Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.
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ABSTRACT:
SUBMITTER: Wu D
PROVIDER: S-EPMC6894233 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.
Wu Dongze D Griffith James F JF Lam Steven H M SHM Wong Priscilla C H PCH Shi Lin L Li Edmund K EK Cheng Isaac T IT Li Tena K TK Hung Vivian W VW Qin Ling L Tam Lai-Shan LS
Arthritis research & therapy 20191204 1
<h4>Background</h4>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 ...[more]
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Project description:Bone health in psoriasis and psoriatic arthritis has been emphasized in recent years. Novel imaging modalities allow investigations into volumetric bone mineral density (vBMD) and bone microstructure in psoriatic patients. However, literature regarding vBMD measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is inconclusive. We conducted a systematic review and meta-analysis to evaluate vBMD in patients with psoriatic disease. We searched PubMed, EMBASE, Web of Science, and Cochrane Library for relevant observational studies. A random-effects meta-analysis with trial sequential analysis (TSA) was performed. The pooled mean difference (MD) and 95% confidence interval (CI) were calculated. Five studies with 780 patients were included. Patients with psoriatic disease showed a lower average vBMD than controls (MD -14.90; 95% CI -22.90 to -6.89; TSA-adjusted CI -23.77 to -6.03; I2 = 41%). Trabecular vBMD and cortical vBMD results were inconclusive because of the small sample size. Patients recruited in Asia and those whose vBMD were measured at the distal radius exhibited a lower average vBMD than controls. Further research should clarify the association of psoriasis with bone microstructure and the underlying pathophysiology.
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Project description:The investigation of cortical porosity is an important aspect of understanding biological, pathoetiological, and biomechanical processes occurring within the skeleton. With the emergence of HR-pQCT as a noninvasive tool suitable for clinical use, cortical porosity at appendicular sites can be directly visualized in vivo. The aim of this study was to introduce a novel topological analysis of the cortical pore network for HR-pQCT data and determine the influence of resolution on measures of cortical pore network microstructure and topology.Cadaveric radii were scanned using HR-pQCT at two different voxel sizes (41 and 82 μm) and also using μCT at a voxel size of 18 μm. HR-pQCT and μCT image sets were spatially coregistered. Segmentation and quantification of cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm) were achieved using an established extended cortical analysis technique. Topological classification of individual pores was performed using topology-preserving skeletonization and multicolor dilation algorithms. Based on the pore skeleton topological classification, the following parameters were quantified: total number of planar surface-skeleton canals (N.Slabs), tubular curve-skeleton canals (N.Tubes), and junction elements (N.Junctions), mean slab volume (Slab.Vol), mean tube volume (Tube.Vol), mean slab orientation (Slab.θ), mean tube orientation (Tube.θ), N.Slabs/N.Tubes, and integral (total) slab volume/integral tube volume (iSlab.Vol/iTube.Vol). An in vivo reproducibility study was also conducted to assess short-term precision of the topology parameters. Precision error was characterized using root mean square coefficient of variation (RMSCV%).Correlations to μCT values for Ct.Po were significant for both the 41 and 82 μm HR-pQCT data (41: r(2) = 0.82, p < 0.001, 82: r(2) = 0.75, p < 0.001). For Ct.Po.Dm, only the 41 μm data were significantly predictive of μCT values (r(2) = 0.72, p < 0.01) Data at both HR-pQCT voxel sizes were strongly predictive of the μCT values for N.Slabs (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.84, p < 0.001), N.Tubes (41: r(2) = 0.94, p < 0.001; 82: r(2) = 0.84, p < 0.001), and N.Junctions (41: r(2) = 0.93, p < 0.001; 82: r(2) = 0.78, p < 0.001), though proportional bias was evident in these correlations. Weak correlations were seen for iSlab.Vol/iTube.Vol at both voxel sizes (41: r(2) = 0.52, p < 0.01; 82: r(2) = 0.39, p < 0.05). Slab.Vol was significantly correlated to μCT data at 41 μm (r(2) = 0.60, p < 0.01) but not at 82 μm, while Tube.Vol was significantly correlated at both voxel sizes (41: r(2) = 0.79, p < 0.001; 82: r(2) = 0.68, p < 0.01). In vivo precision error for these parameters ranged from 2.31 to 9.68 RMSCV%.Strong correlations between μCT- and HR-pQCT-derived measurements were found, particularly in HR-pQCT images obtained at 41 μm. These data are in agreement with our previous study investigating the effect of voxel size on standard HR-pQCT metrics of trabecular and cortical microstructure, and extend our previous findings to include topological descriptors of the cortical pore network.
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Project description:BackgroundMedical imaging plays an important role in determining the progression of joint damage in rheumatoid arthritis (RA). High resolution peripheral quantitative computed tomography (HR-pQCT) is a sensitive tool capable of evaluating bone microarchitecture and erosions, and 3D rigid image registration can be used to visualize and quantify bone remodeling over time. However, patient motion during image acquisition can cause a "stack shift" artifact resulting in loss of information and reducing the number of erosions that can be analyzed using HR-pQCT. The purpose of this study was to use image registration to improve the number of useable HR-pQCT scans and to apply image-based bone remodeling assessment to the metacarpophalangeal (MCP) joints of RA patients.MethodsTen participants with RA completed HR-pQCT scans of the 2nd and 3rd MCP joints at enrolment to the study and at a 6-month follow-up interval. At 6-months, an additional repeat scan was acquired to evaluate reliability. HR-pQCT images were acquired in three individual 1 cm acquisitions (stacks) with a 25% overlap. We completed analysis first using standard evaluation methods, and second with multi-stack registration. We assessed whether additional erosions could be evaluated after multi-stack registration. Bone remodeling analysis was completed using registration and transformation of baseline and follow-up images. We calculated the bone formation and resorption volume fractions with 6-month follow-up, and same-day repositioning as a negative control.Results13/57 (23%) of erosions could not be analyzed from raw images due to a stack shift artifact. All erosions could be volumetrically assessed after multi-stack registration. We observed that there was a median bone formation fraction of 2.1% and resorption fraction of 3.8% in RA patients over the course of 6 months. In contrast to the same-day rescan negative control, we observed median bone formation and resorption fractions of 0%.ConclusionsMulti-stack image registration is a useful tool to improve the number of useable scans when analyzing erosions using HR-pQCT. Further, image registration can be used to longitudinally assess bone remodeling. These methods could be implemented in future studies to provide important pathophysiological information on the progression of bone damage.
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Project description:During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 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).
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Project description:Anorexia nervosa (AN) is associated with decreased bone mineral density and increased risk of fracture. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), trabecular microarchitecture and estimated failure load in weight-bearing vs. non-weight-bearing bones in AN. We included twenty-five females with AN, and twenty-five female controls matched on age and height. Bone geometry, vBMD and trabecular microarchitecture were assessed using high-resolution peripheral quantitative computed tomography of the distal radius and tibia. At both sites, cortical perimeter and total bone area were similar in patients and controls. Total vBMD was lower in the AN group in the tibia (p < 0.0005) but not in the radius. In the tibia, cortical thickness was approximately 25% lower (p < 0.0005) in the AN group, whereas there was no significant difference in the radius. In terms of trabecular microarchitecture, all indices [bone volume/tissue volume (BV/TV); trabecular thickness (Tb.Th.), trabecular number (Tb.N) and trabecular spacing (Tb.Sp.)] were impaired in AN in the tibia (p values range < 0.01-0.0001). In the radius, BV/TV and Tb.N were lower (p < 0.05 and p < 0.001, respectively); Tb.Sp. was higher (p < 0.001), whereas Tb.Th. did not differ, compared to controls. Estimated failure load was lower in patients in both the radius and the tibia (p < 0.0005 and p < 0.0001, respectively), most pronounced in the tibia. In conclusion, the impairment of cortical thickness and estimated failure load were significantly more pronounced in the weight-bearing tibia, compared to the non-weight-bearing radius, implying a direct effect of low body weight on bone loss in AN.
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Project description:Sex differences in bone strength and fracture risk are well documented. However, we know little about bone strength accrual during growth and adaptations in bone microstructure, density, and geometry that accompany gains in bone strength. Thus, our objectives were to (1) describe growth related adaptations in bone microarchitecture, geometry, density, and strength at the distal tibia and radius in boys and girls; and (2) compare differences in adaptations in bone microarchitecture, geometry, density, and strength between boys and girls. We used HR-pQCT at the distal tibia (8% site) and radius (7% site) in 184 boys and 209 girls (9 to 20 years old at baseline). We aligned boys and girls on a common maturational landmark (age at peak height velocity [APHV]) and fit a mixed effects model to these longitudinal data. Importantly, boys showed 28% to 63% greater estimated bone strength across 12 years of longitudinal growth. Boys showed 28% to 80% more porous cortices compared with girls at both sites across all biological ages, except at the radius at 9 years post-APHV. However, cortical density was similar between boys and girls at all ages at both sites, except at 9 years post-APHV at the tibia when girls' values were 2% greater than boys'. Boys showed 13% to 48% greater cortical and total bone area across growth. Load-to-strength ratio was 26% to 27% lower in boys at all ages, indicating lower risk of distal forearm fracture compared with girls. Contrary to previous HR-pQCT studies that did not align boys and girls at the same biological age, we did not observe sex differences in Ct.BMD. Boys' superior bone size and strength compared with girls may confer them a protective advantage. However, boys' consistently more porous cortices may contribute to their higher fracture incidence during adolescence. Large prospective studies using HR-pQCT that target boys and girls who have sustained a fracture are needed to verify this. © 2016 American Society for Bone and Mineral Research.
| S-EPMC5233447 | biostudies-literature
Project description:PurposeIn adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection.MethodsForty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6 kg/m2; median age 57, range 50-69 years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors.ResultsIn regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2 = 0.23; β = 0.03; p = 0.044) and higher radius cortical BMD (R2 = 0.43; β = 8.4; p = 0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2 = 0.38; β = 0.96; p = 0.050), higher radius trabecular number (R2 = 0.31; β = 0.01; p = 0.026), lower tibia and radius trabecular separation (tibia: R2 = 0.30; β = -0.003; p = 0.038; radius: R2 = 0.35; β = -0.003; p = 0.021), and higher radius bone stiffness (R2 = 0.45; β = 0.38; p = 0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2 = 0.44; β = 4.06; p = 0.036), higher tibia bone stiffness (R2 = 0.46; β = 3.06; p = 0.050), and higher tibia estimated failure load (R2 = 0.46; β = 0.17; p = 0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2 = 0.39; β = -41.2; p = 0.042), lower radius trabecular number (R2 = 0.34; β = -0.44; p = 0.009) and greater radius trabecular separation (R2 = 0.42; β = 0.16; p = 0.002), while TDF use without a PI was not associated with reduced bone quality.ConclusionsIn adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.
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Project description:ObjectivesApproximately 20% of people with psoriasis develop PsA. Although genetic, clinical and environmental risk factors have been identified, it is not known why some people with psoriasis develop PsA. The skin disease is traditionally considered the same in both. This study compares transcriptional changes in psoriasis and PsA skin for the first time.MethodsSkin biopsies were collected from healthy controls (HC), and uninvolved and lesional skin from patients with PsA. Bulk tissue sequencing was performed and analysed using the pipeline Searchlight 2.0. Transcriptional changes in PsA skin were compared with existing sequencing data from participants with psoriasis without PsA (GSE121212). Psoriasis and PsA datasets could not be directly compared as different analysis methods were used. Data from participants with PsA in the GSE121212 dataset were used for validation.ResultsSkin samples from 9 participants with PsA and 9 HC were sequenced, analysed and compared with available transcriptomic data for 16 participants with psoriasis compared with 16 HC. Uninvolved skin in psoriasis shared transcriptional changes with lesional skin in psoriasis, but uninvolved skin in PsA did not. Most transcriptional changes in psoriasis and PsA lesional skin were shared, but immunoglobulin genes were upregulated in PsA lesional skin specifically. The transcription factor POU2F1, which regulates immunoglobulin gene expression, was enriched in PsA lesional skin. This was confirmed in the validation cohort.ConclusionsImmunoglobulin genes are upregulated in PsA but not in psoriasis skin lesions. This may have implications for the spread from the cutaneous compartment to other tissues.
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