Fiona Wai Ping Yu

Abnormal bone quality versus low bone mineral density in adolescent idiopathic scoliosis: a case-control study with in vivo high-resolution peripheral quantitative computed tomography

BACKGROUND CONTEXT Adolescent idiopathic scoliosis (AIS) is associated with low bone mass that could persist into early adulthood and is an important prognostic factor for curve progression. Previous studies were confined to areal bone mineral density measurement that was a two-dimensional investigation for a three-dimensional structure. Evaluation of volumetric BMD (vBMD) and other bone quality parameters are important for gaining in-depth understanding of the etiopathogenesis of AIS. PURPOSE The objective of this study was to carry out direct in vivo measurement of bone quality in AIS using high-resolution peripheral quantitative computed tomography (HR-pQCT) and compare the correlation of bone quality with osteopenia between AIS and control subjects. STUDY DESIGN/SETTING A case-control study. PATIENT SAMPLE Newly diagnosed AIS girls (n=112) and non-AIS girls (n=115) between 11 and 13 years. OUTCOME MEASURES Areal bone mineral density of bilateral femoral necks and HR-pQCT of the nondominant distal radius were performed. METHODS Areal bone mineral density of femoral necks was measured by dual-energy X-ray absorptiometry. Subjects were classified into the osteopenic (Z score less than or equal to -1) and nonosteopenic (Z score more than -1) groups. Bone quality parameters, including bone morphometry, trabecular bone microarchitecture, and vBMD, were measured by HR-pQCT (XtremeCT; Scanco Medical, Zurich, Switzerland). RESULTS In AIS, the osteopenic group had lower measurements in cortical area, cortical thickness, average vBMD, compact bone vBMD, trabecular vBMD, trabecular bone volume to tissue volume ratio, and trabecular thickness compared with nonosteopenic AIS subjects. In contrast, among the non-AIS controls, the osteopenic group had lower measurements only in bone morphometry, average vBMD, and compact bone vBMD but not in trabecular vBMD and all other trabecular bone microarchitecture parameters. CONCLUSIONS This is the first study using HR-pQCT to compare the correlation of bone quality with osteopenia in AIS and non-AIS subjects. It provides new insights and highlights the unique bone quality profile with predominant changes in the trabecular compartment in association with osteopenia being notably only detected in the AIS subjects. Further studies in this area are warranted for defining the metabolic nature and biomechanical sequelae of derangement in bone mass and bone quality and their roles in the etiopathogenesis of AIS.

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.

Are volumetric bone mineral density and bone micro-architecture associated with leptin and soluble leptin receptor levels in adolescent idiopathic scoliosis?--A case-control study.

Background Adolescent idiopathic scoliosis (AIS) is associated with low bone mineral density (BMD). The underlying etiology and how it may relate to the development of osteopenia remains unknown. Leptin has been postulated as one of the etiologic factors of AIS because of its profound effects on bone metabolism and pubertal growth. Its modulator, soluble leptin receptor (sOB-R), may affect leptin bioavailability and signaling. This study aimed to investigate whether serum leptin and sOB-R levels may be associated with bone quality, and whether these relationships may differ between young adolescent girls with and without AIS. Methods This was a case-control study involving 94 newly diagnosed AIS girls (Cobb angle 12–48°) aged 12 to 14 years old and 87 age and gender-matched normal controls. Subjects with BMI>23.0 Kg/m2 were excluded. Anthropometric measurements including body weight, height, arm span and sitting height were taken. Serum total leptin and sOB-R were assayed with ELISA. Non-dominant distal radius was scanned with High Resolution pQCT for assessing bone quality in terms of bone morphometry, volumetric BMD (vBMD) and trabecular bone micro-architecture. Results Compared with normal controls, AIS girls had numerically higher sOB-R (p = 0.006), lower average vBMD (p = 0.048), lower cortical vBMD (p = 0.029), higher cortical bone perimeter (p = 0.014) and higher trabecular area (p = 0.027), but none remained statistically significant after the Hochberg-Benjamini procedure. Correlation analysis on serum leptin level indicated that distinctive correlations with trabecular bone parameters occurred only in AIS. Conclusion This study showed that bone quality in AIS girls was deranged as compared with controls. In addition, the distinct differences in correlation pattern between leptin and trabecular bone parameters indicated possible abnormalities in bone metabolism and dysfunction of the leptin signaling pathway in AIS.

MRI-based morphological evidence of spinal cord tethering predicts curve progression in adolescent idiopathic scoliosis.

BACKGROUND CONTEXT Existing prognostic factors for adolescent idiopathic scoliosis (AIS) patients have focused mainly on curve, maturity, and bone-related factors. Previous studies have shown significant associations between curve severity and morphological evidences of relative shorter spinal cord tethering in AIS, and increased prevalence of abnormal somatosensory cortical-evoked potentials and low-lying cerebellar tonsil in severe AIS. Earlier evidence suggests that there might be neural morphological predictors for curve progression. PURPOSE The purpose of this study was to identify any morphological predictors associated with cord tethering, as measured by magnetic resonance imaging (MRI), for curve progression in AIS patients. STUDY DESIGN/SETTING This is a prospective cohort study. PATIENT SAMPLE A total of 81 female AIS subjects between 10 and 14 years were included, without surgical intervention during the follow-up period. OUTCOME MEASURES Magnetic resonance imaging scans of hindbrain and whole spine and areal bone mineral density (BMD) at bilateral femoral necks were performed. METHODS All AIS patients were longitudinally followed up starting from initiation of bracing beyond skeletal maturity in 6-month intervals. Clinical and radiographic data were recorded at each clinic visit. Bone mineral density and MRI measurements including ratio of spinal cord to vertebral column length, ratio of anteroposterior (AP) and transverse (TS) diameter of cord, lateral cord space (LCS) ratio, cerebellar tonsil level, and conus medullaris position were obtained at baseline. Only compliant patients with a minimum 2-year follow-up were analyzed. Adolescent idiopathic scoliosis girls were assigned into three groups according to bracing outcome: Group A, nonprogression (curvature increase of less than or equal to 5°); Group B, progression (curvature increase of greater than or equal to 6°); Group C, progression with surgery indication (Cobb angle of greater than or equal to 50° after skeletal maturity despite bracing). The predictors for curve progression were evaluated using univariate analysis and multivariate ordinal regression model. RESULTS The average duration of follow-up was 3.4 (range, 2.0-5.6) years. There were 46 girls (57%) in Group A, 19 (23%) in Group B, and 16 (20%) in Group C. No significant intergroup differences were found in spinal cord length, tonsil level, and conus position. Group C had significantly longer vertebral column length, smaller cord-vertebral length ratio, and higher AP/TS cord ratio compared with Group A, whereas LCS ratio in Group C was significantly increased compared with both Group A and Group B. In regression model, five significant independent predictors including cord-vertebral length ratio (odds ratio [OR]: 1.993 [95% confidence interval {CI}: 1.053-3.771], p=.034), LCS ratio (OR: 2.639 [95% CI: 1.128-6.174], p=.025), initial Cobb angle (OR: 1.156 [95% CI: 1.043-1.281], p=.006), menarche age (OR: 1.688 [95% CI: 1.010-2.823], p=.046), and BMD (OR: 2.960 [95% CI: 1.301-6.731], p=.010) and a marginally significant predictor namely AP/TS cord ratio (OR: 1.463 [95% CI: 0.791-2.706], p=.096) were obtained. CONCLUSIONS On baseline MRI measurement, cord-vertebral length ratio and LCS ratio are identified as new significant independent predictors for curve progression in AIS, whereas AP/TS cord ratio is suggested as a potential predictor requiring further validations. The earlier MRI parameters can be taken into accounts for prognostication of bracing outcome.

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 R2 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

Sexual Dimorphism in Cortical and Trabecular Bone Microstructure Appears During Puberty in Chinese Children: SEXUAL DIMORPHISM IN BONE MICROSTRUCTURE 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.

Serum 25(OH) vitamin d level is associated with treatment outcome of whole-body vibration (WBV) for osteopenia in girls with adolescent idiopathic scoliosis (AIS)

Objectives AIS was associated with low bone mass which, apart from being an important health issue that could persist into adulthood, was also a significant prognostic factor for curve progression in AIS. We have performed a randomized controlled trial on WBV and reported its effect on increasing femoral neck areal bone mineral density (aBMD) mainly at the dominant leg but less obviously at the non-dominant side. The objective of this study was to evaluate the role of Vit-D in affecting the anabolic bone effect of WBV.

Using your mobile phone for quantitative measurement of spinal motion: a reliability and validity study

MSKROM when compared against the Electronic Inclinometer with Pearson correlation coefficient ranging from 0.925 to 0.991 except 0.757 at the thoracic extension measurement (all with p<0.001). The intra and inter-rater reliability of MSKROM was also excellent with ICC ranging from 0.873 to 0.997. In contrast, concurrent validity of the fingertip-to-floor method was poor with Pearson correlation coefficient ranging from -0.048 to 0.237 and none of the correlation reached statistical significance. Conclusions The results provided strong evidences the MSKROM installed in a readily available mobile phone with an inbuilt accelerometer could give valid and reliable measurement of spinal movement in the frontal and sagittal planes. The measurement was simple and fast. Given the inadequacy with the fingertip-to-floor method which is a measure of combined movement at both the hip and the spine, MSKROM can be disseminated for use both at bedside and for clinical researches.