Gait speed and spasticity are independently associated with estimated failure load in the distal tibia after stroke: an HR-pQCT study.

This HR-pQCT study was conducted to examine bone properties of the distal tibia post-stroke and to identify clinical outcomes that were associated with these properties at this site. It was found that spasticity and gait speed were independently associated with estimated failure load in individuals with chronic stroke. PURPOSE: (1) To examine the influence of stroke on distal tibia bone properties and (2) the association between these properties and clinical outcomes in people with chronic stroke. METHODS: Sixty-four people with stroke (age, 60.8 ± 7.7 years; time since stroke, 5.7 ± 3.9 years) and 64 controls (age: 59.4 ± 7.8 years) participated in this study. High-resolution peripheral quantitative computed tomography (HR-pQCT) was used to scan the bilateral distal tibia, and estimated failure load was calculated by automated finite element analysis. Echo intensity of the medial gastrocnemius muscle and blood flow of the popliteal artery were assessed with ultrasound. The 10-m walk test (10MWT), Fugl-Meyer Motor Assessment (FMA), and Composite Spasticity Scale (CSS) were also administered. RESULTS: The percent side-to-side difference (%SSD) in estimated failure load, cortical area, thickness, and volumetric bone mineral density (vBMD), and trabecular and total vBMD were significantly greater in the stroke group than their control counterparts (Cohen's d = 0.48-1.51). Isometric peak torque and echo intensity also showed significant within- and between-groups differences (p ≤ 0.01). Among HR-pQCT variables, the %SSD in estimated failure load was empirically chosen as one example of the strong discriminators between the stroke group and control group, after accounting for other relevant factors. The 10MWT and CSS subscale for ankle clonus remained significantly associated with the %SSD in estimated failure load after adjusting for other relevant factors (p ≤ 0.05). CONCLUSION: The paretic distal tibia showed more compromised vBMD, cortical area, cortical thickness, and estimated failure load than the non-paretic tibia. Gait speed and spasticity were independently associated with estimated failure load. As treatment programs focusing on these potentially modifiable stroke-related impairments are feasible to administer, future studies are needed to determine the efficacy of such intervention strategies for improving bone strength in individuals with chronic stroke.

Bone density and microarchitecture: relationship between hand, peripheral, and axial skeletal sites assessed by HR-pQCT and DXA in rheumatoid arthritis.

We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4 ± 9.3 years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius (r = 0.201-0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites (r = 0.354-0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA.

Determinants of estimated failure load in the distal radius after stroke: An HR-pQCT study.

Bone health is often compromised after stroke and the distal radius is a common site of fragility fractures. The macro- and mircoproperties of bone tissue after stroke and their clinical correlates are understudied. The objectives of the study were to use High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) to investigate the bone properties at the distal radius, and to identify the correlates of estimated failure load for the distal radius in people with chronic stroke. This was a cross-sectional study of 64 people with stroke (age: 60.8 ± 7.7 years, stroke duration: 5.7 ± 3.9 years) and 64 age- and sex-matched controls. Bilateral bone structural, densitometric, geometric and strength parameters of the distal radius were measured using HR-pQCT. The architecture, stiffness and echo intensity of the bilateral biceps brachii muscle and brachial artery blood flow were evaluated using diagnostic ultrasound. Other outcomes included the Fugl-Meyer Motor Assessment (FMA), Motor Activity Log (MAL), and Composite Spasticity Scale (CSS). The results revealed a significant side (paretic vs non-paretic for the stroke group, non-dominant vs dominant for controls) by group (stroke vs control) interaction effect for estimated failure load, cortical area, cortical thickness, trabecular number and trabecular separation, and all volumetric density parameters. Post-hoc analysis showed percent side-to-side differences in bone outcomes were greater in the stroke group than the control group, with the exception of trabecular thickness and intracortical porosity. Among the HR-pQCT variables, percent side-to-side difference in trabecular volumetric bone mineral density contributed the most to the percent side-to-side difference in estimated failure load in the stroke group (R2 change = 0.334, ß = 1.106). Stroke-related impairments (FMA, MAL, CSS) were found to be significant determinants of the percent side-to-side difference in estimated failure load (R2 change = 0.233, ß = -0.480). This was the first study to examine bone microstructure post-stroke. We found that the paretic distal radius had compromised bone structural properties and lower estimated failure load compared to the non-paretic side. Motor impairment was a determinant of estimated bone strength at the distal radius and may be a potential intervention target for improving bone health post-stroke.

Rat lumbar vertebrae bone densitometry using multidetector CT.

Peripheral quantitative CT (pQCT) is the main method of bone mineral density (BMD) measurement in small animals. However, pQCT is usually only available in specialized centers, while clinical multidetector computed tomography (MDCT) is much more widely available. This study investigated the feasibility of using clinical 64-slice MDCT for measuring the BMD of rat lumbar vertebrae. The lumbar vertebrae of 18 7-month-old female Sprague-Dawley rats were studied. Two MDCT protocols (General Electric LightSpeed), comprising single 2.5-mm and continuous 0.625-mm acquisitions, and a single pQCT protocol (Scanco Densiscan 2000), comprising 1-mm acquisitions, were performed. The following comparisons were carried out: 2.5-mm MDCT densitometry versus 0.625-mm MDCT densitometry; 0.625-mm MDCT densitometry compared to pQCT densitometry; same day repeatability of 0.625-mm MDCT densitometry; longitudinal repeatability of 0.625-mm MDCT densitometry on day 0 and day 28 and longitudinal 0.625-mm MDCT densitometry in ovariectomized rats on day 0 and day 28. Comparisons were made using intra-class correlation coefficient (ICC). Examination time per animal was 5 min for MDCT and 30 min for pQCT. Acquisitions of 2.5-mm MDCT had a larger coefficient of variation (CoV) than 0.625-mm acquisitions. MDCT densitometry had good agreement with pQCT densitometry (ICC = 0.85). Same-day MDCT densitometry with 0.625-mm acquisitions had a small CoV (1.61%). MDCT densitometry of non-ovariectomized animals at 28 days showed no BMD change, while MDCT densitometry of ovariectomized animals showed a 13.7 +/- 6.7% BMD reduction at 28 days. Clinical MDCT can reliably and accurately measure rat lumbar vertebral BMD and is much faster than pQCT.

Bone measurements at multiple skeletal sites in adolescent idiopathic scoliosis-an in vivo correlation study using DXA, HR-pQCT and QCT.

Significant correlations for bone mineral density and bone microstructure between spinal and non-spinal skeletal sites (distal radius and proximal femur) in adolescent idiopathic scoliosis (AIS) patients were observed, indicating that proximal femoral DXA and distal radial HR-pQCT could provide valid clinical assessments in patients with AIS. PURPOSE: Low bone mass is an important feature of adolescent idiopathic scoliosis (AIS), which is a complex 3D spinal deformity that affects girls during puberty. However, no clinical imaging modality is suitable for regular monitoring on their spinal bone qualities in rapid growth period. Therefore, we investigated whether bone mineral density (BMD) and bone microstructure at non-spinal sites correlated with BMD and mechanical property in the spine in AIS patients. METHODS: Thirty-two AIS girls (16.7 ± 3.5 years old with mean Cobb angle of 67 ± 11°) who underwent pre-operative spine CT examination for navigation surgery were recruited. Volumetric BMD (vBMD) of lumbar spine (LS) was measured by quantitative computed tomography (QCT), vBMD and bone microstructure of distal radius (DR) by high-resolution peripheral QCT (HR-pQCT) and areal BMDs of total hip (TH) and femoral necks (FN) by dual-energy X-ray absorptiometry (DXA). Biomechanical properties of the DR and LS were estimated by finite element analysis (FEA). Pearson correlation was performed to study the correlation between bone parameters at these three sites. RESULTS: LS vBMD correlated significantly with both FN and TH aBMD (R = 0.663-0.725, both p < 0.01) and with DR microstructural parameters (R = 0.380-0.576, all p < 0.05). Mechanical properties of LS and DR were also correlated (R = 0.398, p = 0.039). CONCLUSIONS: Bone measurement at proximal femur and distal radius could provide an additional predictive power in estimating the bone changes at spine, which is the primary site of deformity in AIS patients. Our result indicated that DXA and HR-pQCT could provide a valid surrogate for spine bone measurements in AIS patients.

Value of Measuring Bone Microarchitecture in Fracture Discrimination in Older Women with Recent Hip Fracture: A Case-control Study with HR-pQCT.

We aimed to determine whether loss of volumetric bone mineral density (vBMD) and deterioration of microarchitecture imaged by high-resolution peripheral quantitative computed tomography at the distal radius/tibia provided additional information in fracture discrimination in postmenopausal women with recent hip fracture. This case-control study involved 24 postmenopausal Chinese women with unilateral femoral neck fracture (average [SD] age: 79.6[5.6]) and 24 age-matched women without any history of fracture. Each SD decrease in T-score at femoral neck (FN) was associated with a higher fracture risk (odds ratio: 6.905, p = 0.001). At the distal radius, fracture women had significantly lower total vBMD (-17.5%), fewer (-20.3%) and more unevenly spaced (81.4%) trabeculae, and thinner cortices (-14.0%) (all p < 0.05). At the distal tibia, vBMD was on average -4.7% (cortical) to -25.4% (total) lower, trabecular microarchitecture was on average -19.8% (number) to 102% (inhomogeneity) inferior, cortices were thinner (-21.1%) and more porous (18.2%) (all p < 0.05). Adding parameters of vBMD and microarchitecture in multivariate models did not offer additional discriminative capacity of fracture status compared with using T-score at FN. In old postmenopausal women with already excessive loss of bone mass, measuring bone microarchitecture may provide limited added value to improve identification of risk of femoral neck fracture.

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/m(2) 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.

Structure and strength of the distal radius in female patients with rheumatoid arthritis: a case-control study.

The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross-sectional study of 66 middle-aged female RA patients and 66 age-matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were -5.7% to -23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR-pQCT provides new insight into inflammation-associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity.

Abnormal skeletal growth patterns in adolescent idiopathic scoliosis--a longitudinal study until skeletal maturity.

STUDY DESIGN: A cross-sectional and prospective longitudinal study on the anthropometric parameters and growth pattern of girls with adolescent idiopathic scoliosis (AIS). OBJECTIVE: To investigate the growth pattern of girls with AIS with different severities, using cross-sectional and prospective longitudinal data set in comparison with age-matched healthy controls. SUMMARY OF BACKGROUND DATA: AIS occurs in children during their pubertal growth spurt. Although there is no clear consensus on the difference in body height between girls with AIS and healthy controls, it is generally thought that the development and curve progression in girls with AIS is closely associated with their growth rate. There is no concrete prospective longitudinal study to document clearly the growth pattern and growth rate of subjects with AIS . METHODS: A total of 611 girls with AIS and 296 healthy age-matched controls were included in the study and among them, 194 girls with AIS and 116 healthy controls were followed up until skeletal maturity. The girls with AIS were grouped into moderate (AIS20) and severe curve (AIS40) groups on the basis of maximum curve magnitude at skeletal maturity. Clinical data and detailed anthropometric parameters were recorded. In the cross-sectional analysis, the groups of subjects were compared within different age groups (from the age of 12-16 yr). In the longitudinal study, linear mixed modeling with respect to age or years since menarche was employed to formulate the growth trajectory of different anthropometric parameters. RESULTS: In the cross-sectional analysis, the girls with AIS were generally taller, with longer arm span and lower body mass index than the healthy controls. The girls with AIS40 were found to be significantly shorter in height (P = 0.006) and arm span (P = 0.025) at the age of 12 years but caught up and overtook the control group at the age of 14 to 16 years. In the longitudinal study, the average growth rate of arm span in girls with AIS40 was significantly higher than that in girls with AIS20 (> 30%) (P = 0.004) and controls (> 70%) (P = 0.0004). The age of menarche of girls with AIS40 was significantly delayed by 5.9 months and 3.8 months when compared with the control group and girls with AIS20, respectively (P < 0.05). CONCLUSION: The growth patterns of girls with AIS with confirmed curve severities were significantly different from healthy age-matched controls. Girls with severe AIS had delayed menarche with faster skeletal growth rate during the age of 12 to 16 years. Monitoring the rate of change of arm span of girls with AIS could be an important additional clinical parameter in helping predict curve severity in girls with AIS.

Genetic epidemiology and heritability of AIS: A study of 415 Chinese female patients.

Recent familial segregation studies supported a multifactorial genetic model for the etiology of adolescent idiopathic scoliosis (AIS). However, the extent of quantitative genetic effects, such as heritability, have not been fully evaluated. This genetic epidemiology study examined the sibling recurrent risk and heritability of AIS in first-degree relatives of 415 Chinese female patients, which is up to now the largest cohort. They were first diagnosed by community screening program and compared to 203 age-matched normal controls. Out of the total 531 sibs of AIS cases, 94 sibs had scoliosis (sibling recurrence risk = 17.7%). The prevalence of AIS among male and female sibs of an index case were 11.5% (95% CI = 7.5-15.5) and 23.0% (95% CI = 18.1-27.9), respectively. Female sibs of an index case had an increased risk of 8.9-fold (95% CI = 3.2-34.4) for developing AIS. These recurrent risks were significantly higher than the risk in the control group (p < 0.0001). Overall, heritability was estimated to be 87.5 ± 11.1%. The results confirmed the prevailing impression of strong genetic influence on the risk of AIS. Here we provided a large-scale study for the genetic aggregation estimates in an Asian population for the first time. The finding also positioned AIS among other common disease or complex traits with a high heritability.

Fast and accurate 3-D registration of HR-pQCT images.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a new noninvasive bone imaging technology that generates high-resolution 3-D images for quantitatively analysis of the bone microarchitecture in human. To enable quantitative evaluation of bone changes, either bone gain or loss, accurate alignment between the baseline and follow-up scans of the same individual is necessary. The major difficulties in achieving efficient and automatic registration of the HR-pQCT data are the large data size, deformations in the nonskeletal structures, and the complexity of the trabecular bone geometry. In this paper, we propose an automatic surface-based approach for fast and accurate registration of the HR-pQCT data, where the rigid registration is applied on the surfaces of the bony structures extracted from the grayscale HR-pQCT. The bony structure segmentation is performed via an automatic method that can adaptively determine the thresholds for separating the bony structure from the background and nonskeletal tissues. Experimental results performed on ten pairs of baseline and follow-up wrist scans of five adolescents and five elderly patients with osteoporosis showed the advantage of the proposed method in the high degree of automation, while the resultant parameters describing bone mineral density and trabecular architecture after registration were comparable with the outputs of the scanner's software. This automatic and accurate matching procedure may contribute to the clinical application and research of HR-pQCT.

Melatonin receptor 1B (MTNR1B) gene polymorphism is associated with the occurrence of adolescent idiopathic scoliosis.

STUDY DESIGN: A genetic association study to comprehensively investigate variations of melatonin receptor 1B gene polymorphism by a set of tagging single nucleotide polymorphisms (tagSNPs) derived from the International Hapmap project. OBJECTIVES: To determine whether melatonin receptor 1B (MTNR1B) gene polymorphisms are associated with the predisposition and/or disease severity of adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Linkage studies suggested a genetic predisposition for AIS. In addition, evidence showed that AIS might be related to melatonin deficiency and dysfunction of melatonin signaling pathway. Locating in one of the chromosomal regions linked to AIS, MTNR1B gene is a potential candidate gene for AIS. METHODS: This study was carried out in 2-stage case-control analysis: 1) initial screening (472 cases and 304 controls) and 2) separate replication test (342 cases and 347 controls) to confirm results in the screening. In the first screening stage, 5 tagSNPs were selected to cover most of the genetic variation in the MTNR1B gene. In the second stage, SNPs showing association in the screening stage were studied in a separate replication sample set to confirm the association. Genotyping was performed by PCR-RFLP. RESULTS: The first stage showed a putative association between rs4753426 and AIS, which was confirmed in the replication sample set. By meta-analysis, the frequency of C allele of this SNP locating in the promoter was significantly higher in the cases than controls (P = 0.006 aftermeta-analysis). Subjects with the CC genotype had an odds ratio of 1.29 for AIS. Another SNP rs741837 in promoter region, being moderate linkage disequilibrium with rs4753426, was also marginally associated with AIS. CONCLUSION: Polymorphisms of the promoter of MTNR1B gene were associated with AIS, but not with the curve severity in AIS patients. This suggested that MTNR1B was an AIS predisposition gene.