Measures Of Microarchitecture Research Articles

Measurement of Scaphoid Bone Microarchitecture: A Computed Tomography Imaging Study and Implications for Screw Placement

High bone density and quality is associated with improved screw fixation in fracture fixation. The objective of this study was to assess bone density and quality in the proximal and distal scaphoid to determine optimum sites for placement of 2 screws in scaphoid fracture fixation. Twenty-nine cadaveric human scaphoid specimens were harvested and scanned using micro-computed tomography. Bone density (bone volume fraction) and bone quality (relative bone surface area, trabecular number, and trabecular thickness) were evaluated in 4 quadrants within each of the proximal and distal scaphoid. The proximal radial quadrant of the scaphoid had significantly greater bone volume than the distal ulnar (mean difference, 33.2%) and distal volar quadrants (mean difference, 32.3%). There was a significantly greater trabecular number in the proximal radial quadrant than in the distal ulnar (mean difference, 16.7%) and in the distal volar quadrants (mean difference, 15.9%) and between the proximal ulnar and the distal ulnar quadrants (mean difference, 12%). There was a significantly greater bone surface area in the proximal radial and distal radial quadrants than in the distal ulnar and distal volar quadrants. There were no significant differences in trabecular thickness between the 8 analyzed quadrants CONCLUSIONS: Although there are differences in bone volume, trabecular number, and bone surface area between the proximal pole of the scaphoid and that of the distal pole, there were no significant differences in the bone quality (trabecular thickness, trabecular number, and relative bone surface area) and density (bone volume fraction) between the 4 quadrants of the proximal or distal pole of the cadaveric scaphoids studied. Insertion of 2 headless compression screws can be determined by ease of surgical access and ease of screw positioning and not by differences in bone quality or density of the proximal or distal scaphoid.

Bone density, microarchitecture and strength estimates in white versus African American youth with obesity.

African Americans (AA) have more favorable bone density and microarchitecture compared to Whites (W), which may explain their observed lower fracture rates. Obesity has deleterious effects on bone microarchitecture and strength estimates and is associated with an increase in fracture risk. Adolescence and young adulthood are periods of active bone accrual and also periods characterized by an increasing prevalence of obesity. The effect of obesity on the relationship between race and bone parameters remains unclear, particularly in youth. To assess differences in BMD, bone microarchitecture and strength estimates in AA and W adolescents and young adults with moderate to severe obesity. We hypothesized that racial differences in bone endpoints in lean youth would also be noted in youth with moderate to severe obesity. We evaluated 24 AA and 48W adolescent and young adults with a mean age of 18.2±2.4years and a median body mass index (BMI) of 44.8 (40.5-49.4) kg/m2 who underwent dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT), extended cortical analysis (ECA) and micro-finite element analysis (FEA) to obtain measures of volumetric bone mineral density (vBMD), bone geometry, microarchitecture, and strength estimates at the distal radius and tibia. We found no differences between AA and W for total fat and lean mass, and areal BMD Z-scores (p>0.05 for all). At the distal radius, no significant differences were detected in vBMD, bone geometry or microarchitecture (p>0.05 for all); however, stiffness and failure load were higher in the AA group (p=0.031 and 0.047 respectively). At the distal tibia, cortical vBMD was higher in AA vs. W (p=0.012), while trabecular number was higher and trabecular separation lower in W vs. AA (p≤0.028). Stiffness and failure load trended higher in AA vs. W (p=0.052 and p=0.048, respectively). Groups did not differ for any other bone parameter (p>0.05). Racial differences in bone endpoints appear to be less marked in those with moderate to severe obesity, suggesting that effects of obesity may blunt the effect of race on bone endpoints.

Deficits in bone strength, density and microarchitecture in women living with HIV: A cross-sectional HR-pQCT study.

With the advent of combined antiretroviral therapy (cART), life expectancy has increased among persons living with HIV, but so too has risk for comorbidities including osteoporosis and fragility fracture. To explore whether HIV status and cART influence three-dimensional measures of BMD, bone microarchitecture and strength we aimed to compare these outcomes between women living with HIV (WLWH; n=50; 50.4±1.2years, 44% postmenopausal) and without HIV (controls; n=50; 51.8±1.2years, 52% postmenopausal). Outcomes were lumbar spine, total hip and femoral neck areal BMD by DXA; distal radius and tibia trabecular BMD, thickness and number, and cortical BMD and area by HR-pQCT; and finite element analysis-derived bone strength (failure load). Multivariable regression analysis compared bone outcomes between groups adjusting for known osteoporosis risk factors. Within WLWH, we examined associations between bone outcomes and HIV-related factors including disease severity and cART duration. WLWH were diagnosed 20±4years ago, were on cART for 123±37months and 80% had HIV plasma viral load <40 copies/mL. For women ≥50years (n=61), total hip aBMD T-Score was lower among WLWH than controls. Adjusted distal radius trabecular BMD and thickness and distal tibia trabecular BMD and failure load were 8-19% lower in WLWH than controls (p<0.05). Cortical BMD and area did not differ between groups at either site. Lifetime cART duration and current plasma viral load were not associated with bone outcomes in WLWH; however, previous treatment with tenofovir was negatively associated with distal radius trabecular BMD and trabecular number and LS aBMD T-score. WLWH have compromised BMD, bone microarchitecture and strength vs. controls of similar age and reproductive status. Treatment with tenofovir may contribute to bone deficits in WLWH.

Differing Effects of Zoledronic Acid on Bone Microarchitecture and Bone Mineral Density in Men Receiving Androgen Deprivation Therapy: A Randomized Controlled Trial.

Androgen deprivation therapy (ADT) given to men with prostate cancer causes rapid and severe sex steroid deficiency, leading to increased bone remodeling and accelerated bone loss. To examine the effects of a single dose of zoledronic acid on bone microarchitecture, we conducted a 2-year randomized placebo controlled trial in 76 men, mean age (interquartile range [IQR]) 67.8 years (63.8 to 73.9) with non-metastatic prostate cancer commencing adjuvant ADT; 39 were randomized to zoledronic acid and 37 to matching placebo. Bone microarchitecture was measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). Using a mixed model, mean adjusted differences (MAD; 95% confidence interval [95% CI]) between the groups are reported as the treatment effect at several time points. Over 24 months, zoledronic acid showed no appreciable treatment effect on the primary outcomes for total volumetric bone mineral density (vBMD); radius (6.7 mg HA/cm3 [-2.0 to 15.4], p = 0.21) and tibia (1.9 mg HA/cm3 [-3.3 to 7.0], p = 0.87). Similarly, there were no between-group differences in other measures of microarchitecture, with the exception of a modest effect of zoledronic acid over placebo in total cortical vBMD at the radius over 12 months (17.3 mgHA/cm3 [5.1 to 29.5]). In contrast, zoledronic acid showed a treatment effect over 24 months on areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) at all sites, including lumbar spine (0.10 g/cm2 [0.07 to 0.13]), p < 0.001), and total hip (0.04 g/cm2 [0.03 to 0.05], p < 0.001). Bone remodeling markers were initially suppressed in the treatment group then increased but remained lower relative to placebo (MADs at 24 months CTX -176 ng/L [-275 to -76], p < 0.001; P1NP -18 mg/L [-32 to -5], p < 0.001). These findings suggest that a single dose of zoledronic acid over 2 years is ineffective in preventing the unbalanced bone remodeling and severe microstructural deterioration associated with ADT therapy. © 2020 American Society for Bone and Mineral Research.

Bone Microarchitecture, Volumetric or Areal Bone Mineral Density for Discrimination of Vertebral Deformity in Adults: A Cross-sectional Study

Introduction/Background: Both areal bone mineral density (aBMD) and bone microarchitecture have been associated with vertebral deformity (VD), but there are limited data on the utility of bone microarchitecture measures in combination with aBMD in discriminating VD. This study aimed to describe whether radial bone microarchitecture measures alone or in combinations with radial volumetric bone mineral density (vBMD) or spine aBMD can improve discrimination of VD in adults.Methods: Data on 196 subjects (mean age (standard deviation, SD) = 72 (7) years, female 46%) were utilized. VD of T4-L4 and spine aBMD were measured using dual-energy X-ray absorptiometry. VD was defined if anterior to posterior height ratio was more than 3-SD, 4-SD below, or >25% decrease compared with the sex-matched normal means. Bone microarchitecture parameters at distal radius were collected using high-resolution peripheral quantitative computed tomography and analyzed using StrAx.Results: The strongest associations were seen for the cortical thickness (odds ratios (ORs): 2.63/SD decrease for 25% and 2.38/SD decrease for 3-SD criterion) and compact cortical area (OR: 3.33/SD decrease for 4-SD criterion). The area under the receiver operating characteristic curve (AUC) for spine aBMD for VD was 0.594, 0.597, and 0.634 for 25%, 3-SD and 4-SD criteria, respectively (all p < 0.05). Compact cortical area, cortical thickness and compact cortical thickness alone had the largest AUCs for VD (0.680–0.685 for 25% criterion, 0.659–0.674 for 3-SD criterion, and 0.699–0.707 for 4-SD criterion). Adding spine aBMD or radial vBMD to each cortical measure did not improve VD discrimination (∆ AUC 0.8%–2.1%).Conclusions: Cortical measures had the best utility for discriminating VD when used alone. Adding either spine aBMD or radial vBMD did not improve the utility of cortical measures.

Dose-dependent skeletal deficits due to varied reductions in mechanical loading in rats

Reduced skeletal loading leads to marked bone loss. Animal models of hindlimb suspension are widely used to assess alterations in skeleton during the course of complete unloading. More recently, the effects of partial unloading on the musculoskeletal system have been interrogated in mice and rats, revealing dose-dependent effects of partial weight bearing (PWB) on the skeleton and skeletal muscle. Here, we extended these studies to determine the structural and functional skeletal alterations in 14-week-old male Wister rats exposed to 20%, 40%, 70%, or 100% of body weight for 1, 2, or 4 weeks (n = 11–12/group). Using in vivo pQCT, we found that trabecular bone density at the proximal tibia declined in proportion to the degree of unloading and continued progressively with time, without evidence of a plateau by 4 weeks. Ex vivo measurements of trabecular microarchitecture in the distal femur by microcomputed tomography revealed deficits in bone volume fraction, 2 and 4 weeks after unloading. Histologic analyses of trabecular bone in the distal femur revealed the decreased osteoblast number and mineralizing surface in unloaded rats. Three-point bending of the femoral diaphysis indicated modest or no reductions in femoral stiffness and estimated modulus due to PWB. Our results suggest that this rat model of PWB leads to trabecular bone deterioration that is progressive and generally proportional to the degree of PWB, with minimal effects on cortical bone.

The reference value of trabecular bone score (TBS) in the Iranian population.

Trabecular bone score (TBS), as a tool for measurement of bone microarchitecture, represents fracture risk independently of bone density. The aim of this study was to estimate the reference values of TBS in both genders among the Iranian population to evaluate osteoporotic fractures in the future. The study was performed on healthy Iranian subjects who live in urban areas of Bushehr city, the capital of Bushehr province in southwestern Iran. The participants in this study were selected through a multistage, age and sex stratified, cluster random sampling. The TBS of L1-L4 was assessed by spine DXA images using TBS iNsight software (Discovery WI, Hologic Inc, USA). Age-related models of TBS were constructed using piecewise linear regression analysis. In total, 691 participants aged ≥ 18 years (381 men and 310 women) were selected for the study. The mean and standard deviation (SD) of TBS value for men was 1.420 ± 0.094 and the age at the peak TBS was 30.0 years. Among women, the corresponding value for the mean of TBS was 1.428 ± 0.070 and the age at the peak TBS was 24.5 years. Two SDs below the mean of TBS were 1.326 in men and 1.357 in women. Therefore, the following normal range for TBS values has been proposed: Among men, TBS ≥ 1.326 is considered to be normal; TBS between 1.231 and 1.326 is considered to be partially degraded microarchitecture; and TBS ≤ 1.231defined degraded microarchitecture. Among women, TBS categories are defined as normal ≥ 1.357, partially degraded between 1.287 and 1.357 and degraded ≤ 1.287. This was the first study to propose evaluation of the normal range for TBS values in both genders in the Middle- East and Iran. According to our results: TBS ≤ 1.231 in men and TBS ≤ 1.287 in women is considered to be degraded microarchitecture among the Iranian population.

Association between intracortical microarchitecture and the compressive fatigue life of human bone: A pilot study

Many mechanical properties of cortical bone are largely governed by the underlying microarchitecture; however, the influence of microarchitecture on the fatigue life of bone is poorly understood. Furthermore, imaging-based studies investigating intracortical microarchitecture may expose bone samples to large doses of radiation that may compromise fatigue resistance. The purpose of this pilot study was to 1) investigate the relationship between intracortical microarchitecture and the fatigue life of human bone in compression and 2) examine the effects of synchrotron irradiation on fatigue life measurements. Cortical samples were prepared from the femoral and tibial shafts of three cadaveric donors. A subset of samples was imaged using synchrotron X-ray microCT to quantify microarchitecture, including porosity, canal diameter, lacunar density, lacunar volume, and lacunar orientation. A second group of control samples was not imaged and used only for mechanical testing. Fatigue life was quantified by cyclically loading both groups in zero-compression until failure. Increased porosity and larger canal diameter were both logarithmically related to a shorter fatigue life, whereas lacunar density demonstrated a positive linear relationship with fatigue life (r2 = 45–73%, depending on measure). Irradiation from microCT scanning reduced fatigue life measurements by 91%, but relationships with microarchitecture measurements remained. Additional research is needed to support the findings of this pilot study and fully establish the relationship between intracortical microarchitecture and the compressive fatigue life of bone.

Functional Photoacoustic and Ultrasonic Assessment of Osteoporosis: A Clinical Feasibility Study.

Objective and Impact Statement. To study the feasibility of combined functional photoacoustic (PA) and quantitative ultrasound (US) for diagnosis of osteoporosis in vivo based on the detection of chemical and microarchitecture (BMA) information in calcaneus bone. Introduction. Clinically available X-ray or US technologies for the diagnosis of osteoporosis do not report important parameters such as chemical information and BMA. With unique advantages, including good sensitivity to molecular and metabolic properties, PA bone assessment techniques hold a great potential for clinical translation. Methods. By performing multiwavelength PA measurements, the chemical information in the human calcaneus bone, including mineral, lipid, oxygenated-hemoglobin, and deoxygenated-hemoglobin, were assessed. In parallel, by performing PA spectrum analysis, the BMA as an important bone physical property was quantified. An unpaired -test and a two-way ANOVA test were conducted to compare the outcomes from the two subject groups. Results. Multiwavelength PA measurement is capable of assessing the relative contents of several chemical components in the trabecular bone in vivo, including both minerals and organic materials such as oxygenated-hemoglobin, deoxygenated-hemoglobin, and lipid, which are relevant to metabolic activities and bone health. In addition, PA measurements of BMA show good correlations ( up to 0.65) with DEXA. Both the chemical and microarchitectural measurements from PA techniques can differentiate the two subject groups. Conclusion. The results from this initial clinical study suggest that PA techniques, by providing additional chemical and microarchitecture information relevant to bone health, may lead to accurate and early diagnosis, as well as sensitive monitoring of the treatment of osteoporosis.

Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial.

Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol-containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research.

Reproducibility and Radiation Effect of High-Resolution In Vivo Micro Computed Tomography Imaging of the Mouse Lumbar Vertebra and Long Bone.

A moderate radiation dose, in vivo µCT scanning protocol was developed and validated for long-term monitoring of multiple skeletal sites (femur, tibia, vertebra) in mice. A customized, 3D printed mouse holder was designed and utilized to minimize error associated with animal repositioning, resulting in good to excellent reproducibility in most cortical and trabecular bone microarchitecture and density parameters except for connectivity density. Repeated in vivo µCT scans of mice were performed at the right distal femur and the 4th lumbar vertebra every 3weeks until euthanized at 9weeks after the baseline scan. Comparing to the non-radiated counterparts, no radiation effect was found on trabecular bone volume fraction, osteoblast and osteoblast number/surface, or bone formation rate at any skeletal site. However, trabecular number, thickness, and separation, and structure model index were sensitive to ionizing radiation associated with the µCT scans, resulting in subtle but significant changes over multiple scans. Although the extent of radiation damage on most trabecular bone microarchitecture measures are comparable or far less than the age-related changes during the monitoring period, additional considerations need to be taken to minimize the confounding radiation factors when designing experiments using in vivo µCT imaging for long-term monitoring of mouse bone.

The Association between First Fractures Sustained during Childhood and Adulthood and Bone Measures in Young Adulthood

To describe the association between fractures sustained at different stages of growth and bone measures in early adulthood. Participants (n=201) in southern Tasmania were at birth at a higher risk of sudden infant death syndrome; they were followed to age 25. Outcomes were areal bone mineral density at the spine, hip, and total body (by dual-energy x-ray absorptiometry) and trabecular and cortical bone measures at the radius and tibia (by high-resolution peripheral quantitative computed tomography). Fractures were self-reported and confirmed by radiographs at 8, 16, and 25years of age. Multivariable linear regression was used to analyze the association of the occurrence of prepubertal (<9years of age), pubertal (9-16years of age), and postpubertal (17-25years of age) fractures with all bone measures. Over 25years, 99 participants had at least 1 fracture. For high-resolution peripheral quantitative computed tomography measures at age 25, prepubertal fractures were negatively associated with cortical and trabecular volumetric bone mineral density and most microarchitecture measures at both the tibia and radius. Prepubertal fractures had a significant association with smaller increase of areal bone mineral density from age 8 to 16years and at 25years of age compared with participants with no fractures. Pubertal fractures had no association with any bone measures and postpubertal fractures were only associated with a lower trabecular number at thetibia. Prepubertal fractures are negatively associated with areal bone mineral density increases during growth and high-resolution peripheral quantitative computed tomography bone measures in young adulthood. There is little evidence that fractures occurring from age 8years onward with bone measures in young adulthood, implying that prepubertal fractures may be associated with bone deficits later in life.

Fracture prediction, imaging and screening in osteoporosis.

Osteoporosis is associated with increased fragility of bone and a subsequent increased risk of fracture. The diagnosis of osteoporosis is intimately linked with the imaging and quantification of bone and BMD. Scanning modalities, such as dual-energy X-ray absorptiometry or quantitative CT, have been developed and honed over the past half century to provide measures of BMD and bone microarchitecture for the purposes of clinical practice and research. Combined with fracture prediction tools such as Fracture Risk Assessment Tool (FRAX) (which use a combination of clinical risk factors for fracture to provide a measure of risk), these elements have led to a paradigm shift in the ability to diagnose osteoporosis and predict individuals who are at risk of fragility fracture. Despite these developments, a treatment gap exists between individuals who are at risk of osteoporotic fracture and those who are receiving therapy. In this Review, we summarize the epidemiology of osteoporosis, the history of scanning modalities, fracture prediction tools and future directions, including the most recent developments in prediction of fractures.

Association of Dairy Food Intake with Measures of Bone Microarchitecture in Men and Women from the Framingham Study (OR18-08-19)

ObjectivesPrevious studies reported that dairy foods are associated with higher areal bone mineral density (BMD) in older adults. However, data on bone strength and bone microarchitecture are lacking. The objective of this study was to determine the association of milk, yogurt, cheese, cream, milk + yogurt and milk + yogurt + cheese intakes with high resolution peripheral quantitative computed tomography (HR-pQCT) measures of bone in older adults from the Framingham Offspring study. MethodsThis cross-sectional study included 532 men and 694 women (aged 32–81y, mean 64y) with measures of dairy food intake (servings/wk.) from a food frequency questionnaire. Cortical and trabecular BMD and microarchitecture at the distal tibia and radius were measured using HR-pQCT. We focused on five bone parameters: 1) Bone strength assessed via failure load from micro–finite element analysis, 2) Two cortical bone measures: cortical BMD and cortical thickness; and 3) Two trabecular bone measures: trabecular bone density and trabecular number. Sex-combined and sex-specific multivariable linear regression was used to estimate the association of dairy food intake (energy adjusted) with each bone measure adjusting for covariates (sex, age, height, weight, current smoking, energy intake, calcium supplement use, vitamin D supplement use, physical activity and multivitamin use). ResultsOver 90% of the participants consumed the recommended ≥ 3 servings of dairy per day. Mean milk intake ± SD was 5.5 servings/week in both men and women. In sex combined analyses, only cheese intake was associated with cortical BMD at the radius and tibia (Table). None of the other dairy foods were significantly associated with any of the bone measures. In sex-stratified analysis higher cheese intake was associated with lower cortical BMD at the radius and tibia in women alone (radius: β = –9.61 ± 2.73, P = 0.001, tibia: β = –9.41 ± 3.10, P = 0.001). In men, higher cream intake was associated with higher trabecular number (radius: β = 0.021 ± 0.011, P = 0.02, tibia: β = 0.024 ± 0.012, P = 0.05). Higher yogurt intake was also associated with higher trabecular volumetric BMD at the tibia in men alone (tibia: β = 4.86 ± 2.00, P = 0.02). ConclusionsIn this cohort of primarily healthy older men and women with high dairy food consumption, specific dairy foods seem to be more beneficial in men than women. Negative associations for cheese intake and cortical BMD in women should be further confirmed in longitudinal studies. Funding SourcesNIH AR # 053205; FHS N01-HC-25195 R01 AR/AG 41398 and unrestricted institutional research grant from Dairy Management Inc. Supporting Tables, Images and/or Graphs▪

A multi-imaging modality study of bone density, bone structure and the muscle - bone unit in end-stage renal disease.

End stage renal disease (ESRD) is associated with sarcopenia and skeletal fragility. The objectives of this cross-sectional study were to (1) characterize body composition, bone mineral density (BMD) and bone structure in hemodialysis patients compared with controls, (2) assess whether DXA areal BMD (aBMD) correlates with peripheral quantitative CT (pQCT) measures of volumetric BMD (vBMD), cortical dimensions and MRI measures of trabecular microarchitecture, and (3) determine the magnitude of bone deficits in ESRD after adjustment for muscle mass. Thirty ESRD participants, ages 25 to 64 years, were compared with 403 controls for DXA and pQCT outcomes and 104 controls for MRI outcomes; results were expressed as race- and sex- specific Z-scores relative to age. DXA appendicular lean mass index (ALMI kg/m2) and total hip, femoral neck, ultradistal and 1/3rd radius aBMD were significantly lower in ESRD, vs. controls (all p < 0.01). pQCT trabecular vBMD (p < 0.01), cortical vBMD (p < 0.001) and cortical thickness (due to a greater endosteal circumference, p < 0.02) and MRI measures of trabecular number, trabecular thickness, and whole bone stiffness were lower (all p < 0.01) in ESRD, vs. controls. ALMI was positively associated with total hip, femoral neck, ultradistal radius and 1/3rd radius aBMD and with tibia cortical thickness (R = 0.46 to 0.64). Adjustment for ALMI significantly attenuated bone deficits at these sites: e.g. mean femoral neck aBMD was 0.79 SD lower in ESRD, compared with controls and this was attenuated to 0.33 with adjustment for ALMI. In multivariate models within the dialysis participants, pQCT trabecular vBMD and cortical area Z-scores were significant and independently (all p < 0.02) associated with DXA femoral neck, total hip, and ultradistal radius aBMD Z-scores. Cortical vBMD (p = 0.01) and cortical area (p < 0.001) Z-scores were significantly and independently associated with 1/3rd radius areal aBMD Z-scores (R2 = 0.62). These data demonstrate that DXA aBMD captures deficits in trabecular and cortical vBMD and cortical area. The strong associations with ALMI, as an index of skeletal muscle, highlight the importance of considering the role of sarcopenia in skeletal fragility in patients with ESRD.

Influence of soft tissue on bone density and microarchitecture measurements by high-resolution peripheral quantitative computed tomography.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a non-invasive method of measuring volumetric bone mineral density (vBMD) and microarchitecture at the distal radius and tibia. With increasing use of this technology, it is crucial to understand the potential impact of overlying soft tissue on the accuracy of HR-pQCT measures. Thus, we examined the effects of a simulated increase in adiposity (via 6- and 12-mm thick layers of overlying circumferential fat) on HR-pQCT measures of a hydroxyapatite (HA) phantom and in women (n = 20, aged 18-75 years). In the phantom, increasing the amount of overlying fat tissue led to a corresponding decrease in the mean measured density for each HA rod. In women, fat-layering led to a decrease in total vBMD (-2.9 to -3.7%, p < 0.001), cortical vBMD (-1.4% to -5.5%, p < 0.001), and estimated failure load (-1.4 to -5.7%, p = 0.002) at the radius, with similar changes in the tibia. Trabecular microarchitectural measurements were also impacted by simulated adiposity, with fat-layering leading to decreased trabecular thickness and separation and increased trabecular number at the radius (Δ's = 5 to 12%) with more pronounced differences at the tibia (Δ's = 14 to 40%). At the tibia, fat-layering also led to decreased cortical thickness and increased cortical porosity. Altogether, these results demonstrate that overlying adipose tissue can lead to artifacts in bone measurements by HR-pQCT, resulting in an underestimation of vBMD and generally, an overestimation of bone microarchitecture impairment. Therefore, soft tissue artifact should be considered when interpreting HR-pQCT results, particularly in those with high BMI and/or marked changes in adiposity.

SUN-540 No Effect Of Alcohol Use On Bone Microarchitecture Of The Distal Radius Among HIV Infected Adults

The effect of alcohol consumption on cortical and trabecular microarchitecture is not well-understood particularly among patients living with HIV who are at higher risk for metabolic bone disease, osteopenia, and osteoporosis. The aim of this study was to assess the effect of heavy alcohol consumption on bone microarchitecture as measured by high-resolution peripheral quantitative computed tomography compared to low or no alcohol consumption among HIV-infected adults. We hypothesized that heavy alcohol consumption would have a detrimental impact on bone microarchitecture in both the cortical and trabecular compartments at the distal radius. We conducted a cross-sectional analysis among 238 participants (148 men, 42 pre-menopausal women, 48 post-menopausal women). Alcohol consumption status was based on the last 30 days (TimeLine Followback) and categorized into 4 categories based on the distribution in the study population: abstinence (0 grams(g)/day(d)) (n=82), lowest tertile (0.47 -7.0 g/d) (n=53), middle tertile (>7.0 - <35.0 g/d) (n=51), and highest tertile (35.0 - 454.1 g/d) (n=52). Bone microarchitecture measures included total volumetric bone mineral density (D100); Trabecular bone mineral density (Tb.BMD); Cortical bone mineral density (Ct.BMD); Trabecular number (Tb.N); Trabecular thickness (Tb.Th); Trabecular separation (Tb.Sp); Cortical thickness (Ct.Th); Cortical area (Ct.Ar). Associations between alcohol intake and bone microarchitecture measures were assessed using unadjusted and adjusted linear regression models. Covariates included sex, age, race, daily calcium intake, weight bearing physical activity, HIV viral load, number of years since first started taking antiretroviral therapy, intact reactive parathyroid hormone (iPTH), body mass index and number of years of heroin use. Among the density parameters, D100 was similar across all alcohol intake levels (adjusted p=0.75). The mean Tb.BMD was lowest among those who consumed low levels of alcohol (150.6 ± 41.5 mg HA/cm3) and highest among those who drank the heaviest (166.6 ± 48.6 mg HA/cm3). Mean Ct.BMD was highest with abstinence (854.8 ± 73.5 mg HA/cm3) followed by the lowest alcohol tertile (853.5 ± 60.5 mg HA/cm3) and then those reporting the heaviest drinking (829.4 ± 88.8 mg HA/cm3). However, the adjusted regression models showed no significant differences (p=0.94 and p=0.21, respectively) and remained non-significant after adjusting for 25-hydroxyvitamin D. There were no significant differences in the mean trabecular or cortical structural parameters including Tb.N (p=0.85), Tb.Th (p=0.90), Tb.Sp (p=0.73), Ct.Th (p=0.71), Ct.Ar (p=0.93) by alcohol intake after adjusting for covariates. We conclude that in this study population, bone microarchitecture measures did not differ by alcohol consumption status at the distal radius.

Daily Acute Bouts of Weight-bearing During Hindlimb Unloading Mitigate Disuse-Induced Deficits in Cancellous Bone

Abstract International Space Station crewmembers experience microgravity, resulting in musculoskeletal losses. It remains unclear how much mechanical loading during disuse is sufficient to mitigate disuse-induced bone loss. We examined 75 minutes of weight-bearing per day on disuse-induced bone loss during hindlimb unloading (HU). Female C57BL/6J mice, 17 weeks (n=10/group), were exposed to HU for 28 days or were ambulatory controls (CC). Half of the HU animals were continuously unloaded while the remainder were removed from tail suspension for ~75 min/day for cage activity weight-bearing (HU+WB). HU and HU+WB led to total body mass and bone mineral density loss. HU+WB mitigated HU-induced losses in total body fat and lean mass and, in the distal femur, prevented losses in μCT measures of cancellous bone volume and microarchitecture. These findings support the robust impact of short durations of normal loading on preventing or mitigating HU-induced bone loss.

The Correction of Systematic Error due to Plaster and Fiberglass Casts on HR-pQCT Bone Parameters Measured In Vivo at the Distal Radius

Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2–3 times during the course of treatment. This study quantifies the effect of casts within a clinically relevant range of thicknesses on measured bone parameters at the distal radius, and establishes conversion equations to correct for systematic error in due to cast presence. Eighteen nonfractured participants were scanned by HR-pQCT in three conditions: no cast, plaster-of-Paris cast, and fiberglass cast. Measured parameters were compared between the baseline scan (no cast) and each cast scan to evaluate if systematic error exists due to cast presence. A linear regression model was used to determine an appropriate conversion for parameters that were found to have systematic error. Plaster-of-Paris casts had a greater range of thicknesses (3.2–9.5 mm) than the fiberglass casts (3.0–5.4 mm), and induced a greater magnitude of systematic error overall. Key parameters of interest were bone mineral density (total, cortical, and trabecular) and trabecular bone volume fraction, all of which were found to have systematic error due to presence of either cast type. Linear correlations between baseline and cast scans for these parameters were excellent (R2 > 0.98), and appropriate conversions could be determined within a margin of error less than a ±6% for the plaster-of-Paris cast, and ±4% for the fiberglass cast. We have demonstrated the effects of cast presence on bone microarchitecture measurements, and presented a method to correct for systematic error, in support of future use of HR-pQCT to study fracture healing.

Prediction of Fractures in Men Using Bone Microarchitectural Parameters Assessed by High-Resolution Peripheral Quantitative Computed Tomography-The Prospective STRAMBO Study.

Areal bone mineral density (aBMD) poorly identifies men at high fracture risk. Our aim was to assess prediction of fractures in men by bone microarchitectural measures. At baseline, 825 men aged 60 to 87 years had the assessment of bone microarchitecture at distal radius and distal tibia by high-resolution peripheral QCT (HR-pQCT; XtremeCT-I, Scanco Medical, Brüttisellen, Switzerland). Bone strength was estimated by micro-finite element analysis. During the prospective 8-year follow-up, 105 men sustained fractures (59 vertebral fractures in 49 men and 70 nonvertebral fractures in 68 men). After adjustment for age, body mass index (BMI), prior falls, and fractures, most HR-pQCT measures at both skeletal sites predicted fractures. After further adjustment for aBMD, low distal radius trabecular number (Tb.N) was most strongly associated with higher fracture risk (hazard ratio [HR] = 1.63 per SD, 95% confidence interval [CI] 1.31-2.03, p < 0.001). In similar models, low Tb.N was associated with higher risk of major osteoporotic fracture (HR = 1.80 per SD, p < 0.001), vertebral fracture (HR = 1.78 per SD, p < 0.01) and nonvertebral fracture (HR = 1.46 per SD, p < 0.01). In comparison with the reference model (age, BMI, falls, fractures, aBMD), the adjustment for distal radius Tb.N increased the estimated fracture probability in men who sustained fractures versus those who did not have ones (difference = 4.1%, 95% CI 1.9-6.3%, p < 0.001). However, the adjustment for distal radius Tb.N did not increase the area under the curve (AUC, p = 0.37). Similar results were found for distal radius trabecular separation (Tb.Sp) and connectivity density (Conn. D). They were predictive of all fracture types and increased the estimated fracture risk, but not AUC, in men who had incident fractures. Thus, poor distal radius trabecular microarchitecture is predictive of fracture after adjustment for age, BMI, falls, fractures, and aBMD. Although distal radius Tb.N, Conn. D, and Tb.Sp improve the discrimination between men who will or who will not have fracture, they do not provide clinically relevant improvement of fracture prediction in older men. © 2018 American Society for Bone and Mineral Research.