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.

Prevalence of Sarcopenia and Whole-Body Composition in Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformity and disability, as well as muscle involvement. Sarcopenia is characterized by a progressive age-related loss of muscle mass and strength. AIM: The aim of this study was to evaluate the prevalence of sarcopenia and possible contributing factors associated with sarcopenia in RA patients. PATIENTS AND METHODS: Adult RA patients (n = 105) of both sexes and 100 subjects as control group (CG) matched by age, sex, and body mass index were included in this cross-sectional study. Whole-body composition was measured by dual-energy x-ray absorptiometry. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 as low muscle strength (handgrip) and low muscle mass (appendicular skeletal muscle mass [ASM] index by dual-energy x-ray absorptiometry). The association between sarcopenia and associated factors was evaluated using logistic regression analyses. RESULTS: Significantly lower percentage of lean mass and ASM were found in the whole RA group compared with controls. However, lower lean parameters (total lean mass, percentage of lean mass, and ASM) were observed only in female subjects. The ASM index was significantly lower in female subjects with RA (RA 31.0% vs CG 11.9%) without differences in male subjects. On the other hand, fat mass and most adipose indices were significantly higher in both female and male subjects with RA. Female RA patients had higher prevalence of sarcopenia and sarcopenic obesity. Through univariate logistic regression analysis, the time of corticosteroids use, cumulative corticosteroid dose, previous fragility fractures, total lean mass, and ASM were associated with sarcopenia. CONCLUSIONS: Higher prevalence of sarcopenia and sarcopenic obesity were found in female RA patients. Sarcopenia was found in younger female subjects with RA compared with healthy control subjects. Sarcopenia was associated with previous fragility fractures in female patients with RA.

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.

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.

Structural Parameters of the Proximal Femur by 3-Dimensional Dual-Energy X-ray Absorptiometry Software: Comparison With Quantitative Computed Tomography.

Structural parameters of the proximal femur evaluate the strength of the bone and its susceptibility to fracture. These parameters are computed from dual-energy X-ray absorptiometry (DXA) or from quantitative computed tomography (QCT). The 3-dimensional (3D)-DXA software solution provides 3D models of the proximal femur shape and bone density from anteroposterior DXA scans. In this paper, we present and evaluate a new approach to compute structural parameters using 3D-DXA software. A cohort of 60 study subjects (60.9 ± 14.7 yr) with DXA and QCT examinations was collected. 3D femoral models obtained by QCT and 3D-DXA software were aligned using rigid registration techniques for comparison purposes. Geometric, cross-sectional, and volumetric structural parameters were computed at the narrow neck, intertrochanteric, and lower shaft regions for both QCT and 3D-DXA models. The accuracy of 3D-DXA structural parameters was evaluated in comparison with QCT. Correlation coefficients (r) between geometric parameters computed by QCT and 3D-DXA software were 0.86 for the femoral neck axis length and 0.71 for the femoral neck shaft angle. Correlation coefficients ranged from 0.86 to 0.96 for the cross-sectional parameters and from 0.84 to 0.97 for the volumetric structural parameters. Our study demonstrated that accurate estimates of structural parameters for the femur can be obtained from 3D-DXA models. This provides clinicians with 3D indexes related to the femoral strength from routine anteroposterior DXA scans, which could potentially improve osteoporosis management and fracture prevention.

Relationship between Foetal Growth Restriction and Maternal Nutrition Status Measured by Dual-Energy X-Ray Absorptiometry, Leptin, and Insulin-Like Growth Factor.

AIMS: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. METHODS: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. RESULTS: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. CONCLUSIONS: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.

Effect of Liraglutide in Different Abdominal Fat Layers Measured by Ultrasound: The Importance of Perirenal Fat Reduction.

INTRODUCTION: Ultrasonography (US) in patients with obesity allows us to measure different layers of abdominal fat (superficial subcutaneous, deep subcutaneous, preperitoneal, omental, and perirenal), not assessable by DEXA or CT scan. Omental and perirenal fat depots are considered predictors of metabolic complications. Liraglutide is particularly effective in reducing weight in patients with insulin-resistance, but its direct impact on each abdominal fat layer is unknown. METHODS: We measured, at the L4 level, all 5 abdominal fat depots in 860 patients with obesity (72.8% women, mean age 56.6 ± 1.5 years, BMI 34.4 ± 4.7 kg/m2, body fat 47 ± 2%, abdominal circumference 105.8 ± 3 cm), before and after 6 months of liraglutide treatment. Laboratory tests for glucose, insulin, and lipid profile were routinely done. T-student was used to compare intraindividual differences. RESULTS: Weight loss was 7.5 ± 2.8 kg (7.96% from baseline), with no differences by sex/age/BMI. Greater loss was observed in patients with higher dosages and NAFLD. All US-measured fat layers showed a significant reduction (p < 0.05) at 6th months. Preperitoneal fat showed a -26 ± 5.5% reduction and 46% of the patients went below metabolic syndrome (MS) risk cut-off values. Omental fat was reduced by -17.8 ± 5% (67% of the patients below MS risk) and perirenal fat by -22.4 ± 4.4% (56% of the patients below MS). Both omental and perirenal fat reduction correlated with total and LDL cholesterol. Higher perirenal fat reduction (-28%) was seen among patients with obesity and hypertension. Perirenal fat also correlated with blood pressure reduction. CONCLUSION: Liraglutide induces greater fat loss in the layers involved with MS. However, the maximal reduction is seen at perirenal fat, which has been recently related with hypertension and could play an important role in modulating kidney's expansion and intraglomerular pressure. US is a reproducible clinical tool to assess pathologic fat depots in patients living with obesity.

Dapagliflozin added to metformin reduces perirenal fat layer in type 2 diabetic patients with obesity.

Sodium-glucose co-transporters type 2 inhibitors (SLGT2i) are highly effective in controlling type 2 diabetes, but reported beneficial cardiovascular effects suggest broader actions on insulin resistance. Weight loss may be initially explained by glycosuria-induced net caloric output and secondary volumetric reduction, but its maintenance could be due to loss of visceral fat mass. Structured ultrasound (US) imaging of abdominal adipose tissue ("eco-obesity") is a recently described methodology used to measure 5 consecutive layers of abdominal fat, not assessable by DEXA or CT scan: superficial subcutaneous (SS), deep subcutaneous (DS), preperitoneal (PP), omental (Om) and right perirenal (RK). PP, Om and RK are predictors of metabolic syndrome (MS) with defined cut-off points. To assess the effect of SLGT2i on every fat depot we enrolled 29 patients with type 2 Diabetes (HbA1c 6.5-9%) and Obesity (IMC > 30 kg/m2) in an open-label, randomized, phase IV trial (EudraCT: 2019-000979-16): the Omendapa trial. Diabetes was diagnosed < 12 months before randomization and all patients were treatment naïve. 14 patients were treated with metformin alone (cohort A) and 15 were treated with metformin + dapaglifozin (cohort B). Anthropometric measures and laboratory tests for glucose, lipid profile, insulin, HOMA, leptin, ultrasensitive-CRP and microalbuminuria (MAL) were done at baseline, 3rd and 6th months. At 6th month, weight loss was -5.5 ± 5.2 kg (5.7% from initial weight) in cohort A and -8.4 ± 4.4 kg (8.6%) in cohort B. Abdominal circumference showed a -2.7 ± 3.1 cm and -5.4 ± 2.5 cm reduction, respectively (p = 0.011). Both Metformin alone (-19.4 ± 20.1 mm; -21.7%) or combined with Dapaglifozin (-20.5 ± 19.4 mm; -21.8%) induced significant Om fat reduction. 13.3% of cohort A patients and 21.4% of cohort's B reached Om thickness below the cut-off for MS criteria. RK fat loss was significantly greater in cohort B group compared to cohort A, at both kidneys. Only in the Met + Dapa group, we observed correlations between Om fat with leptin/CRP/MAL and RK fat with HOMA-IR. US is a useful clinical tool to assess ectopic fat depots. Both Metformin and Dapaglifozin induce fat loss in layers involved with MS but combined treatment is particularly effective in perirenal fat layer reduction. Perirenal fat should be considered as a potential target for cardiovascular dapaglifozin beneficial effects.

Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome.

OBJECTIVE: We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months. METHODS: 50 males aged 50-65 years with TDS (Aging Males Symptoms Scale [AMS] > 26 and calculated free testosterone [cFT] 250 pmol/l) were administered 50 mg testosterone gel daily for one year. During the second year, patients received 1000 mg of testosterone undecanoate every 2-3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry. RESULTS: There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p < 0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months. CONCLUSIONS: Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.

Validation of the FRAX predictive model for major osteoporotic fracture in a historical cohort of Spanish women.

FRAX is a fracture risk assessment tool to estimate the 10-yr probability of a major osteoporotic fracture or a hip fracture. The aim of the study was to assess the predictive ability of FRAX for major osteoporotic fracture in a cohort of Spanish women. The study was based on a retrospective cohort of women aged 40-90 yr. Patients were followed from their first bone densitometry to the first major osteoporotic fracture event (forearm, proximal humerus, clinical spine, or hip fracture) or for 10 yr whichever comes first. A total of 1231 women were included. Bone mineral density data and self-reported data on risk factors for fracture were obtained. The predictive ability of FRAX was assessed by analyzing calibration and discrimination, with the calculation of observed-to-expected (O/E) fracture ratios and the receiver operating characteristic (ROC) curve, respectively. A total of 222 women (18.1%) reported at least 1 fracture after the first assessment. The incidence of fracture was 14 (95% confidence interval [CI]: 10-17), 19 (95% CI: 15-23), 28 (95% CI: 21-36), and 67 (95% CI: 8-125) cases per 1000 woman-years in women aged <55, 55-64, 65-74, and ≥75 yr, respectively. The O/E ratio was 3.9 (95% CI: 3.4-4.5; p<0.0001). The area under the ROC curve was 61% (95% CI: 57-65%). FRAX underestimated the risk of major osteoporotic fracture in this cohort of Spanish women, particularly in those with a low risk of fracture according to the clinical factors used in the FRAX tool. Our findings highlight the need for validation studies of FRAX in Spain.

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.

The search for a new marker of renal function in older patients with chronic kidney disease stages 3-4: usefulness of cystatin C-based equations.

BACKGROUND/AIM: Cystatin C (Cys C) is an endogenous marker of glomerular filtration rate (GFR) unaffected by body composition. The aim of the present study was to assess the utility of Cys C-based GFR prediction equations (Hoek, Larsson and Stevens) and creatinine (modification of diet in renal disease-isotope dilution mass spectrometry--MDRD-IDMS, and Cockcroft-Gault--CG) compared with 51Cr-EDTA. METHODS: This study was carried out in 40 Caucasian older patients with advanced age (> or = 60) and chronic kidney disease stages 3-4. To assess the utility of prediction equations in relation to body composition, we measured lean mass (LM) with densitometry (DXA). Pearson's, Bland-Altman and Lin's coefficient (Rc) were used to study accuracy and precision. RESULTS: 51Cr-EDTA was 36.9 +/- 9.2 ml/min/1.73 m2 (22-60). Cys C levels were 2.2 +/- 0.8 mg/l (r = 0.085; p = 0.662 LM) and creatinine 2.8 +/- 1.1 mg/dl (r = 0.427; p = 0.021 LM). The most accurate equations were the Hoek, Larsson and Stevens formulae, with a bias of -0.2 (Rc 0.48), -2.9 (Rc 0.44) and 2.6 ml/min/1.73 m2 (Rc 0.58). The biases obtained with MDRD-IDMS and CG were -14.6 (Rc 0.35) and -12.5 (Rc 0.40). All correlations among biases obtained with creatinine-based formulae and LM were negative and statistically significant (p < 0.05). CONCLUSIONS: The results show superiority of Cys C-based GFR formulae over the MDRD-IDMS and CG equations. This significant underestimation obtained with conventional prediction equations was directly related to the influence of LM.

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.

3D-DXA: Assessing the Femoral Shape, the Trabecular Macrostructure and the Cortex in 3D from DXA images.

The 3D distribution of the cortical and trabecular bone mass in the proximal femur is a critical component in determining fracture resistance that is not taken into account in clinical routine Dual-energy X-ray Absorptiometry (DXA) examination. In this paper, a statistical shape and appearance model together with a 3D-2D registration approach are used to model the femoral shape and bone density distribution in 3D from an anteroposterior DXA projection. A model-based algorithm is subsequently used to segment the cortex and build a 3D map of the cortical thickness and density. Measurements characterising the geometry and density distribution were computed for various regions of interest in both cortical and trabecular compartments. Models and measurements provided by the "3D-DXA" software algorithm were evaluated using a database of 157 study subjects, by comparing 3D-DXA analyses (using DXA scanners from three manufacturers) with measurements performed by Quantitative Computed Tomography (QCT). The mean point-to-surface distance between 3D-DXA and QCT femoral shapes was 0.93 mm. The mean absolute error between cortical thickness and density estimates measured by 3D-DXA and QCT was 0.33 mm and 72 mg/cm3. Correlation coefficients (R) between the 3D-DXA and QCT measurements were 0.86, 0.93, and 0.95 for the volumetric bone mineral density at the trabecular, cortical, and integral compartments respectively, and 0.91 for the mean cortical thickness. 3D-DXA provides a detailed analysis of the proximal femur, including a separate assessment of the cortical layer and trabecular macrostructure, which could potentially improve osteoporosis management while maintaining DXA as the standard routine modality.

Interrelationship between bone turnover markers and dietary calcium intake in pregnant women: a longitudinal study.

This longitudinal study evaluated bone turnover and the interrelationship between changes in bone biomarkers and habitual dietary calcium intake during pregnancy in a group of women ranging widely with regard to dietary calcium intake. Thirty-nine healthy pregnant and 30 nonpregnant women were studied. Calcium, phosphorus, 1alpha,25-dihydroxyvitamin D (1,25diHOD), bone alkaline phosphatase (bALP), carboxyterminal propeptides of type I procollagen (PICP) and carboxyterminal telopeptides of type I collagen (betaCTX and ICTP) were measured in serum and calcium, and creatinine and aminoterminal telopeptide (NTX) were determined in urine. Serum calcium and phosphorus did not change but the urinary Ca/Creat ratio and 1,25diHOD increased throughout pregnancy (P < 0.001 and P < 0.0001, respectively). Serum b-ALP and PICP increased during the last two trimesters (P < 0.0001 and P < 0.001, respectively). All studied bone resorption markers increased compared to nonpregnant values throughout pregnancy. The highest increment was observed in the third trimester. The level of significance decreased as follows: betaCTX > NTX >ICTP. Serum 1,25 diHOD versus calcium intake showed a positive and significant correlation (r = 0.51, P < 0.02). A negative correlation between the absolute change in betaCTX, NTX, and b-ALP between the third and second trimester and calcium intake at the end of pregnancy was observed in pregnant women who did not cover adequately calcium intake requirements (r = -0.47, P < 0.03; r = -0.41, P < 0.05; and r = -0.43, P < 0.05, respectively). These results suggest that skeletal response to pregnancy may not be entirely independent of maternal calcium intake, especially in women with usually low calcium intake. In summary, not only hormonal changes in calcium metabolism that occur during pregnancy but also other considerations, such as low dietary calcium intake, may lead to an increment in the biological activity of the skeleton. Additional studies must be conducted to confirm our findings and to gain a better understanding of skeletal response to a low calcium intake during pregnancy.

Is ultrasound of bone relevant for corticosteroid-treated patients? A comparative study with bone densitometry measured by DEXA.

Corticosteroid treatment diminishes bone mass and alters bone quality. The objective was to evaluate bone in corticosteroid-treated patients and controls and in fractured and non-fractured patients treated with corticosteroids using both X-ray densitometry (DEXA) and ultrasound. We evaluated 34 women aged 58 +/- 14 years (X +/- SD), who had been on long-term low dose prednisone therapy for at least 6 months, and who had never received specific treatment for osteoporosis. Bone mineral density of total skeleton (TS), lumbar spine (LS), femoral neck (FN), and vertebral morphometry (MXA) were measured by DEXA. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured using an Achilles Plus system. Forty-two healthy women served as controls. Both densitometric and ultrasound parameters in the patients were significantly diminished compared with controls: TS: P < 0.002, LS: P < 0.025, FS: P < 0.005, Stiffness: P < 0.001, BUA: P < 0.002 and SOS: P < 0.002. The percentage of patients with a Z score below -2 was higher in Stiffness and BUA: 38% and 47%, respectively, compared with a range of 16-24% in the other parameters (P < 0.05 BUA vs. DEXA measurements). Eleven patients with previous bone fracture had values lower than the non-fractured patients, both according to DEXA and ultrasound measurements, but the difference was only significant for BUA (P < 0.02). BUA of the calcaneus was more effective in detecting the specific skeletal alterations and fracture risk of the group of patients receiving chronic corticosteroid treatment.

Genetic analysis of high bone mass cases from the BARCOS cohort of Spanish postmenopausal women.

The aims of the study were to establish the prevalence of high bone mass (HBM) in a cohort of Spanish postmenopausal women (BARCOS) and to assess the contribution of LRP5 and DKK1 mutations and of common bone mineral density (BMD) variants to a HBM phenotype. Furthermore, we describe the expression of several osteoblast-specific and Wnt-pathway genes in primary osteoblasts from two HBM cases. A 0.6% of individuals (10/1600) displayed Z-scores in the HBM range (sum Z-score >4). While no mutation in the relevant exons of LRP5 was detected, a rare missense change in DKK1 was found (p.Y74F), which cosegregated with the phenotype in a small pedigree. Fifty-five BMD SNPs from Estrada et al. [NatGenet 44:491-501,2012] were genotyped in the HBM cases to obtain risk scores for each individual. In this small group of samples, Z-scores were found inversely related to risk scores, suggestive of a polygenic etiology. There was a single exception, which may be explained by a rare penetrant genetic variant, counterbalancing the additive effect of the risk alleles. The expression analysis in primary osteoblasts from two HBM cases and five controls suggested that IL6R, DLX3, TWIST1 and PPARG are negatively related to Z-score. One HBM case presented with high levels of RUNX2, while the other displayed very low SOX6. In conclusion, we provide evidence of lack of LRP5 mutations and of a putative HBM-causing mutation in DKK1. Additionally, we present SNP genotyping and expression results that suggest additive effects of several genes for HBM.

3D reconstruction of the lumbar vertebrae from anteroposterior and lateral dual-energy X-ray absorptiometry.

Current vertebral fracture prevention measures use Dual-energy X-ray Absorptiometry (DXA) to quantify the density of the vertebrae and subsequently determine the risk of fracture. This modality however only provides information about the projected Bone Mineral Density (BMD) while the shape and spatial distribution of the bone determines the strength of the vertebrae. Quantitative Computed Tomography (QCT) allows for the measurement of the vertebral dimensions and volumetric densities, which have been shown to be able to determine the fracture risk more reliably than DXA. However, for the high cost and high radiation dose, QCT is not used in clinical routine for fracture risk assessment. In this work, we therefore propose a method to reconstruct the 3D shape and density volume of lumbar vertebrae from an anteroposterior (AP) and lateral DXA image used in clinical routine. The method is evaluated for the L2, L3 and L4 vertebra. Of these vertebrae a statistical model of the vertebral shape and density distribution is first constructed from a large dataset of QCT scans. All three models are then simultaneously registered onto both AP and lateral DXA image. The shape and volumetric BMD at several regions of the reconstructed vertebrae is then evaluated with respect to the ground truth QCT volumes. For the L2, L3 and L4 vertebrae respectively the shape was reconstructed with a mean (2RMS) point-to-surface distance of 1.00 (2.64) mm, 0.93(2.52) mm and 1.34(3.72) mm and a strong correlation (r > 0.82) was found between the trabecular volumetric BMD extracted from the reconstructions and from the same subject QCT scans. These results indicate that the proposed method is able to accurately reconstruct the 3D shape and density volume of the lumbar vertebrae from AP and lateral DXA, which can potentially improve the fracture risk estimation accuracy with respect to the currently used DXA derived areal BMD measurements.

Time of progression to osteopenia/osteoporosis in chronically HIV-infected patients: screening DXA scan.

BACKGROUND: Algorithms for bone mineral density (BMD) management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA) scan should be performed by assessing time of progression to osteopenia/osteoporosis. METHODS: All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis) was assessed using the Kaplan-Meier method. Strata (tertiles) were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. RESULTS: Of 391 patients (1,639 DXAs), 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6%) with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: "low-risk" (baseline minimum T score >-0.2 SD), "middle-risk" (between -0.2 and -0.6 SD), and "high-risk" (from -0.6 to -1 SD); median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p<0.0001). Of patients with osteopenia, 23.7% progressed to osteoporosis; median progression time was >8.5 years. Progression time was >8.2 years in "low-risk" tertile (T score between -1.1 and -1.6 SD), >8.5 years in "middle-risk" (between -1.6 and -2), and 3.2 years in "high-risk" (from -2 to -2.4) (p<0.0001). CONCLUSIONS: Our results may help to define the BMD testing interval. The lowest T score tertiles would suggest recommending a subsequent DXA in 1-2 years; in the highest tertiles, ≥6 years. Early intervention in patients with bone demineralization could reduce fracture-related morbidity/mortality.

[Risk factors for fragility fractures in a cohort of Spanish women]. / Factores de riesgo de fracturas por fragilidad en una cohorte de mujeres españolas.

INTRODUCTION: Fragility fractures are an important public health issue. The aim of this study was to analyze the association of the main osteoporotic risk factors related to fragility fracture in a cohort of women with an indication of bone densitometry (BD). METHODS: A retrospective cohort was followed-up until a fragile fracture occurred, in a population of women aged 40 to 90 years with a first visit for BD between January 1992 and February 2008. We calculated the incidence rate of fracture per 1000 women-years of follow-up, and the hazard ratio (HR) of fragile fracture using a Cox regression model. RESULTS: A total of 49,735 women were studied. The average age of participants was 57.8 years (SD: 8.5). Of these, 3631 women (7.1%) reported a new fragility fracture in post-baseline visits. Risk factors with higher adjusted HR were age ≥ 75 years compared with age < 55 years (HR: 3.8; 95% CI: 3.3-4.4) and having a BC result evaluated as osteoporosis compared to normal (HR: 2.0; 95% CI: 1.8-2.2). A personal history of humerus, hip or vertebral fractures had an adjusted HR of 1.2 (95% CI: 1.1-1.3). CONCLUSIONS: The main risk factors for fragility fracture were advanced age, BD result and a personal history of fracture, although 74% of fractures were detected with a bone mineral density classified as normal or osteopenia. Other relevant factors were rheumatoid arthritis or having received prolonged corticosteroid therapy.