High-resolution Peripheral Quantitative Computed Tomography Research Articles

Physical Activity, Menstrual History, and Bone Microarchitecture in Female Athletes with Multiple Bone Stress Injuries.

To determine differences in health and physical activity history, bone density, microarchitecture, and strength among female athletes with a history of multiple BSI, athletes with ≤1 BSI, and nonathletes. We enrolled 101 women (age, 18-32 yr) for this cross-sectional study: nonathlete controls (n = 17) and athletes with a history of ≥3 BSIs (n = 21) or ≤1 BSI (n = 63). We collected subjects' health and training history and measured bone microarchitecture of the distal tibia via high-resolution peripheral quantitative computed tomography (HR-pQCT) and areal bone mineral density of the hip and spine by dual-energy X-ray absorptiometry. Groups did not differ according to age, body mass index, age at menarche, areal bone mineral density, or tibial bone microarchitecture. Women with multiple BSI had a higher prevalence of primary and secondary amenorrhea (P < 0.01) compared with other groups. Total hours of physical activity in middle school were similar across groups; however, women with multiple BSI performed more total hours of physical activity in high school (P = 0.05), more hours of uniaxial loading in both middle school and high school (P = 0.004, P = 0.02), and a smaller proportion of multiaxial loading activity compared with other groups. These observations suggest that participation in sports with multiaxial loading and maintaining normal menstrual status during adolescence and young adulthood may reduce the risk of multiple bone stress injuries.

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

ObjectiveTo 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...

Higher Hand Grip Strength Is Associated With Greater Radius Bone Size and Strength in Older Men and Women: The Framingham Osteoporosis Study.

ABSTRACTMechanical loading by muscles elicits anabolic responses from bone, thus age‐related declines in muscle strength may contribute to bone fragility in older adults. We used high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to determine the association between grip strength and distal radius bone density, size, morphology, and microarchitecture, as well as bone strength estimated by micro–finite element analysis (μFEA), among older men and women. Participants included 508 men and 651 women participating in the Framingham Offspring Study with grip strength measured in 2011–2014 and HR‐pQCT scanning in 2012–2015. Separately for men and women, analysis of covariance was used to compare HR‐pQCT measures among grip strength quartiles and to test for linear trends, adjusting for age, height, weight, smoking, and physical activity. Mean age was 70 years (range, 50–95 years), and men had higher mean grip strength than the women (37 kg vs. 21 kg). Bone strength estimated by μFEA‐calculated failure load was higher with greater grip strength in both men (p < 0.01) and women (p = 0.04). Higher grip strength was associated with larger cross‐sectional area in both men and women (p < 0.01), with differences in area of 6% and 11% between the lowest to highest grip strength quartiles in men and women, respectively. Cortical thickness was positively associated with grip strength among men only (p = 0.03). Grip strength was not associated with volumetric BMD (vBMD) in men. Conversely, there was a trend for lower total vBMD with higher grip strength among women (p = 0.02), though pairwise comparisons did not reveal any statistically significant differences in total vBMD among grip strength quartiles. Bone microarchitecture (cortical porosity, trabecular thickness, trabecular number) was not associated with grip strength in either men or women. Our findings suggest that the positive association between hand grip strength and distal radius bone strength may be driven primarily by bone size. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function. Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands’ second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected. Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed. Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

3D computational anatomy of the scaphoid and its waist for use in fracture treatment

BackgroundA detailed understanding of scaphoid anatomy helps anatomic fracture reduction, and optimal screw position. Therefore, we analysed (1) the size and shape variations of the cartilage and osseous surface, (2) the distribution of volumetric bone mineral density (vBMD) and (3) if the vBMD values differ between a peripheral and a central screw pathway?MethodsForty-three fresh frozen hand specimens (17 females, 26 males) were analysed with high-resolution peripheral quantitative computed tomography (HR-pQCT) and dissected to compute a 3D-statistical osseous and cartilage surface model and a 3D-averaged vBMD model of the scaphoid. 3D patterns were analysed using principal component analysis (PCA). vBMD was analysed via averaging HR-pQCT grey values and virtual bone probing along a central and peripheral pathway.Results(1) PCA displayed most notable variation in length ranging from 1.7 cm (− 2SD) to 2.6 cm (mean) and 3.7 cm (+ 2SD) associated with differences of the width and configuration of the dorsal surface (curved and narrow (4 mm) to a wider width (9 mm)). (2) High vBMD was located in the peripheral zone. Lowest vBMD was observed in the centre and waist. (3) Virtual probing along a peripheral pathway near to the cartilage surfaces for the capitate and lunate allowed the center region to be bypassed, resulting in increased vBMD compared to a central pathway.ConclusionHigh anatomical variations regarding the osseous and cartilage surfaces were associated with three distinct concentrically arranged zones with notable different vBMD. The complex scaphoid anatomy with its waist might alter the strategy of fracture fixation, education and research.

Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci

Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. 115 males and 99 females (aged 72-81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011-2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011-2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p=0.005); lower total volumetric BMD (0.53 [0.34,0.84], p=0.007), cortical area (0.53 [0.30,0.95], p=0.032), cortical BMD (0.56 [0.36,0.88], p=0.011) and cortical thickness (0.45 [0.27,0.77], p=0.004); and greater declines in trabecular BMD (p=0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p=0.011) but no other associations were significant (p>0.05). Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

Automated segmentation of fractured distal radii by 3D geodesic active contouring of in vivo HR-pQCT images.

Radius fractures are among the most common fracture types; however, there is limited consensus on the standard of care. A better understanding of the fracture healing process could help to shape future treatment protocols and thus improve functional outcomes of patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows monitoring and evaluation of the radius on the micro-structural level, which is crucial to our understanding of fracture healing. However, current radius fracture studies using HR-pQCT are limited by the lack of automated contouring routines, hence only including small number of patients due to the prohibitively time-consuming task of manually contouring HR-pQCT images. In the present study, a new method to automatically contour images of distal radius fractures based on 3D morphological geodesic active contours (3D-GAC) is presented. Contours of 60 HR-pQCT images of fractured and conservatively treated radii spanning the healing process up to one year post-fracture are compared to the current gold standard, hand-drawn 2D contours, to assess the accuracy of the algorithm. Furthermore, robustness was established by applying the algorithm to HR-pQCT images of intact radii of 73 patients and comparing the resulting morphometric indices to the gold standard patient evaluation including a threshold- and dilation-based contouring approach. Reproducibility was evaluated using repeat scans of intact radii of 19 patients. The new 3D-GAC approach offers contours within inter-operator variability for images of fractured distal radii (mean Dice score of 0.992±0.005 versus median operator Dice score of 0.992±0.006). The generated contours for images of intact radii yielded morphometric indices within the in vivo reproducibility limits compared to the current gold standard. Additionally, the 3D-GAC approach shows an improved robustness against failure (n=5) when dealing with cortical interruptions, fracture fragments, etc. compared with the automatic, default manufacturer pipeline (n=40). Using the 3D-GAC approach assures consistent results, while reducing the need for time-consuming hand-contouring.

Skeletal characterization in a patient with Hajdu-Cheney syndrome undergoing total knee arthroplasty

Hajdu-Cheney syndrome (HCS) is a rare genetic connective tissue disorder caused by gain-of-function mutations in the NOTCH2 gene. We report a 38-year-old male HCS patient with a history of multiple pathologic fractures, poor bone stock under intermittent antiresorptive therapy, and secondary osteoarthritis (OA) of the knee, in which we successfully performed total knee arthroplasty (TKA). Next to a detailed skeletal assessment including laboratory bone metabolism markers, dual energy X-ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT), undecalcified histologic and histomorphometric analysis was performed on intraoperatively obtained tibial cut sections. This multiscale assessment revealed a severe, combined trabecular-cortical microarchitectural deterioration, increased bone turnover indices, and advanced cartilage degeneration, thus demonstrating the crucial role of Notch2 in skeletal and cartilage homeostasis, which is in line with the findings of previous mouse models.

Compromised Volumetric Bone Density and Microarchitecture in Men With Congenital Hypogonadotropic Hypogonadism.

Men with congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) have both low circulating testosterone and estradiol levels. Whether bone structure is affected remains unknown. To characterize bone geometry, volumetric density and microarchitecture in CHH/KS. This cross-sectional study, conducted at a single French tertiary academic medical center, included 51 genotyped CHH/KS patients and 40 healthy volunteers. Among CHH/KS men, 98% had received testosterone and/or combined gonadotropins. High-resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy x-ray absorptiometry (DXA), and measurement of serum bone markers were used to determine volumetric bone mineral density (vBMD) and cortical and trabecular microarchitecture. CHH and controls did not differ for age, body mass index, and levels of vitamin D and PTH. Despite long-term hormonal treatment (10.8 ± 6.8 years), DXA showed lower areal bone mineral density (aBMD) in CHH/KS at lumbar spine, total hip, femoral neck, and distal radius. Consistent with persistently higher serum bone markers, HR-pQCT revealed lower cortical and trabecular vBMD as well as cortical thickness at the tibia and the radius. CHH/KS men had altered trabecular microarchitecture with a predominant decrease of trabecular thickness. Moreover, CHH/KS men exhibited lower cortical bone area, whereas total and trabecular areas were higher only at the tibia. Earlier treatment onset (before age 19 years) conferred a significant advantage for trabecular bone volume/tissue volume and trabecular vBMD at the tibia. Both vBMD and bone microarchitecture remain impaired in CHH/KS men despite long-term hormonal treatment. Treatment initiation during adolescence is associated with enhanced trabecular outcomes, highlighting the importance of early diagnosis.

Longitudinal Evolution of Bone Microarchitecture and Bone Strength in Type 2 Diabetic Postmenopausal Women With and Without History of Fragility Fractures-A 5-Year Follow-Up Study Using High Resolution Peripheral Quantitative Computed Tomography.

IntroductionDiabetic bone disease is characterized by an increased fracture risk which may be partly attributed to deficits in cortical bone quality such as higher cortical porosity. However, the temporal evolution of bone microarchitecture, strength, and particularly of cortical porosity in diabetic bone disease is still unknown. Here, we aimed to prospectively characterize the 5-year changes in bone microarchitecture, strength, and cortical porosity in type 2 diabetic (T2D) postmenopausal women with (DMFx) and without history of fragility fractures (DM) and to compare those to nondiabetic fracture free controls (Co) using high resolution peripheral quantitative computed tomography (HR-pQCT).MethodsThirty-two women underwent baseline HR-pQCT scanning of the ultradistal tibia and radius and a FU-scan 5 years later. Bone microarchitectural parameters, including cortical porosity, and bone strength estimates via µFEA were calculated for each timepoint and annualized. Linear regression models (adjusted for race and change in BMI) were used to compare the annualized percent changes in microarchitectural parameters between groups.ResultsAt baseline at the tibia, DMFx subjects exhibited the highest porosity of the three groups (66.3% greater Ct.Po, 71.9% higher Ct.Po.Volume than DM subjects, p < 0.022). Longitudinally, porosity increased significantly over time in all three groups and at similar annual rates, while DMFx exhibited the greatest annual decreases in bone strength indices (compared to DM 4.7× and 6.7× greater decreases in failure load [F] and stiffness [K], p < 0.025; compared to Co 14.1× and 22.2× greater decreases in F and K, p < 0.020).ConclusionOur data suggest that despite different baseline levels in cortical porosity, T2D women with and without fractures experienced long-term porosity increases at a rate similar to non-diabetics. However, the annual loss in bone strength was greatest in T2D women with a history of a fragility fractures. This suggests a potentially non-linear course of cortical porosity development in T2D bone disease: major porosity may develop early in the course of disease, followed by a smaller steady annual increase in porosity which in turn can still have a detrimental effect on bone strength—depending on the amount of early cortical pre-damage.

Analysis of bone architecture using fractal-based TX-Analyzer™ in adult patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by impaired bone quality and quantity. Established imaging techniques have limited reliability in OI. The TX-Analyzer™ is a new, fractal-based software allowing a non-invasive assessment of bone structure based on conventional radiographs. We explored whether the TX-Analyzer™ can discriminate OI patients and healthy controls. Furthermore, we investigated the correlation between TX-Analyzer™ parameters and (i) bone mineral density (BMD) by Dual Energy X-ray Absorptiometry (DXA), (ii) trabecular bone score (TBS), and (iii) bone microstructure by high-resolution peripheral quantitative computed tomography (HR-pQCT). Data of 29 adult OI patients were retrospectively analyzed. Standard radiographs of the thoracic and lumbar spine were evaluated using the TX-Analyzer™. Bone Structure Value (BSV), Bone Variance Value (BVV), and Bone Entropy Value (BEV) were measured at the vertebral bodies T7 to L5. Data were compared to a healthy, age- and gender-matched control group (n=58). BMD by DXA, TBS, and trabecular bone microstructure by means of HR-pQCT were correlated to TX-Analyzer™ parameters in OI patients. The accuracy of the TX-Analyzer™ parameters in detecting OI was assessed with area under curve (AUC) analysis of receiver operating characteristic (ROC). BEV of the thoracic and the lumbar spine were significantly lower in OI patients compared to controls (both p<0.001). BEV of the thoracic spine was significantly correlated to TBS (ρ=0.427, p=0.042) as well as trabecular number (Tb.N) at the radius (ρ=0.603, p=0.029) and inhomogeneity of the trabecular network (Tb.1/N.SD) at the radius (ρ=-0.610, p=0.027), when assessed by HR-pQCT. No correlations were found between BEV and BMD by DXA. BEV of the thoracic and the lumbar spine had an AUC of 0.81 (95% confidence interval [CI] 0.67-0.94, p<0.001) and 0.73 (95% CI 0.56-0.89, p=0.008), respectively. BSV and BVV did not differ between OI patients and controls. The software TX-Analyzer™ is able to discriminate patients with OI from healthy controls. ROC curves of BEV values suggest a suitable clinical applicability. Low to no correlations with conventional methods suggest, that the TX-Analyzer™ may indicate a new and independent examination tool in OI.

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21–40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%–2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominant sides), and unilateral gains in the nondominant (loaded) cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

Microarchitecture of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva: An HR-pQCT Case Series.

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques (i.e., bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient’s mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matched normative dataset from literature. The bone parameters of the radius were within the interquartile range (IQR) of normative data. In contrast, in the tibiae of both patients, total and trabecular BMD were below the IQR, as were trabecular bone volume fraction, number, and thickness, cortical thickness, and FL. Trabecular separation and heterogeneity were above the IQR. Isolated HO in the Achilles tendon had a lower total, trabecular, and cortical BMD, trabecular bone volume fraction, and cortical thickness than the normative tibia data. Trabecular microarchitecture was within the IQR, and FL was approximately 10% higher than that of the neighboring tibia after accounting for areal differences. Other scanned HO could only be qualitatively assessed, which revealed coalescence with the neighboring skeletal bone, development of a neo-cortex, and partial replacement of the original skeletal cortex with trabeculae. To conclude, isolated HO seemed microarchitecturally more comparable to reference tibia data than the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.

Effect of Testosterone Treatment on Bone Microarchitecture and Bone Mineral Density in Men: A 2-Year RCT.

Testosterone treatment increases bone mineral density (BMD) in hypogonadal men. Effects on bone microarchitecture, a determinant of fracture risk, are unknown. We aimed to determine the effect of testosterone treatment on bone microarchitecture using high resolution-peripheral quantitative computed tomography (HR-pQCT). Men ≥ 50 years of age were recruited from 6 Australian centers and were randomized to receive injectable testosterone undecanoate or placebo over 2 years on the background of a community-based lifestyle program. The primary endpoint was cortical volumetric BMD (vBMD) at the distal tibia, measured using HR-pQCT in 177 men (1 center). Secondary endpoints included other HR-pQCT parameters and bone remodeling markers. Areal BMD (aBMD) was measured by dual-energy x-ray absorptiometry (DXA) in 601 men (5 centers). Using a linear mixed model for repeated measures, the mean adjusted differences (95% CI) at 12 and 24 months between groups are reported as treatment effect. Over 24 months, testosterone treatment, versus placebo, increased tibial cortical vBMD, 9.33 mg hydroxyapatite (HA)/cm3) (3.96, 14.71), P < 0.001 or 3.1% (1.2, 5.0); radial cortical vBMD, 8.96 mg HA/cm3 (3.30, 14.62), P = 0.005 or 2.9% (1.0, 4.9); total tibial vBMD, 4.16 mg HA/cm3 (2.14, 6.19), P < 0.001 or 1.3% (0.6, 1.9); and total radial vBMD, 4.42 mg HA/cm3 (1.67, 7.16), P = 0.002 or 1.8% (0.4, 2.0). Testosterone also significantly increased cortical area and thickness at both sites. Effects on trabecular architecture were minor. Testosterone reduced bone remodeling markers CTX, -48.1 ng/L [-81.1, -15.1], P < 0.001 and P1NP, -6.8 μg/L[-10.9, -2.7], P < 0.001. Testosterone significantly increased aBMD at the lumbar spine, 0.04 g/cm2 (0.03, 0.05), P < 0.001 and the total hip, 0.01 g/cm2 (0.01, 0.02), P < 0.001. In men ≥ 50 years of age, testosterone treatment for 2 years increased volumetric bone density, predominantly via effects on cortical bone. Implications for fracture risk reduction require further study.

The Role of Imaging in Predicting the Development of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) remains a chronic debilitating disease with a significant negative societal impact, despite the expanding landscape of treatment options. This condition is often preceded by a phase of systemic autoimmunity with circulating autoantibodies, elevated pro-inflammatory cytokines, or subtle structural changes. The capability of identifying individuals in the preclinical phase of RA disease makes a "preventive window of opportunity" possible. Much recent work has focused on the role of imaging modalities including ultrasound (US), magnetic resonance imaging (MRI), and high-resolution peripheral quantitative computer tomography (HR-pQCT) in identifying at-risk individuals with or without early joint symptoms for the development of inflammatory arthritis. This article will review the evidence and discuss the challenges as well as opportunities of proactive risk assessment by imaging in RA.

Using 3D image registration to maximize the reproducibility of longitudinal bone strength assessment by HR-pQCT and finite element analysis

We developed and validated a finite element (FE) approach for longitudinal high-resolution peripheral quantitative computed tomography (HR-pQCT) studies using 3D rigid-body registration (3DR) to maximize reproducibility by accounting for misalignment between images. In our proposed approach, we used the full common bone volume defined by 3DR to estimate standard FE parameters. Using standard HR-pQCT imaging protocols, we validated the 3DR approach with ex vivo samples of the distal radius (n = 10, four repeat scans) by assessing whether 3DR can reduce measurement variability from repositioning error. We used in vivo data (n = 40, five longitudinal scans) to assess the sensitivity of 3DR to detect changes in bone strength at the distal radius by the standard deviation of the rate of change (σ), where the ideal value of σ is minimized to define true change. FE estimates by 3DR were compared to estimates by no registration (NR) and slice-matching (SM). Group-wise comparisons of ex vivo variation (CVRMS, %) found that FE measurement precision was improved by SM (CVRMS < 0.80%) and 3DR (CVRMS < 0.62%) compared to NR (CVRMS~2%), and 3DR was advantageous as repositioning error increased. Longitudinal in vivo reproducibility was minimized by 3DR for failure load estimates (σ = 0.008 kN/month). Although 3D registration cannot negate motion artifacts, it plays an important role in detecting and reducing variability in FE estimates for longitudinal HR-pQCT data and is well suited for estimating effects of interventions in in vivo longitudinal studies of bone strength.

Medical imaging examination in psoriasis and early psoriatic arthritis patients: an updated systematic review and meta-analysis.

Psoriatic arthritis appears in one in four skin psoriasis patients.Early detection of the presence of joint involvement and early interception of its developments may minimize long-term functional disability, and the radiological methods may be a perfect choice. To summarize and compare different imaging methods for diagnosing early-stage psoriatic arthritis and determine the necessity of joint examination in all psoriasis patients, several electronic databases, including MEDLINE and EMBASE, were searched for English language studies. A specific selection criterion followed the retrieval of studies. Thirteen studies were finally enrolled in the meta-analysis, eight of which compared the bone changes presentat on medical imaging examination between psoriasis patients without psoriatic arthritis and healthy people; three studies focused on differences between psoriatic arthritis patients and free joint involvement psoriasis patients shown on medical imaging tests. Medical imaging examination, including ultrasound (US), high-resolution peripheral quantitative CT scans (HR-pQCT), and magnetic resonance imaging (MRI), can be good choices for detecting the start of asymptomatic joint inflammation in psoriasis patients, which is essential to early detection and interception of joint damage to lower joint deformities and improve the future quality of life for patients. Additionally, the examination for psoriasis patients with arthralgia is also highly recommended.

Pre-flight exercise and bone metabolism predict unloading-induced bone loss due to spaceflight

ObjectivesBone loss remains a primary health concern for astronauts, despite in-flight exercise. We examined changes in bone microarchitecture, density and strength before and after long-duration spaceflight in relation to biochemical...

Cortical bone thickness predicts the quantitative bone mineral density of the proximal humerus.

Quantitative bone mineral density (BMD) of the humerus is difficult to determine but relevant for osteoporosis and fracture treatment. Dual-energy X-ray absorptiometry (DXA) of the femur and lumbar spine overestimates the humeral BMD and is not ubiquitously available. Therefore, this study evaluated whether the cortical bone thickness (CBT) of the humerus or DXA of the forearm is able to predict humeral BMD. Humeral BMD of 54 upper cadaver extremities (22 pairs, 10 single) (19-90 years) was determined by high-resolution peripheral-quantitative-computed-tomography (HR-pQCT) (volumetric BMD (vBMD)) and DXA (areal BMD (aBMD)) of the proximal humerus and distal forearm. Average and gauge cortical bone thickness (CBTavg/ CBTg) of the humeral diaphysis was determined from standard radiographs (XR) and computed-tomography (CT) and compared to the humeral BMD. Pearson (r) and intraclass-correlation-coefficients (ICC) were used to compare results and rater-reliability. CBTavg from XR strongly correlated with the humeral BMD (r = 0.78 aBMD (DXA) and r = 0.64 vBMD (HR-pQCT) (p < 0.0001)). The CBTg revealed a weaker correlation (r = 0.57 aBMD and r = 0.43 vBMD). CBT derived from XR strongly correlated to those from the CT (r = 0.82-0.90) and showed an excellent intra- and inter-rater correlation (ICC 0.79-0.92). Distal forearm aBMD correlated well with the humeral aBMD (DXA) (r = 0.77) and paired specimens highly correlated to the contralateral side (humerus r = 0.89, radius r = 0.97). The CBTavg can reliably be determined from standard radiographs and allows a good prediction of quantitative humeral bone mineral density (aBMD or vBMD) if measurements are not available. Furthermore, the distal forearm or the contralateral humerus can serve as a side to estimate the BMD if the ipsilateral side is impaired.

Abstract PS9-23: Second-generation HR-pQCT analysis of bone mineral density and microstructure in women with breast cancer who underwent adjuvant endocrine therapy

Abstract Background: Adjuvant endocrine therapy for 5-10 years reduces breast cancer (BC) mortality in women with hormone receptor-positive BC. However, aromatase inhibitors (AIs) decrease bone mineral density (BMD), and increase fractures, joint stiffness, and joint pain. Although dual energy X-ray absorptiometry (DXA) is widely used to assess BMD, it is a two-dimensional method and thus cannot analyze trabecular and cortical bone microstructure. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows in vivo analysis of peripheral bone microarchitecture with high spatial resolution and low radiation exposure. We used HR-pQCT to evaluate changes in volumetric bone density and microstructure consisting of trabecular and cortical bone associated with AI treatment in patients with early BC. Methods: This was a prospective single-center observational study of nonosteoporotic, postmenopausal women with hormone receptor-positive BC, whose baseline DXA lumber spine and femoral neck T-scores were &amp;gt; −2.5. All patients were scheduled to receive DXA and HR-pQCT at baseline and at 6 and 12 months after starting AI therapy. The primary endpoint was to examine changes in total volumetric BMD (Tt. vBMD), trabecular volumetric BMD (Tb. vBMD), cortical volumetric BMD (Ct. vBMD) change at the distal radius and the distal radius between baseline and 6 and 12 months after starting endocrine therapy. Results: Of the 20 women in the study (median age: 57.5 years; range: 55-72 years), 8 had undergone chemotherapy before registration. Their mean change in Tt. vBMD between baseline and 1 year were distal radius: −5.7% (SD: 2.5%, P&amp;lt;0.01); distal tibia: −3.8% (SD: 1.8%, P&amp;lt;0.01), Tb. vBMD distal radius: −4.0% (SD: 3.9%, P&amp;lt;0.01); distal tibia: −0.9% (SD: 2.4%, P&amp;lt;0.05), Ct. vBMD distal radius: −3.1% (SD: 1.6%, P&amp;lt;0.01); distal tibia: −2.9% (SD: 1.7%, P&amp;lt;0.01). Furthermore, at 1 year in trabecular bone, mean trabecular bone volume fraction (p&amp;lt;0.01), trabecular thickness (p&amp;lt;0.05), and trabecular number (p&amp;lt;0.01) were significantly decreased, and trabecular separation (p&amp;lt;0.01) increased, in both the distal radius and tibia. At 1 year in cortical bone, mean changes in cortical thickness (p&amp;lt;0.01) and cortical bone area (p&amp;lt;0.01) were significantly decreased in both the distal radius and tibia; however, the endocortical perimeter of cortical bone did not significantly change and cortical porosity (p&amp;lt;0.05) was significantly greater than that at baseline. At 1 year, DXA decreased at the total hip (−4.4%, P&amp;lt;0.01) and femoral neck (−0.6%, P=0.03) compared with baseline. However, no significant difference was seen in median values for lumbar spine BMD at 1 year, or for tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (PINP). Conclusion: Postmenopausal women who took AIs for early BC experience volumetric bone density decline and both trabecular and cortical bone deterioration. A decade of AI treatment is a standard treatment for early BC; however, healthcare professionals should monitor bone health during and after these treatments. Citation Format: Sayaka Kuba, Konosuke Watanabe, Megumi Matsumoto, Ko Chiba, Kosho Yamanouchi, Ayako Fukushima, Michi Morita, Ryota Otsubo, Hiroshi Yano, Kengo Kanetaka, Makoto Osaki, Takeshi Nagayasu, Susumu Eguchi. Second-generation HR-pQCT analysis of bone mineral density and microstructure in women with breast cancer who underwent adjuvant endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-23.