Quantitative computed tomography (QCT) of the forearm using general purpose spiral whole-body CT scanners: Accuracy,precision and comparison with dual-energy X-ray absorptiometry (DXA)

BackgroundDual-energy X-ray absorptiometry (DXA) allows clinically relevant measurement of bone mineral density (BMD) at central and appendicular skeletal sites, but DXA has a limited ability to assess bone geometry and cannot distinguish between the cortical and trabecular bone compartments. Quantitative computed tomography (QCT) can supplement DXA by enabling geometric and compartmental bone assessments. Whole-body spiral CT scanners are widely available and require only seconds per scan, in contrast to peripheral QCT scanners, which have restricted availability, limited spatial resolution, and require several minutes of scanning time.This study evaluated the accuracy and precision of whole-body spiral CT scanners for quantitatively assessing the distal radius, a common site of non-vertebral osteoporosis-related fractures, and compared the CT-measured densitometric values with those obtained from dual-energy-X-ray absorptiometry.Subjects and methodsA total of 161 postmenopausal women with baseline lumbar spine BMD T-scores between ? 1.0 and ? 2.5 underwent left forearm QCT using whole-body spiral CT scanners twice, 1 month apart. QCT volumes of interest were defined and analyzed at 3 specific radial regions: the ultradistal region by using slices at 8, 9, and 10 mm proximal to the ulnar styloid tip; the distal region by a slice 20 mm proximal; and the middle region by a slice 40 mm proximal. BMD, bone mineral content (BMC), volume, and average cortical thickness and circumference were measured. We evaluated QCT accuracy and precision and also report correlations between QCT and DXA for BMD and BMC.ResultsOverall accuracy and precision errors for BMD, BMC and volume were consistent with known skeletal QCT technology precision and were generally less than 3%. BMD and BMC assessed by QCT and DXA were correlated (r = 0.55 to 0.80).DiscussionWhole-body spiral CT scanners allow densitometric evaluations of the distal radius with good accuracy and very good precision. This original and convenient method provides a tool to further investigate cortical and trabecular bone variables in the peripheral skeleton in osteoporotic patients. These assessments, coupled with evaluation of the effects on cortical and trabecular bone measured in response to therapies for osteoporosis, may advance our understanding of the contributors to non-vertebral fracture occurrence.     

Low Bone Mineral Content and Challenges in Interpretation of Dual-Energy X-Ray Absorptiometry in Children With Mucopolysaccharidosis Types I,II, and VI

Osteoporosis has been described in animal models of mucopolysaccharidosis (MPS). Whether clinically significant osteoporosis is common among children with MPS is unknown. Therefore, cross-sectional data from whole body (WB; excluding head) and lumbar spine (LS) bone mineral density (BMD) compared with sex-, chronologic age–, and ethnicity-matched healthy individuals (Z_age), height-for-age (HAZ) Z-score (Z_HAZ) and bone mineral content (BMC) measured by dual-energy X-ray absorptiometry (DXA) in 40 children with MPS were analyzed. A subset of these children (n = 24) was matched 1:3 by age and sex to a group of healthy children (n = 72) for comparison of BMC adjusted for Tanner stage, race, lean body mass, height, and bone area. Low BMD Z-score was defined as Z-score of −2 or less. In children with MPS, 15% had low WB Z_age and 48% had low LS Z_age; 0% and 6% had low WB Z_HAZ and low LS Z_HAZ, respectively. Adjusted WB BMC was lower in MPS participants (p = 0.009). In conclusion, children with MPS had deficits in WB BMC after adjustments for stature and bone area. HAZ adjustment underestimated bone deficits (i.e., overestimated WB BMD Z-scores) in children with MPS likely owing to their abnormal bone shape. The influence of severe short stature and bone geometry on DXA measurements must be considered in children with MPS to avoid unnecessary exposure to antiresorptive treatments.     

Influence of the weight status on bone mineral content and bone mineral density in a group of Lebanese adolescent girls

AimThe aim of this study was to determine the influence of being overweight on whole-body (WB) bone mineral content (BMC) and bone mineral density (BMD) in a group of Lebanese adolescent girls.MethodsThis study included 32 overweight (BMI > 25 kg/m²) adolescent girls (15.3 ± 2.3 years old) and 24 maturation-matched (15.7 ± 1.7 years old) controls (BMI < 25 kg/m²). Bone mineral area (BMA), BMC, BMD at the WB and body composition (lean mass and fat mass) were assessed by dual-energy X-ray absorptiometry (DXA). Calculation of the ratio BMC/height and bone mineral apparent density (BMAD) were completed for the WB.ResultsExpressed as crude values, BMA, BMC and the ratio BMC/height were higher in overweight adolescent girls compared to controls. After adjusting for body weight, there were no differences in BMC or in the ratio BMC/height between the two groups. However, BMA was lower in overweight girls compared to controls. After adjusting for either lean mass or fat mass, there were no significant differences between the two groups regarding these variables: BMC, BMA, BMD, BMC/height and BMAD.ConclusionThis study suggests that the positive effect of overweight on BMC is due to body weight. In fact, the difference in BMC between the overweight and the control girls disappears after adjusting for body weight. In contrast, overweight girls have lower BMA compared to controls when values are adjusted to body weight.     

Use of selective serotonin reuptake inhibitors and bone mass in adolescents: An NHANES study

ContextSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications to treat depression and anxiety. SSRIs exert their effects by inhibiting the serotonin transporter and modulating extracellular serotonin levels, a neurotransmitter that has been shown to affect bone metabolism in animals. Studies in adults suggest a negative association between SSRI use and bone mineral density (BMD), greater rates of bone loss with SSRI use and increased risk of fractures. However, the results on bone mass have been inconsistent. Furthermore, there is a dearth of studies examining an association between SSRI use and bone mass in the pediatric and adolescent age group.ObjectiveTo investigate associations between SSRI use and bone mass in adolescents.DesignCross-sectional analysis of data from the 2005–2010 National Health and Nutrition Examination Study (NHANES).Participants4303 NHANES participants aged 12–20 years. The mean age was 15.65 ± 2.42 years.Main outcomesTotal femur, femoral neck and lumbar spine bone mineral content (BMC) and BMD assessed via dual-energy X-ray absorptiometry (DXA).Results62 out of 4303 subjects used SSRIs. SSRI use was an independent predictor of bone mass after adjusting for age, gender, height and weight Z score, socioeconomic status, physical activity, serum cotinine level and race/ethnicity. After multivariable adjustment, total femur BMC was 8.8% lower among SSRI users versus non-users (mean difference 2.98 g, SE ± 0.105 g, p = 0.0006), while total femur BMD was 6.1% lower (mean difference 0.06 g/cm², SE ± 0.002 g/cm², p = 0.016). Femoral neck BMC and BMD and lumbar spine BMC were similarly negatively associated with SSRI use. Compared to nonusers, lumbar spine BMC was 7% lower among SSRI users (mean difference 0.97 g, SE ± 0.048 g, p = 0.02) and BMD was 3.2% lower (mean difference 0.03 g/cm², SE ± 0.015 g/cm², p = 0.09). Sub-analysis of those individuals treated for more than 6 months yield similar results. Finally, the association of SSRIs with bone mass persisted after excluding individuals with Body Mass Index (BMI) less than 5th percentile thus accounting for the possible confounding effect of anorexia nervosa, which can be treated with SSRIs.ConclusionIn this NHANES study, adolescents treated with SSRIs had lower DXA measurements of the total femur and lumbar spine compared to SSRI non-users. These findings support the need for future prospective studies to examine the effects of SSRI use on bone mass in adolescents.     

Inter-rater agreement on assessment of outcome within a trauma registry

IntroductionTo better evaluate the degree of ongoing disability in trauma patients, it has been recommended that trauma registries introduce routine long-term outcome measurement. One of the measures recommended for use is the Extended Glasgow Outcome Scale (GOS-E). However, few registries have adopted this measure and further research is required to determine its reliability with trauma populations. This study aimed to evaluate the inter-rater agreement of GOS-E scoring between an expert rater and trauma registry follow-up staff with a sample of detailed trauma case scenarios.MethodsSixteen trauma registry telephone interviewers participated in the study. They were provided with a written summary of 15 theoretical adult trauma cases covering a spectrum of disability and asked to rate each case using the structured GOS-E interview. Their ratings were compared with those of an expert rater in order to calculate the inter-rater agreement for each individual rater-expert rater pair. Agreement was reported as the percentage of agreement, the kappa statistic, and weighted kappa. A multi-rater kappa value was also calculated for agreement between the 16 raters.ResultsAcross the 15 cases, the percentage of agreement between individual raters and the expert ranged from 63% to 100%. Across the 16 raters, the percentage of agreement with the expert rater ranged from 73–100% (mean = 90%). Kappa values ranged from 0.65 to 1.00 across raters (mean = 0.86) and weighted kappa values ranged from 0.73 to 1.00 (mean = 0.89) The multi-rater kappa value was 0.78 (95% CI: 0.66, 0.89).ConclusionsSixteen follow-up staff achieved ‘substantial’ to ‘almost perfect’ agreement with an expert rater using the GOS-E outcome measure to score 15 sample trauma cases. The results of this study lend support to the use of the GOS-E within trauma populations and highlight the importance of ongoing training where multiple raters are involved to ensure reliable outcome reporting. It is also recommended that the structured GOS-E interview guide be used to achieve better agreement between raters. Ensuring the reliability of trauma outcome scores will enable more accurate evaluation of patient outcomes, and ultimately, more targeted trauma care.     

Denosumab Densitometric Changes Assessed by Quantitative Computed Tomography at the Spine and Hip in Postmenopausal Women With Osteoporosis

FREEDOM was a phase 3 trial in 7808 women aged 60–90 yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6 mo for 3 yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N = 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36 mo (all p ≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p < 0.0001) largely related to significant BMC improvement in the cortical compartment (p < 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments.     

Dual-Energy X-ray Absorptiometry Assessment of Tibial Mid-third Bone Mineral Density in Young Athletes

We suggested a new reproducible method to measure densitometric values at mid-third part of the tibia by dual-energy X-ray absorptiometry (DXA; Delphi, Hologic^®, Waltham, MA) in a population of young adults. Our population was composed of 170 subjects aged 22.7 ± 4.0 yr: athlete men (n = 67) and women (n = 40); control men (n = 33) and women (n = 30). Athletes practiced collective sports, judo or weightlifting for 10.0 ± 3.6 h/wk. We measured bone area (cm²), bone mineral content (BMC, g), and bone mineral density (BMD,g/cm²) at the left total hip and the mid-third part of the tibia with DXA. For the tibia scan, we used the whole body mode. To ensure the reproducibility of the method, both legs were extended and the feet were maintained on a support in an internal rotation of 35°. The region of interest of the lumbar spine from the whole body scan was positioned around the mid-third part of the tibia. Area, BMC, and BMD values were significantly higher in athletes compared with those of controls. The intra- and interobserver variability of the image analysis were 0.38% and 1.01%, respectively. For BMD measurements, the short-term (4 scans/d) and mid-term (4 scans/mo) reproducibility were 1.33% and 1.94%, respectively. DXA is a suitable tool to evaluate densitometric measurements at the mid-third part of the tibia and the influence of physical activity on that bone site.     

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

In the clinical environment dual-energy X-ray absorptiometry (DXA) is the current tool of first choice for assessing and monitoring skeletal integrity. A major drawback of standard DXA is that the bone mineral density (BMD) data cannot be used with certainty to predict who will sustain a vertebral fracture. However, measurement of BMD within vertebral subregions, instead of relying on a gross estimate of vertebral BMD, may improve diagnostic sensitivity. The aim of this article was to describe a validation study for subregional BMD measurement using lateral-projection DXA and to present preliminary data. Concurrent validity of measuring subregional BMD with DXA was established against measures of volumetric subregional BMD from peripheral quantitative computed tomography (pQCT) and subregional bone volume fraction from μCT at the L2 vertebral body in 8 cadaver spine specimens. The novel approaches for measuring subregional parameters with each imaging modality are described. Significant differences in bone parameters between vertebral subregions were observed for each imaging modality (p < 0.05). Correspondence ranged from R² = 0.01–0.79 and R² = 0.06–0.80 between “DXA vs. pQCT” and “DXA vs. micro-CT,” respectively. For both imaging modalities, correspondence with DXA was high for centrally and anteriorly positioned subregions. These data provide a basis for larger studies to examine the biological significance of heterogeneity in vertebral BMD.     

Associations among endocrine,inflammatory, and bone markers,body composition and weight loss induced bone loss

IntroductionWeight loss reduces co-morbidities of obesity, but decreases bone mass.PurposeOur aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; and 3) model the contribution of these variables to post weight-loss BMD and BMC.MethodsOverweight/obese women (BMI: 28–37 kg/m²) were enrolled in an energy reduced (− 500 kcal/d; − 2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n = 25, 32.2 ± 8.8 years) or low dairy (LD: ≤ 1 serving/d; n = 26, 31.7 ± 8.4 years). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry.ResultsFollowing weight loss, AD intake resulted in significantly greater (p = 0.004) lumbar spine BMD and serum osteocalcin (p = 0.004) concentration compared to LD. Pre- and post-body fat was negatively associated with hip and lumbar spine BMC (r = − 0.28, p = 0.04 to − 0.45, p = 0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = − 0.29 (p = 0.04) to r = − 0.34 (p = 0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss factors. Pre-weight loss factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the factors contributed to the variance in lumbar spine BMD.ConclusionAD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD. Significant negative associations were observed between bone and inflammatory markers suggesting that inflammation suppresses bone metabolism. Using factor analysis, 19.6% of total variance in post-weight loss hip BMD could be explained by endocrine, immune, and anthropometric variables, but not lumbar spine BMD.     

Bone Mineral Density in Premenopausal Arab Women With Type 2 Diabetes Mellitus

IntroductionThis study compares an ethnically uniform group of premenopausal type 2 diabetic (T2DM) Arab women with a matched control group of nondiabetic subjects, in terms of their bone mineral density (BMD) and anthropometric measurements.MethodsThe study included 252 premenopausal Arab women. Their age ranged from 26 to 50 yr with a mean ± SD of 43.65 ± 8.97 yr. One hundred and twenty-two women were T2DM patients and 130 women were nondiabetic controls. The controls matched the subjects in gender, age, and body mass index (BMI). BMD was measured at total lumbar spine (L1–L4) and total left hip, using dual-energy X-ray absorptiometry (DXA; HOLOGIC, QRS SERIES, Europe, Belgium). Difference in BMD and its relationship to the anthropometric measurements in T2DM and control groups were assessed.ResultsSignificant difference was found between T2DM patients and nondiabetic patients in their mean hip BMD (0.92 ± 0.16 vs. 0.87 ± 0.14, p < 0.05) and spine BMD (0.93 ± 0.15 vs. 0.88 ± 0.14, p < 0.01). No significant difference was found in age, height, weight, and BMI (p > 0.05). The increase in hip BMD in T2DM patients normalized and the increase in spine BMD persisted after controlling for the confounding effect of age and anthropometric measurements.ConclusionPremenopausal Arab women with T2DM have higher BMD at the spine than women without T2DM. The underlying mechanism causing this increase does not seem to be related to ethnicity, gender, hormonal status, or anthropometric measurements.     

Measurement of Bone Density Around the Oxford Medial Compartment Knee Replacement Using iDXA. A Precision Study

The goal of this study was to evaluate whether the Lunar iDXA densitometer can accurately measure the bone mineral density (BMD) around the tibial component of the Oxford unicompartment knee replacement (UKR). Both knees in 20 patients were measured 3 times in the supine position with repositioning between each scan. We chose 7 regions of interest to evaluate the bone density around the implant. Small but significant differences between the implant and nonimplanted knee were noticed with the nonimplanted knee having slightly higher BMD and bone mineral content (BMC) in areas 1–3 (p ≤ 0.001) and area 6 (p = 0.002). There was higher BMD in area 4 (p = 0.028). The precision for BMD in the 7 areas of interest in the implanted knee varied between 0.55% and 4.04% and BMC between 1.8% and 5.3%. There was no significant difference in the precision between the nonimplanted and implanted knees. Prospective serial measurements around the Oxford UKR using iDXA will be able to assess specific areas of stress shielding and potential implant stability, which is likely to help predict the survival of the implant.     

Bone structure and geometry in young men: The influence of smoking,alcohol intake and physical activity

BackgroundThe development of osteoporosis is influenced by peak bone mass attained in youth — the influence of lifestyle factors upon which is poorly described, especially amongst males. We sought to address this issue in a large scale study.MethodsHip bone mineral density (dual X-ray absorptiometry, DXA), bone microarchitecture (calcaneal quantitative ultrasound, QUS) and femoral geometry (magnetic resonance imaging, MRI) were characterised in 723 healthy male military recruits (mean ± S.E. age 19.92 ± 0.09 years [range 16–18 years], height 177.67 ± 0.24 cm, weight 73.17 ± 0.37 kg) on entry to UK Army training. Association was sought with prior physical activity, smoking status and alcohol intake.ResultsDXA measures were made in 651, MRI measures in 650, and QUS measures in 572 recruits. Increasing levels of weight-bearing physical activity enhanced periostial bone apposition, increases in both total hip and femoral neck bone mineral density (BMD; p ≤ 0.0001 in both cases), and cortical [p < 0.0001] and periostial bone volumes [p = 0.016]. Smoking habit was associated with preserved bone geometry, but worse BMD [p = 0.0001] and QUS characteristics [p ≤ 0.0005]. Moderate alcohol consumption was associated with greater BMD [p ≤ 0.015].ConclusionsWhilst exercise (and perhaps moderate alcohol intake) is beneficial to bone morphometry, smoking is detrimental to bone mineral density in young males notable for the likely short duration of smoking to influence skeletal properties. However, differences in socio-economic status, lifestyle and related environmental factors may to some extent confound our results.     

Bone Mineral Density Measured by a Portable X-ray Device Agrees With Dual-Energy X-ray Absorptiometry at Forearm in Preschool Aged Children

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) are generally not feasible in fieldwork. The present study determined the agreement between BMD measured by DXA and portable peripheral DXA in preschool aged children. Fifty-seven children (4.2 ± 1.0 yr) had their nondominant distal forearm scanned using a peripheral DXA scanner (PIXI; GE Medical Systems Lunar, Madison, WI) at their daycare and a DXA (4500A Discovery Series; Hologic Inc., Bedford, MA) at our research clinic. Correlation analysis, one-way analysis of variance, and Bland-Altman plots were performed to examine the agreement between measurements. Data were also divided into tertiles for cross-classification analysis and calculation of kappa coefficients. Distal forearm BMD measured by PIXI was significantly correlated with DXA measures of total forearm BMD (r > 0.51; p < 0.001), proximal 1/3 BMD (r > 0.41; p < 0.001), mid-BMD (r > 0.37; p < 0.001), and ultradistal (UD) BMD (r > 0.57; p < 0.001). Cross-classification in the same or adjacent tertile between measures (UD forearm: 96.5%; UD radius: 94.4%; total forearm: 87.7%; total radius: 84.2%) resulted in weighted kappa coefficients of 0.46, 0.58, 0.42, and 0.43, respectively. Bland-Altman plots further clarified these agreements as all had low bias (UD forearm: bias = 0.003 ± 0.002; UD radius: ?0.015 ± 0.021; total forearm: ?0.062 ± 0.027; total radius: ?0.077 ± 0.026). These results demonstrate that portable DXA measures of forearm BMD agree moderately with DXA.     

Assessing Body Composition in Healthy Newborn Infants: Reliability of Dual-Energy X-Ray Absorptiometry

Dual-energy X-ray absorptiometry (DXA) is used to measure body composition in newborns; however, data on DXA accuracy are limited. We investigated the reliability of body composition measurements by DXA. The present study included 207 normal-term newborn babies, recruited from a larger study on the determinants of birth weight in healthy pregnancies (STORK) between 2005 and 2008. Reliability analysis of total fat mass (FM_DxA), fat-free mass, lean mass (LM_DxA), bone mineral content (BMC), and bone mineral density (BMD) were based on 2 DXA scans of 50 neonates. We also performed a comparison analysis for DXA (FM_DxA) measurements and caliper (CLP) or circumference (CF) measurements of trunk and extremities (performed on all neonates, n = 207). Reliability: All intraclass correlation coefficients (ICC) were satisfactory to excellent for total body and the extremity-compartment FM_DxA, LM_DxA, BMD, and BMC; ICC ranged from 0.86 to 0.96 but with a lower ICC for trunk FM_DxA. For comparison analysis, the Pearson correlation coefficients for CLP vs DXA and CF vs DXA ranged from 0.48 to 0.79 and 0.41 to 0.77, respectively. Quadriceps CLP and CF measurements correlated best with the most reliable DXA results, whereas more modest correlations were found for the trunk region. DXA measurements of body composition demonstrated good reliability and can be used as a reference method in neonates. CLP and CF measurements are appropriate for larger cohorts or when DXA is unavailable, and they provide fair rough estimations of fat mass.     

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients

PurposeCancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD.MethodsWe validated DECT in pre-clinical and phase I clinical trials and verified with water–fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12 months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck.ResultsMeasured precision (3 mg/cm³) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r = 0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r = 0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p < 0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p < 0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p < 0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment.ConclusionOur study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.     

Bone mineral density of young boy soccer players at different pubertal stages: relationships with hormonal concentration

ObjectivesTo examine the effects of soccer in relation with the hormonal concentration, on the bone mass of young Tunisian players at different pubertal stages.MethodsTwo groups of 152 young boys (age: 13.3 ± 0.9 years) participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys used as control subjects. The bone mineral density (BMD) and the bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal stages were assessed, and serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone (GH) and the total testosterone were measured.ResultsThe BMD and BMC for whole body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer players than in controls (p < 0.001). In early puberty, the soccer players also exhibited significantly greater BMD and BMC in the whole body and in weight-bearing bones compared with the controls (p < 0.001). However, there was no intersubject variability due to puberty in either BMD or BMC. The pubescent soccer players had significantly higher hormonal concentrations of IGF-1 and IGFBP-3 than their counterpart controls (p < 0.05). Moreover, the whole body BMD was significantly (p < 0.001) correlated with GH, IGF-1 and IGFBP-3 but not with the testosterone concentrations.ConclusionThe soccer participation of boys is generally associated with the improvement of their bone mass which is mainly marked at early and late puberty. The relationships between somatotropic axis hormones and BMD of the players may be linked to the parallel development of these two parameters during puberty.     

Dual-Energy X-Ray Absorptiometry and Evaluation of the Osteoporosis Self-Assessment Tool in Men With Rheumatoid Arthritis

Males with rheumatoid arthritis (RA) are at risk for osteoporosis but infrequently undergo dual-energy X-ray absorptiometry (DXA). We examined the frequency of DXA in males enrolled in the Veterans Affairs Rheumatoid Arthritis Registry. The Osteoporosis Self-Assessment Tool (OST) index, a formula using age and weight, was calculated for all subjects. DXA was performed on 282 (35.5%) of the males who were younger (p < 0.01), had lower mean OST index score (p < 0.05), and were more likely to have been prescribed prednisone (p < 0.01) than subjects without DXA. Low bone mass (T-score < ?1) was present in 73% of subjects with DXA; 37% of subjects with low-risk OST index scores had normal bone mineral density (BMD) compared with 5.6% of those with high-risk OST index scores (p < 0.01). There was a significant but modest correlation between BMD and the OST index (r = 0.17, p < 0.01). No OST score had a sensitivity and specificity of more than 80%. Association between OST index and BMD was strongest in non-Hispanic whites, subjects older than 60 yr, and smokers. DXA was underutilized in males with RA. The OST index correlated with low bone mass but could not reliably predict osteoporosis in this population.     

High resolution quantitative computed tomography-based assessment of trabecular microstructure and strength estimates by finite-element analysis of the spine,but not DXA,reflects vertebral fracture status in men with glucocorticoid-induced osteoporosis

High-resolution quantitative computed tomography (HRQCT)-based analysis of spinal bone density and microstructure, finite element analysis (FEA), and DXA were used to investigate the vertebral bone status of men with glucocorticoid-induced osteoporosis (GIO). DXA of L1–L3 and total hip, QCT of L1–L3, and HRQCT of T12 were available for 73 men (54.6 ± 14.0 years) with GIO. Prevalent vertebral fracture status was evaluated on radiographs using a semi-quantitative (SQ) score (normal = 0 to severe fracture = 3), and the spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Thirty-one (42.4%) subjects had prevalent vertebral fractures. Cortical BMD (Ct.BMD) and thickness (Ct.Th), trabecular BMD (Tb.BMD), apparent trabecular bone volume fraction (app.BV/TV), and apparent trabecular separation (app.Tb.Sp) were analyzed by HRQCT. Stiffness and strength of T12 were computed by HRQCT-based nonlinear FEA for axial compression, anterior bending and axial torsion. In logistic regressions adjusted for age, glucocorticoid dose and osteoporosis treatment, Tb.BMD was most closely associated with vertebral fracture status (standardized odds ratio [sOR]: Tb.BMD T12: 4.05 [95% CI: 1.8–9.0], Tb.BMD L1–L3: 3.95 [1.8–8.9]). Strength divided by cross-sectional area for axial compression showed the most significant association with spine fracture status among FEA variables (2.56 [1.29–5.07]). SDI was best predicted by a microstructural model using Ct.Th and app.Tb.Sp (r² = 0.57, p < 0.001). Spinal or hip DXA measurements did not show significant associations with fracture status or severity.In this cross-sectional study of males with GIO, QCT, HRQCT-based measurements and FEA variables were superior to DXA in discriminating between patients of differing prevalent vertebral fracture status. A microstructural model combining aspects of cortical and trabecular bone reflected fracture severity most accurately.     

Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm

BackgroundPreterm infants are at risk of metabolic bone disease due to inadequate mineral intake with unknown consequences for later bone health.ObjectiveTo test the hypotheses that (1) early diet programs peak bone mass and bone turnover; (2) human milk has a beneficial effect on these outcomes; (3) preterm subjects have reduced peak bone mass compared to population reference data.Design20 year follow-up of 202 subjects (43% male; 24% of survivors) who were born preterm and randomized to: (i) preterm formula versus banked breast milk or (ii) preterm versus term formula; as sole diet or supplement to maternal milk. Outcome measures were (i) anthropometry; (ii) hip, lumbar spine (LS) and whole body (WB) bone mineral content (BMC) and bone area (BA) measured using DXA; (iii) bone turnover markers.ResultsInfant dietary randomization group did not influence peak bone mass or turnover. The proportion of human milk in the diet was significantly positively associated with WBBA and BMC. Subjects receiving > 90% human milk had significantly higher WBBA (by 3.5%, p = 0.01) and BMC (by 4.8%, p = 0.03) than those receiving < 10%. Compared to population data, subjects had significantly lower height SDS (? 0.41 (SD 1.05)), higher BMI SDS (0.31 (1.33)) and lower LSBMD SDS (? 0.29 (1.16)); height and bone mass deficits were greatest in those born SGA with birthweight < 1250 g (height SDS ? 0.81 (0.95), LSBMD SDS ? 0.61 (1.3)).ConclusionInfant dietary randomization group did not affect peak bone mass or turnover suggesting the observed reduced final height and LS bone mass, most marked in growth restricted subjects with the lowest birthweight, may not be related to sub-optimal early nutrition. The higher WB bone mass associated with human milk intake, despite its low nutrient content, may reflect non-nutritive factors in breast milk. These findings may have implications for later osteoporosis risk and require further investigation.     

Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys

The effect of treatment for 9 months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n = 8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150 μg/kg QD of minodronic acid or 500 μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8 months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8 months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150 μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8 months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9 months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC.