Subregional Bone Mineral Density Research Articles

Automatic Measurement of Subregional Vertebral Bone Mineral Density via Deep Learning of Quantitative Computed Tomography Images

Background: Measurement of subregional Bone Mineral Density (BMD) of the vertebral body has been shown to hold a critical role in osteoporotic fracture risk analysis. The reproducibility and precision of the measurement rely highly on the vertebral body region of interest segmentation accuracy, which requires expert-level experience in medical image preprocessing and is time-consuming work. The establishment of a reliable automatic method could enhance the efficiency and precision of these measurements in clinical practice. Purpose: To develop and validate a deep learning-based segmentation approach for subregional vertebral BMD measurement with quantitative CT scans. Materials and Methods: Quantitative CT images from 115 subjects (62 women and 53 men with a mean age of 66.4 ± 13.4 years) were retrospectively collected. A deep learning-based segmentation pipeline was trained on a total of 403 manual segmented lumbar vertebral bodies. The performance was evaluated by its accuracy, Dice Score, and Intersection over Union (IoU) score. A scan-rescan test was performed to evaluate the subregional BMD measurement reliability and reproducibility by analyzing the intraclass correlation coefficient and Bland-Altman analysis. Results: This automatic approach achieved high segmentation performance for the entire vertebral body segmentation (accuracy 0.98 ± 0.02, dice coefficient 0.92 ± 0.06, and IoU 0.87 ± 0.09), cortical bone segmentation (accuracy 0.95 ± 0.02, dice coefficient 0.92 ± 0.03, and IoU 0.85 ± 0.05), and endplate segmentation (accuracy 0.89 ± 0.05 and Dice coefficient 0.75 ± 0.09, IoU 0.61 ± 0.12). The scan-rescan test further showed the automatic measurement is highly reproducible (r = 0.96, limit of agreement [LoA] = -20.4~17.9 mg/cm3 for entire region; r = 0.95, LoA = -39.5~33.3 mg/cm3 for cortical region; r = 0.89, LoA = -23.4~20.9 mg/cm3 for cancellous region; r = 0.82, LoA = -44.9~58.9 mg/cm3 for superior endplate; r = 0.63, LoA = -81.6~106.5 mg/cm3, respectively). Conclusion: The deep learning-based approach is feasible for vertebral body subregions segmentation, which ensures the precision and reproducibility of BMD measurement. The cortical and cancellous BMD can be separately measured by the deep learning-based approach, providing an automatic and reliable framework for the investigation of subregional osteoporosis changes with Quantitative Computed Tomography (QCT) spine scans.

Associations between objectively-measured sedentary behaviour and physical activity with bone mineral density in adults and older adults, the NHANES study

BackgroundLack of physical activity (PA) is an important modifiable risk factor for bone mineral density (BMD). Time spent in sedentary behaviour (SB), or time spent in non-exercising seated and reclining postures, has recently emerged as a new public health risk, independent of the amount of time someone spends being active. As national surveys report that adults spend on average 8h per day being sedentary, rising to 10h a day in older age, it has been hypothesised that a repeated exposure to sitting in modern daily life, whether it is for travelling, working or leisure, might have a deleterious effect on bone health in a way that mirrors the results of studies into the effect of lengthy periods of bed-rest. The aim of this study was to investigate for the first time a) how time spent in SB is associated with bone mineral density (BMD), b) whether this association changes depending on the amount of time spent engaging in different intensity levels of PA, and c) if the pattern of accumulation of SB and long uninterrupted periods of SB are associated with BMD. MethodsThe 2005/2006 National Health and Nutrition Examination Survey (NHANES), is a cross-sectional study of a representative sample of the US population that is conducted biannually by the National Centers for Disease Control. PA and SB were assessed objectively over 7days using an Actigraph accelerometer and BMD was measured via dual-energy X-ray absorptiometry. In this study, data are presented on four regions of the femur (femoral neck, trochanter, inter trochanter and total femur) and total spine (L1–L4). The associations between BMD, SB and PA levels were examined using multiple linear regressions stratified by gender. In addition, the association between the pattern of accumulation of SB (quantified as frequency and duration of SB) and BMD was also investigated. All models were adjusted for known risk factors associated with BMD. In total, data for 2117 individuals, aged 23–90+years (males N=1158), were available to analyse SB and femur BMD and 1942 individuals (males N=1053) for analysis of SB and spine BMD. ResultsThere was no evidence of an association between SB time and hip or spinal BMD in men. For men, time spent doing moderate to vigorous activity (MVPA) and vigorous activity (VIG) was associated with higher total femur and the other hip sub-region BMD. The regression coefficient was BMVPA=0.306 (95% CI: 0.021–0.591)g/cm2 for each 10minute increment in daily MVPA. For VIG, the regression coefficient is BVIG=0.320 (95% CI: 0.058–0.583) but this cannot be interpreted linearly as time spent in vigorous activity was square root transformed. In women, SB was negatively associated with total femur BMD and all sub-regions but not MVPA nor VIG. The regression coefficient for total femur BMD was BSB=−0.159 (95% CI: −0.241–0.076)g/cm2 for each 10minute increment spent being sedentary each day. In addition, the duration of SB bouts was deleteriously associated with BMD for the total femur and of other hip sub-regions, but the number of bouts of SB did not have a significant effect. These associations were found to be independent of the amount of MVPA and VIG that women engage in. No associations were found between SB or PA and spinal BMD for either men or women. ConclusionsThese results provide the first evidence that repeated exposure to sitting (SB), measured objectively in daily life, is deleteriously associated with BMD of the total femur and of all hip sub-regions in women, independent of the amount of time women engage in moderate and vigorous activity. This suggests that SB might be a risk factor for bone health in women independent of whether they engage in physical activity. In addition, the duration of SB bouts, rather than their frequency, appears to be deleteriously associated with BMD of the total femur and of all hip sub-regions. Future research should investigate the effect on bone health of interventions which set out to reduce SB and the duration of SB bouts in comparison, and as adjunct, to the promotion of PA. For men, SB is not significantly associated with BMD of the femur or spine and the results appear to confirm that moderate and vigorous activity has a protective effect.

Dual-energy X-ray absorptiometry of human metatarsals: Precision, least significant change and association to ex vivo fracture force

BackgroundFractures are common in foot bones, but clinicians lack adequate indices of bone strength. ObjectivesWe used dual-energy X-ray absorptiometry (DXA) to measure bone mineral density (BMD) and content (BMC) of excised human metatarsals, determined intra- and inter-rater measurement precision, and assessed associations between BMD/BMC and ex vivo bone fracture strength. MethodsTwo raters each made two measurements of whole-bone and sub-regional BMD and BMC in both second and third metatarsals from 10 cadavers. Variance components analysis was used to assess variability attributable to repeat measurements, raters, sub-regions, bones, sides, and cadavers. Root-mean-square standard deviation (RMS-SD) and least-significant change (LSC) were used to assess rater precision and ultimate forces during 3-point bending were tested for correlations with BMD and BMC. ResultsVariation due to repeat measurements and rater was low (<1% combined) for BMD and BMC. RMS-SD for whole metatarsal BMD of both metatarsals ranged from 0.004 to 0.010g/cm2 and 0.062 to 0.086g for BMC. Whole metatarsal and sub-region BMD and BMC were strongly correlated to ex vivo fracture force (r2=0.67–0.93). ConclusionsDXA measurements of BMD and BMC have high intra- and inter-rater precision and are strongly correlated to ex vivo bone strength.

Predicting ex vivo failure loads in human metatarsals using bone strength indices derived from volumetric quantitative computed tomography

We investigated the capacity of bone quantity and bone geometric strength indices to predict ultimate force in the human second metatarsal (Met2) and third metatarsal (Met3). Intact lower extremity cadaver samples were measured using clinical, volumetric quantitative computed tomography (vQCT) with positioning and parameters applicable to in vivo scanning. During processing, raw voxel data (0.4mm isotropic voxels) were converted from Hounsfield units to apparent bone mineral density (BMD) using hydroxyapatite calibration phantoms to allow direct volumetric assessment of whole-bone and subregional metatarsal BMD. Voxel data were realigned to produce cross-sectional slices perpendicular to the longitudinal axes of the metatarsals. Average mid-diaphyseal BMD, bone thickness, and buckling ratio were measured using an optimized threshold to distinguish bone from non-bone material. Minimum and maximum moments of inertia and section moduli were measured in the mid-diaphysis region using both a binary threshold for areal, unit-density measures and a novel technique for density-weighted measures.BMD and geometric strength indices were strongly correlated to ultimate force measured by ex vivo 3-point bending. Geometric indices were more highly correlated to ultimate force than was BMD; bone thickness and density-weighted minimum section modulus had the highest individual correlations to ultimate force. Density-weighted geometric indices explained more variance than their binary analogs. Multiple regression analyses defined models that predicted 85–89% of variance in ultimate force in Met2 and Met3 using bone thickness and minimum section modulus in the mid-diaphysis. These results have implications for future in vivo imaging to non-invasively assess bone strength and metatarsal fracture risk.

Novel Assessment of Subregional Bone Mineral Density Using DXA and pQCT and Subregional Microarchitecture Using Micro-CT in Whole Human Vertebrae: Applications, Methods, and Correspondence Between Technologies

In the clinical environment dual-energy X-ray absorptiometry (DXA) is the current tool of first choice for assessing and monitoring skeletal integrity. A major drawback of standard DXA is that the bone mineral density (BMD) data cannot be used with certainty to predict who will sustain a vertebral fracture. However, measurement of BMD within vertebral subregions, instead of relying on a gross estimate of vertebral BMD, may improve diagnostic sensitivity. The aim of this article was to describe a validation study for subregional BMD measurement using lateral-projection DXA and to present preliminary data. Concurrent validity of measuring subregional BMD with DXA was established against measures of volumetric subregional BMD from peripheral quantitative computed tomography (pQCT) and subregional bone volume fraction from μCT at the L2 vertebral body in 8 cadaver spine specimens. The novel approaches for measuring subregional parameters with each imaging modality are described. Significant differences in bone parameters between vertebral subregions were observed for each imaging modality ( p < 0.05). Correspondence ranged from R 2 = 0.01–0.79 and R 2 = 0.06–0.80 between “DXA vs. pQCT” and “DXA vs. micro-CT,” respectively. For both imaging modalities, correspondence with DXA was high for centrally and anteriorly positioned subregions. These data provide a basis for larger studies to examine the biological significance of heterogeneity in vertebral BMD.

Associations with subregional BMD-measurements in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have bone loss to various degrees at different skeletal sites. The subregional bone mineral density (BMD) of the hand and the correlation of BMD to other regional bone losses, parameters of inflammation or bone resorption was evaluated in 421 patients with RA and controls. RA patients had significantly (P<0.01) lower BMD values in the carpus (0.405+/-0.004 g/cm2), metacarpal joint II (0.318+/-0.036 g/cm2) and metacarpal joint III (0.326+/-0.022 g/cm2) compared to controls. There was no difference in bone density at the lumbar spine or hip. Significant (P<0.001) correlations were found between BMD total of the hand, its subregions, the forearm and hip. Parameters of inflammation correlated significantly (P<0.001) with pyridinolines (r=0.378), desoxypyridinolines (r=0.183), forearm (r=-10, P<0.05), MCP II (r=-0.190, P<0.001), MCP III (r=0.204, P<0.001) and carpus (r=0.191, P<0.001).

The prevalence of significant left-right differences in hip bone mineral density

We determined the prevalence of left-right differences in hip bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and the resultant consequence, namely: the frequency at which patients would be classified differently if lumbar spine and only one hip (rather than both hips) were measured. This was a retrospective DXA scan reanalysis of 3012 white women >or=50 yrs who had scans of both hips using Hologic DXA systems. The difference between left and right hips was considered significant if it exceeded the least significant change (LSC) for any of three hip subregions (total hip, femoral neck, trochanter). The number of women with osteoporosis in both hips, the left hip only, or the right hip only was determined by lowest T-score from total hip, femoral neck, or trochanter. Despite high left-right correlations of subregion BMD, significant left-right differences in BMD were common: the difference exceeded the LSC for 47% of women at total hip, 31% at femoral neck, and 56% at trochanter. Left-right differences in BMD that exceeded the LSC affected the percent agreement of left-right hip classification: for all women irrespective of spine status, there was 77% classification (diagnostic) agreement in hip pairs in which the left-right hip BMD difference exceeded the LSC versus 87% agreement in which LSC was not exceeded (significant difference in proportions, P<0.0001). The greatest risk of different classification would occur in women with normal spines as the diagnosis might be determined by hip T-scores. Using L1-4 lumbar spine T-scores, 1229 women were normal at the spine. Twenty-four (2%) were osteoporotic at both hips. However, 12 women (1%) were osteoporotic only in the left hip (significantly different from zero, P<0.001) and 11 (1%) only in the right hip (P<0.001); of these 23 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 16 (70% of those with osteoporosis in only one hip). Using L1-4 lumbar spine T-scores, 1159 women were osteopenic at the spine. Of these, 126 (11%) were osteoporotic at both hips, 54 (5%) only in the left hip (P<0.001), and 42 (4%) only in the right hip (P<0.001); of these 96 women, the difference in BMD between the osteoporotic hip and the contralateral hip exceeded the LSC in 56 (58% of those with osteoporosis in only one hip). A statistically significant number of women with osteoporosis are potentially classified differently when scanning only one hip as a result of the high prevalence of left-right differences in BMD. Although the percentages are low, the total number of women affected may be large. From a public health perspective, the practice of scanning both hips could potentially identify more women with osteoporosis and may help prevent future hip fractures.

Bisphosphonate treatment in ochronotic osteoporotic patients

In ochronotic patients, abnormalities in bone metabolism leading to increased bone loss have been reported. Therefore, we attempted antiresorptive therapy to (almost) partially reverse bone loss in four out of five osteopenic or osteoporotic ochronotic patients, two men and two women, aged 56-82 years. Each patient was treated with a 70-mg tablet of alendronate weekly and 1,000 mg/day of elemental calcium, such as gluconolactate or carbonate, throughout 24 months. Before starting therapy, and after 1 and 2 years of treatment, the bone mineral density (BMD) at the femoral subregions and at the lumbar spine was measured (in grams per square centimeter and as a T score) by dual energy X-ray absorptiometry. A 50-year-old osteopenic ochronotic man refusing the treatment underwent the same checks. The BMD was measured in all patients on the same densitometer by the same operator. The results showed a progressive decrease of the femoral subregion BMD measurements both in the bisphosphonate-treated patients and in the untreated patient. In particular, the percentage differences with respect to the basal values of the total femur BMD measurements ranged from -0.52 to -6.72% in the first year and from -5.29 to -9.05% in the second year. The lumbar spine BMD measurements provided spuriously overestimated results. Moreover, two treated patients and the untreated patient experienced fragility fractures of the femur. The study showed that osteoporosis and fragility fractures are prominent manifestations in the natural history of ochronosis. Matrix microdamage, osteocyte viability, and collagen cross-linking impairment, due to homogentisic acid and to its polymer, might be the processes involved. For this reason, the bisphosphonate therapy was ineffective.

In Vivo Intrarater and Interrater Precision of Measuring Apparent Bone Mineral Density in Vertebral Subregions Using Supine Lateral Dual-Energy X-Ray Absorptiometry

Analysis of apparent bone mineral density (BMD) in the lumbar spine is commonly based on anteroposterior (AP) scanning using dual-energy X-ray absorptiometry (DXA). Although not widely used, clinically important information can also be derived from lateral scanning. Vertebral bone density, and therefore strength, can may vary in different subregions of the vertebral body. Therefore, subregional BMD measurements might be informative about fracture risk. However, the intrarater and interrater precision of in vivo subregional BMD assessments from lateral DXA remains unknown. Ten normal, young (mean: 24 yr) and 10 older (mean: 63 yr) individuals with low BMD were scanned on one occasion using an AP/lateral sequence. Each lateral scan was reanalyzed six times at L2 by three raters to determine the intrarater and interrater precision in selecting seven regions of interest (subregions). Precision was expressed using percentage coefficients of variation (% CV) and intraclass correlation coefficients (ICC). Intrarater precision ranged from ICC(1,1) 0.971 to 0.996 (% CV: 0.50-3.68) for the young cohort and ICC(1,1) 0.934 to 0.993 (% CV: 1.46-5.30) for the older cohort. Interrater precision ranged from ICC(2,1) 0.804 to 0.915 (% CV: 1.11-2.35) for the young cohort and ICC(2,1) 0.912 to 0.984 (% CV: 1.85-4.32) for the older cohort. Scanning a subgroup of participants twice with repositioning was used to assess short-term in vivo precision. At L2, short-term in vivo precision ranged from ICC(1,1) 0.867 to 0.962 (% CV: 3.38-9.61), at L3 from ICC(1,1) 0.961 to 0.988 (% CV: 2.02-5.57) and using an L2/L3 combination from ICC(1,1) 0.942 to 0.980 (% CV: 2.04-4.61). This study demonstrated moderate to high precision for subregional analysis of apparent BMD in the lumbar spine using lateral DXA in vivo.

Poster 82: A preliminary study of dual-energy X-ray absorptiometry positioning protocols for women and girls with mobility disabilities

Objective: To establish a protocol compensating for contractures in dual-energy x-ray absorptiometry (DXA) hip scans in people with mobility impairments using the DPX-IQ Lunar Pencil Beam Scanner. Design: 3 sets of proximal femur scans taken at 0°, 20°, and 30° of hip flexion, with repositioning between. The bone mineral density (BMD) in hip subregions and the precision of BMD with repeated scans at each angle were determined. Repeated DXA scans of the ipsilateral distal femur in lateral view were made for comparison with hip data as a potential surrogate site to substitute for direct hip data. Setting: This study was conducted as part of a research program examining BMD in premenopausal women and girls with mobility impairments, in whom standard hip positioning required by the typical DXA protocol may not be achievable. Participants: Female volunteers without mobility impairments (N=14), ages 22 to 44 years. Interventions: Not applicable. Main Outcome Measures: Total and subregion BMD at 0°, 20°, and 30° of hip flexion; and BMD in 4 subregions in the distal femur using a generic lumbar spine scan protocol (g/cm 2). Results: Data analysis examined both the average standard deviation among repeats and the differences between 20° and 30° compared with the 0° positions. Statistical comparisons using paired t tests for the cohort indicated little change in hip BMD readings up to 20° of flexion. At 30° of hip flexion, BMD appeared to increase in the shaft region and global reading by 9% and 7%, respectively ( P<.001). There was a modest correlation between the distal third lateral femur BMD and the hip shaft BMD ( r=.55) and neck BMD ( r=0.5). Conclusions: Hip flexion angles of >20° can give false-positive or negative DXA readings. Distal femur readings correlated modestly with shaft and neck data, a possible surrogate site when typical extension is affected by contractures.

Standardization of bone mineral density at femoral neck, trochanter and Ward's triangle.

The International Committee for Standards in Bone Measurement (ICSBM) has published standardization formulas for total hip bone mineral density (BMD). In many applications, however, BMD of hip subregions, such as femoral neck (FN), trochanter (TR), and Ward's triangle (WT), are commonly measured. This paper addresses whether the standardization formulas for total hip BMD can be adequately used for hip subregions. We used data from 100 healthy women, from 20 to 80 years old, who had hip BMD measured in both the total hip and hip subregions by a Hologic QDR 2000, a Lunar DPX, and a Norland XR26 Mark II. The same women were used by ICSBM for the standardization of total hip BMD. In addition, we used data of 3139 patients from a clinical trial to validate our results. We derived standardization formulas for FN, TR, and WT using the same statistical method as that used for total hip BMD. We applied both total hip calibration formulas and subregion-specific formulas to the data and compared the corresponding effect. We found that the total hip calibration formulas can partially reduce BMD differences between the Hologic and Lunar as well as the Lunar and Norland scanners in hip subregions, but increase differences between the Hologic and Norland scanners. The subregion calibration formulas are most appropriate for calibrating subregion BMD values and their absolute changes, and should be adopted. Standardization is unnecessary for BMD percentage changes in our clinical trial data.

Bone mineral density and body composition in patients with ulcerative colitis

OBJECTIVE: Reduced bone mineral density (BMD) has been reported in ulcerative colitis (UC) patients, but body composition (fat and lean mass) has never been concomitantly studied. We sought to investigate BMD and body composition in a group of UC outpatients with the following characteristics: age 18–60 yr (men) and 18–45 yr (women); no intestinal resection; no immunosuppressive treatment; and regular menstruation. METHODS: Whole body and subregional BMD and body composition in 43 UC patients (21 men, 22 women; male mean age, 36.5 [21–57] yr; female mean age, 35.3 [23–45] yr) and 121 healthy volunteers were studied by means of dual X-ray photon absorptiometry. RESULTS: There were no differences in total and subregional BMD, or fat and lean mass between the patients and controls, except that the total and trunk lean mass of the UC women was lower than that in the normal controls. No correlation was found between lifetime steroid intake and BMD. CONCLUSIONS: UC outpatients do not differ from normal subjects in terms of BMD and fat mass. Mild and moderate UC does not represent a risk factor for osteopenia.