The Influence of Body Composition on Bone Health in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: Analyses by Dual-energy Radiograph Absorptiometry and Peripheral Quantitative Computed Tomography.

BACKGROUND: The normal interrelationship of body composition with bone health is less clear in the context of disease. Survivors of acute lymphoblastic leukemia (ALL) exhibit sarcopenic obesity and osteopenia. The impact of body composition on bone health in such survivors was examined. SUBJECTS AND METHODS: Survivors of ALL (N=74), >10 years from diagnosis, underwent dual-energy radiograph absorptiometry and peripheral quantitative computed tomography. RESULTS: Whole-body bone mineral content (WB BMC) Z scores were greater in males than females, but WB BMC indices (WB BMC/height 2 ) were comparable (0.74±0.125 and 0.72±0.069, respectively). WB BMC index (I) and fat-free mass index correlated significantly with trabecular bone mineral density, only in males. Fat mass index and appendicular lean mass index showed no such correlations. WB BMCI and fat-free mass index also correlated, again predominantly in males, with measures of strength in both trabecular and cortical bone. WB BMCI also correlated strongly with trabecular number, thickness, and hole size, also only in males. CONCLUSIONS: The results point to the need for enhancing muscle mass, measured by appendicular lean mass index, while reducing fat mass and maintaining good bone mineralization in long-term survivors of ALL to ensure the integrity of healthy bones.

Bone health in long-term survivors of pediatric acute lymphoblastic leukemia. An assessment by peripheral quantitative computed tomography.

BACKGROUND: Loss of bone mineral is a common concomitant of the treatment of acute lymphoblastic leukemia (ALL) due mainly to chemotherapy, especially with corticosteroids. Osteopenia/osteoporosis may be encountered long into survivorship. Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry is limited to two-dimensionality and cannot distinguish trabecular from cortical bone. METHODS: A sample of 74 subjects, ages 13.5-38.3 years more than 10 years from diagnosis, underwent peripheral quantitative computed tomography (pQCT) at metaphyseal (trabecular bone) and diaphyseal (cortical bone) sites in the radius and tibia. pQCT provides three-dimensional assessment of bone geometry, density, and architecture. RESULTS: Average values in multiple metrics were similar to those in healthy individuals, but deficits in both trabecular and cortical bones were revealed by lower Z scores using an ethnically comparable sample of healthy individuals. Connectivity, a measure of bone architecture and a surrogate measure of bone strength, was lower in females than males. Survivors of standard-risk ALL had greater connectivity in and more compact trabecular bone than high-risk survivors who had received more intensive osteotoxic chemotherapy. There were no statistically significant differences in any of the metrics at any of the sites between subjects who had or had not a history of fracture, cranial irradiation, or use of a bisphosphonate. CONCLUSIONS: These long-term survivors of ALL have somewhat compromised bone health, but data in comparable healthy populations are limited. Longitudinal studies in larger and more ethnically diverse cohorts will provide greater insight into bone health in this vulnerable population.

Measuring apparent trabecular structure with pQCT: a comparison with HR-pQCT.

We evaluated how comparable peripheral quantitative computed tomography (pQCT) measurements of cortical thickness, density, and apparent trabecular structure at the ultradistal tibia were with those measured with high-resolution pQCT (HR-pQCT). We also examined whether the accuracy of the pQCT-based trabecular and cortical measurements improved with reductions in slice thickness from the standard 2.2mm to 1.1 and 0.6mm. We immersed 15 dry tibia specimens in saline in a sealed cylinder and scanned 22.5mm from the distal tibia plateau using pQCT and HR-pQCT. pQCT underestimated cortical thickness by Stratec (CThStratec) and trabecular spacing (Tb.Sp) by 21.4% and 72.9%, whereas bone volume to total volume (BV/TV) and cortical density (CDen) were overestimated by 265.8% and 13.1%, respectively. Measurements of trabecular volumetric bone mineral density, trabecular area, total area, cortical thickness by custom software were comparable, but for CThStratec, Tb.Sp, BV/TV, and CDen, the differences between imaging devices varied with magnitude of the estimate. We recommend that researchers or clinicians interested in using pQCT to measure apparent trabecular structure or cortical thickness at the epiphyses, or in comparing findings from different devices, be aware of the differences between HR-pQCT and pQCT.

Changes in trabecular bone microarchitecture in postmenopausal women with and without type 2 diabetes: a two year longitudinal study.

BACKGROUND: The risk of experiencing an osteoporotic fracture is greater for adults with type 2 diabetes despite higher than normal bone mineral density (BMD). In addition to BMD, trabecular bone microarchitecture contributes to bone strength, but is not assessed using conventional BMD measurement by dual x-ray absorptiometry (DXA). The aim of this study was to compare two year changes in trabecular bone microarchitecture in women with and without type 2 diabetes. METHODS: We used a 1 Tesla magnetic resonance imaging (MRI) scanner to acquire axial images (resolution 195 µm × 195 µm × 1000 µm) of the distal radius. We report the change in the number and size of trabecular bone holes, bone volume fraction (BVTV), trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), endosteal area, nodal and branch density for each group. Lumbar spine and proximal femur BMD were measured with DXA (Hologic, Discovery QDR4500A) at baseline and follow-up. Using a multivariable linear regression model, we evaluated whether the percent change in the trabecular bone microarchitecture variables differed between women with and without type 2 diabetes. RESULTS: Of the 54 participants at baseline with valid MRI image sets, 37 participants (baseline mean [SD] age, 70.8 [4.4] years) returned for follow-up assessment after 25.4 [1.9] months. Lumbar spine BMD was greater for women with diabetes compared to without diabetes at both baseline and follow-up. After adjustment for ethnicity, women with diabetes had a higher percent increase in number of trabecular bone holes compared to controls (10[1] % versus -7 [2]%, p=0.010), however results were no longer significant after adjustment for multiple comparisons (p=0.090). There were no differences in the change in other trabecular bone microarchitecture variables between groups. CONCLUSION: There were no differences in percent change in trabecular bone microarchitecture variables over two years in women with type 2 diabetes compared to women without diabetes. This study provides feasibility data, which will inform future trials assessing change in trabecular bone microarchitecture in women with type 2 diabetes. Larger studies using higher resolution imaging modalities that can assess change in trabecular and cortical bone compartments in women with type 2 diabetes are needed.

Multiplanar reconstruction recovers morphological cartilage assessment reproducibility from maloriented coronal MRI scans.

The study's purpose was to assess the effect of multiplanar reconstruction on precision of weight-bearing medial and lateral femoral cartilage (cMF, cLF) morphometry in maloriented coronal MR images. Twenty knees were scanned four times with a 1.0 Tesla extremity imager using a fat-suppressed T1-weighted three-dimensional spoiled gradient recalled echo sequence; twice with "best as" double bull's-eye orientation of the femoral condyles, and once each with 5° internal and external rotation. Multiplanar reconstruction was applied to maloriented scans to recover double bull's-eye orientation. Medial and lateral femoral cartilages were segmented and precision of bone area, cartilage volume and thickness (ThCtAB) evaluated for all scans. Test-retest precision (RMSCV%) of the double bull's-eye scans was 1.1% for total bone area and 4.1% for cartilage volume. Differences in precision between double bull's-eye and maloriented images were assessed. Higher precision errors were observed in malorientated images for all outcomes (1.7-4.8% for internally rotation scans; 1.7-4.8% for external rotation scans). Precision generally improved with multiplanar reconstruction correction (1.7-5.6% for internally rotated scans; 1.2-3.5% for external rotation scans). Precision of femoral cartilage morphometry is generally reduced when maloriented images are acquired. Multiplanar reconstruction can correct malorientated scans and recover precision losses. Measurements are affected in a rotationally and compartmentally dependent manner.

Comparison of pQCT-based measures of radial bone geometry and apparent trabecular bone structure using manufacturer and in-house-developed algorithms.

Peripheral quantitative computed tomography (pQCT) provides noninvasive densitometric and morphometric measures of total, trabecular, and cortical bone compartments. Skeletal changes over time can be determined by repeated measurements. Image thickness of 2.5mm is thought to be advantageous with respect to test-retest reliability through interrogation of a significant tissue volume. However, the error associated with slight shifts in image location is unknown. The primary purpose of this study was to determine the effects of positional variability around the 4% site on radial bone measures. The secondary objective was to compare different software algorithms for estimating the same bone characteristics. Eight left cadaveric forearms (aged 65-88 yr) were imaged at 0.5-mm intervals around the 4% site of the radial bone using pQCT (10 slices; in-plane resolution: 0.2 × 0.2mm; thickness: 2.5mm; Stratec XCT2000L. We used the manufacturer's software (Stratec v6.0B) to determine the total bone mineral density (BD_tot), total bone mineral content (BMC_tot), total bone area (Area_tot), trabecular bone mineral density (BD_trab), trabecular bone mineral content (BMC_trab), and trabecular bone area (Area_trab) from each image. For comparison, in-house-developed software was also used to analyze Area_tot and Area_trab at the 4% site. The in-house software also produced measures of apparent trabecular structure, including number (App.Tb.N), thickness (App.Tb.Th), and spacing (App.Tb.Sp), quantified using 2 different stereological approaches: the parallel-plate method using trabecular perimeter lengths and mean intercept length analysis. The effect of slice position was assessed using a 1-way repeated-measures analysis of variance (ANOVA). Reliability of nonsignificant slice distances around the 4% site was determined using intraclass correlation coefficients (ICCs). One-way repeated-measures ANOVA was used to compare measures of similar bone characteristics at the 4% site. Bland-Altman plots were created to assess the level of agreement between pairs of algorithms quantifying comparable apparent trabecular structure. Area_tot and Area_trab differed significantly at greater than or equal to 1.0mm proximal and greater than or equal to 0.5mm distal to the 4% site. BMC_tot and BMC_trab differ significantly greater than or equal to 1.5mm proximally (for both) and greater than or equal to 2.0 and 1.0mm distally, respectively. BD_tot differed significantly at greater than or equal to 1mm proximal and distal to the 4% site. BD_trab did not differ among the 10 slices. For images acquired at the 4% site, and 0.5mm more proximally, reliability was excellent (ICC=0.98 to 0.99). Although the in-house software yielded a higher value for Area_tot and Area_trab at the 4% site (p<0.05), no systematic bias was observed. The parallel-plate method yielded higher values for App.Tb.N and lower values for App.Tb.Th (p<0.05), with no systematic bias. App.Tb.Sp values were smaller using the parallel-plate method, and the difference in methods increased as App.Tb.Sp values increased. Statistically, tolerance for repositioning around the 4% site of the radial bone is least for measures of bone area and greatest for BD_trab. On repeated measures, a proximal shift of 0.5mm will not influence the results.

Analysis of the subchondral microarchitecture of the distopalmar aspect of the third metacarpal bone in racing Thoroughbreds.

OBJECTIVE: To determine the anisotropic characteristics of the microarchitecture of the subchondral bone (SCB) plate and trabecular bone (TBB) of the distopalmar aspect of the metacarpal condyles in horses with different stages of SCB disease. SAMPLE POPULATION: 12 third metacarpal bone pairs from racing Thoroughbreds euthanized for diverse reasons. PROCEDURES: Both metacarpi were collected from horses with SCB changes that were mild (sclerosis and focal radiolucencies; n=6) or severe (multifocal radiolucencies and articular surface defects; 6). Sample blocks of SCB plate and TBB were collected from the distopalmar aspect of both condyles and the sagittal ridge and examined via 3-D micro-computed tomography at 45-?m isotropic voxel resolution. For each sample, the angle between the principal orientation of trabeculae and the sagittal plane and the degree of anisotropy (DA) were calculated from mean intercept length measurements. RESULTS: Condylar samples had significantly lower angle (mean, 8.9°; range, 73° to 10.9°) than sagittal ridge samples (mean, 40.7°; range, 33.6° to 49.2°), TBB had significantly higher DA (mean±SE, 1.75±0.04) than SCB plate (1.29±0.04), and mildly diseased TBB had higher DA (1.85±0.06) than severely diseased TBB (1.65±0.06). CONCLUSIONS AND CLINICAL RELEVANCE: The highly ordered appearance of trabeculae within the condyles supports the concept that joint loading is primarily transmitted through the condyles and not the sagittal ridge. The sharp changes in the trajectories of the SCB trabeculae at the condylar grooves may be indicative of hypothetical tensile forces at this location contributing to the pathogenesis of condylar fractures.

Longitudinal changes in intermuscular fat volume and quadriceps muscle volume in the thighs of women with knee osteoarthritis.

OBJECTIVE: To quantify rates of change in quadriceps muscle (QM) and intermuscular fat (IMF) volumes over 2 years in women in the Osteoarthritis Initiative (OAI) study and examine group differences between those with radiographic osteoarthritis (ROA) and those without ROA. METHODS: The OAI database was queried for women ≥50 years of age in the incident and progression cohorts with and without ROA at baseline. Midthigh magnetic resonance imaging scans (15 contiguous slices, 5 mm slice thickness) of eligible women were randomly selected and anonymized. Image pairs were registered. QM and IMF were segmented in the 12 most proximal matching slices with the segmenter blinded to image time point. Age-adjusted differences in QM and IMF volume changes between groups were tested using analysis of covariance. RESULTS: Forty-one women without ROA (mean ± SD age 60.7 ± 7.6 years) and 45 women with ROA (mean ± SD age 64.5 ± 6.7 years) were included. Mean ± SD QM and IMF volume changes in the non-ROA group were -4.1 ± 11.1 cm(3) and 3.4 ± 7.1 cm(3), respectively, and -5.4 ± 13.5 cm(3) and 3.1 ± 7.4 cm(3) in the ROA group, respectively. Age-adjusted between-group differences in QM and IMF changes were not significant (P > 0.05). CONCLUSION: Two-year changes in QM and IMF volumes appear consistent with aging and do not seem to be related to OA status. Direct comparison with a control cohort without OA risk factors could confirm this. Since group assignment was based on baseline data, there may have been women in the non-ROA group who developed ROA over followup, resulting in some overlap between groups.

Association of larger holes in the trabecular bone at the distal radius in postmenopausal women with type 2 diabetes mellitus compared to controls.

OBJECTIVE: Adults with type 2 diabetes mellitus (DM) have an elevated fracture risk despite normal areal bone mineral density (aBMD). The study objective was to compare trabecular bone microarchitecture of postmenopausal women with type 2 DM and women without type 2 DM. METHODS: An extremity 1T magnetic resonance imaging system was used to acquire axial images (195 × 195 × 1,000 µm(3) voxel size) of the distal radius of women recruited from outpatient clinics or by community advertisement. Image segmentation yielded geometric, topologic, and stereologic outcomes, i.e., number and size of trabecular bone network holes (marrow spaces), endosteal area, trabecular bone volume fraction, nodal and branch density, and apparent trabecular thickness, separation, and number. Lumbar spine (LS) and proximal femur BMD were measured with dual x-ray absorptiometry. Microarchitectural differences were assessed using linear regression and adjusted for percent body fat, ethnicity, timed up-and-go test, Charlson Index, and calcium and vitamin D intake; aBMD differences were adjusted for body mass index (BMI). RESULTS: Women with type 2 DM (n = 30, mean ± SD age 71.0 ± 4.8 years) had larger holes (+13.3%; P = 0.001) within the trabecular bone network than women without type 2 DM (n = 30, mean ± SD age 70.7 ± 4.9 years). LS aBMD was greater in women with type 2 DM; however, after adjustment for BMI, LS aBMD did not differ between groups. CONCLUSION: In women with type 2 DM, the average hole size within the trabecular bone network at the distal radius is greater compared to controls. This may explain the elevated fracture risk in this population.