Peripheral Quantitative Computed Tomography Imaging Research Articles

Open-source image analysis tool for the identification and quantification of cortical interruptions and bone erosions in high-resolution peripheral quantitative computed tomography images of patients with rheumatoid arthritis.

Identification of bone erosions and quantification of erosion volume is important for rheumatoid arthritis diagnosis, and can add important information to evaluate disease progression and treatment effects. High-resolution peripheral quantitative computed tomography (HR-pQCT) is well suited for this purpose, however analysis methods are not widely available. The purpose of this study was to develop an open-source software tool for the identification and quantification of bone erosions using images acquired by HR-pQCT. The collection of modules, Bone Analysis Modules (BAM) - Erosion, implements previously published erosion analysis techniques as modules in 3D Slicer, an open-source image processing and visualization tool. BAM includes a module to automatically identify cortical interruptions, from which erosions are manually selected, and a hybrid module that combines morphological and level set operations to quantify the volume of bone erosions. HR-pQCT images of the second and third metacarpophalangeal (MCP) joints were acquired in patients with RA (XtremeCT, n=14, XtremeCTII, n=22). The number of cortical interruptions detected by BAM-Erosion agreed strongly with the previously published cortical interruption detection algorithm for both XtremeCT (r2=0.85) and XtremeCTII (r2=0.87). Erosion volume assessment by BAM-Erosion agreed strongly (r2=0.95) with the Medical Image Analysis Framework. BAM-Erosion provides an open-source erosion analysis tool that produces comparable results to previously published algorithms, with improved options for visualization. The strength of the tool is that it implements multiple image processing algorithms for erosion analysis on a single, widely available, open-source platform that can accommodate future updates.

Open-Source Image Analysis Tool for the Identification and Quantification of Cortical Interruptions and Bone Erosions in High-Resolution Peripheral Quantitative Computed Tomography Images of Patients with Rheumatoid Arthritis

Open-Source Image Analysis Tool for the Identification and Quantification of Cortical Interruptions and Bone Erosions in High-Resolution Peripheral Quantitative Computed Tomography Images of Patients with Rheumatoid Arthritis

Prior Physical Activity Influences Changes In Tibial Bone Microarchitecture During U.S. Army Basic Combat Training

Bone stress injuries (BSIs) are common among military personnel due to heightened physical activity. Whereas we have previously shown significant tibial bone adaptation following 8 weeks of Basic Combat Training (BCT), it is not known whether prior exercise habits influence the skeletal response to BCT. PURPOSE: Determine the relationship between exercise history and changes in tibial bone microarchitecture induced by BCT. METHODS: We collected high-resolution peripheral quantitative computed tomography images of the distal tibia, pre- and post-BCT, on U.S. Army trainees. We created low (LOW; 0-2 days/wk, n = 312), moderate (MOD; 3-4 days/wk, n = 597), and high (HIGH; 5+ days/wk, n = 696) exercise groups based on self-reported average days/wk of exercise during the 2 months prior to BCT. Linear mixed models were used to estimate within and between group differences from pre- to post-BCT controlling for sex, race, age, height, and weight. RESULTS: We enrolled 552 female and 1053 male trainees (20.7 ± 3.7 yrs) with normal BMI (24.7 ± 3.5 kg/m2). Trabecular thickness (Tb.Th), cortical thickness (Ct.Th), Ct area (Ct.Ar), total volumetric bone mineral density (Tt.vBMD), Tb.vBMD and Ct.vBMD increased significantly among all exercise groups over the BCT period (0.46-1.9%; all p < 0.0001, Fig 1). However, there was a greater increase in Ct.Th (p < 0.0001), Ct.Ar (p = 0.02), Tb.vBMD (p < 0.0001) and Tt.vBMD (p = 0.001) in LOW vs. HIGH. Similarly, MOD had greater increases in Tb.Th (p = 0.003), Ct.Th (p = 0.004), Ct.Ar (p = 0.001), Tb.vBMD (p = 0.0001), and Tt.vBMD (p < 0.0001) compared to HIGH. There were no differences between LOW and MOD CONCLUSION: All groups saw improved bone microarchitecture in response to BCT. LOW compared to MOD had greater increases than HIGH, perhaps due to a greater relative increase in novel physical activity during BCT experienced by LOW and MOD. Ongoing work will determine whether a more robust skeletal response to BCT reduces BSI incidence.

Bone Microarchitecture in Transgender Adults: A Cross-Sectional Study

ABSTRACTGender‐affirming hormone therapy aligns physical characteristics with an individual's gender identity, but sex hormones regulate bone remodeling and influence bone morphology. We hypothesized that trans men receiving testosterone have compromised bone morphology because of suppression of ovarian estradiol production, whereas trans women receiving estradiol, with or without anti‐androgen therapy, have preserved bone microarchitecture. We compared distal radial and tibial microarchitecture using high‐resolution peripheral quantitative computed tomography images in a cross‐sectional study of 41 trans men with 71 cis female controls, and 40 trans women with 51 cis male controls. Between‐group differences were expressed as standardized deviations (SD) from the mean in age‐matched cisgender controls with 98% confidence intervals adjusted for cross‐sectional area (CSA) and multiple comparisons. Relative to cis women, trans men had 0.63 SD higher total volumetric bone mineral density (vBMD; both p = 0.01). Cortical vBMD and cortical porosity did not differ, but cortices were 1.11 SD thicker (p < 0.01). Trabeculae were 0.38 SD thicker (p = 0.05) but otherwise no different. Compared with cis men, trans women had 0.68 SD lower total vBMD (p = 0.01). Cortical vBMD was 0.70 SD lower (p < 0.01), cortical thickness was 0.51 SD lower (p = 0.04), and cortical porosity was 0.70 SD higher (p < 0.01). Trabecular bone volume (BV/TV) was 0.77 SD lower (p < 0.01), with 0.57 SD fewer (p < 0.01) and 0.30 SD thicker trabeculae (p = 0.02). There was 0.56 SD greater trabecular separation (p = 0.01). Findings at the distal radius were similar. Contrary to each hypothesis, bone microarchitecture was not compromised in trans men, perhaps because aromatization of administered testosterone prevented bone loss. Trans women had deteriorated bone microarchitecture either because of deficits in microstructure before treatment or because the estradiol dosage was insufficient to offset reduced aromatizable testosterone. Prospective studies are needed to confirm these findings. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Prior Tobacco Use Is Associated With Tibial Microarchitecture In U.S. Army Recruits: A Preliminary Analysis

Tobacco use is common and is associated with less favorable bone properties in older adults at risk for osteoporosis. Baseline bone properties are related to stress fracture risk in military populations. Whether a history of tobacco use is associated with less favorable bone microarchitectural properties in military recruits is unknown. PURPOSE: To examine the influence of prior tobacco use on bone microarchitecture using data from a large prospective field study (789 men and women from a larger planned cohort of 4000 U.S. Army recruits). METHODS: We collected high-resolution peripheral quantitative computed tomography images of the ultradistal tibia at the 4% site during the first week of basic combat training (BCT) from 556 male and 233 female recruits. Also, self-reported history of tobacco use was assessed via questionnaire. Generalized linear models stratified by sex were used to evaluate the relationship between a history of tobacco use and baseline bone microarchitecture. Models were further stratified by tobacco type. All models were adjusted for prior physical activity, recruit and parents’ level of education, race/ethnicity, age, and body mass index (BMI). RESULTS: 21.29% of recruits reported prior tobacco use. Tobacco users were more likely to be male (25.5%, p<0.0001) and white (26.8%, p=0.0007). There were no differences in tobacco use by socioeconomic status, prior physical activity, or BMI. At the ultradistal tibia, tobacco use in female recruits was associated with lower indices of cortical thickness and cortical area, with decrements ranging from -2.53% to -10.46% depending on the method of tobacco consumption (all p<0.05). In male recruits, use of tobacco pipe was associated with a 17.39% lower cortical thickness (p=0.026). There were no significant differences reported in trabecular bone parameters associated with prior tobacco use in male or female recruits. CONCLUSIONS: These data show that recruits, particularly female recruits, with a history of tobacco use may enter BCT with some less favorable microarchitectural properties, potentially placing them at greater risk for stress fracture, although this remains to be determined.

SUN-381 Cortical Porosity Is Associated with Peripheral Small Vessel Disease in Adult Patients with Type 2 Diabetes

Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.

Associations Between Breastfeeding History and Early Postmenopausal Bone Loss.

This studyaimed to evaluate associations of parity and breastfeeding history with postmenopausal bone loss. Early postmenopausal women from the Canadian Multicentre Osteoporosis Study were divided into three groups based on their reproductive histories: nulliparous (NP, n = 10), parous with < 6months breastfeeding (P-NBF, n = 14), and parous with > 6months breastfeeding (P-BF, n = 21). Women underwent dual X-ray absorptiometry and high-resolution peripheral quantitative computed tomography imaging at baseline and after 6years to evaluate bone mineral density (BMD), bone microstructure, and finite element-estimated failure load. Average age at baseline was 57years. Baseline density, microstructure, and failure load were not different among groups. In all women, total and cortical BMD decreased significantly at the tibia and radius. P-BF women only experienced a significant decline in tibial trabecular BMD, with a greater magnitude of change for P-BF than NP women (p = 0.002). Overall, results suggest thatearly postmenopausal bone health did not differ based on parity or breastfeeding history. Over the 6-year follow-up period, postmenopausal bone loss was evident in all women, with subtle differences in the rate of postmenopausal change among women with varying breastfeeding histories. Parous women who had breastfed for at least 6months showed an elevated rate of trabecular BMD loss at the tibia. Meanwhile, correlation analyses suggest that longer durations of breastfeeding may be associated with reduced cortical bone loss at the radius. The lack of differences among groups in FE-derived failure load suggests that parity and breastfeeding history is unlikely to significantly affect postmenopausal risk of fracture.

Dovitinib dilactic acid reduces tumor growth and tumor-induced bone changes in an experimental breast cancer bone growth model

Advanced breast cancer has a high incidence of bone metastases. In bone, breast cancer cells induce osteolytic or mixed bone lesions by inducing an imbalance in bone formation and resorption. Activated fibroblast growth factor receptors (FGFRs) are important in regulation of tumor growth and bone remodeling. In this study we used FGFR1 and FGFR2 gene amplifications containing human MFM223 breast cancer cells in an experimental xenograft model of breast cancer bone growth using intratibial inoculation technique. This model mimics bone metastases in breast cancer patients. The effects of an FGFR inhibitor, dovitinib dilactic acid (TKI258) on tumor growth and tumor-induced bone changes were evaluated. Cancer-induced bone lesions were smaller in dovitinib-treated mice as evaluated by X-ray imaging. Peripheral quantitative computed tomography imaging showed higher total and cortical bone mineral content and cortical bone mineral density in dovitinib-treated mice, suggesting better preserved bone mass. CatWalk gait analysis indicated that dovitinib-treated mice experienced less cancer-induced bone pain in the tumor-bearing leg. A trend towards decreased tumor growth and metabolic activity was observed in dovitinib-treated mice quantified by positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose at the endpoint. We conclude that dovitinib treatment decreased tumor burden, cancer-induced changes in bone, and bone pain. The results suggest that targeting FGFRs could be beneficial in breast cancer patients with bone metastases.

Intensive terrestrial or marine locomotor strategies are associated with inter- and intra-limb bone functional adaptation in living female athletes.

ObjectivesTo systematically characterize intra‐limb patterns of skeletal plasticity to loading among living women, in order to better understand regional complexity in structural adaptation within the lower limb and more accurately infer behavior in the past.Materials and methodsWe used peripheral quantitative computed tomography imaging of the femur, tibia, first and second metatarsals to quantify bone morphology among female controls and athletes representative of either terrestrial or marine mobility, grouped by loading category (odd‐impact, repetitive low‐impact, and high‐magnitude). Parameters included midshaft bone density, areas, rigidity, and shape, epiphyseal bone densities and areas. We assessed between‐group differences and the influence of training history on significant variation among the loading groups.ResultsTerrestrial mobility strategies were best distinguished by significant midshaft periosteal hypertrophy across the lower limb/foot relative to controls, and by particularly high midshaft femoral and tibial cortical bone areas relative to rowers. Enhanced midshaft bone area was typically paired with decreased bone density among athlete groups. Sport‐specific variation in training duration/timing was significantly correlated with multiple midshaft parameters.DiscussionResults demonstrate characteristic patterns of intra‐limb adaptation to terrestrial and marine mobility strategies among active women relative to controls, and highlight components of these patterns that may be shaped in part by differences in loading duration/timing. Additionally, our findings support constraints on skeletal variation in the distal tibia and foot relative to more proximal locations about the knee among living women. For example, metatarsal variation was constrained, but where present reflected sport‐specific variation in force distribution in the foot.

Regional variation of bone density, microarchitectural parameters, and elastic moduli in the ultradistal tibia of young black and white men and women.

Whole-bone analyses can obscure regional heterogeneities in bone characteristics. Quantifying these heterogeneities might improve our understanding of the etiology of injuries, such as lower-extremity stress fractures. Here, we performed regional analyses of high-resolution peripheral quantitative computed tomography images of the ultradistal tibia in young, healthy subjects (age range, 18 to 30 years). We quantified bone characteristics across four regional sectors of the tibia for the following datasets: white women (n = 50), black women (n = 51), white men (n = 50), black men (n = 34), and all subjects (n = 185). After controlling for potentially confounding variables, we observed statistically significant variations in most of the characteristics across sectors (p < 0.05). Most of the bone characteristics followed a similar trend for all datasets but with different magnitudes. Regardless of race or sex, the anterior sector had the lowest trabecular and total volumetric bone mineral density and highest trabecular separation (p < 0.001), while cortical thickness was lowest in the medial sector (p < 0.05). Accordingly, the anterior sector also had the lowest elastic modulus in the anterior-posterior and superior-inferior directions (p < 0.001). In all sectors, the mean anisotropy was ~3, suggesting cross-sector similarity in the ratios of loading in these directions. In addition, the bone characteristics from regional and whole-bone analyses differed in all datasets (p < 0.05). Our findings on the heterogeneous nature of bone microarchitecture in the ultradistal tibia may reflect an adaptation of the bone to habitual loading conditions.

Feasibility of rigid 3D image registration of high-resolution peripheral quantitative computed tomography images of healing distal radius fractures.

For accurate analysis of bone formation and resorption during fracture healing, correct registration of follow-up onto baseline image is required. A per-fragment approach could improve alignment compared to standard registration based on the whole fractured region. In this exploratory study, we tested the effect of fragment size and displacement on a per-fragment registration, and compared the results of this per-fragment registration to the results of the standard registration in two stable fractures and one unstable fracture.To test the effect of fragment size and displacement, high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of three unfractured radii were divided into subvolumes. Different displacements in x-, y, or z-direction or rotations around each axis were applied, and each subvolume was registered onto the initial volume to realign it. Next, registration of follow-up onto baseline scan was performed in two stable and one unstable fracture. After coarsely aligning the follow-up onto the baseline scan, a more accurate registration was performed of the whole fracture, i.e. the standard registration, and of each fracture fragment separately, i.e. per-fragment registration. Alignment was checked using overlay images showing baseline, follow-up and overlap between these scans, and by comparing correlation coefficients between the standard and per-fragment registration.Generally, subvolumes as small as 300 mm3 that were displaced up to 0.82 mm in x- or y-, or up to 1.64 mm in z-direction could be realigned correctly. For the fragments of all fractures, correlation coefficients were higher after per-fragment registration compared to standard registration. Most improvement was found in the unstable fracture and one fragment of the unstable fracture did not align correctly.This exploratory study showed that image registration of individual subvolumes, such as fracture fragments, is feasible in both stable and unstable fractures, and leads to better alignment of these fragments compared to an approach that is based on registration using the whole fractured region. This result is promising for additional analysis of bone formation and resorption in HR-pQCT studies on fracture healing.

An automated algorithm for the detection of cortical interruptions on high resolution peripheral quantitative computed tomography images of finger joints.

ObjectivesTo introduce a fully-automated algorithm for the detection of small cortical interruptions (≥0.246mm in diameter) on high resolution peripheral quantitative computed tomography (HR-pQCT) images, and to investigate the additional value of manual correction of the automatically obtained contours (semi-automated procedure).MethodsTen metacarpophalangeal joints from seven patients with rheumatoid arthritis (RA) and three healthy controls were imaged with HR-pQCT. The images were evaluated by an algorithm according to the fully- and semi-automated procedure for the number and surface of interruptions per joint. Reliability between the fully- and semi-automated procedure and between two independent operators was tested using intra-class correlation coefficient (ICC) and the proportion of matching interruptions. Validity of single interruptions detected was tested by comparing it to visual scoring, as gold standard. The positive predictive value (PPV) and sensitivity were calculated.ResultsThe median number of interruptions per joint was 14 (range 2 to 59) and did not significantly differ between the fully- and semi-automated procedure (p = 0.37). The median interruption surface per joint was significantly higher with the fully- vs. semi-automated procedure (respectively, 8.6mm2 vs. 5.8mm2 and 6.1mm2, p = 0.01). Reliability was almost perfect between the fully- and semi-automated procedure for both the number and surface of interruptions (ICC≥0.95) and the proportion of matching interruptions was high (≥76%). Also the inter-operator reliability was almost perfect (ICC≥0.97, proportion of matching interruptions 92%). The PPV ranged from 27.6% to 29.9%, and sensitivity from 69.7% to 76.3%. Most interruptions detected with the algorithm, did show an interruption on a 2D grayscale image. However, this interruption did not meet the criteria of an interruption with visual scoring.ConclusionThe algorithm for HR-pQCT images detects cortical interruptions, and its interruption surface. Reliability and validity was comparable for the fully- and semi-automated procedures. However, we advise the use of the semi-automated procedure to assure quality. The algorithm is a promising tool for a sensitive and objective assessment of cortical interruptions in finger joints assessed by HR-pQCT.

High-resolution Peripheral Quantitative Computed Tomography Imaging in the Assessment of Periarticular Bone of Metacarpophalangeal and Wrist Joints.

To synthesize descriptions of periarticular findings at the metacarpophalangeal (MCP) and wrist joints in different types of arthritis and in the normal state imaged by high-resolution peripheral quantitative computed tomography (HR-pQCT); to assemble the literature reporting on the ability of HR-pQCT to detect findings relative to other imaging modalities; and to collate results on the reproducibility of image interpretation. A systematic literature review was performed using terms for HR-pQCT and MCP or wrist joints using medical literature databases and conference abstracts. Any study describing predefined pathology findings, comparison to another radiographic technique, or a measure of reproducibility was included with no limitation by disease state. We identified 44 studies meeting inclusion criteria from the 1901 articles identified by our search. All 44 reported on pathology findings, including erosions (n = 31), bone microarchitecture (n = 10) and bone mineral density (n = 10) variables, joint space evaluation (n = 7), or osteophyte characterization (n = 7). Seventeen of the studies compared HR-pQCT findings to either plain radiography (n = 9), ultrasound (n = 4), magnetic resonance imaging (n = 5), or microcomputed tomography (n = 2), with HR-pQCT having high sensitivity for erosion detection. Twenty-four studies included an assessment of reproducibility with good to excellent metrics, and highlighting the critical importance of positioning when assessing joint space variables. Despite high sensitivity for erosion detection and good reproducibility, more research is required to determine where HR-pQCT can be applied to enhance our understanding of periarticular bone changes in a variety of arthritis conditions.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76±8, body mass index (BMI): 26.74±4.26kg/m2) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using 109Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200μm in-plane resolution, 2.3±0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (−0.972 (−1.882, −0.061) per 100μg Pb/g of bone mineral) and integral volumetric BMD (−3.05 (−6.05, −0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (−26.83 (−50.37, −3.29)) and trabecular number (−0.08 (−0.14, −0.02)), per 100μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD.

Body composition during childhood and adolescence: relations to bone strength and microstructure.

Numerous studies have examined the association of body composition with bone development in children and adolescents, but none have used micro-finite element (μFE) analysis of high-resolution peripheral quantitative computed tomography images to assess bone strength. This study sought to examine the relations of appendicular lean mass (ALM) and total body fat mass (TBFM) to bone strength (failure load) at the distal radius and tibia. This was a cross-sectional study of 198 healthy 8- to <15-year-old boys (n = 109) and girls (n = 89) performed in a Clinical Research Unit. After adjusting for bone age, height, fracture history, ALM, and TBFM, multiple linear regression analyses in boys and girls, separately, showed robust positive associations between ALM and failure loads at both the distal radius (boys: β = 0.92, P < .001; girls: β = 0.66, P = .001) and tibia (boys: β = 0.96, P < .001; girls: β = 0.66, P < .001). By contrast, in both boys and girls the relationship between TBFM and failure load at the distal radius was virtually nonexistent (boys: β = -0.07; P = .284; girls: β = -0.03; P = .729). At the distal tibia, positive, albeit weak, associations were observed between TBFM and failure load in both boys (β = 0.09, P = .075) and girls (β = 0.17, P = .033). Our data highlight the importance of lean mass for optimizing bone strength during growth, and suggest that fat mass may have differential relations to bone strength at weight-bearing vs non-weight-bearing sites in children and adolescents. These observations suggest that the strength of the distal radius does not commensurately increase with excess gains in adiposity during growth, which may result in a mismatch between bone strength and the load experienced by the distal forearm during a fall. These findings may explain, in part, why obese children are over-represented among distal forearm fracture cases.

Cortical measurements of the tibia from high resolution peripheral quantitative computed tomography images: A comparison with micro-computed tomography

Cortical measurements of the tibia from high resolution peripheral quantitative computed tomography images: A comparison with micro-computed tomography

Can high-resolution peripheral quantitative computed tomography imaging of subchondral and cortical bone predict condylar fracture in Thoroughbred racehorses?

High-resolution 3D imaging may improve the prediction and/or early identification of condylar fractures of the distal metacarpus/tarsus and reduce the frequency of breakdown injury in racehorses. To test the hypotheses that horses suffering condylar fractures have higher bone volume fraction (BV/TV) of the distal metacarpal epiphysis, greater subchondral bone thickness at the fracture site and higher second moment of inertia in the metacarpal midshaft as identified with high-resolution 3D imaging. Cross-sectional study using cadaver material. Thoroughbreds that died on racetracks were grouped as: 1) horses with third metacarpal (McIII) fractures with a condylar component (cases, n = 13); 2) horses with no limb fracture (controls, n = 8); 3) horses with fractures in other bones or suspensory apparatus disruption (other fatal injuries, n = 16). The palmar condyles of McIII and the midshaft were examined with high resolution peripheral quantitative computed tomography (HR-pQCT). Statistical analysis included logistic regression and Spearman's correlation. There were no significant differences in BV/TV of distal McIII and second moment of inertia of the midshaft between cases and controls. Epiphyseal bone BV/TV was greater in injured limbs of horses with any fatal limb injury (Groups 1 and 3 combined) compared with controls (odds ratio = 1.20, 95% confidence interval 1.01-1.42, P = 0.034). An epiphyseal BV/TV>0.742 resulted in a sensitivity of 82.8% and specificity of 62.5% in identifying horses with fatal limb injury. In horses without condylar fracture, increased subchondral bone thickness was associated with palmar osteochondral disease lesions in the adjacent condyle (rs = 0.65, P<0.001). Increased BV/TV of the distal metacarpus may have some value for identifying horses at risk of any fatal breakdown injury but not metacarpal condylar fractures. Measurement of parasagittal groove subchondral bone thickness is complicated by adjacent palmar osteochondral disease lesions. Thus, high-resolution imaging of the distal metacarpus appears to have limited ability to identify horses at risk of condylar fractures.

A trabecular plate-like phenotype is overrepresented in Chinese-American versus Caucasian women.

This study used extreme phenotype selection to define two trabecular bone phenotypes in a cohort of Chinese-American and Caucasian women. A trabecular plate-predominant phenotype is more common in Chinese-Americans while the rod-predominant phenotype is more typical of Caucasians. The robustness of these phenotypic associations with respect to lifestyle factors suggests that this trait may have a genetic basis and that these phenotypes can be utilized in future genetic studies. Compared to Caucasians, Chinese-Americans have more plate-like trabecular bone when measured by individual trabecula segmentation (ITS). These findings suggest a phenotypic difference between the races, which may be amenable to genetic analysis. We sought to identify a single ITS plate trait to pursue in genetic studies by conducting an extreme phenotype selection strategy to numerically define two distinct phenotypes-plate-like and rod-like-and determine whether the selected phenotypic associations were independent of lifestyle factors in order to conduct future genetic studies. A previously described cohort of 146 Chinese-American and Caucasian women with high-resolution peripheral quantitative computed tomography imaging and ITS analyses were studied with logistic regression and receiver operator characteristic analyses. The tibial plate-to-rod (TPR) ratio was the best ITS discriminator of race. Using extreme phenotypic selection, two TPR ratio phenotypes were defined numerically: plate-like as a TPR ratio value in the highest quartile (≥1.336) and rod-like as a TPR ratio value in the lowest quartile (≤0.621). Women with a plate-like phenotype were 25.7 times more likely (95 % CI 7.3-90.1) to be Chinese-American than women with rod-like morphology. After controlling for constitutional and lifestyle covariates, women in the highest vs. lowest TPR ratio quartile were 85.0 times more likely (95 % CI 12.7-568.0) to be Chinese-American. Using extreme phenotype selection, we defined a plate- and rod-like trabecular bone phenotype for the TPR ratio trait. The former phenotype is more common in Chinese-American women, while the latter is more typical of Caucasian women. The robustness of these phenotypic associations after controlling for differences in constitution and lifestyle suggest that the TPR ratio may have a genetic basis and that the extreme phenotypes defined in this analysis can be utilized for future studies.

Cortical measurements of the tibia from high resolution peripheral quantitative computed tomography images: A comparison with synchrotron radiation micro-computed tomography

High resolution-peripheral quantitative computed tomography (HR-pQCT) measurements are carried out in clinical research protocols to analyze cortical bone. Micro-computed tomography (micro-CT) is a standard tool for ex vivo examination of bone in 3D. The aim of this work was to evaluate cortical measurements derived from HR-pQCT images compared to those from synchrotron radiation (SR) micro-CT in a distal position (4.2cm from the distal pilon).Twenty-nine tibia specimens were scanned with HR-pQCT using protocols provided by the manufacturer. The standard measured outcomes included volumetric bone density (gHA/cm3) of the cortical region (Dcomp), and the cortical thickness (Ct.Th, mm). New features, such as cortical porosity (Ct.Po) and mean pore diameter (Ct.Po.Dm), were measured by an auto-contouring process. All tibias were harvested from the posterior region and imaged with SR micro-CT (voxel size=7.5μm). The cortical thickness, (Ct.Thmicro-CT), porosity (PoV/TV), pore diameter, pore spacing, pore number, and degree of mineralization of bone (DMB) were obtained for SR micro-CT images. For standard measurements on HR-pQCT images, site matched analyses with micro-CT were completed to obtain Dcomplocal and Ct.Thlocal.Dcomp was highly correlated to PoV/TV (r=−0.84,p<10−4) but not to DMB. Dcomplocal was correlated to PoV/TV (r=−0.72, p<10−4) and to DMB (r=0.40, p>0.05). Ct.Thlocal and Ct.Thmicro-CT were moderately correlated (r=0.53,p<0.01). Ct.Th and Ct.Po results from the autocontouring process are influenced by the level of trabecularization of the cortical bone and need manual correction of the endosteal contour.Distal tibia is a reliable region to study cortical bone with Dcomp as the best parameter because it reflects both the micro-porosity (Havers canals) and macro-porosity (resorption lacunae) of the cortical bone.

Experimental and numerical analysis of soft tissue stiffness measurement using manual indentation device – significance of indentation geometry and soft tissue thickness

Indentation techniques haves been applied to measure stiffness of human soft tissues. Tissue properties and geometry of the indentation instrument control the measured response. Mechanical roles of different soft tissues were characterized to understand the performance of the indentation instrument. An optimal instrument design was investigated. Experimental indentations in forearm of human subjects (N = 11) were conducted. Based on peripheral quantitative computed tomography imaging, a finite element (FE) model for indentation was created. The model response was matched with the experimental data. Optimized values for the elastic modulus of skin and adipose tissue were 130.2 and 2.5 kPa, respectively. The simulated indentation response was 3.9 ± 1.2 (mean ± SD) and 4.9 ± 2.0 times more sensitive to changes in the elastic modulus of the skin than to changes in the elastic modulus of adipose tissue and muscle, respectively. Skin thickness affected sensitivity of the instrument to detect changes in stiffness of the underlying tissues. Finite element modeling provides a feasible method to quantitatively evaluate the geometrical aspects and the sensitivity of an indentation measurement device. Systematically, the skin predominantly controlled the indentation response regardless of the indenter geometry or variations in the volume of different soft tissues.