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.

Distinguishing risk of curve progression in adolescent idiopathic scoliosis with bone microarchitecture phenotyping - a 6-year longitudinal study.

Low bone mineral density and impaired bone qualities have been shown to be important prognostic factors for curve progression in Adolescent Idiopathic Scoliosis (AIS). There is no evidence-based integrative interpretation method to analyse high-resolution peripheral quantitative computed tomography (HR-pQCT) data in AIS. This study aimed to (a) utilize unsupervised machine learning to cluster bone microarchitecture phenotypes on HR-pQCT parameters in AIS girls, (b) assess the phenotypes' risk of curve progression and progression to surgical threshold at skeletal maturity (primary cohort), and (c) investigate risk of curve progression in a separate cohort of mild AIS girls whose curve severity did not reach bracing threshold at recruitment (secondary cohort). Patients were followed up prospectively for 6.22 ± 0.33 years in the primary cohort (N = 101). Three bone microarchitecture phenotypes were clustered by Fuzzy C-Means at time of peripubertal peak height velocity (PHV). Phenotype-1 had normal bone characteristics. Phenotype-2 was characterized by low bone volume and high cortical bone density, and Phenotype-3 had low cortical and trabecular bone density and impaired trabecular microarchitecture. The difference in bone qualities amongst the phenotypes was significant at peripubertal PHV and continued to skeletal maturity. Phenotype-3 had significantly increased risk of curve progression to surgical threshold at skeletal maturity (Odd Ratios (OR) = 4.88; 95% Confidence Interval (CI): 1.03-28.63). In the secondary cohort (N = 106), both Phenotype-2 (adjusted OR = 5.39; 95%CI: 1.47-22.76) and Phenotype-3 (adjusted OR = 3.67; 95%CI: 1.05-14.29) had increased risk of curve progression ≥6° with mean follow-up of 3.03 ± 0.16 years. In conclusion, three distinct bone microarchitecture phenotypes could be clustered by unsupervised machine learning on HR-pQCT generated bone parameters at peripubertal PHV in AIS. The bone qualities reflected by these phenotypes were found to have significant differentiating risk of curve progression and progression to surgical threshold at skeletal maturity in AIS.

Adolescent Idiopathic Scoliosis (AIS) is an abnormal spinal curvature commonly presents during puberty growth. Evidence has shown that low bone mineral density and impaired bone qualities are important risk factors for curve progression in AIS. High-resolution peripheral quantitative computed tomography (HR-pQCT) has improved our understanding of bone qualities in AIS. It generates a large amount of quantitative and qualitative bone parameters from a single measurement, but the data are not easy for clinicians to interpret and analyse. This study enrolled AIS girls and used unsupervised machine learning model to analyse their HR-pQCT data at first clinic visit. The model clustered the patients into 3 bone microarchitecture phenotypes (i.e. Phenotype-1: normal, Phenotype-2: low bone volume and high cortical bone density, and Phenotype-3: low cortical and trabecular bone density and impaired trabecular microarchitecture). They were longitudinally followed up for 6 years until skeletal maturity. We observed the three phenotypes were persistent, and Phenotype-3 had a significantly increased risk of curve progression to severity that requires invasive spinal surgery (Odds Ratio = 4.88, P = 0.029). The difference in bone qualities reflected by these 3 distinct phenotypes could aid clinicians to differentiate risk of curve progression and surgery at early stages of AIS.

Investigation on the site of coronal deformities in Hallux valgus.

Hallux valgus (HV) is a common foot deformity that is more prevalent in females, characterised by abnormal adduction of the first metatarsal (MT) and valgus deviation of the phalanx on the transverse plane. Increasing evidence indicates that HV is more than a 2D deformity but a 3D one with rotational malalignment. Pronation deformity is seen during clinical examination for HV patients, but the exact origin of this rotational deformity is still unknown. Some attribute it to first tarsometatarsal (TMT) joint rotation, while others attribute it to intra-metatarsal bony torsion. In addition, the correlation between the rotational and transverse plane deformity is inconclusive. Identifying the origin of the rotational deformity will help surgeons choose the optimal surgical procedure while also enhancing our understanding of the pathophysiology of HV. This study aims to (1) develop an objective method for measuring the first MT torsion and first TMT joint rotation; (2) investigate the exact location of the coronal deformity in HV; (3) investigate the relationship between the severity of deformity on the transverse and coronal planes as well as the correlation between deformity severity and foot function/symptoms in HV. Age-matched females with and without HV were recruited at the Foot and Ankle Clinic of the Department of Orthopaedics and Traumatology. Computed tomography was conducted for all subjects with additional weight-bearing dorsal-plantar X-ray examination for HV subjects. Demographic information of all subjects was recorded, with symptoms and functions related to HV evaluated. The intra-class correlation was used to explore the relationship between deformities on different planes and the deformity severity and functional outcomes, respectively. An Independent t-test was used to compare joint rotation and bone torsion degrees. TMT joint rotation is significantly correlated with foot function. HV patients had more TMT joint rotation but not MT torsion compared to normal controls. No relationship was found between the coronal rotation and the 1,2-intermetatarsal angle (IMA) or Hallux valgus angle (HVA) on the transverse plane. Our results indicate that coronal deformities in HV may originate from TMT joint rotation. In addition, the severity of the TMT joint coronal rotation correlates with worse foot function; thus, multi-plane assessment and examination will be necessary for more precise surgical correction.

More Prevalent and Severe Low Bone-Mineral Density in Boys with Severe Adolescent Idiopathic Scoliosis Than Girls: A Retrospective Study of 798 Surgical Patients.

INTRODUCTION: A total of 0.1-0.8% of AIS patients progress to severe stages without clear mechanisms, and AIS girls are more prone to curve progression than boys. Recent studies suggest that AIS girls have systemic and persistent low bone-mineral density (BMD), which has been shown to be a significant prognostic factor of curve progression in AIS. The present study aimed to (a) investigate the prevalence of low BMD in patients with severe AIS and (b) assess the sexual dimorphism and independent risk factors of low BMD in severe AIS patients. MATERIALS AND METHODS: A total of 798 patients (140 boys vs. 658 girls) with AIS who reached surgical threshold (Cobb ≥ 40°) were recruited. BMD were assessed using BMD Z-scores from dual-energy X-ray absorptiometry (DXA). Demographic, clinical, and laboratory values of the subjects were collected from their medical records. Logistic regression analysis was performed to identify independent risk factors of low BMD. RESULTS: The overall prevalence of BMD Z-score ≤ -2 and ≤ -1 were 8.1% and 37.5%, respectively. AIS boys had significantly lower BMD Z-scores (-1.2 ± 0.96 vs. -0.57 ± 0.92) and higher prevalence of low BMD (Z-score ≤ -2: 22.1% vs. 5.2%, p < 0.001; Z-score ≤ -1: 59.3% vs. 32.8%, p < 0.001) than girls. Sex, BMI, serum alkaline phosphatase, and potassium were independent factors of low BMD in the severe AIS patients. CONCLUSIONS: The present large cohort of surgical AIS patients revealed that low BMD is more prevalent and severe in boys than in girls with severe curves. Low BMD may serve as a more valuable predictive factor for curve progression to the surgical threshold in boys than girls with AIS.

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.

HR-pQCT for the Evaluation of Muscle Quality and Intramuscular Fat Infiltration in Ageing Skeletal Muscle.

Myosteatosis is the infiltration of fat in skeletal muscle during the onset of sarcopenia. The quantification of intramuscular adipose tissue (IMAT) can be a feasible imaging modality for the clinical assessment of myosteatosis, important for the early identification of sarcopenia patients and timely intervention decisions. There is currently no standardized method or consensus for such an application. The aim of this study was to develop a method for the detection and analysis of IMAT in clinical HR-pQCT images of the distal tibia to evaluate skeletal muscle during the ageing process, validated with animal and clinical experimentation. A pre-clinical model of ovariectomized (OVX) rats with known intramuscular fat infiltration was used, where gastrocnemii were scanned by micro-computed tomography (micro-CT) at an 8.4 µm isotropic voxel size, and the images were analyzed using our modified IMAT analysis protocol. IMAT, muscle density (MD), and muscle volume (MV) were compared with SHAM controls validated with Oil-red-O (ORO) staining. Furthermore, the segmentation and IMAT evaluation method was applied to 30 human subjects at ages from 18 to 81 (mean = 47.3 ± 19.2). Muscle-related parameters were analyzed with functional outcomes. In the animal model, the micro-CT adipose tissue-related parameter of IMAT% segmented at −600 HU to 100 HU was shown to strongly associate with the ORO-positively stained area (r = 0.898, p = 0.002). For the human subjects, at an adjusted threshold of −600 to −20 HU, moderate positive correlations were found between MV and MD (r = 0.642, p < 0.001), and between MV and IMAT volume (r = 0.618, p < 0.01). Moderate negative correlations were detected between MD and IMAT% (r = −0.640, p < 0.001). Strong and moderate associations were found between age and MD (r = −0.763, p < 0.01), and age and IMAT (r = 0.559, p < 0.01). There was also a strong correlation between IMAT% and chair rise time (r = 0.671, p < 0.01). The proposed HR-pQCT evaluation protocol for intramuscular adipose-tissue produced MD and IMAT results that were associated with age and physical performance measures, and were of good predictive value for the progression of myosteatosis or sarcopenia. The protocol was also validated on animal skeletal muscle samples that showed a good representation of histological lipid content with positive correlations, further supporting the clinical application for the rapid evaluation of muscle quality and objective quantification of skeletal muscle at the peripheral for sarcopenia assessment.

Muscle plays a more superior role than fat in bone homeostasis: A cross-sectional study of old Asian people.

Objectives: The aim of this study was to discover the role of fat and muscle in bone structures, as well as the relationship between obesity and sarcopenia on age-related osteoporosis. Methods: A total of 400 participants (65.0 ± 8.2 years old, 42.3% women) were recruited. Fat, muscle, bone parameters, basic demographics, medical history, physical performance and activity, and calcium intake of participants were obtained from datasets. The diagnosis of osteoporosis, sarcopenia, and obesity was based on current recommendations. Pearson correlation, non-linear regression models, and decision tree analyses were performed to study the relationship between fat, muscle, and bone. Logistic regression analyses were used to explore the risk of osteoporosis in old people with obesity or sarcopenia via Model 1 (unadjusted) and Model 2 (adjusted by age, physical activity, and calcium intake). Results: Correlation analysis showed that limb muscle mass and index, and age were best related to bone mineral density (BMD) (|r| = 0.386-0.632, p < 0.001). On the contrary, body mass index (BMI) and increased body fat percentage (BF%) were harmful for bone health. An increase of BMI and fat mass index slowed the increase of BMD in the spine, while skeletal muscle mass index accelerated the increase. People with sarcopenia had low muscle mass and strength. When separating subjects into sarcopenia and non-sarcopenia status, sarcopenia was independently related to higher risks of osteoporosis in both models (OR > 1, p < 0.05). BMI-defined obesity in Model 1 as well as BF%-defined obesity in both models did not reduce the risk of osteoporosis in both models (p > 0.05). The decision tree classification (85% accuracy) showed that greater body weight and larger lower limb muscle performance were negatively related to osteoporosis, while fat mass and percentage did not play roles in this prediction. Conclusion: Low muscle mass and function were harmful to bone health. Obesity defined by both BMI and BF% had limited protective roles in osteoporosis. The benefits for bone from increased muscle mass and function play a more superior role than increased fat mass in old people. Sarcopenia prevention and treatment instead of controlling obesity should be recommended as an approach to reduce the risks of age-related osteoporosis and fragility fracture for elderly people.

Performance of HR-pQCT, DXA, and FRAX in the discrimination of asymptomatic vertebral fracture in postmenopausal Chinese women.

Volumetric bone density (vBMD) and trabecular microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) can discriminate the patients with high risk of asymptomatic vertebral fracture (VF) in postmenopausal Chinese women. These findings suggested that HR-pQCT could provide additional information on bone quality of the patients with asymptomatic VF. INTRODUCTION: Although there were several studies using HR-pQCT to investigate asymptomatic VF, it remains uncertain if HR-pQCT parameters can discriminate asymptomatic VF patients, especially in Chinese population. The purpose of this study was to investigate whether bone quality measured by HR-pQCT could discriminate asymptomatic VF independent of hip areal bone mineral density (aBMD) measured by dual-energy x-ray absorptiometry (DXA) and fracture risks evaluated using built-in Fracture Risk Assessment Tool (FRAXBMD). METHODS: This is a nested case-control study. One hundred seventy-five ambulatory Chinese postmenopausal women aged 60-79 years were retrieved from Normative Reference Standards (NRS) cohort in Hong Kong. DXA was used to identify VF from lateral spine images (VFA) using Genant's semi-quantitative method. Major osteoporotic fracture risk was calculated using FRAX tool. HR-pQCT was used to assess vBMD, microarchitecture, and estimated strength at both distal radius and tibia. Comparison of HR-pQCT parameters between asymptomatic VF and control was performed using covariance analysis. Logistic regression analysis was performed for calculating the adjusted odds ratio (OR) with 95% confidence intervals (CI) of fracture status as per SD decrease in HR-pQCT parameters. RESULTS: Women with asymptomatic VF were older than those of the control in our NRS cohort. Nevertheless, after adjusted for covariance, asymptomatic VF showed significantly lower trabecular vBMD (Tb.vBMD) at radius but higher SMI at tibia as compared with those of the control. Tb.vBMD at radius yielded the highest value of area under the curve (AUC) as compared with total hip aBMD and FRAXBMD. However, no significant difference was found among each other. CONCLUSION: Tb.vBMD at the radius and SMI at the tibia provided by HR-pQCT can discriminate asymptomatic VF independent of hip aBMD and FRAXBMD by DXA in postmenopausal women.

Diagnosis of sarcopenia by evaluating skeletal muscle mass by adjusted bioimpedance analysis validated with dual-energy X-ray absorptiometry.

BACKGROUND: This study aimed to adjust and cross-validate skeletal muscle mass measurements between bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) for the screening of sarcopenia in the community and to estimate the prevalence of sarcopenia in Hong Kong. METHODS: Screening of sarcopenia was provided to community-dwelling older adults. Appendicular skeletal muscle mass (ASM) was evaluated by BIA (InBody 120 or 720) and/or DXA. Handgrip strength and/or gait speed were assessed. Diagnosis of sarcopenia was based on the 2019 revised Asian Working Group for Sarcopenia cut-offs. Agreement analysis was performed to cross-validate ASM measurements by BIA and DXA. Multiple regression was used to explore contribution of measured parameters in predicting DXA ASM from BIA. RESULTS: A total of 1587 participants (age = 72 ± 12 years) were recruited; 1065 participants were screened by BIA (InBody 120) with 18 followed up by DXA, while the remaining 522 participants were assessed by the BIA (InBody 720) and DXA. The appendicular skeletal muscle mass index (ASMI) evaluated by BIA showed a mean difference of 2.89 ± 0.38 kg/m2 (InBody 120) and 2.97 ± 0.45 kg/m2 (InBody 720) against DXA gold standard. A significant overestimation of muscle mass was measured by BIA compared with DXA (P < 0.005). BIA data were adjusted using prediction equation and mean difference reduced to -0.02 ± 0.31 kg/m2 in cross-validation. Prevalence of sarcopenia in older adults ≥65 ranged from 39.4% (based on ASMI by DXA) to 40.8% (based on predicted DXA ASMI from BIA). Low ASMI by DXA was found in 68.5% of the older adults screened. The percentage of older adults exhibited low handgrip strength ranged from 31.3% to 56%, while 49% showed low gait speed. CONCLUSIONS: Bioimpedance analysis was found to overestimate skeletal muscle mass compared with DXA. With adjustment equations, BIA can be used as a quick and reliable tool for screening sarcopenia in community and clinical settings with limited access to better options.

Best Performance Parameters of HR-pQCT to Predict Fragility Fracture: Systematic Review and Meta-Analysis.

Osteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual-energy X-ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta-analysis was designed to investigate which HR-pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR-pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta-analysis. HR-pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR-pQCT parameters, our meta-analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR-pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR-pQCT, the non-weight-bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white-based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR-pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Global sagittal alignment after surgery of right thoracic idiopathic scoliosis in adolescents and adults with and without thoracic hypokyphosis.

This study aimed to characterize global sagittal alignment in adolescent idiopathic scoliosis (AIS) with normal kyphosis (NTK, kyphosis > 10°) and with thoracic hypokyphosis (THK, kyphosis < 10°), before and after posterior spinal fusion, and compare them with asymptomatic controls. 27 AIS girls and young adults with right thoracic curves were included (seventeen with age ≤ 18 years, then age > 21). Biplanar radiographies were acquired at baseline, immediate post-operatively, 1-year and 2-year follow-up, and 3D reconstruction of the spine and pelvis was performed. NTK and THK showed different global sagittal alignment, as well as differences compared to controls. AIS with THK at baseline had higher SVA/SFD (2.0 ± 2.9 vs - 0.4 ± 1.9; P < 0.05) and OD-HA (0.2 ± 1.4° vs - 1.3 ± 1.6°; P < 0.05) than controls, indicating that THK had compensated balance with unusual forward leaning posture. Immediately post-operation, SVA/SFD remained high (1.3 ± 3.0) while OD-HA reversed (- 1.2 ± 1.7°), indicating that THK patients had found partially compensated balance. After 2-yeas, both SVA/SFD (- 1.3 ± 2.1) and OD-HA (- 1.4 ± 0.9°) were normalized. The changes in global sagittal alignment and mechanism of balance are different in AIS with or without THK. As the head plays a critical role on balance during immediate and delayed post-operation, OD-HA can be complementary parameter for assessing global balance during post-operative follow-up of AIS patients with THK.

The association of disproportionate skeletal growth and abnormal radius dimension ratio with curve severity in adolescent idiopathic scoliosis.

Abnormal anthropometric measurements during the peripubertal growth spurt have been documented in adolescent idiopathic scoliosis (AIS). Magnetic resonance (MR) imaging studies of the spine have suggested a disproportionate endochondral and membranous ossification in AIS. The present study aimed at investigating whether disproportional ossification and skeletal growth occurred in the peripheral bone of AIS patients using the radius as the target bone. Skeletally mature AIS girls with different severity (n = 290) and age-matched control healthy girls (n = 80) were recruited. The anthropometric parameters were recorded. The midshaft of non-dominant radius was scanned with peripheral quantitative computed tomography (pQCT) and the radius diameter was calculated from the cross-sectional area. Radius dimension ratio was derived from the ratio of radius diameter to radius length. The anthropometric parameters were compared between AIS and control with adjustment for age. The radius dimension ratio was further correlated with curve severity in AIS girls using Pearson's correlation test. The analysis showed that the arm span and radius length were slightly longer in AIS girls. The BMI of AIS girls was significantly lower than the controls. The radius dimension ratio in severe AIS girls was significantly lower than the controls and the ratio of AIS girls correlated with the curve severity (r = -0.120; p = 0.039). The abnormal radius dimension ratio supported the presence of systemic growth abnormalities in AIS. Disproportional endochondral-membranous ossification could explain for the observation. The observation of the association of radius dimension ratio with curve severity provides an important potentially clinically measurable parameter for further longitudinal studies on the prognostication of curve progression in AIS.

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.

Validation Study of the Thumb Ossification Composite Index (TOCI) in Idiopathic Scoliosis: A Stage-to-Stage Correlation with Classic Tanner-Whitehouse and Sanders Simplified Skeletal Maturity Systems.

BACKGROUND: The new simplified thumb ossification composite index (TOCI) based on ossification of the thumb epiphyses and adductor sesamoid has demonstrated simplicity, excellent reliability, and high accuracy for predicting skeletal maturity, comparable with the Sanders simplified skeletal maturity system (SSMS). It was our belief that, because the terminology of the SSMS system has been commonly used for skeletal maturity prediction in idiopathic scoliosis in publications over the past decade, the clinical applicability of the TOCI system would increase if the stages in the 2 systems were found to be interchangeable and highly correlated. METHODS: Hand radiographs of 125 premenarchal girls with newly diagnosed adolescent idiopathic scoliosis who had been followed longitudinally until skeletal maturity were all scored with use of the Tanner-Whitehouse III (TW3) system (stages E through I), the TOCI, and the SSMS. The scores for the epiphyses of the ulnar 4 digits were compared with those for the thumb and correlated with the timing of peak height velocity. Correlations were analyzed with the chi-square test and Cramer V and Somers delta correlations. RESULTS: Six hundred and forty-five hand radiographs (an average of 5 for each girl with idiopathic scoliosis) and 11,517 epiphyses were scored. The rate of concordance between TW3 stages F, G, and I for the thumb proximal phalangeal epiphysis and those for all of the epiphyses of the ulnar 4 digits were 72.5%, 72.5%, and 89.9%, respectively. The overall concordance rate (including all epiphyses) was 71.3%, with a very high Cramer V correlation and significance (p < 0.01). High interchangeability was demonstrated for the TOCI and SSMS stages, supported by a high Somers delta correlation (>0.8) with significance (p < 0.05). CONCLUSIONS: The TOCI is highly practical for clinical use, and its stages are highly interchangeable with those of the SSMS. CLINICAL RELEVANCE: The TOCI could serve as a simplified "marker" of skeletal maturity on hand radiographs and minimize the learning-curve problems associated with the SSMS in a busy clinical practice.

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.

Trabecular bone status in ultradistal tibia under habitual gait loading: a pQCT study in postmenopausal women.

This study investigated regional volumetric trabecular bone mineral density (tBMD) and bone area at the ultradistal tibia in Chinese women using peripheral quantitative computed tomography. Fifty-six postmenopausal women aged 47-62 yr participated in BMD measurements at baseline and 22 of them were followed at both 1-yr and 3-yr follow-up scans. Regional baseline tBMD, rate of annual bone loss, and trabecular bone area were determined. Baseline measurements showed that the tBMD of both the posterior (252.9+/-63.4 mg/cm(3)) and medial (226.6+/-68.9 mg/cm(3)) regions was significantly higher than that of the anterior (126.3+/-61.9 mg/cm(3)) and lateral regions (149.8+/-50.6 mg/cm(3)), respectively (p<0.001). Both the 1-yr and 3-yr follow-up measurements showed that there was significant physiological annual tBMD loss on an average of 1.61%, at the four regions. Inter-slice regional tBMD and trabecular bone area measurements demonstrated a significant linear decrease from the distal to proximal aspects (p<0.001). Findings suggest that dynamic compressive loading during the heel strike and the body weight vector shifting toward the medial aspect during the stance phase in a normal gait might account for the regional tBMD differences. Increased tBMD and bone area toward the distal tibial endplate may adapt to withstand the axial impact loading. However, the low-impact weight-bearing nature of a normal gait may not be osteogenic to prevent regional bone loss. An exercise program specific to the women at risk should be contemplated.

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.

Structural, densitometric and biomechanical evaluations of Chinese patients with long-term bisphosphonate treatment.

BACKGROUND: The association of long-term bisphosphonate treatment for osteoporosis and related safety problems such as atypical fractures were not clearly defined. This study was to evaluate the structural, densitometric and biomechanical properties of the prolonged bisphosphonate-loaded bones. METHODS: Bone mineral density (BMD) at hip and femoral midshaft, bone cross-sectional area, moment of inertia of both femurs, bone formation and resorption biochemical markers were compared between 28 elderly with at least 4 years of bisphosphonate treatment from 2002 through 2006 and age-matched group of 37 elderly. RESULTS: The total hip BMD and t-score were found not different between two groups. However, bisphosphonate treated patients were found to have significantly lower bone mineral content in the femoral shaft (P < 0.05); morphological study showed lower cross-sectional area in subtrochanteric and mid-diaphyseal region and thus significantly lower moment of inertia (P < 0.01). High resolution-peripheral quantitative computed tomography showed significantly decreased trabecular density, bone volume ratio, trabecular number but increased trabecular spacing in tibia and distal radius. Finite element analysis further confirmed significantly lower stiffness and failure load in tibia. Biochemical studies also showed lower bone resorption and severely suppressed bone formation activity (P < 0.001). CONCLUSIONS: The unchanged total hip BMD between two groups confirmed the beneficial effects of bisphosphonate on trabecular bone, thus preventing osteoporotic fractures at large in previous studies. However, the inferior structural, densitometric and biomechanical properties at cortical bones, especially femur midshaft, need a special attention to look into the association between long-term bisphosphonate intake and the occurrence of stress fractures. When patients taking bisphosphonate complain of proximal thigh pain or discomfort, plain X-ray film can be the first line screening. All patients prescribed with bisphosphonate should be informed of such a complication though we must stress its rarity.

Quantitative ultrasound for predicting curve progression in adolescent idiopathic scoliosis: a prospective cohort study of 294 cases followed-up beyond skeletal maturity.

Adolescent idiopathic scoliosis (AIS) is prevalent among adolescents and can carry significant morbidities. We evaluated the use of quantitative ultrasound (QUS) for predicting curve progression in patients with AIS. We recruited 294 girls with AIS at a mean age of 13.4 years, and they were prospectively followed beyond skeletal maturity for curve progression. We recorded 3 calcaneal QUS measurements at baseline, namely broadband ultrasound attenuation (BUA), velocity of sound (VOS), and stiffness index (SI). Logistic regression analysis indicated that SI, age, menarchal status, and Cobb angle were significant prognostic factors to be included in the final prediction model. The adjusted odds ratio of curve progression for Z-score of SI≦0 was 2.00 (95% CI: 1.08-3.71). The area under the ROC curve was 0.831 (95% CI: 0.785-0.877). The results of this study indicate that SI was an independent and significant prognostic factor for AIS and could be considered in addition to other prognostic factors when estimating the risk for curve progression and planning treatment for patients with AIS.

Abnormal bone quality in adolescent idiopathic scoliosis: a case-control study on 635 subjects and 269 normal controls with bone densitometry and quantitative ultrasound.

STUDY DESIGN: A case-control study comparing bone quality in Adolescent Idiopathic Scoliosis (AIS) with normal controls. OBJECTIVE: To evaluate bone quality with quantitative ultrasound (QUS) in AIS and normal controls so as to detect any derangement in bone quality among AIS subjects. SUMMARY OF BACKGROUND DATA: AIS is characterized by complex spinal deformities. Despite its high prevalence and clinical impact in adolescents, etiology of AIS remains unknown but one possible mechanism is related to derangement of bony mechanical stability, as quantified by bone mineral density (BMD) and bone quality. AIS is known for its association with osteopenia, but little is known about the bone quality in AIS. With technological advancement, QUS can provide objective measurement of bone quality. In this study, we sought to compare bone quality in AIS with normal controls using QUS in addition to the conventional BMD measurement. METHODS: Six hundred thirty-five AIS girls and 269 age-matched normal girls were investigated. Broadband ultrasound attenuation (BUA), velocity of sound (VOS), and stiffness index (SI) were measured over the nondominant calcaneus using QUS. The results were correlated with anthropometric measurement, radiologic assessment, and BMD of both hips. RESULTS: The z-score of BMD at the femoral neck of AIS subjects (-0.47 ± 0.97) was significantly lower than that of normal controls (-0.12 ± 1.01, P < 0.001). Crude comparison showed that BUA, VOS, and SI of AIS group were 3.8% (P < 0.01), 0.5% (P = 0.042), and 6.9% (P < 0.01) lower than controls, respectively. After controlling confounding from maturity, body weight, body height, and BMD with multiple linear regression analysis for both mild (Cobb's angle ≤ 25°) and severe (Cobb's angle > 25°) curves, BUA and SI were found to be statistically significantly lower in AIS as compared with controls (P < 0.05). CONCLUSION: In addition to higher prevalence of osteopenia, AIS patients were also found to have deranged bone quality. These might contribute to the etiopathogenesis of spinal deformities in AIS.