Role of inflammatory burden and treatment on joint space width in psoriatic arthritis-a high-resolution peripheral quantitative computed tomography study.

BACKGROUND: To investigate the relationship between disease-related parameters and joint space width (JSW) on high-resolution peripheral quantitative computed tomography (HR-pQCT) in psoriatic arthritis (PsA) patients. METHODS: PsA patients who underwent HR-pQCT examination of the second to fourth metacarpophalangeal joint (MCPJ 2-4) were recruited in this cross-sectional study. The joint space metrics included joint space volume (JSV), mean, minimum, and maximum JSW, JSW asymmetry, and distribution. Correlation analysis and multivariable linear regression models were used to determine the association between disease-related variables and JSW. RESULTS: Sixty-seven patients [37 (55.2%) males; median (IQR) age: 57.0 (53.0, 63.0); median disease duration: 21 (16, 28) years] were included in this analysis. Multivariable linear regression analysis demonstrated that males had larger JSV (MCPJ 2-4), mean (MCPJ 4), and maximum JSW (MCPJ 3). Longer disease duration (MCPJ 2-3) and higher ESR values (MCPJ 3) were negatively associated with mean and maximum JSW, while higher damage joint count was negatively associated with mean and minimum JSW (MCPJ 2). Use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) was negatively associated with minimum JSW (MCPJ 3) while use of biologic DMARDs (bDMARDs) was positively associated with minimum JSW (MCPJ 2). CONCLUSION: Higher inflammatory burden as reflected by longer disease duration, higher ESR levels, and damage joint count was negatively associated with mean, maximum, and minimum JSW, while suppression of inflammation using bDMARDs seems to limit the decline in JSW.

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 Geometry, Density, Microstructure, and Biomechanical Properties in the Distal Tibia in Patients With Primary Hypertrophic Osteoarthropathy Assessed by Second-Generation High-Resolution Peripheral Quantitative Computed Tomography.

Periosteosis refers to pathological woven bone formation beneath the cortical bone of the long bones. It is an imaging hallmark of primary hypertrophic osteoarthropathy (PHO) and also considered as one of the major diagnostic criteria of PHO patients. Up to date, detailed information on bone quality changes in long bones of PHO patients is still missing. This study aimed to evaluate bone microarchitecture and bone strength in PHO patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT). The study comprised 20 male PHO patients with the average age of 27.0 years and 20 age- and sex-matched healthy controls. The areal bone mineral density (aBMD) was assessed at the lumbar spine (L1 -L4 ) and hip (total hip and femoral neck) by dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric bone mineral density (vBMD), and microstructure parameters at the distal tibia were evaluated by using HR-pQCT. Bone strength was evaluated by finite element analysis (FEA) based on HR-pQCT screening at distal tibia. Urinary prostaglandin E2 (PGE2 ), serum phosphatase (ALP), beta-C-telopeptides of type I collagen (ß-CTX), soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG), and neuronal calcitonin gene-related peptide (CGRP) were investigated. As compared with healthy controls, PHO patients had larger bone cross-sectional areas; lower total, trabecular, and cortical vBMD; compromised bone microstructures with more porous cortices, thinned trabeculae, reduced trabecular connectivity, and relatively more significant resorption of rod-like trabeculae at distal tibia. The apparent Young's modulus was significantly lower in PHO patients. The concentration of PGE2 , biomarkers of bone resorption (ß-CTX and sRANKL/OPG ratio), and the neuropeptide CGRP were higher in PHO patients versus healthy controls. PGE2 level correlated negatively with vBMD and estimated bone strength and positively with bone geometry at distal tibia. The present HR-pQCT study is the first one illustrating the microarchitecture and bone strength features in long bones. © 2021 American Society for Bone and Mineral Research (ASBMR).

Effects of RANKL inhibition on promoting healing of bone erosion in rheumatoid arthritis using HR-pQCT: a 2-year, randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of denosumab on erosion healing at 2-4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease. METHODS: This was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2-4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined. RESULTS: At 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months. CONCLUSION: Although no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months. TRIAL REGISTRATION NUMBER: NCT03239080.

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.

Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.

BACKGROUND: Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. METHODS: HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). RESULTS: A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3, P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. CONCLUSION: Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.

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.

Effect of treat-to-target strategies on bone erosion progression in early rheumatoid arthritis: An HR-pQCT study.

OBJECTIVES: To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI ≤ 3.3) compared to DAS28 remission (DAS28 < 2.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI ≤ 3.3 and group 2 (n = 43) aimed at DAS28-CRP < 2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months. RESULTS: After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor >16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair. CONCLUSIONS: Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair.

Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High-Resolution Peripheral Quantitative Computed Tomography Study.

OBJECTIVE: To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography. METHODS: This is a post hoc analysis of a randomized controlled trial. Forty patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60 mg) once or oral alendronate (70 mg) weekly for 6 months. The size of individual bone erosions and the presence and extent of erosion-associated sclerosis (marginal osteosclerosis) were measured in the second metacarpal head of the nondominant hand at baseline, 3 months, and 6 months. RESULTS: Forty-two erosions were identified at baseline. After 6 months, the width, depth, and volume of erosion significantly decreased in the denosumab group (-0.23 mm, -0.16 mm, -0.91 mm3 , respectively; all P < 0.01), whereas these parameters significantly increased in the alendronate group (0.19 mm, 0.32 mm, and 1.38 mm3 , respectively; all P < 0.01; between-group differences, P < 0.01 for all). Quantitative analysis showed that the bone mineral density of the erosion margin significantly increased only after treatment by denosumab (19.75 mg/cm3 ; P < 0.05 for denosumab, and -5.44 mg/cm3 ; P = 0.51 for alendronate; P < 0.05 for between-group differences). CONCLUSION: Inhibition of receptor activator of NF-κB ligand by denosumab can induce partial repair of erosions in patients with RA, while erosions continued to progress in patients treated with alendronate. Combining denosumab with disease-modifying antirheumatic drugs may be considered for RA patients with progressive bone erosions.

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.

Alterations of bone density, microstructure, and strength of the distal radius in male patients with rheumatoid arthritis: a case-control study with HR-pQCT.

In this cross-sectional study, we investigated volumetric bone mineral density (vBMD), bone microstructure, and biomechanical competence of the distal radius in male patients with rheumatoid arthritis (RA). The study cohort comprised 50 male RA patients of average age of 61.1 years and 50 age-matched healthy males. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius provided measures of cortical and trabecular vBMD, microstructure, and biomechanical indices. aBMD of the hip but not the lumbar spine or ultradistal radius was significantly lower in RA patients than controls after adjustment for body weight. Total, cortical, and trabecular vBMD at the distal radius were, on average, -3.9% to -23.2% significantly lower in RA patients, and these differences were not affected by adjustment for body weight, testosterone level, or aBMD at the ultradistal radius. Trabecular microstructure indices were, on average, -8.1% (trabecular number) to 28.7% (trabecular network inhomogeneity) significantly inferior, whereas cortical pore volume and cortical porosity index were, on average, 80.3% and 63.9%, respectively, significantly higher in RA patients. RA patients also had significantly lower whole-bone stiffness, modulus, and failure load, with lower and more unevenly distributed cortical and trabecular stress. Density and microstructure indices significantly correlated with disease activity, severity, and levels of pro-inflammatory cytokines (interleukin [IL] 12p70, tumor necrosis factor, IL-6 and IL-1ß). Ten RA patients had focal periosteal bone apposition most prominent at the ulnovolar aspect of the distal radius. These patients had shorter disease duration and significantly higher cortical porosity. In conclusion, HR-pQCT reveals significant alterations of bone density, microstructure, and strength of the distal radius in male RA patients and provides new insight into the microstructural basis of bone fragility accompanying chronic inflammation.

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.

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.

Increased organ damage associated with deterioration in volumetric bone density and bone microarchitecture in patients with systemic lupus erythematosus on longterm glucocorticoid therapy.

OBJECTIVE: To evaluate bone quality in patients with systemic lupus erythematosus (SLE) who were undergoing longterm glucocorticoid (GC) therapy, and to focus on the correlation between bone quality and organ damage. METHODS: Seventy-eight female patients with SLE and organ damage taking longterm GC, and 72 age-matched SLE patients without damage taking longterm GC were recruited for study. Clinical variables of interest included disease activity, cumulative organ damage (by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SDI), major organ involvement (musculoskeletal damage and neuropsychiatric damage, etc.), and use of medication. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), microarchitecture, and biomechanical properties were measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Patients were mean age of 45 years (SD 10) and 54% were postmenopausal. The median SDI score of the cohort was 1 (interquartile range 1-2, range 1-5). Compared with patients without damage, the prevalence of osteopenia at either total hip or lumbar spine was significantly higher, and there were trends of deterioration of bone geometry, vBMD, microarchitecture, and biomechanical properties in patients with organ damage. Potential risk factors for bone quality in patients with damage were screened by univariate analysis. During multiple regression analysis, SDI was the only clinical variable consistently associated with deterioration of vBMD and microarchitecture. CONCLUSION: Cumulative organ damage consistently correlated with deterioration of vBMD and bone microarchitecture in SLE patients with damage on longterm GC therapy. HR-pQCT provides an insight into the underlying mechanism of bone loss in SLE.

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.

Bone microarchitecture assessment by high-resolution peripheral quantitative computed tomography in patients with systemic lupus erythematosus taking corticosteroids.

OBJECTIVE: We assessed the relationship between vertebral fracture and bone microarchitecture in patients with systemic lupus erythematosus (SLE) on chronic corticosteroid therapy using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Fifty-nine Chinese women with SLE taking corticosteroid were selected to participate in a cross-sectional study. Vertebral fracture was confirmed semiquantitatively by lateral radiographs of the thoracic and lumbar spine. Density and microarchitecture at the distal radius were measured with HR-pQCT. Areal bone mineral density (aBMD) at hip and lumbar spine was measured by dual-energy X-ray absorptiometry (DEXA). RESULTS: Twelve patients had vertebral fractures. The aBMD of spine or hip did not differ between those with and without vertebral fractures. Measures by HR-pQCT revealed that patients with vertebral fractures had significantly lower level of average bone density (p = 0.007), cortical bone density (p = 0.029), trabecular bone density (p = 0.024), trabecular bone volume to tissue volume (p = 0.023), and trabecular thickness (p = 0.011) than those without vertebral fractures. Independent explanatory variables associated with higher risk of vertebral fractures were older age (p = 0.013) and lower average cortical bone density (p = 0.029). CONCLUSION: Vertebral fracture in patients with SLE on chronic corticosteroid treatment was associated with alterations of bone density and microarchitectures measured by HR-pQCT and DEXA. However, alterations were more pronounced in measurements by HR-pQCT. Low cortical bone density and old age were significant predictors of vertebral fracture risk.

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.