Multi-site phantomless bone mineral density from clinical quantitative computed tomography in males.

Volumetric bone mineral density (vBMD) is commonly assessed using QCT. Although standard vBMD calculation methods require phantom rods that may not be available, internal-reference phantomless (IPL) and direct measurements of Hounsfield units (HU) can be used to calculate vBMD in their absence. Yet, neither approach has been systemically assessed across skeletal sites, and HU need further validation as a vBMD proxy. This study evaluated the accuracy of phantomless methods, including IPL and regression-based phantomless (RPL) calibration using HU to calculate vBMD, compared to phantom-based (PB) methods. vBMD from QCT scans of 100 male post-mortem human subjects (PMHS) was calculated using site-specific PB calibration at multiple skeletal sites throughout the body. A development sample of 50/100 PMHS was used to determine site-specific reference material density for IPL calibration and RPL equations. Reference densities and equations from the development sample were used to calculate IPL and RPL vBMD on the remaining 50/100 PMHS for method validation. PB and IPL/RPL vBMD were not significantly different (p > .05). Univariate regressions between PB and IPL/RPL vBMD were universally significant (p < 0.05), except for IPL Rad-30 (p = 0.078), with a percent difference across all sites of 6.97% ± 5.95% and 5.22% ± 4.59% between PB and IPL/RPL vBMD, respectively. As vBMD increased, there were weaker relationships and larger differences between PB vBMD and IPL/RPL vBMD. IPL and RPL vBMD had strong relationships with PB vBMD across sites (R2 = 97.99, R2 = 99.17%, respectively), but larger residual differences were found for IPL vBMD. As the accuracy of IPL/RPL vBMD varied between sites, phantomless methods should be site-specific to provide values more comparable to PB vBMD. Overall, this study suggests that RPL calibration may better represent PB vBMD compared to IPL calibration, increases the utility of opportunistic QCT, and provides insight into bone quality and fracture risk.

Male-female spatio-temporal differences of age-related bone changes show faster bone deterioration in older women at femoral regions associated with incident hip fracture.

A better understanding of how age-related bone loss affects the fracture-prone regions of the proximal femur could lead to more informed fracture-prevention strategies. Therefore, the aim of this work was to assess the spatio-temporal distribution of bone deterioration in older men and women with aging. A subset of 305 men (74.87 ± 4.76 years; mean ± SD) and 371 age-matched women (74.84 ± 4.71 years) with no history of fracture was randomly selected from the Age, Gene/Environment Susceptibility-Reykjavik study. Quantitative computed tomography (QCT) scans of the left proximal femur obtained at baseline and at 5.2 ± 0.4 years follow-up were processed to assess local changes in volumetric bone mineral density (vBMD), cortical bone thickness (Ct.Th), and internal bone structure using voxel-based morphometry (VBM), surface-based statistical parametric mapping (surf-SPM), and tensor-based morphometry (TBM). Local parametric changes within each sex and sex differences in these changes were statistically assessed using linear mixed effects models allowing for baseline and time-varying covariates, yielding Student's t-test and p-value statistical maps of the proximal femur. The statistical maps indicated regions with significant parametric changes in each sex and with significant different parametric changes between older men and older women with aging. Older women manifested significantly larger losses in vBMD, (Ct.Th), and structure than older men, and they did so in regions where deficiency in these parameters has been associated with incident hip fracture. Using longitudinal QCT scans of the proximal femur and Computational Anatomy, we provided new insights into the higher fracture rates of the proximal femur in older women compared with men of similar age providing new information on the pathophysiology of osteoporosis.

Correlation analysis of positron emission tomography/computed tomography-magnetic resonance imaging of cannabinoid type 1 receptor in the lumbar spine and brain of aged osteoporosis female cynomolgus monkeys.

Background: Although cannabinoid receptor 1 (CB1R) antagonists can inhibit bone loss in osteoporosis mouse models, different strains of mice show different bone mass phenotypes after knock out the CB1R gene. The relationship between CB1R and bone metabolism is complex, and its regulatory role in bone metabolism and as a therapeutic target for osteoporosis requires further investigation. Methods: Based on lumbar spine volumetric bone mineral density (vBMD) data of healthy female cynomolgus monkeys aged 1-25 years, naturally aged postmenopausal female osteoporotic monkeys and normal young monkeys were screened by detecting lumbar vertebrae vBMD and estradiol levels in this study. Positron emission tomography-computed tomography (PET/CT) and magnetic resonance imaging (MRI) scans were performed on the lumbar spine and brain of the two groups of monkeys using the probe [11C]OMAR, which specifically targets CB1R, and the difference in the CB1R expression of osteoporotic monkeys was evaluated. Results: The vBMD values of two standard deviations (SDs) below the peak bone value (428.1±53.8 g/cm3) were set as the reference standard for osteoporosis vBMD. Of the 49 healthy female cynomolgus monkeys, 4 postmenopausal older osteoporotic monkeys (18-26 years) and 5 young control monkeys (6-7 years) were selected, and the mean vBMD of the lumbar spine of the two groups was 295.07±19.11 and 419.72±16.14 g/cm3, respectively (P<0.0001). Radioactive uptake in the lumbar spine was linearly and negatively correlated with vBMD (r=-0.7977; P=0.01). Dynamic PET/MR imaging of the brains showed that CB1R was upregulated in the osteoporosis group, and there was a negative linear correlation between the vBMD and area under the time-radioactivity curve (AUC) of the thalamus (r=-0.8506; P=0.0153) and prefrontal cortex (r=-0.8306; P=0.0207). Conclusions: In this study, PET/CT-MRI molecular imaging technology revealed that CB1R was upregulated in the lumbar spine and brain of the osteoporosis monkeys and that CB1R may be regulated by the brain-bone axis. CB1R antagonist may be a potential drug for the treatment of osteoporosis.

Age-related changes in lumbar bone mineral density measured using quantitative computed tomography in healthy female cynomolgus monkeys.

Background: Cynomolgus monkeys are widely used in studies related to osteoporosis, and there is no evidence of age-related changes in volumetric bone mineral density (vBMD) measured using quantitative computed tomography (QCT) in nonhuman primates. This study aimed to describe changes in the characteristics of lumbar vBMD with age, to analyze the relationship between lumbar vBMD and body composition, and to investigate the precision of QCT measurements in healthy female cynomolgus monkeys. Methods: Age-related changes in lumbar vBMD were described using cubic regression models, and the accumulated bone loss rates (ABLR) of the lumbar spine were calculated. Spearman rank correlation and ridge regression analysis were used to investigate the relationship of the average lumbar vBMD and body components. Thirty animals were selected to analyze the short-term in vivo precision of the QCT measurements. The precision was expressed as the root-mean-square coefficient of variation (RMS-CV%) or root-mean-square standard deviation (RMS-SD). Results: A total of 72 healthy female cynomolgus monkeys, aged 1-25 years, were included in this study. The average lumbar vBMD of female cynomolgus monkeys increased with age until the age of 10 years, around which it reached peak bone mass, with a relatively marked decline after the age of 13 years. The ABLRs of female cynomolgus monkeys in the premenopausal (13-19 years) and postmenopausal age groups (20-25 years) were -4.9% and -21.2%, respectively. Ridge regression analysis showed that age and subcutaneous adipose tissue (SAT) contributed positively to the average lumbar vBMD in animals aged ≤10 years, whereas in animals aged >10 years, age contributed negatively to lumbar vBMD. The RMS-CV% (RMS-SD) of the lumbar vBMD measured using QCT ranged from 0.47% to 1.60% (1.91-6.31 mg/cm3). Conclusions: Age-related changes in lumbar vBMD measured using QCT in healthy female monkeys showed similar trends to those in humans. Age and SAT may affect the lumbar vBMD in female cynomolgus monkeys. QCT revealed good precision in measuring the lumbar vBMD in female cynomolgus monkeys.

Quantitative assessment of zonal trabecular volumetric bone mineral density in middle-aged and elderly women using quantitative computed tomography.

Background: To explore the feasibility of the 9 zonal trabecular volumetric bone mineral density (trabecular vBMD) method in the first lumbar vertebral body (L1) and to assess the zonal trabecular vBMD distribution of L1 in women aged 50-80 years. Methods: A total of 578 women patients underwent a quantitative computed tomography (CT) scan of the L1 vertebra, and these patients were categorized into 3 age subgroups with 10-year intervals. L1 was segmented into 9 zones, based on which, L1 was then divided into 6 regions [i.e., vBMD-anterior (vBMD-A), vBMD-medial (vBMD-M), and vBMD-posterior (vBMD-P) from the ventral to the dorsal side, vBMD-upper (vBMD-U), vBMD-medial (vBMD-M'), and vBMD-lower (vBMD-L) from the head to the foot]. Independent samples t-test, intraclass correlation coefficient (ICC), and one-way analysis of variance (ANOVA) were used for statistical analyses. Results: There were no significant differences of the 9 zonal vBMDs measured by the 2 analysts (P≥0.638), and ICCs were all greater than or equal to 0.990. There was significant difference of global vBMD among the 3 age groups (P<0.001), and so as to the 9 zonal vBMDs among the 3 age groups (P<0.001). Age was negatively correlated with global vBMD and the 9 zonal vBMDs (P<0.001). There were significant differences among vBMD-A, vBMD-M, and vBMD-P (P<0.001), and vBMD-A and vBMD-M were both lower than vBMD-P. There were significant differences among vBMD-U, vBMD-M', and vBMD-L (P<0.001), and vBMD-U and vBMD-L were both lower than vBMD-M'. Conclusions: The 9 zonal trabecular vBMD method of L1 is stable and feasible, and the 9 zonal trabecular vBMD method may quantitatively explain osteoporotic vertebral deformity from the perspective of vBMD in middle-aged and elderly women.

Addressing gaps in osteoporosis screening in kuwait using opportunistic quantitative computer tomography (QCT): a retrospective study.

Osteoporosis is a common skeletal disorder which is underdiagnosed and undertreated. Consequent fragility fractures are associated with high morbidity and mortality. Prevention of these fractures is possible by timely osteoporosis screening followed by timely therapeutic interventions when needed. Utilizing all available modalities such as bone density measurements on preexisting CT scans could help narrow the diagnostic gap. PURPOSE: To demonstrate the feasibility and clinical utility of opportunistic osteoporosis screening in Kuwait using QCT, aiming to increase screening rates in a country with a relatively high prevalence of osteoporosis and an alarming trend of increasing incidence of fractures. METHODS: At a tertiary referral center, all abdominal CT scans performed on females ≥60 years old between 12/2020 and 12/2021 were retrospectively utilized for asynchronous QCT acquisition. The average volumetric bone mineral density (vBMD) was calculated, and rates of osteoporosis (vBMD < 80 mg/cm3 calcium hydroxyapatite) and osteopenia (80-120 mg/cm3) were determined. CT images were reviewed to assess for the presence of vertebral fractures. For each patient, the electronic health record was reviewed for any previous DXA scans. RESULTS: vBMD was calculated in 305 females ≥60 years old (mean [SD] 71 [8.7], range 60-93). Low bone mass was detected in 258 patients (84.6%); 148 (48.5%) met criteria for osteopenia and 110 (36.1%) for osteoporosis. Osteoporotic vertebral fractures were observed in 64 (21.0%) study participants. Only 73 patients (23.9% of total) had a previous DXA documented in the reviewed health records. For 231 patients who were ≥65 years old, who would routinely qualify for a screening DXA, only 63 (27.3%) had a documented DXA available. CONCLUSION: vBMD measurements obtained by opportunistic QCT had comparable rates of osteopenia and osteoporosis detection to those previously reported using DXA in a similar population in Kuwait. These findings suggest that opportunistic QCT on preexisting CT scans can be effectively utilized to narrow gaps in osteoporosis screening.

A Chinese case of CHST3-related skeletal dysplasia and a systematic review.

PURPOSE: We reported a case with carbohydrate sulfotransferase 3 (CHST3) spondyloepiphyseal dysplasia and made a systematic review of all previously reported cases. METHODS: A 14.8-year-old boy underwent clinical, radiological, and genetic evaluations. The patients and five age-matched healthy boys accepted high-resolution peripheral quantitative computed tomography evaluation. All CHST3-related skeletal dysplasia cases from PubMed and Embase were collected and summarized. The genotype-phenotype correlation was analyzed. RESULTS: The proband complained of aggravated joint pain and had a compression fracture of L2 during his second decade. Physical examination showed a height Z score of -4.94, short limbs, and restricted movement of the elbows and knees. X-rays showed carpal epiphyseal dysplasia, enlargement of elbow and knee joints, and subluxation of the left hip. Echocardiography showed abnormal cardiac valves. Compared with the norm, his total and trabecular volumetric bone mineral density (BMD), and the microarchitecture of the trabecular bone had trends to be worse at the distal radius and tibia. Two novel missense variants of c.1343T>G and c.761C>G in CHST3 were inherited from his father and mother, respectively. In the systematic review, short stature, limited joint extension, joint pain, and joint dislocation were the most common characteristics of this disorder. Height Z score and the proportion of hearing impairment had no significant differences between the missense and nonmissense mutations groups. CONCLUSION: Progressive joint pain and movement restriction are the main characteristics of CHST3-related skeletal dysplasia. BMD and bone microarchitecture of this disorder needs further exploration. There is no apparent genotype-phenotype correlation in this disorder.

Reduced Volumetric Bone Mineral Density of the Spine in Adolescent Rett Girls with Scoliosis.

In advanced Rett syndrome (RTT), limited or complete loss of ambulation, nutritional problems and scoliosis are unfavorable factors for bone mineral density (BMD). Still, there are few data available in this research area. Spinal quantitative computed tomography (QCT) allows an exact measurement of the volumetric BMD (vBMD) in this patient group. Two examiners measured vBMD of thoracic and lumbar vertebrae on asynchronous calibrated CTs that were acquired prior to surgical scoliosis correction (n = 21, age 13.6 ± 2.5 years). The values were compared to age- and sex-matched healthy controls to additionally derive Z-scores (n = 22, age 13.8 ± 2.0 years). The results showed the most significant reduction of vBMD values in non-ambulatory RTT patients, with p < 0.001 and average BMD-Z-score −1.5 ± 0.2. In the subgroup comparison, non-ambulatory patients with valproate treatment had significant lower values (p < 0.001) than ambulatory patients without valproate therapy, with an average BMD-Z-score of −2.3 ± 0.2. Comparison of the Z-scores to critical BMD thresholds of 120 and 80 mg/cm3 showed normal Z-scores in case of the ambulatory RTT subgroup, as opposed to BMD-Z-scores of the non-ambulatory RTT subgroups, which were partially below osteopenia-equivalent values. Furthermore, valproate treatment seems to have a direct effect on vBMD in RTT patients and when combined with loss of ambulation, BMD-Z-scores are reduced to osteoporosis-equivalent levels or even further.

Tibial Bone Geometry Is Associated With Bone Stress Injury During Military Training in Men and Women.

Bone stress injuries (BSI) are a common musculoskeletal condition among exercising and military populations and present a major burden to military readiness. The purpose of this investigation was to determine whether baseline measures of bone density, geometry, and strength, as assessed via peripheral quantitative computed tomography (pQCT), are predictive of tibial BSI during Marine Officer Candidates School training. Tibial pQCT scans were conducted prior to the start of physical training (n = 504; Male n = 382; Female n = 122) to measure volumetric bone mineral density (vBMD), geometry, robustness, and estimates of bone strength. Bone parameters were assessed at three tibial sites including the distal metaphysis (4% of tibial length measured from the distal endplate), mid-diaphysis (38% of tibial length measured from the distal endplate), and proximal diaphysis (66% of tibial length measured from the distal endplate). Injury surveillance data was collected throughout training. Four percent (n = 21) of the sample were diagnosed with a BSI at any anatomical site during training, 10 injuries were of the tibia. Baseline bone parameters were then tested for associations with the development of a tibial BSI during training and it was determined that cortical bone measures at diaphyseal (38 and 66%) sites were significant predictors of a prospective tibial BSI. At the mid-diaphysis (38% site), in a simple model and after adjusting for sex, age, and body size, total area [Odds Ratio (OR): 0.987, 0.983], endosteal circumference (OR: 0.853, 0.857), periosteal circumference (OR: 0.863, 0.824), and estimated bending strength (SSI; OR: 0.998, 0.997) were significant predictors of a BSI during training, respectively, such that lower values were associated with an increased likelihood of injury. Similarly, at the proximal diaphysis (66% site), total area (OR: 0.989, 0.985), endosteal circumference (OR: 0.855, 0.854), periosteal circumference (OR: 0.867, 0.823), robustness (OR: 0.007, 0.003), and SSI (OR: 0.998, 0.998) were also significant predictors of BSI in the simple and adjusted models, respectively, such that lower values were associated with an increased likelihood of injury. Results from this investigation support that narrower bones, with reduced circumference, lower total area, and lower estimated strength are associated with increased risk for tibial BSI during military training.

Relationship of abdominal aortic calcification with lumbar vertebral volumetric bone mineral density assessed by quantitative computed tomography in maintenance hemodialysis patients.

INTRODUCTION: This cross-sectional study aimed to investigate the relationship between abdominal aortic calcification (AAC), which is a marker of vascular calcification, and volumetric bone mineral density (vBMD) by quantitative computed tomography (QCT) in maintenance hemodialysis (MHD) patients. METHODS: All participants underwent lumbar vertebral vBMD measurement by QCT. Eight cross-sections were extracted sequentially and analyzed by ImageJ software to obtain the ratio of the calcified area to the abdominal aortic area (the calcification ratio). The AAC score was determined by the sum of the calcification ratios. The relationship between AAC and vBMD was analyzed using multivariate logistic regression. RESULTS: Ninety MHD patients (58.89% male) with a mean age of 63.43 (standard deviation [SD] = 13.20) years were included in the study. AAC was present (AAC score > 0) in 93.33% of the patients. The 75th percentile of the AAC score corresponding to 119 was used as the cutoff point between the mild and severe groups. After full adjustment in the logistic model, AAC was found to be inversely associated with vBMD (odds ratio [OR], 0.970; 95% confidence interval [CI], 0.944 to 0.996; P = 0.025), and patients with osteoporosis had a significantly higher risk of severe AAC than those with normal bone mass (OR, 14.498; 95% CI, 1.507 to 139.486; P = 0.021). The independent inverse association was still stable after adjusting for variables measured at different time periods and using different cutoff points of the AAC score. CONCLUSION: There was an independent inverse association between AAC and vBMD, and osteoporosis was significantly associated with severe AAC in patients with MHD.

Experimental testing and biomechanical CT analysis of Chinese cadaveric vertebrae with different modeling approaches.

Osteoporosis is characterized by reduced bone strength predisposing to an increased risk of fracture. Biomechanical computed tomography (BCT), predicting bone strength via CT-based finite element analysis (FEA), is now clinically available in the USA for diagnosing osteoporosis or assessing fracture risk. However, it has not been previously validated using a cohort of only Chinese subjects. Additionally, the effect of various modeling approaches on BCT outcomes remains elusive. To address these issues, we performed DXA and QCT scanning, compression testing, and BCT analyses on thirteen vertebrae derived from Chinese donors. Three BCT models were created (voxBCT and tetBCT: voxel-based and tetrahedral element-based FE models generated by a commercial software; matBCT: tetrahedral element-based FE model generated by a custom MATLAB program). BCT-computed outcomes were compared with experimental measures or between different BCT models. Results showed that, DXA-measured areal bone mineral density (aBMD) showed weak correlations with experimentally-measured vertebral stiffness (R2 = 0.28) and strength (R2 = 0.34). Compared to DXA-aBMD, BCT-computed stiffness provided improved correlations with experimentally-measured stiffness (voxBCT: R2 = 0.82; tetBCT: R2 = 0.77; matBCT: R2 = 0.76) and strength (voxBCT: R2 = 0.55; tetBCT: R2 = 0.57; matBCT: R2 = 0.53); BCT-computed mechanical parameters (stiffness, stress and strain) of the three different models were highly correlated with each other, with coefficient of determination (R2) values of 0.89-0.98. These results, based on a cohort of Chinese vertebral cadavers, suggest that BCT is superior over aBMD to consistently predict vertebral mechanical characteristics, regardless of the modeling approaches of choice.

Moderate/subclinical calcium deficiency attenuates trabecular mass, microarchitecture and bone growth in growing rats.

Adequate dietary calcium (Ca) intake is essential for bone accretion, peak bone mass (PBM) attainment, bone quality and strength during the mammalian growth period. Severe Ca deficiency during growing age results in secondary hyperparathyroidism (SHPT) and poor bone quality and strength. However, the impact of moderate Ca deficiency during rats early growth period on bone health and the reversibility with supplementing calcium later in adult life remains unclear. Female Sprague-Dawley (SD) rats (postnatal 28th day, P28) were initiated either with a moderate calcium-deficient diet (MCD, 0.25% w/w Ca) or a control diet (0.8% w/w Ca, control group) till P70. Thereafter, MCD rats were continued either with MCD diet or supplemented with calcium diet (0.8% w/w Ca, calcium supplemented group, CaS) till P150. Another group (control rats) were fed 0.8% w/w Ca containing diet from P28 till P150. MCD group, as compared to the control group, had significantly reduced serum ionized Ca and procollagen type 1 N-terminal propeptide (P1NP) at P70 while no significant change was observed in serum corrected Ca, inorganic phosphate (P), alkaline phosphatase (ALP), 25-hydroxy vitamin D [25(OH)D], intact parathyroid hormone (iPTH), and urinary C-terminal telopeptide of collagen 1 (CTX-1), Ca, and P. Femoral and tibial metaphysis in MCD rats had significantly reduced linear growth, cortical and trabecular volumetric BMD (vBMD), trabecular microarchitecture (BV/TV%, trabecular thickness, separation and number, structural model index and connectivity density), cortical thickness, and bone stiffness despite the absence of secondary hyperparathyroidism (SHPT). Continued MCD at P70-P150 results in persistence of compromised bone strength while calcium supplementation (CaS group) improved all the parameters related to bone strength and microarchitecture. Our results indicate that uncorrected moderate/subclinical calcium deficiency in growing rats can result in poor bone quality and strength despite the absence of SHPT. This finding could have relevance in children with poor calcium intake in childhood and adolescence.

Hyperglycemia Is Not Associated With Higher Volumetric BMD in a Chinese Health Check-up Cohort.

Background and Purpose: Type 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort. Materials and Methods: 10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models. Results: In the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064). Conclusion: We did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients.

Peripheral quantitative computed tomography (pQCT) in 12- and 24-month-old children - Practical aspects and descriptive data.

BACKGROUND: Peripheral quantitative computed tomography (pQCT) is a useful tool to assess detailed bone characteristics. Its utility in infants is however limited due to lack of reference data and technical challenges. The purpose of this study was to provide data on length- and weight-adjusted pQCT values and to present a quality grading system for healthy children aged 12 and 24 months. MATERIAL AND METHODS: As a part of the Vitamin D intervention in Infants (VIDI) trial, we collected pQCT and anthropometric data from 855 children at 12 months and from 784 children at 24 months. Bone mineral content (BMC; mg/mm), volumetric bone mineral density (vBMD; mg/cm3), cross-sectional area (CSA; mm2), polar-moment of inertia (PMI; mm4), and periosteal circumference (PsC; mm) were assessed for total bone at 20% distal site of the left tibia using pQCT (Stratec XCT2000L). We evaluated the impact of scan quality on bone measures. Total bone parameters were assessed for boys and girls separately. The means of the bone parameters were also compared in relation to age. The associations between bone parameters and weight, length, sex and scan quality were analyzed. RESULTS: We included scans with sufficient quality (Grade 1-5) in the final analyses: 679/855 (79%) at 12 months and 709/784 (90%) at 24 months. Altogether 39% of the scans at 12 months and 51% at 24 months were of good or excellent quality (Grade 1-2). Scan quality had an impact on BMCs at 12 and 24 months (p = 0.001 and p = 0.017, respectively) but not on other bone parameters. Boys presented greater total bone BMC, CSA, PMI and PsC values at 12 and 24 months but vBMDs were similar. All bone parameters showed a significant increase between 12 and 24 months for both sexes. When adjusting bone parameters for weight, length and scan quality, differences between sexes disappeared. Weight was the strongest modifier of BMC, CSA, PMI and PsS at 12 and 24 months. CONCLUSIONS: This study increases our understanding on bone parameters in young children and demonstrates the suitability of pQCT in bone research in infants. The described pQCT data and scan quality grading system should prove useful in evaluating data reliability in research settings. CLINICAL TRIAL REGISTRATION NUMBER: NCT1723852.

Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women.

BACKGROUND: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments. METHODS: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR. RESULTS: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c. CONCLUSIONS: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.

Relationship of volumetric bone mineral density by quantitative computed tomography with abdominal aortic calcification.

OBJECTIVE: This multicenter study aimed to evaluate the association between volumetric bone mineral density (vBMD) and abdominal aortic calcification (AAC) in a Chinese population. METHODS: Quantitative computed tomography (QCT) and Agatston score (AS) were used to measure vBMD and AAC, respectively, in 3457 participants during 2013-2017. The association between vBMD and AAC was assessed using multivariate regression analysis, adjusted for age, residence, education, body mass index, and other cardiovascular risk factors. RESULTS: The mean age of women and men was 61.4 and 62.7 years, respectively. In total, 30.4% of women and 37.7% of men were found to have AAC. After full adjustment, higher vBMD was associated with lower AAC score (ß, -0.095; 95% confidence interval [CI], -0.167 to -0.024; P = 0.0087) and lower AAC prevalence (odds ratio [OR], 0.873; 95% CI, 0.824 to 0.924; P < 0.0001) in men. Inverse trends were also observed in the association of vBMD quartile with AAC severity (lowest vs highest quartile; ß = 0.235; 95% CI, 0.011 to 0.459; Ptrend < 0.0001) and AAC prevalence (lowest vs highest quartile; OR = 1.329; 95% CI, 1.087 to 1.625; Ptrend < 0.0001) in men. However, no significant result was obtained in women, except for the association between quartiles of vBMD and AAC score. CONCLUSIONS: In our study, vBMD was inversely associated with AAC among men independent of age and shared risk factors. However, the association was not significant among women.

Bone geometry and lower extremity bone stress injuries in male runners.

Bone stress injuries (BSI) are common among distance runners and research investigations examining risk factors for BSI among men are limited. Therefore, investigations are needed to determine if men with a history of BSI have skeletal properties that may heighten BSI incidence. OBJECTIVES: To analyze differences in bone density, bone geometry, and estimates of bone strength in male runners with and without a BSI history. DESIGN: Cross-sectional. METHODS: We recruited 36 male distance runners ages 18-41 for this study. We used peripheral quantitative computed tomography (pQCT) to assess volumetric bone mineral density (vBMD, mg/mm3), bone geometry (total and cortical bone area, mm2), tibia robustness (total area/tibia length, mm) and estimates of bone strength (section modulus and polar strength-strain index, mm3) at 5 tibial sites. RESULTS: After adjusting for age, the BSI group had more slender tibias (9%), lower stress strain indices (-16%), lower section moduli (-17%) and smaller total cross-sectional (-11%) and cortical areas (-12%) at the 66% site of the tibia compared with controls (P < 0.05 for all). Similar differences were found at all other measurement sites. After adjusting for body size, differences in bone outcomes remained significant at the 66% site. CONCLUSIONS: These results indicate that men with a history of BSI have lower estimated bending strength compared to controls because of narrower tibias. However, differences are largely attenuated in the distal ½ of the tibia after adjusting for body size. Thus, smaller tibia size, particularly at the mid-diaphysis, may be an important indicator for BSI incidence.

Bone mineral density averaged over a region of interest on femur is affected by age-related change of bone geometry.

Femur expansion occurs during normal aging in both men and women. Average bone mineral density (BMD) over a region of interest (ROI) on the femur may considerably decrease with age even in healthy people, and therefore, it is inaccurate if used to monitor treatment-induced bone change. INTRODUCTION: Areal bone mineral density (BMD), averaged over a region of interest (ROI) on the femur, is widely used in the diagnosis of osteoporosis, assessment of fracture risk, and monitoring of treatment effectiveness. We studied the effect of age-related change in femur geometry on average BMD. METHODS: The effect of age-related bone geometric change on averaged BMD was investigated by a cross-sectional study. Total 83 healthy subjects were selected for this study. For each subject, QCT of left femur was scanned using clinical scanner. For each standard volume of interest (VOI), integral/cortical/trabecular bone volume, volumetric BMD (vBMD), and bone mass were measured using QCT Pro; the corresponding areal BMD (aBMD) was projected using CTXA-Hip. Both QCT Pro and CTXA-Hip are commercial software. Correlations between bone volume/density/mass and age were studied. RESULTS: In the studied population, there was no association between body weight/BMI (body mass index) and age, correlation between normalized femoral neck width and age was 0.24 (p < 0.05). Both aBMD and integral vBMD decreased with age (after adjusted by BMI, for aBMD, r = - 0.21 to - 0.24, p ≤ 0.05 except at trochanter; for vBMD, r = - 0.20 to - 0.31, p < 0.05); cortical vBMD had no significant change; trabecular vBMD decreased at all VOIs except at trochanter (after adjusted by BMI, r = - 0.22 to 0.32, p ≤ 0.05). Integral volume showed slight increase but only significant at the trochanter after adjusted by body size, cortical volume showed insignificant decrease, and trabecular volume considerably increased with age in all VOIs (after adjusted by body size, r = 0.27-0.40, p < 0.05). Integral, cortical, and trabecular mass had no significant change in all VOIs, except that at the trochanter trabecular mass slightly increased with age (r = 0.31, p < 0.05). CONCLUSIONS: Even though there is no change in bone mass, average BMD may considerably decrease with age due to bone expansion. Comparatively, aBMD is less affected than vBMD.

High-fat/high-sucrose diet results in higher bone mass in aged rats.

Intake of high-fat/high-sucrose (HFS) diet or high fat diet influences bone metabolism in young rodents, but its effects on bone properties of aged rodents still remain unclear. This study aimed to examine the effects of HFS diet intake on trabecular bone architecture (TBA) and cortical bone geometry (CBG) in aged rats. Fifteen male Wistar rats over 1 year were randomly divided into two groups. One group was fed a standard laboratory diet (SLD) and the other group was fed a HFS diet for six months. The femur/tibia, obtained from both groups at the end of experimental period, were scanned by micro-computed tomography for TBA/CBG analyses. Serum biochemical analyses were also conducted. Body weight was significantly higher in the HFS group than in the SLD group. In both femur and tibia, the HFS group showed higher trabecular/cortical bone mass in reference to bone mineral content, volume bone mineral density and TBA/CBG parameters compared with the SLD group. In addition, serum calcium, inorganic phosphorus, total protein, triacylglycerol, HDL and TRACP-5b levels were significantly higher in the HFS group than in the SLD group. There were good correlations between body weight and bone parameters in the femur and tibia. These results suggest that HFS diet intake results in higher bone mass in aged rats. Such effects of HFS diet intake might have been induced by increased body weight.

Effects of Contrast Enhancement on In-Body Calibrated Phantomless Bone Mineral Density Measurements in Computed Tomography.

We aimed to test the potential of phantomless volumetric bone mineral density (PLvBMD) measurements for the determination of volumetric bone mineral density (vBMD) in routine contrast-enhanced computed tomography (CECT). We evaluated 56 tri-phasic abdominal computed tomography scans, including an unenhanced scan as well as defined CECT scans in the arterial and portalvenous phase. PLvBMD analysis was performed by 4 radiologists using an FDA-approved tool for phantomless evaluation of bone density (IntelliSpace, Philips, The Netherlands). Mean vBMD of the first 3 lumbar vertebrae in each contrast phase was determined and interobserver variance of vBMD independent of contrast phase was analyzed using intraclass correlation, Bland-Altman plots, and Student's t test. CECT scans were associated with a significantly higher PLvBMD compared with unenhanced scans (unenhanced computed tomography: 97.8 mg/cc; arterial CECT: 106.3 mg/cc, portalvenous CECT: 106.3 mg/cc). Overall, there was no significant difference of PLvBMD between data acquisition in arterial and portalvenous phases (increase of 8.6% each, standard deviation ratio 37.7%-38.3%). In Bland-Altman analysis, there was no evidence of a relevant reader-related bias or an increase in standard deviation of PLvBMD measurements in contrast-enhanced scans compared with unenhanced scans. The following conversion formulas for unenhanced PLvBMD were determined: unenhancedPLvBMD=0.89×arterialPLvBMD+3,74mg/cc(r2 = 0.94) and unenhancedPLvBMD=0.88×venousPLvBMD+4,56mg/cc(r2 = 0.93). Compared with the results of phantom-based quantitative computed tomography measurements reported in the literature, the PLvBMD changes associated with contrast enhancement were relatively moderate with an increase of 8.6% in average. The time-point of the contrast-enhanced PLvBMD measurements after injection of contrast media did not appear to affect the results. With the adjustment formulas provided in this study, the method can improve osteoporosis screening through detection of reduced bone mass of the vertebrae in routinely conducted CECT.