Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis.

BACKGROUND: Low hip bone mineral density (BMD) in patients who undergo total hip arthroplasty (THA) increases the risk of periprosthetic fractures, implant instability, and other complications. Recently, emphasis has been placed on bone health optimization: treating low BMD prior to a planned orthopaedic implant procedure in an effort to normalize BMD and reduce the potential risk of future complications. Abaloparatide is a U.S. Food and Drug Administration-approved osteoanabolic agent for men and postmenopausal women with osteoporosis and a candidate drug for bone health optimization that, in addition to benefits at the spine, increases hip BMD and reduces nonvertebral fracture risk. We hypothesized that abaloparatide would improve BMD in proximal femoral regions surrounding a virtual THA stem. METHODS: This post hoc analysis obtained dual x-ray absorptiometry (DXA) hip scans from 500 randomly selected postmenopausal women with osteoporosis from the Phase-3 Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE, NCT01343004) study after 0, 6, and 18 months of abaloparatide (250 patients) or placebo (250 patients). Hip DXA scans underwent 3-dimensional (3D) modeling via 3D-Shaper, followed by virtual resection of the proximal femur and simulated placement of a tapered, flat-wedge hip stem that guided delineation of the Gruen zones that were fully (zones 1 and 7) or largely (zones 2 and 6) captured in the scanning region. Integral, cortical, and trabecular volumetric BMD, cortical thickness, and cortical surface BMD (the product of cortical volumetric BMD and cortical thickness) were determined for each zone. RESULTS: Compared with placebo, the abaloparatide group showed greater increases in integral volumetric BMD in all zones at months 6 and 18; cortical surface BMD in zones 1, 6, and 7 at month 6; cortical thickness, cortical volumetric BMD, and cortical surface BMD in all zones at month 18; and trabecular volumetric BMD in zones 1 and 7 at months 6 and 18. CONCLUSIONS: Abaloparatide increases BMD in proximal femoral regions that interact with and support femoral stems, suggesting that abaloparatide may have value for preoperative or potentially perioperative bone health optimization in patients with osteoporosis undergoing THA. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

3D-modeling from hip DXA shows improved bone structure with romosozumab followed by denosumab or alendronate.

Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 yr. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from 2 randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate). For each study, data from a subset of ~200 women per treatment group who had TH DXA scans at baseline and months 12 and 24 and had provided consent for future research were analyzed post hoc. 3D-SHAPER software v2.11 (3D-SHAPER Medical) was used to generate patient-specific 3D models from TH DXA scans. Percentage changes from baseline to months 12 and 24 in areal BMD (aBMD), integral volumetric BMD (vBMD), cortical thickness, cortical vBMD, cortical surface BMD (sBMD), and trabecular vBMD were evaluated. Data from 377 women from FRAME (placebo, 190; romosozumab, 187) and 368 women from ARCH (alendronate, 185; romosozumab, 183) with evaluable 3D assessments at baseline and months 12 and 24 were analyzed. At month 12, treatment with romosozumab vs placebo in FRAME and romosozumab vs alendronate in ARCH resulted in greater increases in aBMD, integral vBMD, cortical thickness, cortical vBMD, cortical sBMD, and trabecular vBMD (P < .05 for all). At month 24, cumulative gains in all parameters were greater in the romosozumab-to-denosumab vs placebo-to-denosumab sequence and romosozumab-to-alendronate vs alendronate-to-alendronate sequence (P < .05 for all). 3D-SHAPER analysis provides a novel technique for estimating changes in cortical and trabecular parameters from standard hip DXA images. These data add to the accumulating evidence that romosozumab improves hip bone density and structure, thereby contributing to the antifracture efficacy of the drug.

Osteoporosis is a chronic condition in which bones become weak and are more likely to break (fracture) with minimal force such as tripping or falling. A fracture, especially in the elderly, is a serious condition that affects daily activities and quality of life. Romosozumab, an approved medication for patients with osteoporosis, increases bone mass and bone strength thereby reducing fracture risk. In this study, 3D reproductions of patients' hip bones were generated from standard images of a bone density test with DXA from women in the FRAME clinical trial where they received romosozumab or placebo for 12 mo followed by 12 mo of denosumab or the ARCH clinical trial where they received romosozumab or alendronate for 12 mo, followed by 12 mo of alendronate. We found that patients treated with romosozumab for the first 12 mo had significantly greater increases in bone strength compared with those who received placebo or alendronate. After 24 mo, total gains in bone strength measurements were greater in patients treated with romosozumab first. Our study shows that DXA-based 3D modelling provides a novel technique for examining changes in bone strength and supports the use of romosozumab to improve hip bone strength and reduce fracture risk.

3D-DXA Based Finite Element Modelling for Femur Strength Prediction: Evaluation Against QCT.

Osteoporosis is characterised by the loss of bone density resulting in an increased risk of fragility fractures. The clinical gold standard for diagnosing osteoporosis is based on the areal bone mineral density (aBMD) used as a surrogate for bone strength, in combination with clinical risk factors. Finite element (FE) analyses based on quantitative computed tomography (QCT) have been shown to estimate bone strength better than aBMD. However, their application in the osteoporosis clinics is limited due to exposure of patients to increased X-rays radiation dose. Statistical modelling methods (3D-DXA) enabling the estimation of 3D femur shape and volumetric bone density from dual energy X-ray absorptiometry (DXA) scan have been shown to improve osteoporosis management. The current study used 3D-DXA based FE analyses to estimate femur strength from the routine clinical DXA scans and compared its results against 151 QCT based FE analyses, in a clinical cohort of 157 subjects. The linear regression between the femur strength predicted by QCT-FE and 3D-DXA-FE models correlated highly (coefficient of determination R2 = 0.86) with a root mean square error (RMSE) of 397 N. In conclusion, the current study presented a 3D-DXA-FE modelling tool providing accurate femur strength estimates noninvasively, compared to QCT-FE models.

Long-Term Effect of Denosumab on Bone Disease in Patients with CKD.

BACKGROUND: The effect of long-term denosumab therapy and of denosumab discontinuation on the cortical bone of the hip regions in dialysis patients has not been studied. METHODS: This retrospective study investigated the cortical and trabecular compartments and estimated strength indices of the hip region, obtained using 3D-SHAPER software, after a maximum of 5 years of denosumab therapy in 124 dialysis patients. A Wilcoxon signed-rank test was used to identify the differences in each parameter before and after denosumab initiation. Similarly, we investigated the changes in these parameters after denosumab discontinuation in 11 dialysis patients. RESULTS: Integral and trabecular volumetric bone mineral densities (BMD) were significantly lower at the start of denosumab therapy than those in 1 year before denosumab initiation. After starting denosumab, areal BMD (median change +7.7% [interquartile range (IQR), +4.6 to +10.6]), cortical volumetric BMD (median change +3.4% [IQR, +1.0 to +4.7]), cortical surface BMD (median change +7.1% [IQR, +3.4 to +9.4]), and cortical thickness (median change +3.2% [IQR, +1.8 to +4.9]) showed a significantly higher trend for 3.5 years, which then stabilized at a higher value compared with baseline. A similar trend in the trabecular volumetric BMD (median change +9.8% [IQR, +3.8 to +15.7]) was observed over 2.5 years, with a higher value maintained thereafter. The whole area of the hip region improved after denosumab therapy. Similar trajectories were also found in the estimated strength indices. Conversely, at 1 year after denosumab discontinuation, these 3D parameters and estimated strength indices tended to largely worsen. The lateral aspect of the greater trochanter was the most pronounced location showing volumetric BMD loss. CONCLUSIONS: The BMD of both cortical and trabecular components in the hip region was significantly higher after starting denosumab therapy. However, these measurements exhibited a trend of declining substantially after the discontinuation of denosumab.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1 years for integral vBMD, 7.4 years for trabecular vBMD and 9.2 years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Femur 3D-DXA Assessment in Female Football Players, Swimmers, and Sedentary Controls.

Cortical and trabecular volumetric bone mineral density (vBMD), cortical thickness and surface BMD (sBMD, density-to-thickness ratio) were analyzed in the proximal femur of elite female football players and artistic swimmers using three-dimensional dual-energy X-ray absorptiometry (3D-DXA) software and compared to sedentary controls. Football players had significantly higher (p<0.05) vBMD (mg/cm3) in the trabecular (263±44) and cortical femur (886±69) than artistic swimmers (224±43 and 844±89) and sedentary controls (215±51 and 841±85). Football players had also higher (p<0.05) cortical thickness (2.12±0.19 mm) and sBMD (188±22 mg/cm2) compared to artistic swimmers (1.85±0.15 and 156±21) and sedentary controls (1.87±0.16 and 158±23). Artistic swimmers did not show significant differences in any parameter analyzed for 3D-DXA when compared to sedentary controls. The 3D-DXA modeling revealed statistical differences in cortical thickness and vBMD between female athletes engaged in weight-bearing (football) and non-weight bearing (swimming) sports and did not show differences between the non-weight bearing sport and the sedentary controls. 3D-DXA modeling could provide insight into bone remodeling in the sports field, allowing evaluation of femoral trabecular and cortical strength from standard DXA scans.

Proximal Femur Responses to Sequential Therapy With Abaloparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis by 3D Modeling of Hip Dual-Energy X-Ray Absorptiometry (DXA).

Previous subgroup analyses from the ACTIVE trial in women with postmenopausal osteoporosis (NCT01343004) using three-dimensional (3D)-processing of dual X-ray absorptiometry (DXA) scans indicated greater increases in total hip cortical volumetric bone mineral density (Ct.vBMD) and estimated indices of hip strength following 18 months of abaloparatide (ABL) versus placebo or teriparatide. The current post hoc analyses describe hip 3D-DXA data for ACTIVExtend (NCT01657162), in which 18 months of ABL followed by 24 months of alendronate (ABL/ALN) increased hip and spine areal BMD (aBMD) and reduced fracture risk versus placebo (PBO) followed by ALN (PBO/ALN). In an ACTIVExtend subgroup (ABL/ALN, n = 204; PBO/ALN, n = 202), hip DXA scans retrospectively underwent 3D modeling via 3D-Shaper software. Changes from baseline in cortical and trabecular compartments were calculated for total hip and hip subregions (femoral neck, trochanter, and shaft). Estimated strength indices comprising cross-sectional moment of inertia, section modulus, and buckling ratio were calculated for each hip subregion. Correlations between bone turnover marker levels at the time of alendronate initiation and subsequent BMD gains with alendronate were also investigated within each group. Total hip trabecular and cortical 3D-DXA parameters increased from baseline in both groups (all p < 0.001), with greater average increases for ABL/ALN versus PBO/ALN (trabecular vBMD: 10.87% versus 4.3%; cortical thickness: 2.32% versus 1.14%; Ct.vBMD: 3.41% versus 1.86%; cortical surface BMD: 5.82% versus 3.0%; all p < 0.001). Strength indices in the ABL/ALN group improved in all subregions versus baseline (all p < 0.0001) and versus PBO/ALN (all p < 0.02). In the ABL/ALN group, collagen type I N-terminal propeptide (P1NP) levels at the time of alendronate initiation correlated with subsequent percent changes in all 3D-DXA parameters with 24 months of alendronate therapy. In conclusion, sequential ABL/ALN or PBO/ALN treatment improves trabecular and cortical 3D-DXA parameters at the hip, as well as strength indices of hip subregions, with greater increases with ABL/ALN versus PBO/ALN. © 2022 Radius Health, Inc. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abaloparatide Effects on Cortical Volumetric BMD and Estimated Strength Indices of Hip Subregions by 3D-DXA in Women With Postmenopausal Osteoporosis.

In ACTIVE, abaloparatide increased areal BMD (aBMD) of the hip and femoral neck vs teriparatide and placebo in women with osteoporosis. Previously, 3D-processing of dual X-ray absorptiometry (DXA) scans of a subgroup of ACTIVE subjects showed similar increases in trabecular volumetric BMD (Tb.vBMD) and greater increases in cortical vBMD (Ct.vBMD) of the total hip with abaloparatide vs teriparatide. The current analyses from this subgroup describe 2D- and 3D-DXA data for hip subregions. Randomly selected subjects from ACTIVE (n = 250/treatment group) who received 18 mo of placebo, abaloparatide 80 µg, or open-label teriparatide 20 µg by daily subcutaneous injection underwent hip DXA at baseline, and mo 6 and 18 of treatment. Areal BMD of the femoral neck, trochanter, and femoral shaft was determined using standard 2D-DXA and 3D-SHAPER software to retrospectively evaluate changes from baseline in volumetric parameters of these 3 hip subregions, including trabecular and cortical segmentation. Changes in biomechanical parameters cross-sectional moment of inertia (CSMI), section modulus (Z), and buckling ratio were also evaluated. Femoral neck, trochanter, and shaft aBMD increased in the abaloparatide and teriparatide groups at mo 6 and 18 vs placebo, with greater increases for abaloparatide vs teriparatide at the femoral neck at mo 6 and the shaft at mo 6 and 18. All 3 subregions showed similar significant increases in Tb.vBMD with abaloparatide and teriparatide vs placebo, whereas Ct.vBMD of all 3 subregions showed greater increases after 18 mo of abaloparatide vs teriparatide. Biomechanical parameters improved in all subregions with abaloparatide and teriparatide vs placebo, with greater improvements in CSMI and Z of the femoral neck and lower shaft after 6 and 18 mo of abaloparatide vs teriparatide. Differential femoral neck and shaft Ct.vBMD responses may explain the greater increases in CSMI and Z of those subregions with abaloparatide vs teriparatide.

3D analysis of bone mineral density in a cohort: age- and sex-related differences.

Women have lower areal BMD (g/cm2) than men; however, the women have smaller-size bones. Our study showed that women ≤ 59 years have a hip volumetric BMD by DXA 3D similar to that of men of the same age. This makes us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass. PURPOSE: Women have lower areal BMD (g/cm2) than men; however, these studies do not take into account that women have smaller-size bones. Recently, three-dimensional (3D) modeling methods were proposed to analyze volumetric BMD (vBMD). We want to determine the values of vBMD at the hip by DXA-based 3D modeling in a cohort of people in order to know the age- and sex-related differences. METHODS: A total of 2647 people of both sexes (65% women) were recruited from a large cohort (Camargo cohort, Santander, Spain). 3D-SHAPER® software (version 2.8, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from the hip DXA scans at baseline RESULTS: The differences were less pronounced for vBMD (cortical sBMD 9.3%, trabecular vBMD 6.4%, integral vBMD 2.2%) compared to aBMD (FN aBMD 11.4% and TH aBMD 13.3%). After stratifying by age (≤ 59 years, 60-69 years, 70-79 years, and ≥ 80 years), we observed in ≤ 59 years that aBMD was lower in women compared to men, at FN (0.758 [0.114] g/cm2 vs. 0.833 [0.117] g/cm2; p = 1.4 × 10-20) and TH (0.878 [0.117] g/cm2 vs. 0.990 [0.119] g/cm2; p = 4.1 × 10-40). Nevertheless, no statistically significant difference was observed for integral vBMD (331 [58] mg/cm3 in women and 326 [51] mg/cm3 in men; p = 0.19) and trabecular vBMD (190 [41] mg/cm3 in women and 195 [39] mg/cm3 in men; p = 0.20). CONCLUSION: Our results make us think about the importance of taking into account bone size at the time of analyzing the sex-related differences in bone mass.

Modification of bone mineral density, bone geometry and volumetric BMD in young women with obesity.

BACKGROUND: Most obese women with low-trauma fractures present normal areal bone mineral density (aBMD), suggesting that other bone parameters are more determinant for fracture risk in these patients. OBJECTIVES: (i) Determine the effects of obesity in young women on areal bone mineral density (aBMD), bone geometry, strength, and volumetric BMD determined by advanced DXA-based methods; (ii) model the profiles of bone parameters for each population with age; and (iii) determine the factors related to body composition (i.e. lean tissue mass and fat mass) potentially implicated in the "bone adaptation" in the femoral region. SUBJECTS AND METHODS: Two hundred and twenty adolescent and young women from 18 to 35 years old were enrolled in this study: 128 patients with obesity and 92 age-matched (±6 months) normal-weight controls. aBMD was determined with DXA, whereas hip geometry and strength parameters were assessed by hip structural analysis (HSA) and volumetric BMD by 3D-SHAPER® software. RESULTS: Compared with controls, subjects with obesity presented significantly higher aBMD at all bone sites, but the difference was greater at hip compared with lumbar spine or radius. Bone size estimates (i.e. cortical thickness), as well as strength estimates (i.e. cross-sectional area) were higher at all femoral subregions including femoral neck, intertrochanteric region and femoral shaft in young women with obesity. In whole proximal femur and all femoral compartments, vBMD was also higher in subjects with obesity, but the difference between groups was greater for cortical vBMD compared with trabecular vBMD. When hip bone parameters were modelled for each group from individual values, maximal values were reached between 20 and 26 years in both groups but, whatever the age, subjects with obesity presented higher values than controls. In both groups, lean body mass (LBM) was the parameter most positively associated with the greatest number of bone parameters studied. CONCLUSION: Our study confirmed that young women with obesity presented higher aBMD, better hip geometry and greater strength compared with normal-weight controls. Additionally, cortical and trabecular compartments measured by 3D-SHAPER® were favourably and concomitantly modified. However, it remains to be demonstrated whether the evaluation of these new parameters would provide better prediction of fracture risk in this population than aBMD.

Association between osteoporotic femoral neck fractures and DXA-derived 3D measurements at lumbar spine: a case-control study.

A case-control study assessing the association of DXA-derived 3D measurements at lumbar spine with osteoporotic hip fractures was performed. Stronger association was found between transcervical hip fractures and integral (AUC = 0.726), and cortical (AUC = 0.696) measurements at the lumbar spine compared with measurements at the trabecular bone (AUC = 0.617); although femur areal bone mineral density (aBMD) remains the referent measurement for hip fracture risk evaluation (AUC = 0.838). PURPOSE: The aim of the present study was to evaluate the association between DXA-derived 3D measurements at lumbar spine and osteoporotic hip fractures. METHODS: We analyzed a case-control database composed by 61 women with transcervical hip fractures and 61 age-matched women without any type of fracture. DXA scans at lumbar spine were acquired, and areal bone mineral density (aBMD) was measured. Integral, trabecular and cortical volumetric BMD (vBMD), cortical thickness, and cortical surface BMD (sBMD) at different regions of interest were assessed using a DXA-based 3D modeling software. Descriptive statistics, tests of difference, odds ratio (OR), and area under the receiver operating curve (AUC) were used to compare hip fracture and control groups. RESULTS: Integral vBMD, cortical vBMD, cortical sBMD, and cortical thickness were the DXA-derived 3D measurements at lumbar spine that showed the stronger association with transcervical hip fractures, with AUCs in the range of 0.685-0.726, against 0.670 for aBMD. The highest AUC (0.726) and OR (2.610) at the lumbar spine were found for integral vBMD at the posterior vertebral elements. Significantly, lower AUC (0.617) and OR (1.607) were found for trabecular vBMD at the vertebral body. Overall, total femur aBMD remains the DXA-derived measurement showing the highest AUC (0.838) and OR (6.240). CONCLUSION: This study showed the association of DXA-derived measurements at lumbar spine with transcervical hip fractures. A strong association between vBMD at the posterior vertebral elements and transcervical hip fractures was observed, probably because of global deterioration of the cortical bone. Further studies should be carried out to investigate on the relative risk of transcervical fracture in patients with long-term cortical structural deterioration.

DXA-Based 3D Analysis of the Cortical and Trabecular Bone of Hip Fracture Postmenopausal Women: A Case-Control Study.

Methods using statistical shape and appearance models have been proposed to analyze bone mineral density (BMD) in 3D from dual energy X-ray absorptiometry (DXA) scans. This paper presents a retrospective case-control study assessing the association of DXA-derived 3D measurements with osteoporotic hip fracture in postmenopausal women. Patients who experienced a hip fracture between 1 and 6 years from baseline and age-matched controls were included in this study. The 3D-SHAPER software (version 2.7, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from hip DXA scans at baseline. DXA and 3D measurements were compared between groups. Total hip areal BMD of hip fracture group as measured by DXA was 10.7% lower compared to control group. Differences in volumetric BMD (total hip) as measured by 3D-SHAPER were more pronounced in the trabecular compartment (-23.3%) than in the cortex (-8.2%). The area under the receiver operating curve was 0.742 for trabecular volumetric BMD, 0.706 for cortical volumetric BMD, and 0.712 for total hip areal BMD. Differences in the cortex were locally more pronounced at the medial aspect of the shaft, the lateral aspect of the greater trochanter, and the superolateral aspect of the neck. Marked differences in volumetric BMD were observed in the greater trochanter. This case-control study showed the association of DXA-derived 3D measurements with hip fracture. Analysis of large cohorts will be performed in future work to determine if DXA-derived 3D measurements could improve fracture risk prediction in clinical practice.

Analysis of volumetric BMD in people with Down syndrome using DXA-based 3D modeling.

We analyzed volumetric bone mineral density, by 3D analysis, in 76 people with Down syndrome and 76 controls. People with Down syndrome, particularly men, have a lower hip volumetric bone mineral density than the general population. Besides, volumetric bone mineral density declines more rapidly in Down syndrome. INTRODUCTION: People with Down syndrome (DS) have a lower areal bone mineral density (aBMD) estimated by dual-energy X-ray absorptiometry (DXA). However, they have smaller-sized bones, which could influence the measurements. Therefore, our objective was to determine volumetric BMD in these patients. MATERIALS AND METHODS: We included 76 outpatients with DS and 76 control healthy volunteers matched for age and sex distribution. Clinical data were obtained with a standardized interview and physical exam, including age, sex, height, weight, and body mass index (BMI). aBMD was measured by dual-energy X-ray at the femoral neck (FN) and total hip (TH). The 3D-SHAPER® software (version 2.8, Galgo Medical, Barcelona, Spain) was used to derive 3D analysis from participants' hip DXA scans. RESULTS: DS femurs had a similar 3D geometry, compared with the femurs of controls. However, 3D analysis showed that participants with DS had smaller cortical thickness (1.84 mm ± 0.17 vs. 2.02 ± 0.20 mm; p < 0.0001), cortical vBMD (777 ± 49 mg/cm3 vs. 809 ± 43 mg/cm3; p < 0.0001), and cortical sBMD (143 ± 19 mg/cm2 vs. 164 ± 22 mg/cm2; p < 0.0001). After adjustment for age and BMI, all 3D measurements remained lower in DS than in controls. These differences were more marked in men than in women. vBMD decreased with age in controls and DS, but the decline was greater in DS for all 3D parameters. CONCLUSION: People with DS, particularly men, have a lower hip vBMD than the general population. Besides, vBMD declines more rapidly in DS.

Associations of Health-Related Quality of Life, Fear of Falling and Objective Measures of Physical Function with Bone Health in Postmenopausal Women with Low Bone Mass.

Health-related quality of life (HRQoL) and physical function deteriorate with age and may adversely impact bone health in older adults. We determined associations of objective measures of physical function and HRQoL with bone health in postmenopausal women with low areal bone mineral density (aBMD). Fifty postmenopausal women (64.4 7.7 years old, mean standard deviation) with low spine, hip or femoral neck aBMD (T- or Z-score < -1.0) on dual-energy X-ray absorptiometry (DXA) participated. Femoral surface BMD, trabecular, integral and cortical volumetric BMD (vBMD) measurements were obtained using 3D-SHAPER software on DXA. Distal tibial vBMD and microarchitecture were assessed using high-resolution peripheral quantitative computed tomography (HRpQCT). Participants completed self-administered EuroQol-5D (EQ-5D) and modified falls efficacy scale (MFES) questionnaires, and physical function assessments. Stair climb power was positively associated with bone parameters at the hip, femoral neck, and distal tibia (all p < 0.05) in multivariable linear regression. EQ-5D demonstrated no significant associations with bone parameters and MFES was positively associated only with distal tibial cortical vBMD and cortical von Mises stress (both p < 0.05). Objective measures of physical function, particularly muscle power, are more consistently associated with bone parameters compared with self-administered HRQoL questionnaires.

Computational anatomy for multi-organ analysis in medical imaging: A review.

The medical image analysis field has traditionally been focused on the development of organ-, and disease-specific methods. Recently, the interest in the development of more comprehensive computational anatomical models has grown, leading to the creation of multi-organ models. Multi-organ approaches, unlike traditional organ-specific strategies, incorporate inter-organ relations into the model, thus leading to a more accurate representation of the complex human anatomy. Inter-organ relations are not only spatial, but also functional and physiological. Over the years, the strategies proposed to efficiently model multi-organ structures have evolved from the simple global modeling, to more sophisticated approaches such as sequential, hierarchical, or machine learning-based models. In this paper, we present a review of the state of the art on multi-organ analysis and associated computation anatomy methodology. The manuscript follows a methodology-based classification of the different techniques available for the analysis of multi-organs and multi-anatomical structures, from techniques using point distribution models to the most recent deep learning-based approaches. With more than 300 papers included in this review, we reflect on the trends and challenges of the field of computational anatomy, the particularities of each anatomical region, and the potential of multi-organ analysis to increase the impact of medical imaging applications on the future of healthcare.

3D patient-specific finite element models of the proximal femur based on DXA towards the classification of fracture and non-fracture cases.

Osteoporotic bone fractures reduce quality of life and drastically increase mortality. Minimally irradiating imaging techniques such as dual-energy X-ray absorptiometry (DXA) allow assessment of bone loss through the use of bone mineral density (BMD) as descriptor. Yet, the accuracy of fracture risk predictions remains limited. Recently, DXA-based 3D modelling algorithms were proposed to analyse the geometry and BMD spatial distribution of the proximal femur. This study hypothesizes that such approaches can benefit from finite element (FE)-based biomechanical analyses to improve fracture risk prediction. One hundred and eleven subjects were included in this study and stratified in two groups: (a) 62 fracture cases, and (b) 49 non-fracture controls. Side fall was simulated using a static peak load that depended on patient mass and height. Local mechanical fields were calculated based on relationships between tissue stiffness and BMD. The area under the curve (AUC) of the receiver operating characteristic method evaluated the ability of calculated biomechanical descriptors to discriminate fracture and control cases. The results showed that the major principal stress was better discriminator (AUC > 0.80) than the volumetric BMD (AUC ≤ 0.70). High discrimination capacity was achieved when the analysis was performed by bone type, zone of fracture and gender/sex (AUC of 0.91 for women, trabecular bone and trochanter area), and outcomes suggested that the trabecular bone is critical for fracture discrimination. In conclusion, 3D FE models derived from DXA scans might significantly improve the prediction of hip fracture risk; providing a new insight for clinicians to use FE simulations in clinical practice for osteoporosis management.

Cortical and trabecular bone analysis of professional dancers using 3D-DXA: a case-control study.

Given the lack of relevant data, the aim of this study was to examine femur cortical and trabecular bone in female and male professional ballet dancers. 40 professional ballet dancers and 40 sex- and age-matched non-exercising controls volunteered. Femoral bone density was scanned by dual-energy X-ray absorptiometry (DXA) scan. A 3D-DXA software was used to analyse trabecular and cortical bone. Anthropometry, maturation (Tanner staging), menstrual parameters (age at menarche and primary amenorrhea), energy availability and nutritional analysis (3-day record) were also assessed.Compared to non-exercising participants, dancers exhibited significantly higher volumetric density for integral, cortical and trabecular bone, and thicker cortex at the femur. Ballet dancers demonstrated lower body weight compared to controls (p < 0.01). Female dancers had their menarche later than controls, and the prevalence of primary amenorrhea were significantly higher in dancers than controls (p < 0.01). Dancer's energy availability was below the normal range (<30 kcal/kgFFM/day). Despite the presence of certain osteoporosis risk factors such as low energy availability, primary amenorrhoea and lower body weight, professional ballet dancers revealed higher bone density for both cortical and trabecular bone compartments compared to controls.

3D Analysis of Cortical and Trabecular Bone From Hip DXA:Precision and Trend Assessment Interval in PostmenopausalWomen.

The 3D distribution of the cortical and trabecular bone mass is a critical component in determining the resistance of a bone to fracture that is not assessed in standard dual-energy X-ray absorptiometry (DXA) exams. In this work, we assessed in vivo short-term precision of measurements provided by 3D modeling techniques from DXA scans and trend assessment intervals (TAIs) in postmenopausal women. Subjects included to study precision errors were scanned twice, with repositioning for duplicate hip scans, using either a Lunar iDXA scanner (GE Healthcare, Madison, WI) or a Discovery W scanner (Hologic, Inc., Waltham, MA). Postmenopausal women having baseline and 18-mo follow-up visit were scanned using a Lunar iDXA device to assess TAIs. TAIs indicate what time intervals are required to allow accurate assessment of response to treatment or progression of disease. The 3D-SHAPER software (Galgo Medical, Barcelona, Spain) was used to derive 3D measurements from hip DXA scans. Least significant changes were 10.39 and 8.72 mg/cm3 for integral volumetric bone mineral density (BMD), 9.64 and 9.59 mg/cm3 for trabecular volumetric BMD, and 6.25 and 5.99 mg/cm2 for cortical surface BMD, using the Lunar iDXA and Discovery W scanners, respectively. TAIs in postmenopausal women were 2.9 yr (integral volumetric BMD), 2.6 yr (trabecular volumetric BMD), and 3.5 yr (cortical surface BMD), using the Lunar iDXA scanner. As a comparison, TAIs for areal BMD were 2.8 yr at neck and 2.7 yr at total femur. Least significant changes of measurements provided by 3D modeling techniques from DXA were assessed. TAIs in postmenopausal women were similar to those measured for areal BMD measurements. DXA-derived 3D measurements could potentially provide additional indicators to improve patient monitoring in clinical practices.

3-D Subject-Specific Shape and Density Estimation of the Lumbar Spine From a Single Anteroposterior DXA Image Including Assessment of Cortical and Trabecular Bone.

Dual Energy X-ray Absorptiometry (DXA) is the standard exam for osteoporosis diagnosis and fracture risk evaluation at the spine. However, numerous patients with bone fragility are not diagnosed as such. In fact, standard analysis of DXA images does not differentiate between trabecular and cortical bone; neither specifically assess of the bone density in the vertebral body, which is where most of the osteoporotic fractures occur. Quantitative computed tomography (QCT) is an alternative technique that overcomes limitations of DXA-based diagnosis. However, due to the high cost and radiation dose, QCT is not used for osteoporosis management. We propose a method that provides a 3-D subject-specific shape and density estimation of the lumbar spine from a single anteroposterior (AP) DXA image. A 3-D statistical shape and density model is built, using a training set of QCT scans, and registered onto the AP DXA image so that its projection matches it. Cortical and trabecular bone compartments are segmented using a model-based algorithm. Clinical measurements are performed at different bone compartments. Accuracy was evaluated by comparing DXA-derived to QCT-derived 3-D measurements for a validation set of 180 subjects. The shape accuracy was 1.51 mm at the total vertebra and 0.66 mm at the vertebral body. Correlation coefficients between DXA and QCT-derived measurements ranged from 0.81 to 0.97. The method proposed offers an insightful 3-D analysis of the lumbar spine, which could potentially improve osteoporosis and fracture risk assessment in patients who had an AP DXA scan of the lumbar spine without any additional examination.