESULTS: The average z-BMD were comparable between AIS cohort and controls at 11 years old (-0.532 vs -0.602), but at 19 years old z-BMD worsened among AIS subjects (-0.860) while controls z-BMD improved (-0.455). During growth period until skeletal maturity, persistence of low-normal BMD was high in both cohorts (>80%) and the AIS group with severe curve presented 100% persistence. Subgroup analysis revealed that z-BMD of AIS patients at skeletal maturity and peak bone mass were highly correlated (r2 = 0.905) and with good agreement. CONCLUSION: AIS patients had poorer BMD that is associated with curve severity and more likely to persist beyond peripubertal period and at peak bone mass when compared to controls.

Trial Protocol: The use of mindfulness-based intervention for improving bracing compliance for adolescent idiopathic scoliosis patients: protocol for a randomised, controlled trial.

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is the most prevalent deforming orthopaedic condition; it causes significant disability when spinal curves progress beyond 45deg. Bracing is the primary treatment prescribed for adolescents with an immature skeleton who have spinal curves between 25 and 45deg. New evidence suggests that compliance with bracing significantly decreases the progression of high-risk curves to the threshold for surgery. Nonetheless, bracing is a stressful experience. Therefore, interventions that mediate health-related quality of life for AIS patients are of great interest. In the past few decades, numerous studies have documented the benefits of mindfulness training on chronic pain, stress management, anxiety and emotional disorders. Mindfulness might additionally provide AIS patients with psychosocial support. RESEARCH QUESTIONS: This study will investigate the effects of a mindfulness-based intervention on bracing compliance and quality of life among AIS patients with poor bracing compliance. The study also plans to evaluate if the mindfulness-based intervention effect is sustained after the intervention period. The potential mechanism by which mindfulness affects bracing compliance will be explored. DESIGN: Single-blind, two-arm, randomised, controlled trial. PARTICIPANTS AND SETTING: The study will recruit 120 AIS patients aged between 10 and 15 years with non-satisfactory bracing compliance. Patients who have previously practised or are currently practising meditation or mindful yoga or who cannot finish the whole intervention will be excluded. The study will take place at the Jockey Club School of Public Health and Primary Care building. INTERVENTION: Patients in the mindfulness-based intervention group will join weekly sessions for 8 weeks. This program is a short version of a mindfulness-based stress relaxation program to address the specific issues of AIS patients. Two to three experienced instructors will deliver the program. CONTROL: Control group patients will participate in an 8-week physiotherapy exercise program as recommended in the International Scientific Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) 2011 guideline. MEASUREMENTS: The primary outcome is the 6-month post-intervention total score of bracing compliance. Secondary measures are non-bracing-specific quality of life, bracing-specific quality of life, self-compassion, emotional regulation, mindful awareness and acceptance, self-efficacy, perception of stress, and general measure of health outcome. PROCEDURE: 120 participants will be assigned to either an intervention or control arm by simple randomisation, and the randomisation result will only be revealed once participants have confirmed availability to attend intervention classes. Clinicians of the scoliosis clinic and research staff will be blinded to the treatment allocation. ANALYSIS: ANCOVA will be conducted to compare the effect of mindfulness-based intervention versus physiotherapy exercise on the outcome measures. To investigate significant change over time, linear mixed models analyses will be conducted following the intention-to-treat principle. The R-package lavaan will be used to conduct structural equation modelling to study the potential mechanism of mindfulness. DISCUSSION/SIGNIFICANCE: This will be the first psychosocial intervention study conducted on braced AIS patients with the aim of improving patients' bracing compliance and quality of life. The results from this study will potentially carry significant impact on future AIS treatment by emphasising psychosocial care for braced AIS patients.

Sexual Dimorphism in Cortical and Trabecular Bone Microstructure Appears During Puberty in Chinese Children.

Distal forearm fractures during growth are more common in males than females. Because metaphyseal cortical bone is formed by coalescence of trabeculae emerging from the periphery of the growth plate, we hypothesized that the later onset of puberty in males produces a longer delay in trabecular bone formation and coalescence, which leaves a transient phase of high cortical porosity, low matrix mineral density, and high trabecular density relative to females. We quantified the nondominant distal radial microstructure using high-resolution peripheral quantitative computed tomography in 214 healthy Chinese boys and 219 Chinese girls aged between 7 and 17 years living in Hong Kong. Measurements of 110 slices (9.02 mm) were acquired 5 mm proximal to the growth plate of the nondominant distal radius. Porosity was measured using StrAx1.0 (Straxcorp, Melbourne, VIC, Australia) and trabecular plate and rod structure were measured using individual trabecula segmentation (ITS). Mechanical properties were estimated using finite element analysis (FEA). Results were adjusted for age, total bone cross-sectional area (CSA), dietary calcium intake, and physical activity. In boys, total bone CSA was 17.2% to 22.9% larger throughout puberty, cortical/total bone CSA was 5.1% smaller in Tanner stage 2 only, cortical porosity was 9.4% to 17.5% higher, and matrix mineral density was 1.0% to 2.5% lower in Tanner stage 2 to 5, than girls. Boys had higher trabecular rod BV/TV in Tanner stage 3 and 4, but higher trabecular plate BV/TV and plate to rod ratio in Tanner stage 5, than girls. Boys had 17.0% lower apparent modulus than girls in Tanner stage 2. A transient phase of higher porosity due to dissociation between bone mineral accrual and linear growth may contribute to higher distal radial bone fragility in Chinese boys compared to girls. © 2018 American Society for Bone and Mineral Research.

Prognostic Value of Bone Mineral Density on Curve Progression: A Longitudinal Cohort Study of 513 Girls with Adolescent Idiopathic Scoliosis.

Osteopenia has been found to occur in about 30% of Adolescent Idiopathic Scoliosis (AIS) patients. This study aimed to investigate its prognostic value on the risk of curve progression to surgical threshold. Newly diagnosed AIS girls (N = 513) with Cobb angle 10°-40° were recruited with follow-up till maturity. Bilateral hips were assessed with dual-energy x-ray absorptiometry (DXA). Distal radius of a subgroup of 90 subjects was further assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT). 55 patients progressed to surgical threshold or underwent spine surgery at the end of follow-up. Cox model with osteopenia status performed significantly better than the model without (p = 0.010). Osteopenic patients had significantly higher risk of surgery (HR2.25, p = 0.011), even after adjustment for menarche status, age and initial Cobb angle. The incremental predictive value of osteopenia was, however, not statistically significant. In the subgroup analysis, cortical bone density was identified as a better marker to improve the sensitivity of the prediction, but requires further larger study to validate this finding. These consistent results of bone density measured at different sites suggest a systemic effect, rather than local effect to the deformed spine, and support to the link of abnormal bone density to the etiopathogenesis in AIS patients.

How Does the Supine MRI Correlate With Standing Radiographs of Different Curve Severity in Adolescent Idiopathic Scoliosis?

STUDY DESIGN: A retrospective study. OBJECTIVE: To study how the supine magnetic resonance image (MRI) correlates with standing radiographs of different curve severity in adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Linear correlation between Cobb angles measured on supine MRI and standing radiographs has been identified. However, the effects of different curve severity on the correlation have not been studied in depth. METHODS: Girls with AIS with standing radiographs and supine MRI were reviewed. From standing radiographs, all structural and nonstructural Cobb angles were measured. For those with simultaneous lateral radiographs, thoracic kyphosis (TK) and lumbar lordosis (LL) angles were measured. On supine MRI, the coronal Cobb angles, TK and LL were measured accordingly. The coronal Cobb angles were divided into 3 groups based on values measured on standing radiographs: mild group for Cobb angles less than 20°, moderate group for 20° to 40°, and severe group for more than 40°. Correlation was analyzed using scatter plot. RESULTS: Eighty patients with AIS with 122 coronal curves were reviewed. On standing radiographs, the coronal Cobb angles were 14.7°± 3.2°, 28.2°± 5.1°, and 54.9°± 11.3° for mild, moderate, and severe groups. On supine MRI, the Cobb angles averaged 10.1°± 5.6°, 20.0°± 6.3°, and 49.4 ± 12.3° for each group, respectively. TK were 16.3 ± 9.1° and 11.8 ± 6.1° for radiographs and MRI (P < 0.001), whereas the LL averaged 45.5 ± 12.2° and 39.5 ± 10.5° for radiographs and MRI (P < 0.001). Cobb angles measured on standing radiographs and supine MRI were linearly correlated with the adjusted R being 0.0627, 0.2118, and 0.7999 for the mild, moderate, and severe groups. CONCLUSION: Cobb angles measured on supine MRI were linearly correlated with Cobb angles measured on standing radiographs and the correlation was more reliable in those with Cobb angles more than 40°. Therefore, the supine MRI could serve as a reliable alternative to standing radiographs in the assessment of Cobb angles more than 40° in AIS. LEVEL OF EVIDENCE: 3.

Bone structural and mechanical indices in Adolescent Idiopathic Scoliosis evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Adolescent Idiopathic Scoliosis (AIS) is associated with systemic low bone mass. It could persist into adulthood and was shown to be an important prognostic factor for curve progression in AIS. Previous studies were confined to areal bone mineral density (aBMD) measured by Dual-energy X-ray Absorptiometry (DXA) which was a two-dimensional measurement for a three-dimensional structure. This conventional measurement was inadequate to evaluate volumetric bone density and bone quality which are important determinants for bone strength and bone health status as defined in the 2000 NIH consensus statement. High-resolution peripheral quantitative computed tomography (HR-pQCT) was therefore used in this study for three-dimensional evaluation of volumetric bone mineral density and bone micro-architecture as well as estimation of bone strength. In this study, 214 newly diagnosed AIS girls and 187 age and gender-matched normal control aged between 11 and 13years old were recruited for HR-pQCT evaluations on bone geometry, trabecular bone micro-architecture and volumetric BMD (vBMD) at the non-dominant distal radius. We demonstrated that AIS was associated with lower Cortical Bone Area, Cortical Bone vBMD, Trabecular Number and greater Trabecular Separation. With multivariate linear regression analysis and after adjustment for age, dietary calcium intake and physical activity level, the association of AIS with lower Cortical Bone vBMD, lower Trabecular Number and greater Trabecular Separation remained statistically significant. The findings of this study indicated that AIS was associated with an abnormal bone quality profile suggestive of alteration in endocortical modeling, derangement in trabecular bone structure and disturbance in bone mineralization. The cause for these changes and how they are related to the etiopathogenesis of AIS warrant further studies.