Body size influences bone mineral density (BMD) in health. Relationships of BMD with body mass index, fat mass (FM), fat-free mass, and appendicular lean mass were explored in acute lymphoblastic leukemia (ALL) survivors (n=75; 41 males; 45 standard risk ALL) >10 years from diagnosis. Dual energy radiograph absorptiometry performed body composition analysis. Relationships were assessed by regression analyses and Pearson correlation coefficients (r). Twenty subjects (26.3%) were osteopenic; lumbar spine (LS) BMD Z score <-1.00. Age at diagnosis, sex, ALL risk-category, type of post-induction steroid or cranial radiation did not correlate with LS or whole body (WB) BMD. Body mass index correlated significantly with LS BMD (r=0.333, P=0.004) and WB BMD (r=0.271, P=0.033). FM index (FM/height²) Z score showed no significant correlation with LS or WB BMD. Fat-free mass index Z score correlated strongly with LS BMD (r=0.386, P=0.013) and WB BMD (r=0.605, P<0.001) in males but not in females. The appendicular lean mass index, a surrogate for skeletal muscle mass, correlated significantly with LS BMD (r=0.367, P=0.018) and WB BMD (r=0.604, P<0.001) in males but not in females. Future studies to evaluate interventions to enhance BMD focused on improving body composition particularly skeletal muscle mass are warranted.

Objective and Approach: A study, conducted in Toronto, Canada, between 2009 and 2011, measured the bone lead concentrations of volunteers aged 1-82 years using in vivo x-ray fluorescence (XRF) technology. Main results: Bone lead levels were lower compared to Ontario in vivo XRF studies from the early 1990s. In adults, the slope of tibia lead content versus age was reduced by 36-56%, i.e. bone lead levels for a given age group were approximately half compared to the same age group 17 years prior. Further, bone lead levels of individuals fell over that time period. In 2010, an average person aged 57 years had a bone lead level approximately 1/3 less than their bone lead level age 40 years in 1993. Using this data, the half-lives of lead in the tibia were estimated as 7-26 years. Tibia lead levels were found to be low in children. The reduction in bone tibia content in children was not significant (p = 0.07), but using data from additional north eastern US studies, there is evidence that childhood tibia stores are lower than in the 1990s. Significance: In vivo XRF analysis shows that there has been a reduction in the level of lead in bone in Canada over the last two decades. Public health measures have been very successful in reducing ongoing exposure to lead and in reducing bone lead stores.

BACKGROUND:The late effects of treatment for acute lymphoblastic leukemia (ALL) include disordered body composition, especially obesity. Less attention has been focused on the loss of skeletal muscle mass (SMM) and the combined morbidity of sarcopenic obesity. METHODS:A cross-sectional study of body composition was undertaken via dual-energy x-ray absorptiometry in 75 long-term survivors of ALL (more than 10 years after the diagnosis). Measures were obtained of the fat mass (FM), fat-free mass (equivalent to the lean body mass [LBM]), and whole-body bone mineral content. Health-related quality of life (HRQL) was measured with the Health Utilities Index. RESULTS:The sum of the FM, LBM, and whole-body bone mineral content matched the total body weight measured directly (r = 0.998). The appendicular lean mass (ALM) was derived from the LBM in all 4 limbs and accounted for approximately 75% of the SMM. According to the fat mass index (FMI; ie, FM/height2 ), 12% of females and 18% of males were frankly obese by World Health Organization criteria. The median FMI z score was + 0.40, whereas the median z score for the appendicular lean mass index (ALMI; ie, ALM/height2 ) was -0.40. Sarcopenic obesity, defined as a positive FMI z score with a negative ALMI z score, was present in 32 subjects (43%). There were statistically significant and clinically important differences in overall HRQL between subjects with and without sarcopenic obesity. CONCLUSIONS:Sarcopenic obesity is prevalent in long-term survivors of ALL, and this places them in double jeopardy from excess body fat and inadequate SMM (eg, a combination of metabolic and frailty syndromes). It is associated with an adverse impact on overall HRQL. Cancer 2018;124:1225-31. © 2017 American Cancer Society.

Part II of this 3-part series demonstrated 1-yr precision, standard error of the estimate, and 1-yr least significant change for volumetric bone outcomes determined using peripheral (p) quantitative computed tomography (QCT) and peripheral magnetic resonance imaging (pMRI) modalities in vivo. However, no clinically relevant outcomes have been linked to these measures of change. This study examined 97 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m 2 , demonstrating a lack of association between fragility fractures and standard deviation, least significant change and standard error of the estimate-based unit differences in volumetric bone outcomes derived from both pMRI and pQCT. Only cortical volumetric bone mineral density and cortical thickness derived from high-resolution pQCT images were associated with an increased odds for fractures. The same measures obtained by pQCT erred toward significance. Despite the smaller 1-yr and short-term precision error for measures at the tibia vs the radius, the associations with fractures observed at the radius were larger than at the tibia for high-resolution pQCT. Unit differences in cortical thickness and cortical volumetric bone mineral density able to yield a 50% increase in odds for fractures were quantified here and suggested as a reference for future power computations.

The previous article in this 3-part series demonstrated short-term precision and validity for volumetric bone outcome quantification using in vivo peripheral (p) quantitative computed tomography (pQCT) and magnetic resonance imaging (MRI) modalities at resolutions 200 μm or higher. However, 1-yr precision error and clinically significant references are yet to be reported for these modalities. This study examined 59 women with mean age of 75 ± 9 yr and body mass index of 26.84 ± 4.77 kg/m², demonstrating the lowest 1-yr precision error, standard errors of the estimate, and least significant change values for high-resolution (hr) pQCT followed by pQCT, and 1.0-T pMRI for all volumetric bone outcomes except trabecular number. Like short-term precision, 1-yr statistics for trabecular separation were similar across modalities. Excluding individuals with a previous history of fragility fractures, or who were current users of antiresorptives reduced 1-yr change for bone outcomes derived from pQCT and pMR images, but not hr-pQCT images. In Part II of this 3-part series focused on trimodality comparisons of 1-yr changes, hr-pQCT was recommended to be the prime candidate for quantifying change where smaller effect sizes are expected, but pQCT was identified as a feasible alternative for studies expecting larger changes.

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76±8, body mass index (BMI): 26.74±4.26kg/m2) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using 109Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200μm in-plane resolution, 2.3±0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (−0.972 (−1.882, −0.061) per 100μg Pb/g of bone mineral) and integral volumetric BMD (−3.05 (−6.05, −0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (−26.83 (−50.37, −3.29)) and trabecular number (−0.08 (−0.14, −0.02)), per 100μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD.

The K‐shell X‐ray fluorescence technique that was developed for measurement of lead in bone in living human subjects was applied to measurement of lead in archived human bone samples. The skull from a person who had suffered from Paget's disease was found to have lead concentrations of 97.5±3.6–532.2±3.2 µg Pb/g bone mineral. A femur sample from a different person, who had also suffered from Paget's disease, had a lead concentration of 18–43.5 with uncertainties between 1.6 and 2.0 µg Pb/g bone mineral. The skull lead concentrations were highly raised compared with findings from in vivo bone Pb measurements, whereas the femur lead concentrations were somewhat raised. In the past, the hypothesis has been put forward that lead can be involved in the etiology of Paget's disease; however, other reports in the literature have not supported that hypothesis. The current findings, while intriguing, are too few to be in any way conclusive but merit further study. Copyright © 2015 John Wiley & Sons, Ltd.

The biological effects of exposure to radioactive fluorodeoxyglucose (18F-FDG) were investigated in the lymphocytes of patients undergoing positron emission tomography (PET) procedures. Low-dose, radiation-induced cellular responses were measured using 3 different end points: (1) apoptosis; (2) chromosome aberrations; and (3) γH2AX foci formation. The results showed no significant change in lymphocyte apoptosis, or chromosome aberrations, as a result of in vivo 18F-FDG exposure, and there was no evidence the PET scan modified the apoptotic response of lymphocytes to a subsequent 2 Gy in vitro challenge irradiation. However, lymphocytes sampled from patients following a PET scan showed an average of 22.86% fewer chromosome breaks and 39.16% fewer dicentrics after a subsequent 2 Gy in vitro challenge irradiation. The effect of 18F-FDG exposure on phosphorylation of histone H2AX (γH2AX) in lymphocytes of patients showed a varied response between individuals. The relationship between γH2AX foci formation and increasing activity of 18F-FDG was not directly proportional to dose. This variation is most likely attributed to differences in the factors that combine to constitute an individual’s radiation response. In summary, the results of this study indicate18F-FDG PET scans may not be detrimental but can elicit variable responses between individuals and can modify cellular response to subsequent radiation exposures.

Permanent joint damage is a major consequence of rheumatoid arthritis (RA), the most common and destructive form of inflammatory arthritis. In aggressive disease, joint damage can occur within 6 months from symptom onset. Early, intensive treatment with conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) can delay the onset and progression of joint damage. The primary objective of the study is to investigate the value of magnetic resonance imaging (MRI) or radiography (X-ray) over standard of care as tools to guide DMARD treatment decision-making by rheumatologists for the care of RA.

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 μm or higher. However, validity and in vivo test-retest reproducibility of apparent bone microstructure have yet to be determined on 1.0 T pMRI (196 μm) and pQCT (200 μm). This study examined 67 women with a mean age of 74 ± 9 yr and body mass index of 27.65 ± 5.74 kg/m2, demonstrating validity for trabecular separation from pMRI, cortical thickness, and bone volume fraction from pQCT images compared with high-resolution pQCT (hr-pQCT), with slopes close to unity. However, because of partial volume effects, cortical and trabecular thickness of bone derived from pMRI and pQCT images matched hr-pQCT more only when values were small. Short-term reproducibility of bone outcomes was highest for bone volume fraction (BV/TV) and densitometric variables and lowest for trabecular outcomes measuring microstructure. Measurements at the tibia for pQCT images were more precise than at the radius. In part I of this 3-part series focused on trimodality comparisons of precision and validity, it is shown that pQCT images can yield valid and reproducible apparent bone structural outcomes, but because of longer scan time and potential for more motion, the pMRI protocol examined here remains limited in achieving reliable values.

Maintenance of adequate nutrition is important in the care of children with cancer. In clinical practice, determination of nutritional status can be accomplished with measurement of body composition by dual-energy x-ray absorptiometry (DXA). However, DXA is seldom available in low-income countries where most children with cancer live. This study sought to provide predictive equations for lean body mass and fat mass, measured by DXA, on the basis of simple arm anthropometry providing measures of mid-upper arm circumference and triceps skin-fold thickness in a population (N=99) of children diagnosed with cancer. Such equations were derived successfully with the inclusion of absolute body weight, the body weight Z-score, and the predicted whole-body bone mineral content on the basis of age and sex. Attempted validation in a small sample (N=7) of children who completed therapy for acute lymphoblastic leukemia revealed disparities reflective of the prevalence of obesity in such survivors. Further validation must be undertaken in large samples of children with a variety of malignant diseases to assess the robustness of the equations predictive of body composition.

Children with acute lymphoblastic leukemia experience musculoskeletal morbidity during therapy. We examined the patterns of change in skeletal muscle mass (SMM) and the relationship between change in SMM and the burden of illness as reflected in days of hospitalization. Ninety-one children had dual energy x-ray absorptiometry (DXA scans) during treatment, yielding the sum of lean tissue mass in all 4 limbs; the appendicular lean mass. SMM was derived from appendicular lean mass. The number of inpatient days was recorded. DXA scans at 5 time points showed a profile of change in SMM characterized by a drop in the mean Z score from -0.18 at diagnosis to -1.08 after 6 months of therapy, with a partial recovery 12 to 24 months after diagnosis. Levels of serum creatinine, a surrogate measure of SMM, were mainly unchanged. The extent of the drop in SMM during early therapy was associated with the duration of hospitalization (r=0.31, P < 0.05). Children with acute lymphoblastic leukemia experience a notable reduction in SMM early in treatment, with incomplete recovery. The degree of loss is associated with the burden of illness. These findings provide a target for a therapeutic intervention and a measure to determine its efficacy.

Strontium ranelate is an approved pharmacotherapy for osteoporosis in Europe and Australia, but not in Canada or the United States. Strontium citrate, an alternative strontium salt, however, is available for purchase over-the-counter as a nutritional supplement. The effects of strontium citrate on bone are largely unknown. The study's objectives were 1) to quantify bone strontium accumulation in female Sprague Dawley rats administered strontium citrate (N = 7) and compare these levels to rats administered strontium ranelate (N = 6) and vehicle (N = 6) over 8 weeks, and 2) to verify an in vivo X-ray fluorescence spectroscopy (XRF) system for measurement of bone strontium in the rat. Daily doses of strontium citrate and strontium ranelate were determined with the intention to achieve equivalent amounts of elemental strontium. However, post-hoc analyses of each strontium compound conducted using energy dispersive spectrometry microanalysis revealed a higher elemental strontium concentration in strontium citrate than strontium ranelate. Bone strontium levels were measured at baseline and 8 weeks follow-up using a unique in vivo XRF technique previously used in humans. XRF measurements were validated against ex vivo measurements of bone strontium using inductively coupled plasma mass spectrometry. Weight gain in rats in all three groups was equivalent over the study duration. A two-way ANOVA was conducted to compare bone strontium levels amongst the three groups. Bone strontium levels in rats administered strontium citrate were significantly greater (p < 0.05) than rats administered strontium ranelate and vehicle. ANCOVA analyses were performed with Sr dose as a covariate to account for differences in strontium dosing. The ANCOVA revealed differences in bone strontium levels between the strontium groups were not significant, but that bone strontium levels were still very significantly greater than vehicle.

The primary purpose was to estimate intrarater reliability of vertebral body height (VH) measures in postmenopausal women based on duplicate analyses of vertebral fracture assessment (VFA) images. The secondary purpose was to determine the consistency in classification of vertebral deformity on duplicate analyses. Thirty-two VFA were randomly selected from a database of 464 scans acquired in postmenopausal women using dual-energy X-ray absorptiometry (Discovery A; Hologic Inc., Waltham, MA). Visible endplates were marked on each image on 2 occasions (4 wk apart) by a single rater; the semiautomated software derived measures of anterior, middle, and posterior VH and classified severity of vertebral deformity. Intrarater reliability was assessed using the intraclass correlation coefficient (with 95% confidence interval [CI]) when ≥ 22 VFA could be analyzed. Reliability of grading deformity of 267 vertebrae was assessed using Cohen's unweighted kappa (with 95% CI). Reliability of anterior, middle, and posterior height measures from T8 to L4 was 0.85 and greater except for T8 anterior VH and T9 posterior VH (0.76 [0.43, 0.90] and 0.62 [0.15, 0.83], respectively). Chance-corrected agreement for 4 grades of vertebral deformity was 0.48 (0.30, 0.66) and for 2 categories (normal/mild and moderate/severe) was 0.70 (50, 0.90). Intrarater reliability was acceptable for VH measures from T10 to L4. Reliability in grading severity of deformity was improved by classifying as <25% deformity (nonfracture) and as >25% deformity (fracture).

AIM: To establish the prevalence of vertebral fracture (VF) in a representative sample of 750 Canadians and to examine the relationships between VF prevalence and bone mineral density (BMD) at the spine and proximal femur.MATERIALS AND METHODS: X-ray-based dual-photon absorptiometry (DXA) was used to perform measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA).RESULTS: Two hundred and fifty-nine VFs were identified in 156 patients and the prevalence of unknown or unsuspected VF was 18.7%. For premenopausal women and for men, there was no difference in BMD at either the spine or the hip whether or not there was at least one VF. For postmenopausal women, BMD of the total region of the proximal femur was statistically lower (p < 0.001) in women with at least one VF whereas spine BMD only tended to be less (0.10 > p > 0.05). Proximal femur BMD was lower for postmenopausal women with more VF, while spine BMD was virtually unchanged as the number of VF increased. Neither spine nor hip BMD was lower for men with more VF. A strong association was observed in postmenopausal women between an age-dependent increase in VF prevalence and a reduction in femoral BMD. Such an association was not present in men.CONCLUSION: VFs are common, are often independent of either spine or hip BMD, and frequently go unnoticed. Therefore, VFA should be part of a routine assessment of fracture risk. (C) 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

We compared the distribution of vertebral fractures in adults and children and found that fractures occurred in different locations in the two age groups. This likely relates to the different shape of the immature spine.