Dual-energy X-ray Absorptiometry Lumbar Research Articles

Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne muscular dystrophy

Osteoporosis is a major problem in boys with Duchenne Muscular Dystrophy (DMD), attributable to muscle weakness and glucocorticoid therapy. Consensus regarding bone health assessment and management is lacking. Lumbar spine areal bone mineral density (defined as bone mass per area of bone) by dual-energy X-ray absorptiometry (DXA) is frequently the primary measure used, but has limitations for boys with DMD. We retrospectively studied 292 ambulant glucocorticoid-treated boys with DMD categorized by functional mobility score, FMS 1, 2 or 3. We assessed DXA whole body and lumbar spine areal bone mineral density and content Z-scores adjusted for age and height, lateral distal femur areal bone mineral density Z-scores, frequency of fractures, and osteoporosis by International Society for Clinical Densitometry 2013 criteria. Whole body and femoral DXA indices decreased, while spine fractures increased, with declining motor function. Lumbar spine areal bone mineral density Z-scores appeared to improve with declining motor function. Bone mineral content Z-scores were consistently lower than corresponding bone mineral density Z-scores. Our findings highlight the complexity of assessing bone health in boys with DMD. Bone health indices worsened with declining motor function in ambulant boys, but interpretation was affected by measure and skeletal site examined. Whole body bone mineral content may be a valuable measure in boys with DMD. Lumbar spine areal bone mineral density Z-score as an isolated measure could be misleading. Comprehensive management of osteoporosis in boys with DMD should include vertebral fracture assessment.

Post–Renal Transplantation Bone Health in Children Evaluated by Means of Quantitative Ultrasound and Densitometry

BackgroundPatients with end-stage renal disease develop bone mineral disease, which is not always resolved after a successful renal transplantation; moreover, some of the immunosuppressants used to prevent graft rejection may affect bone health. The aim of this study was to evaluate bone health in post–renal transplantation children with the use of quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA). MethodsA descriptive study was performed in children >3 months after renal transplantation and with stable function of graft. Radial QUS and DXA (lumbar spine and total body less head (TBLH) were performed on the same day. ResultsA total of 35 patients were included. Mean age was 13.9 ± 3.9 years. Ten subjects had total bone density score <2 (28.5%), 4 a lumbar spine (L1-L4) Z-score of <2 (11.4%) as well as TBLH <2, and 6 subjects had a radial QUS Z-score of <2 (17.1%), and only 2 of them had concomitant Z-score <2 with the use of DXA. There was a positive non-significant correlation between TBLH and radial QUS Z-scores (Pearson r = 0.317; P = .016) and a positive significant correlation of DXA lumbar spine and radial QUS Z-scores (Pearson r = 0.452; P = .014). ConclusionsDespite a good correlation between TBLH and QUS Z-scores, there are subjects that can be considered normal by QUS and have osteopenia by TBLH DXA and vice versa; this could be due to the different bone areas evaluated.

Hypovitaminosis D and Low Bone Mineral Density in Inflammatory Bowel Disease Patients

Background: Increasing evidences suggest that hypovitaminosis D can play an important role in immuno-mediated diseases, such as Inflammatory Bowel Diseases (IBD). The hypovitaminosis D is an established risk factor for the development of osteopenia, osteoporosis and pathological fractures. Studies have reported a correlation between hypovitaminosis D, disease history and clinical features in Crohn's Disease (CD) and Ulcerative Colitis (UC). The aim of this study is to evaluate the vitamin D serum levels and the prevalence of bone mineral density (BMD) alterations in a population of Italian IBD patients and to correlate the prevalence of hypovitaminosis D with disease history and clinical features. Method: Between October 2013 and November 2014 we enrolled patients from our center that were affected by UC or CD. Exclusion criteria were age below 18 and over 60, concomitant vitamin D replacement therapy and concomitant gastrointestinal or endocrinological diseases which may alter vitamin D metabolism. All patients underwent 25-OH-vitamin D, ESR, C-reactive protein (CRP), PTH, serum calcium and phosphorus, β-CTX, alkaline phosphatase (bone isoenzyme) plasma assay and bone mass density (BMD) evaluation by lumbar and femoral dual-energy X-ray absorptiometry (DXA) scan. Both measurements were made at the same time, during the autumn and winter months. Following 2012 Osteoporosis Italian Society Guidelines, we defined as hypovitaminosis D plasmatic values <30 ng/mL, vitamin D levels were considered as insufficient if between 20 and 30 ng/ mL and deficient if <20 ng/mL. We collected data regarding patients’ life habits and clinical history, disease course and disease clinical activity at enrollment. For BMD evaluation T-score and/or Z-score were calculated for each patient at lumbar (L1-L4) and femoral neck level, and the diagnosis of osteopenia or osteoporosis was made according to international guidelines. Results: We enrolled 88 patients (62 CD, 26 UC); median age at enrollment was 42 years for CD and 43 years for UC. Mean Body Mass Index (BMI) was 22.6 in CD and 23.7 in UC patients. Age at diagnosis was 29.8 years for CD and 33.5 years for UC, with mean disease duration of 12.8 years for CD and 9.1 years for UC.Hypovitaminosis D was observed in 84.1% of the patients. Of these, 31.8% had insufficient vitamin D levels, whereas 57.3% deficient. Mean vitamin D level was 20.4 ng/mL, but there was no difference with respect to sex or disease type. Indeed, there was no correlation between hypovitaminosis D and disease duration or patients age at diagnosis. A statistically significant correlation was found between hypovitaminosis D and history of steroid-dependancy (p=0.03), need of therapy with anti- TNF-α drugs (p=0.01) and cigarette smoke habit in CD patients (p=0.01). In CD patients we also found a correlation, at the limit of statistical significance (p=0.05), between hypovitaminosis D, high CRP values and HarveyBradshaw Index (HBI) at enrollment.70 patients underwent the lumbar DXA analysis, 67 the femoral DXA. Lumbar BMD was found to be below the normal range in 37.1% of the patients, suggesting that 24.2% and 12.9% were affected by osteopenia or osteoporosis, irrespective of sex and disease type (CD or UC). Similarly, femoral BMD was below the normal range for age in 43.3% of the patients. This figure is consistent with osteopenia or osteoporosis in 34.3% and 9%, irrespective of sex and disease type and femoral Z-score that was found significantly lower in CD than UC patients (p=0.03). Reduced BMD correlated with lower BMI and hypovitaminosis D. Conclusion: In our study we found a high prevalence of hypovitaminosis D in an IBD population irrespective of patients' sex, type and duration of disease. Our data show a strong correlation between hypovitaminosis D and a more aggressive disease course in terms of history of steroiddependancy, need of therapy with anti TNF-α drugs and smoke habit in CD patients. Hypovitaminosis D may play a crucial role in causing a more severe clinical behavior of IBD. Alteration of bone metabolism is a concern in IBD patients. We observed a high prevalence of BMD alterations in both men and women affected by UC and CD, even if of young age and with a short disease duration, irrespective of the type of IBD. Such patients may be prescribed lumbar and femoral, especially in cases of hypovitaminosis D and low BMI. This would allow an early diagnosis of BMD alterations, to start specific therapy and to prevent further complications.

Quantitative Assessment of Abdominal Aortic Calcifications Using Lateral Lumbar Radiograph, Dual-Energy X-ray Absorptiometry, and Quantitative Computed Tomography of the Spine

Abdominal aortic calcifications (AACs) represent an independent determinant of cardiovascular events and are strongly associated with cardiovascular disease. To our knowledge, a comparison between lateral lumbar radiography, lateral spine dual-energy x-ray absorptiometry (DXA), and quantitative computed tomography (QCT) in the assessment of AAC has not been performed. Our objective was to compare those methods in the detection and quantification of AAC using a simplified 8-point score system (AAC-8). Three hundred twenty-three postmenopausal women underwent lateral lumbar radiography, lateral spine DXA, and QCT for osteoporosis screening and were scored for AAC using the AAC-8. Lateral lumbar radiographs, lateral spine DXA, and QCT detected AAC in 58%, 55%, and 60% of the subjects, respectively. The nonparametric intraclass correlation coefficient between lateral lumbar radiograph and lateral spine DXA and lateral lumbar radiograph and QCT were 0.699 (95% confidence interval [CI]: 0.638–0.752) and 0.829 (95% CI: 0.783–0.865). Area under operating curve (receiver operating characteristic [ROC]) for lateral spine DXA was 0.826 (95% CI: 0.764–0.888), whereas for QCT was 0.948 (95% CI: 0.922–0.974) considering lateral lumbar radiograph as gold standard. AAC has been shown to be a significant predictive marker of overall cardiovascular disease. DXA may be a screening tool among asymptomatic patients with low radiation exposure to identify an important cardiovascular disease risk factor. QCT represents a reliable technique that may be applied as a future standard to facilitate the detection of abdominal aortic calcification as well as to provide more accurate measurement of bone densitometry.

Associated Factors and Liver Disease Severity for Decreased Bone Mineral Density in HIV Mono- and HIV/HCV Co-infected Patients

Objective: We assessed the prevalence and risk factors of decreased bone mineral density (BMD) in patients mono-infected with human immunodeficiency virus (HIV) or co-infected with hepatitis C virus (HIV/HCV). We also evaluated whether bone loss was linked to lipid asset in both groups and to severity of liver fibrosis in the co-infected group. Methods: We consecutively enrolled 194 HIV-patients (129 mono-infected and 65 co-infected). All HIV-patients underwent dual-energy X-ray absorptiometry (DXA), while co-infected patients underwent transient elastography. Advanced liver fibrosis was defined as a median liver stiffness ≥ 9.5 kPa. Fibrosis was also assessed in all the HIVpatients using FIB-4. Results: The overall prevalence of low BMD and osteoporosis was 26.8% and 26.0%, respectively. It was significantly higher among HIV/HCV co-infected than mono-infected patients in lumbar/femoral sites (P<0.04 and P<0.05, respectively). HDL-cholesterol levels correlated independently with lumbar DXA Z-score (P<0.03) in HIV mono-infected subjects. Liver stiffness correlated negatively and independently with femoral Z- and T-scores among co-infected patients (P<0.003; P<0.01, respectively). Stratifying co-infected subjects by sex, liver stiffness and lumbar/ femoral Z-scores (P<0.04) or T-scores (P<0.05; P<0.04, respectively) correlated negatively only in the females. Longer PI exposure was negatively and independently correlated with BMD. Conclusion: Our HIV-infected patients appeared at high risk for low BMD and osteoporosis. Severity of liver fibrosis was an independent predictor of bone loss in co-infection, although other factors could affect the skeletal system in HIV/HCV co-infection. Further research into the impact of liver fibrosis and lipid asset on bone disease in HIV-infection is necessary

Lack of clinical predictors for low mineral density in children with celiac disease.

Metabolic bone disease remains a significant and common complication of celiac disease (CD). Several studies have demonstrated low bone mineral density (BMD) at the time of CD diagnosis in both children and adults. Low BMD in children and adolescents is defined as an areal BMD <2 SD below the age-adjusted mean value (z score <-2 SD). The aim of the study was to evaluate the BMD in a pediatric population with CD at diagnosis and to correlate z score value, anti-tissue transglutaminase type 2 antibody (anti-tTG2) titer, symptoms, and Marsh-Oberhuber (MO) grading. We enrolled 99 patients with celiac disease (male 35, female 64) ages 4 to 15 years at the diagnosis. All of the patients had positive test results for anti-tTG2 antibodies and histological lesions graded according to MO classification, and underwent lumbar dual-energy x-ray absorptiometry. BMD was estimated by z score. Low BMD (z score ≤-2 SD) was found in 13 (13.13%) patients; 22 (22.22%) patients with CD showed -2 < z score ≤ -1; -1 < z score < 0 was found in 41 (41.41%) patients. z score ≥ 0 was detected only in 23 (23.23%) patients with CD. Mean BMD value in patients with CD is z score -0.68. No correlations were found between z score value and anti-tTG2 titer (Spearman ρ 0.13), between z score value and MO degree (Spearman ρ -0.17), and between z score and symptoms (Spearman ρ-0.10). BMD of patients with CD at diagnosis does not seem to correlate with MO degree, anti-tTG2 titer, and symptoms. At the moment, we do not have clinical predictors for low mineral density in children with CD.

Bone Densitometry in Infants and Young Children: The 2013 ISCD Pediatric Official Positions

Infants and children <5 yr were not included in the 2007 International Society for Clinical Densitometry Official Positions regarding Skeletal Health Assessment of Children and Adolescents. To advance clinical care of very young children, the International Society for Clinical Densitometry 2013 Position Development Conference reviewed the literature addressing appropriate methods and skeletal sites for clinical dual-energy X-ray absorptiometry (DXA) measurements in infants and young children and how results should be reported. DXA whole-body bone mineral content and bone mineral density for children ≥3 yr and DXA lumbar spine measurements for infants and young children 0–5 yr were identified as feasible and reproducible. There was insufficient information regarding methodology, reproducibility, and reference data to recommended forearm and femur measurements at this time. Appropriate methods to account for growth delay when interpreting DXA results for children <5 yr are currently unknown. Reference data for children 0–5 yr at multiple skeletal sites are insufficient and are needed to enable interpretation of DXA measurements. Given the current scarcity of evidence in many areas, it is likely that these positions will change over time as new data become available.

Short-term Precision Error in Dual Energy X-Ray Absorptiometry, Bone Mineral Density and Trabecular Bone Score Measurements; and Effects of Obesity on Precision Error

Introduction: Bone mineral density (BMD) measured by dual energy x-ray absorptiometry (DXA) is the primary screening tool for diagnosis of osteopenia and osteoporosis. BMD alone does not provide information regarding the structural characteristics of bone and this limitation has been a driver for the development of techniques, including trabecular bone score (TBS) software, to assess bone microarchitecture. Precision error in DXA is important for accurately monitoring changes in BMD and it has been demonstrated that BMD precision error increases with increasing body mass index (BMI). Information on in vivo precision error for TBS is very limited. This study evaluated short-term precision error (STPE) of lumbar spine BMD & TBS measurement, and investigated the effect of obesity on DXA precision error. Method: DXA lumbar spine scans (L1-L4) were performed using GE Lunar Prodigy. STPE was measured in ninety-one women at a single visit by duplicating scans with repositioning in-between. Precision error was calculated as the percentage coefficient of variation. Participants were sub-divided into four groups based on BMI to assess the effect of obesity on STPE. Results: STPE is poorer for TBS than for BMD. STPE is adversely affected for both BMD and TBS measurements by increasing BMI but this effect is mitigated for TBS in the highest BMI category where use of the thick scanning mode improves signal to noise ratio. Conclusion: Results from serial BMD and TBS measurements should take account of differences in precision error in the two techniques and in different BMI categories.

The Relationship between H. pylori Infection and Osteoporosis in Japan.

Background and Objective. H. pylori infection causes a chronic inflammation in the gastric mucosa. However, this local inflammation may result in extra-digestive conditions. Our aim is to investigate the relationship between H. pylori infection and osteoporosis in Japan. Methods. This cross-sectional study was conducted among outpatients at the Juntendo University Hospital between 2008 and 2014. Participants for patient profile, H. pylori infection status, comorbidity, internal medical therapies, lumbar dual-energy X-ray absorptiometry (DXA), and bone turnover marker were collected and upper gastrointestinal endoscopy for reflux esophagitis, hiatal hernia, peptic ulcer disease (PUD), and endoscopic gastric mucosal atrophy (EGA) was performed. The diagnosis of osteoporosis was performed in accordance with the Japanese criteria. We investigated risk factors of osteoporosis. Results. Of the eligible 200 study subjects, 41 cases were of osteoporosis. Bivariate analysis showed that age, being female, BMI, alcohol, smoking, H. pylori, bone-specific ALP, PUD, and EGA were related to osteoporosis. Multivariate analysis showed that age (OR 1.13; 95%CI 1.07–1.20), being female (OR 4.77; 95%CI 1.78–12.77), BMI (OR 0.79; 95%CI 0.68–0.92), H. pylori (OR 5.33; 95%CI 1.73–16.42), and PUD (OR 4.98; 95%CI 1.51–16.45) were related to osteoporosis. Conclusions. H. pylori infection may be a risk factor of osteoporosis in Japan.

Spine Trabecular Bone Score Subsequent to Bone Mineral Density Improves Fracture Discrimination in Women

Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis and assess fracture risk. However, DXA cannot evaluate trabecular microarchitecture. This study used a novel software program (TBS iNsight; Med-Imaps, Geneva, Switzerland) to estimate bone texture (trabecular bone score [TBS]) from standard spine DXA images. We hypothesized that TBS assessment would differentiate women with low trauma fracture from those without. In this study, TBS was performed blinded to fracture status on existing research DXA lumbar spine (LS) images from 429 women. Mean participant age was 71.3 yr, and 158 had prior fractures. The correlation between LS BMD and TBS was low (r = 0.28), suggesting these parameters reflect different bone properties. Age- and body mass index–adjusted odds ratios (ORs) ranged from 1.36 to 1.63 for LS or hip BMD in discriminating women with low trauma nonvertebral and vertebral fractures. TBS demonstrated ORs from 2.46 to 2.49 for these respective fractures; these remained significant after lowest BMD T-score adjustment (OR = 2.38 and 2.44). Seventy-three percent of all fractures occurred in women without osteoporosis (BMD T-score > −2.5); 72% of these women had a TBS score below the median, thereby appropriately classified them as being at increased risk. In conclusion, TBS assessment enhances DXA by evaluating trabecular pattern and identifying individuals with vertebral or low trauma fracture. TBS identifies 66–70% of women with fracture who were not classified with osteoporosis by BMD alone.

The Association Between Osteoporosis and Hypertension: The Role of A Low Dairy Intake

Hypertension and related cardiovascular diseases are reported to be associated with osteoporosis. A nutritional pathway related to dairy intake has been postulated for both diseases. The aim of this study was to assess calcium intake from dairy sources as a possible pathogenic link between osteoporosis and hypertension. This was a cross-sectional observational study performed on 3,301 postmenopausal women referred for a densitometry screening. Osteoporosis was diagnosed by lumbar dual-energy X-ray absorptiometry and hypertension was defined by blood pressure data and/or the use of antihypertensive medication. Dairy food consumption was evaluated using a weekly food-frequency questionnaire. The odds of being affected by osteoporosis, hypertension, or both diseases were calculated for quartiles of dairy intake by logistic regression analyses. Women with hypertension were affected more frequently by osteoporosis (33.2 vs. 23.3 %; p = 0.000), and there was a higher prevalence of hypertension among women with osteoporosis (32.2 vs. 22.5 %; p = 0.000). The proportion of women with hypertension, osteoporosis, and both diseases significantly increased across decreasing quartiles of dairy intake. A dairy intake in the lowest quartile was a significant predictor of osteoporosis [OR (95 % CI): 1.43 (1.12, 1.82)] and hypertension [OR (95 % CI): 1.46 (1.15, 1.85)] when compared to the highest quartile. Similarly, a low dairy intake was associated with increased odds to have both the diseases [OR (95 % CI): 1.60 (1.10, 2.34)]. From these results we conclude that osteoporosis and hypertension are associated in postmenopausal women, and a low dairy intake may increase the risk of both diseases, acting as a possible pathogenic link.

Proximal humerus cortical bone thickness correlates with bone mineral density and can clinically rule out osteoporosis

Bone mineral density measurements with dual-energy x-ray absorptiometry (DXA) are commonly used to diagnose osteoporosis and assess fracture risk. This study describes the association between radiographic measures of proximal humeral cortical bone thickness and bone mineral density measured by DXA. The study also assesses the discriminative capability of clinical cortical bone thickness measurements at the proximal humerus to differentiate patients with osteoporosis. Patients (N = 108) with shoulder radiographs and DXA studies were evaluated. Cortical bone thickness was assessed with 2 techniques, the gauge method and the average method. Pearson correlations were used to describe the relationship between cortical bone thickness measurement techniques and femoral and lumbar DXA. Sensitivity, specificity, and negative predictive value for predicting osteoporosis were determined for several cortical bone thickness thresholds. Rater reliability of measures was assessed with intraclass correlation coefficients. The intra-rater and inter-rater reliability of measures was excellent (intraclass correlation coefficient > 0.85). Average cortical bone thickness measurements at the proximal humerus strongly correlated with DXA femur measurements (r = 0.64, P < .0001) and moderately correlated with DXA lumbar measurements (r=0.49, P < .0001). Gauge cortical thickness measurements also correlated with DXA femur measurements (R = 0.53, P < .0001) and DXA lumbar measurements (R = 0.35, P < .001). An average proximal humerus cortical thickness measurement of 6 mm was identified as a potential threshold value for predicting osteoporosis, with a sensitivity of 93%, specificity of 52%, and negative predictive value of 95%. Average cortical bone thickness measurements obtained from standard anteroposterior shoulder radiographs are correlated with DXA. Furthermore, they provide a clinically relevant, rapid, sensitive, and inexpensive method for ruling out osteoporosis.

Association between degenerative spondylolisthesis and spinous process fracture after interspinous process spacer surgery

Spinous process fracture is a recognized complication associated with interspinous process spacer (IPS) surgery. Although occasionally identified by plain radiographs, computed tomography (CT) appears to identify a higher rate of such fractures. Although osteoporotic insufficiency fracture is considered a contraindication for IPS surgery, a formal risk factor analysis for this complication has not previously been reported. To identify risk factor(s) associated with early spinous process fracture after IPS surgery. Prospective cohort study of 39 consecutive patients with lumbar stenosis and neurogenic claudication undergoing IPS surgery at a single institution. Patients underwent preoperative dual-energy X-ray absorptiometry (DXA) scans, lumbar spine CT, and plain radiographs. Postoperatively, patients underwent repeat CT imaging within 6 months of surgery and serial radiographs at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year. Preoperative CT scans were analyzed by calculating average Hounsfield units for a 1 cm(2) area of the midsagittal reconstructed image for four separate locations: midvertebral body, subcortical bone subjacent to the superior margin of the midspinous process, subcortical bone above the inferior margin of the midspinous process, and the midspinous process. Thirty-eight patients underwent IPS surgery at a total of 50 levels (38 L4-L5, 12 L3-L4; 26 one-level, 12 two-level). One patient underwent laminectomy at index surgery and was excluded from the analysis. Implants included 34 titanium X-STOP (Medtronic, Memphis, TN, USA), 8 polyaryletheretherketone X-STOP (Medtronic, Memphis, TN, USA), and 8 Aspen (Lanx, Broomfield, CO, USA) devices. Eleven spinous process fractures were identified by CT in 11 patients (22.0% of levels). No fractures were apparent on plain radiographs. The rate of spondylolisthesis observed on preoperative radiographs was 100% (11 of 11) among patients with fractures compared with 33.3% (9 of 27) of patients without fracture (p=.0001). Overall, 21 of 39 patients in this series had spondylolisthesis, and the rate of fracture in this group was 52%. Among patients without spondylolisthesis, the fracture rate was 0%. A trend was observed toward decreased DXA lumbar spine and hip T-scores among fracture patients versus nonfracture patients (0.2 ± 1.7 vs. 0.8 ± 1.7; p=.389; -1.1 ± 1.4 vs. -0.3 ± 1.4; p=.201), but these differences were not significant. Similarly, bone density based on CT measurements at four different locations revealed a trend toward decreased density among fracture patients, but these differences were not significant. Degenerative spondylolisthesis appears strongly associated with the occurrence of spinous process fracture after IPS surgery. There is a trend toward increased fracture risk in patients with decreased bone mineral density as measured by both DXA scan and CT-based volume averaging of Hounsfield units, but osteoporosis appears to be a relatively weaker risk factor. The association between spondylolisthesis and fracture observed in this study may account for the relatively poorer outcome of IPS surgery in patients with spondylolisthesis that has been reported in previous series.

Response to “Vertebral fracture and intervertebral discs”

We thank Drs. Adams and Dolan for their interest in our work and the opportunity to further discuss the association between vertebral bone mineral density (BMD) and disc degeneration (DD) in the lumbar spine. Their comments arise from our discussion of study limitations, in which we acknowledged that ‘‘the age of our subjects was relatively young and a mean age of 50 years is probably too young to determine the full extent of the association studied.’’ We went on to speculate that there may be a stronger association between greater vertebral BMD and more severe DD in older spines, which they question. This was, of course, only speculation, as the association in the elderly could not be addressed with our data and was based on a number of previous studies of elderly women that revealed an association between greater vertebral BMD and more severe lumbar DD. In one such study of 630 women older than 60 years (73.3 6.9 years), higher dual-energy X-ray absorptiometry (DXA) lumbar spine BMD was associated with greater disc space narrowing and Kellgren-Lawrence DD scores. In another study of older women (>60 years, 72.8 6.6 years), greater radiographic disc space narrowing was found to associate with both anterior-posterior and lateral DXA vertebral BMD measurements. An association between greater disc bulging and higher DXA lumbar vertebral BMDwas also observed in women aged up to 86 years. Such associations, however, have been less studied in men, although a similar association between greater disc space narrowing and lumbar BMD acquired with DXA was observed in a cohort of 250 men (65.4 9.0 years). We were not suggesting that the relation between the structure and function of the vertebrae and discs is a simple one. Although our study was not designed to investigate underlying mechanisms of the BMD-DD association we identified, particularly in older spines, it is an important and interesting topic that Adams and Dolan highlight. Adams and Dolan discuss a possible mechanism that could lead to focal bone loss–related specifically to severe disc narrowing, seen in late-stage DD, which may be particularly relevant in the elderly. In pursuing such knowledge, distinguishing different definitions of lumbar vertebral BMD is of great importance. Whereas BMD measured using DXA is areaadjusted, BMD measured with QCT or micro–computed tomography (mCT) is volume-adjusted. The measurements acquired in the study by Adams and colleagues, are substantially different from those used in our study. They used measures of regional bone architecture parameters, such as bone volume/total volume (BV/TV) and trabecular thickness (Tb.Th), to examine focal bone variations, whereas we measured global BMD of the whole vertebra and its vertebral body. Thus, the two studies are not directly comparable. Causal inferences are uncertain and the chicken and egg dilemma remains in cross-sectional studies, including those of the BMD-DD relation. Adams’ and Dolan’s view that ‘‘in middle age, dense vertebral bone may promote disc degeneration’’ is one possible explanation for the association observed between vertebral body BMD and DD, but there are others. We did not suggest and do not agree with the view that vertebral BMD is likely to interfere withmetabolite transport through the vertebral endplate, because we did not observe an association between endplate BMD and DD in a previous study. On the other hand, we agree with Adams and colleagues that severe disc narrowing may shift more mechanical loading posteriorly to the facet joints and thus, stress-shield the anterior vertebral body. As for the measurement of disc degeneration, disc space narrowing was not selected because it is a nonspecific DD indicator and cannot reflect early DD. Furthermore, disc height measurements are prone to bias by osteophytes and endplate sclerosis, which likely are confounders of the BMD-DD association. Therefore, we used discography, which can display ‘‘successive stages in disc degeneration,’’ as a superior measure to disc space narrowing. As we have discussed in detail, although it is possible that DD is influenced by altered mechanical loading due to BMD changes, it is also possible that elevated BMD is an adaption of the vertebral bone to the changing mechanical environment related to DD. Therefore, we agree with Adams’ and Dolan’s view that ‘‘interactions between vertebrae and their adjacent discs cannot be summarized simply.’’ REPLY JBMR

Changes in Body Composition and Mitochondrial Dna in HIV-1-Infected Patients Switching to Fixed-Dose Abacavir/Lamivudine or Tenofovir/Emtricitabine: A Substudy of the Bicombo Trial

Fat distribution, bone mineral density (BMD) and mitochondrial DNA (mtDNA) may improve, in the long-term, after switching from nucleoside reverse transcriptase inhibitors (NRTIs) to fixed-dose abacavir (ABC)/lamivudine (3TC) or tenofovir (TDF)/emtricitabine (FTC). This was a prospective, randomized, open-label, multicentre substudy of the BICOMBO trial in which virologically suppressed patients had their NRTIs switched to ABC/3TC or TDF/FTC. Whole-body dual-energy X-ray absorptiometry (DXA) was used to measure limb, trunk and total body fat and total BMD. Lumbar and hip DXA scans were used to measure lumbar and hip BMD. Fat mass ratio (FMR; % trunk fat/% leg fat by whole-body DXA) was used to assess fat distribution. mtDNA was measured in peripheral blood mononuclear cells (PBMCs). Parameters of interest were measured at baseline, 48 and 96 weeks, and were compared between treatment groups. Of 56 patients included, 45 (20 ABC/3TC and 25 TDF/FTC) completed the substudy. After 96 weeks, ABC/3TC (+756 g, +12.1%) and TDF/FTC (+337 g, +7.6%) led to non-significantly different increases in limb fat (P=0.60). By contrast, trunk fat showed a significant increase (P=0.04) with ABC/3TC (+1,184 g, +10.6%) relative to TDF/FTC (-370 g, -4.2%). Median (IQR) FMR remained unchanged with ABC/3TC (-0.01 [-0.16-0.06]; P=0.23), but it decreased significantly with TDF/FTC (-0.13 [-0.30-0.00]; P=0.007). Total BMD and mtDNA significantly increased after 96 weeks, without differences between groups. Switching from NRTIs to either ABC/3TC or TDF/FTC led to similar increases in limb fat, BMD and PBMC mtDNA after 96 weeks.

Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment

IntroductionOsteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.MethodsMethods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).ResultsAS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.ConclusionsOsteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.

The Influence of Exogenous Fat and Water on Lumbar Spine Bone Mineral Density in Healthy Volunteers

PurposeChanges in human body composition can affect the accuracy of spine bone mineral density (BMD) measurements. The purpose of this study was to evaluate whether fat and water in the soft tissue of the abdomen influence lumbar spine BMD measurements obtained using dual energy X-ray absorptiometry (DXA).Materials and MethodsDuplicate BMD measurements were carried out on healthy volunteers (10 men and 10 women) and the Hologic anthropomorphic spine phantom had on the same day before and after placement of following 3 materials in the abdominal area: lard 900 g, 1.5 cm thick; oil 1.4 liters in a vinyl bag; and water 1.2 liters in a vinyl bag.ResultsIn the case of human participants, following the placement of exogenous water to mimic extracellular fluid (ECF), there was a significant decrease in lumbar spine BMD (-0.012 g/cm2, p=0.006), whereas the placement of exogenous lard and oil to mimic abdominal fat produced a slight increase in lumbar spine BMD (0.006 g/cm2, p=0.301; 0.008 g/cm2, p=0.250, respectively). The average percentage of lumbar spine BMD change with and without exogenous lard, oil, and water showed increase of 0.51%, and 0.67%, and decrease of 1.02%, respectively. Using the phantom, BMD decreased with the placement of both lard (-0.002 g/cm2, p=0.699) and water (-0.006 g/cm2, p=0.153); however, there was no difference in BMD after oil placement.ConclusionThese results suggest that in cases where changes in fat and ECF volume are similar, ECF exerts a greater influence than fat on DXA lumbar BMD measurements.

Determination of Osteopenia in Children on Digital Radiography Compared with a DEXA Reference Standard

The aim of this study was to explore the reliability of osteopenia diagnosis based on digital radiographs of appendicular skeleton obtained as part of routine clinical practice as compared with dual-energy x-ray absorptiometry (DEXA) gold standard (Z-score <-1). The study was an institutional review board-approved retrospective study of 58 children (mean age 12 years [4-18]). Digital radiographs of appendicular skeleton obtained within 6 months of DEXA scanning were presented in a blinded fashion to two musculoskeletal radiologists who were instructed to grade the level of mineralization. Sensitivity and specificity of each reviewer's osteopenia grading were calculated in comparison to lumbar DEXA Z-score values. Interobserver agreement was also calculated and significance evaluated with Bowker's test. The reviewers correctly identified 28% of all patients with severe osteopenia (Z-score ≤-2.0) as well as 26% of all patients with mild osteopenia (-2< Z-score <-1). Interobserver agreement for the correct diagnosis of bone mineral density (BMD) category ranged from 71% for normal BMD (Z-score >-1) to 0 and 25% for mild and severe osteopenia respectively. Visual diagnosis of osteopenia based on digital radiographs of appendicular skeleton has poor sensitivity and interobserver agreement. Clinical features and risk factors of pediatric patients should therefore guide DEXA evaluation and treatment recommendations.

Quantitative ultrasound of the phalanges and DXA of the lumbar spine and proximal femur in evaluating the risk of osteoporotic vertebral fracture in postmenopausal women

This study was undertaken to compare the quantitative ultrasound (QUS) parameters of amplitude-dependent speed of sound (AD-SoS) and ultrasound bone profile index (UBPI) of the phalanges with bone mineral density (BMD) of the lumbar spine and proximal hip using dual-energy X-ray absorptiometry (DXA) in discriminating women with vertebral fracture. A total of 692 postmenopausal Caucasian women were included in the study. The presence of vertebral fracture was evaluated by radiography. AD-SoS and UBPI were measured at the phalangeal metaphysis using a DBM Sonic device. Multiple logistic regression analysis was performed to estimate the odds ratio (OR) for vertebral fractures. The ORs were also adjusted for the significant anthropometric variables of age, weight and height. Furthermore, for QUS parameters, the ORs were also adjusted for lumbar spine and total hip BMD. All measurements obtained with DXA and QUS significantly discriminated between women with and without fractures (p<0.0001). However, the OR was higher for lumbar spine BMD (OR 4.01), AD-SoS (OR 3.81), total hip (OR 3.7) and femoral neck BMD (OR 3.62). The QUS parameter AD-SoS showed diagnostic sensitivity equal to that of lumbar DXA in discriminating between women with and without osteoporotic vertebral fractures.

Prevalence of low bone mineral density in a low-income inner-city population.

Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole-body dual-energy X-ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site-specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T-score of –2.5 or less for men 50 years of age and older and postmenopausal women and a Z-score of –2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African-American, middle-aged people with a high prevalence of illicit drug use, 50% HIV+, and 39% hepatitis C+. Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole-body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD. © 2011 American Society for Bone and Mineral Research.