Relationships of Bone Mineral Density to Whole Body Mass, Fat Mass and Fat-free Mass in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood.

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.

Body composition in long-term survivors of acute lymphoblastic leukemia diagnosed in childhood and adolescence: A focus on sarcopenic obesity.

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.

Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women.

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 ± 4.26 kg/m(2)) 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 (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 µm 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 100 µg 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 100 µg 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.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part III: SD, SEE, LSC Association With Fragility Fractures.

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.

A trimodality comparison of volumetric bone imaging technologies. Part I: Short-term precision and validity.

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.

A Trimodality Comparison of Volumetric Bone Imaging Technologies. Part II: 1-Yr Change, Long-Term Precision, and Least Significant Change.

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.

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled trial.

BACKGROUND: 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. METHODS: A double-blind, randomized controlled trial has been designed. Rheumatoid and undifferentiated inflammatory arthritis patients will undergo an MRI and X-ray assessment every 6 months. Baseline adaptive randomization will be used to allocate participants to MRI, X-ray, or sham-intervention groups on a background of standard of care. Prognostic markers, treating physician, and baseline DMARD therapy will be used as intervention allocation parameters. The outcome measures in rheumatology RA MRI score and the van der Heijde-modified Sharp score will be used to evaluate the MRI and X-ray images, respectively. Radiologists will score anonymized images for all patients regardless of intervention allocation. Disease progression will be determined based on the study-specific, inter-rater smallest detectable difference. Allocation-dependent, intervention-concealed reports of positive or negative disease progression will be reported to the treating rheumatologist. Negative reports will be delivered for the sham-intervention group. Study-based radiology clinical reports will be provided to the treating rheumatologists for extra-study X-ray requisitions to limit patient radiation exposure as part of diagnostic imaging standard of care. DMARD treatment dose escalation and therapy changes will be measured to evaluate the primary objective. A sample size of 186 (62 per group) patients will be required to determine a 36% difference in pharmacological treatment escalation between the three groups with intermediate dispersion of data with 90% power at a 5% level of significance. DISCUSSION: This study will determine if monitoring RA and undifferentiated inflammatory arthritis patients using MRI and X-ray every 6 months over 2 years provides incremental evidence over standard of care to influence pharmacotherapeutic decision-making and ultimately hinder disease progression. TRIAL REGISTRATION: This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).

Accumulation of bone strontium measured by in vivo XRF in rats supplemented with strontium citrate and strontium ranelate.

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.

Sarcopenia in children with acute lymphoblastic leukemia.

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.

Intrarater reliability of dual-energy X-ray absorptiometry-based measures of vertebral height in postmenopausal women.

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).

Age- and gender-dependent values of skeletal muscle mass in healthy children and adolescents.

BACKGROUND: Skeletal muscle mass (SMM) can be extracted from whole-body scans obtained by X-ray-based dual-photon absorptiometry (DXA). There is a need to establish expected age-dependent values for children and adolescents. METHODS: Appendicular lean tissue mass (ALM) was extracted from whole-body DXA scans in 140 healthy children and adolescents (68 females and 72 males). Whole-body SMM was calculated from ALM using equations developed by Kim et al. (Am J Clin Nutr 84:1014-1020, 2006). Age-dependent patterns of increase in SMM were derived by fitting SMM values to equations that consisted of the sum of two logistic expressions, one accounting for SMM changes during growth and the other for SMM changes during puberty. Normal ranges were defined so that 95% of the SMM values were included. The reproducibility of SMM measurements was obtained from whole-body DXA scans repeated on three occasions in each of a separate group of 32 normal children with repositioning between scans. RESULTS: Normal ranges are presented as equations describing the age-dependent pattern of increase in SMM as well as population standard deviations that increased steadily with age. For 15 children below age 10, SMM reproducibility (95% CI) was 149 g (119-199 g) while for 17 children and adolescents over age 10, reproducibility was 170 g (138-223 g). CONCLUSION: DXA-based measurements of SMM in children and adolescents are reproducible and can be expressed in terms of age-dependent Z scores.

In vivo quantification of bone-fluorine by delayed neutron activation analysis: a pilot study of hand-bone-fluorine levels in a Canadian population.

Humans can be exposed to fluorine (F) through their diet, occupation, environment and oral dental care products. Fluorine, at proper dosages, is believed to have positive effects by reducing the incidence of dental caries, but fluorine toxicity can occur when people are exposed to excessive quantities of fluorine. In this paper we present the results of a small pilot in vivo study on 33 participants living in Southwestern Ontario, Canada. The mean age of participants was 45 ± 18 years with a range of 20-87 years. The observed calcium normalized hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to 8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone above the detection limit of the system. The average fluorine concentration in bone was found to be 3.5 ± 0.4 mg F/g Ca. No difference was observed in average concentration for men and women. In addition, a significant correlation (r(2) = 0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The amount of fluorine was found to increase at a rate of 0.084 ± 0.014 mg F/g Ca per year. There was no significant difference observed in this small group of subjects between the accumulation rates in men and women. To the best of our knowledge, this is the first time data from in vivo measurement of fluorine content in humans by neutron activation analysis have been presented. The data determined by this technique were found to be consistent with results from ex vivo studies from other countries. We suggest that the data demonstrate that this low risk non-invasive diagnostic technique will permit the routine assessment of bone-fluorine content with potential application in the study of clinical bone-related diseases. This small study demonstrated that people in Southern Ontario are exposed to fluoride in measureable quantities, and that fluoride can be seen to accumulate in bone with age. However, all volunteers were found to have levels below those expected with clinical fluorosis, and only one older subject was found to have levels comparable with preclinical exposure.

Predictors of bony morbidity in children with acute lymphoblastic leukemia.

BACKGROUND: To evaluate the relationship between lumbar spine (LS) bone mineral density (BMD) and patient-, disease-, and therapy-related variables, and to define the risk-factors for fractures in children receiving therapy on Dana-Farber Cancer Institute acute lymphoblastic leukemia (ALL) protocols. METHODS: Children (≤18 years) diagnosed with ALL during the period 1995-2006, who are in first clinical remission, were included (n = 124). Dual-energy X-ray absorptiometry provided LS-BMD at diagnosis (n = 46) and during continuation therapy. LS-BMD was expressed as Z scores based on local population norms. Regression analyses evaluated the risk of osteopenia (Z-score -1.01 to -1.99, osteoporosis (Z-score -2.00 or less) and fractures. RESULTS: At diagnosis, 14 0f 46 (30%) patients had osteopenia and 5 (11%) had osteoporosis; whereas, during continuation therapy, 47 of 124 (39.5%) patients had osteopenia, and 10 (8%) had osteoporosis. LS-BMD at diagnosis had a positive linear relationship with LS-BMD during continuation therapy (Pearson correlation coefficient 0.619, P < 0.0001). Multivariable analyses identified age ≥10 years and LS-BMD at diagnosis as independent predictors of LS-BMD during continuation therapy. Twenty-three (18.5%) patients developed fractures. Dexamethasone therapy (OR 3.4, 95% CI 1.31, 7.52, P = 0.01) and lower LS-BMD during the continuation therapy (OR 1.8, 95% CI 1.2, 2.8, P = 0.01) were independent predictors of fracture. CONCLUSIONS: Older age and lower LS-BMD at diagnosis are predictors of lower LS-BMD during continuation therapy. Dexamethasone and lower LS-BMD during continuation therapy are associated with fractures. Using these variables it is feasible to develop a predictor model to define the risk of bony morbidity in children receiving ALL therapy.

The Relationship between Radial Bone Properties and Disease Activity and Physical Function in Individuals with Rheumatoid Arthritis.

PURPOSE: People with rheumatoid arthritis (RA) are at increased risk for osteoporosis. This study explored the relationships between compartment-specific (cortical and trabecular) bone properties in the distal radius, a common site for osteoporotic fracture, and RA-related pain, upper-limb disease activity, and hand function in adults diagnosed within the previous 8 years. METHODS: Cortical and trabecular bone properties (mass, density, and apparent trabecular structure) were assessed at the 4% site of the radius in 21 adults with RA using peripheral quantitative computed tomography (pQCT). Clinical measures included upper-limb active joint count; self-reported pain (AIMS-2 Arthritis Pain scale) and physical function (AIMS-2 Hand and Finger Function scale); and grip strength (modified sphygmomanometer). Associations were characterized using correlations (Pearson correlation coefficients or Spearman's rho). RESULTS: Cortical and trabecular bone mass and trabecular bone density were negatively associated with the number of active joints (r=-0.47, -0.54, and -0.47, respectively). Cortical bone density and mass were associated with grip strength (r=0.61 and 0.51, respectively). Cortical and trabecular bone density and cortical bone mass were negatively associated with scores on the Hand and Finger Function scale (r=-0.49, -0.45 and -0.56, respectively). CONCLUSIONS: Although the patterns differed slightly for cortical and trabecular bone, better bone health in both compartments was associated with fewer active joints and lower self-reported hand disability in adults with RA.

Objectif : Les personnes qui sont atteintes de polyarthrite rhumatoïde (PR) courent un plus grand risque de souffrir aussi d'ostéoporose. Cette étude se penche sur la relation entre les propriétés des compartiments osseux (cortical et trabéculaire) du radius inférieur, qui est un site fréquent de fracture attribuable à l'ostéoporose, à la douleur associée à la PR, à l'activité de la maladie sur les membres supérieurs et à la fonction des mains chez les adultes diagnostiqués au cours des derniers huit ans. Méthode : Les propriétés des os corticaux et trabéculaires (masse, densité et structure trabéculaire apparente) ont été évaluées à l'emplacement situé à 4% du radius chez 21 adultes avec PR, à l'aide d'une tomographie quantitative par ordinateur (pQCT). Les mesures cliniques recueillies sont le décompte de l'activité de l'articulation du membre actif, la douleur déclarée par le sujet (échelle AIMS-2 de douleur provoquée par l'arthrite), la fonction physique (échelle AIMS-2 de fonction des mains et des doigts); et la force de préhension (avec sphygmomanomètre modifié). Des associations ont été caractérisées à l'aide de corrélations (coefficient de corrélation de Pearson ou de Spearman). Résultats : La masse osseuse corticale et trabéculaire et la densité de l'os trabéculaire ont été associées négativement au nombre d'articulations actives (r=−0,47, −0,54 et −0,47, respectivement). La densité et la masse de l'os cortical ont été associées à la force de préhension de la main et des doigts (r=0,61 et 0,51, respectivement). Les densités osseuses corticale et trabéculaire ont été associées négativement au pointage obtenu sur l'échelle de fonction des mains et des doigts (r=−0,49, −0.45 et −0,56, respectivement). Conclusions : Bien que les modèles différaient légèrement pour l'os cortical et l'os trabéculaire, une meilleure santé osseuse des deux compartiments a pu être associée avec moins d'articulations actives et avec une moins grande incapacité des mains signalée par les adultes avec PR.

Radiation doses originating from diagnostic procedures during the treatment and follow-up of children and adolescents with malignant lymphoma.

Children with malignant lymphoma undergo many diagnostic procedures that involve exposure to ionising radiation. In addition, many, but by no means all, undergo further exposure to ionising radiation during radiotherapy. While therapeutic radiation exposures are prescribed, the extent of radiation exposure arising from diagnostic procedures utilised in such children is largely unknown. We completed an audit of the radiation doses arising from diagnostic imaging procedures performed in a cohort of children with malignant lymphoma. The cumulative effective radiation dose associated with radiographic and radioisotopic procedures was derived for 81 children and adolescents with malignant lymphoma during their diagnosis, treatment and follow-up. Thirty-eight of the 42 patients (90%) with Hodgkin lymphoma were alive at study termination, with follow-up periods ranging from 1.9 to 11.7 years (median 5.3). Thirty-three of the 39 patients (85%) with non-Hodgkin lymphoma were alive at study termination with follow-up periods ranging from 2.4 to 12.3 years (median 7.5). The median effective dose was 518 mSv for patients with Hodgkin lymphoma and 309 mSv for those with non-Hodgkin lymphoma. The maximum effective dose was 1.7 Sv. The principal contributors to the effective dose were computed tomography (CT) and nuclear medicine imaging procedures using (67)Ga. Protocols for the management of children and adolescents with malignant lymphoma should be reviewed in order to reduce the radiation detriment without loss of essential diagnostic information.

Creatinine as a measure of lean body mass during treatment of acute lymphoblastic leukemia in childhood.

Protein energy malnutrition is well-recognized in children with acute leukemia and may result in loss of lean body mass (LBM) with attendant morbidities. Much of the LBM consists of skeletal muscle, the mass of which is reflected in urinary creatinine excretion. As accurate 24 hours urine collections are challenging in children, we investigated the prospect that serum creatinine concentration provides a measure of LBM. Eleven children with acute lymphoblastic leukemia were assessed at 7 time points (6-mo intervals) from diagnosis to 1 year after the completion of therapy. LBM was measured as fat-free mass by dual energy x-ray absorptiometry (DXA scans) and correlated with serum creatinine concentration and 24 hours urine creatinine excretion. As expected, there was a strong correlation between 24 hours urinary creatinine excretion and LBM from DXA scans (r=0.79, P<0.001). Serum creatinine concentration also correlated with LBM (r=0.52, P<0.001). Serum creatinine concentration provides a surrogate measure of LBM in children with acute lymphoblastic leukemia. This will be especially useful in countries with limited resources in which more sophisticated measures, such as DXA scans, are seldom available.

Reproducibility of peripheral quantitative computed tomography measurements at the radius and tibia in healthy pre- and postmenopausal women.

PURPOSE: The objectives of this study were to utilise the XCT-2000 pQCT scanner to determine the mean values and the reproducibility of in vivo total, trabecular, and cortical volumetric bone measurements at distal and diaphyseal sites of the radius and the tibia, as well as calf muscle and subcutaneous fat areas, in healthy pre- and postmenopausal women. METHODS: Twenty-nine women (14 premenopausal and 15 postmenopausal) were recruited to participate in this study. Distal and diaphyseal sites of the radius (at 4% and 20% of the length of the radius) and tibia (at 4%, 38%, and 66% of the length of the tibia) were examined. RESULTS: The root mean square coefficient of variation for measurements at the distal tibia gave the most favorable reproducibility values for total (1.5%) and trabecular (1.6%) density, whereas the diaphyseal tibia showed the most favorable reproducibility value for cortical density (0.3%). The root mean square coefficients of variation for measurements of muscle and fat cross-sectional areas at the calf were 0.6% and 0.7%, respectively. At the distal tibia, the mean values for total (P < .05) and trabecular (P < .01) density were significantly lower in postmenopausal women than in premenopausal women. CONCLUSIONS: The data presented here indicate that XCT-2000 pQCT scans at the tibia provide highly reproducible measurements of total, cortical, and trabecular bone as well as muscle and fat cross-sectional areas. Furthermore, significant differences in volumetric bone measurements between healthy pre- and postmenopausal women were evident only at the distal tibia, suggesting that this site warrants further study.

Is a fixed value for the least significant change appropriate?

The least significant change (LSC) represents the smallest difference between successive measurements of bone mineral density (BMD) that can be considered to be a real change and not attributable to chance. The LSC is derived from same-day in vivo BMD precision measurements. Our first objective was to determine if the LSC differs between technologists. Our second objective was to determine if patient body size influenced the LSC. Each of 8 technologists measured same-day precision in groups of 30 patients for the lumbar spine and the total trochanter and neck regions of the proximal femur. At the spine, precision ranged from 0.008 to 0.011g/cm(2) and did not differ between technologists. Precision for the total region of the left proximal femur ranged from 0.006 to 0.016g/cm(2) and did differ between technologists. For the trochanter and neck regions, precision ranged from 0.008 to 0.013g/cm(2) for the former and from 0.010 to 0.020g/cm(2) for the latter, again, with inter-technologist differences. The LSC for the lumbar spine increased linearly from 0.022 to 0.031g/cm(2) when body mass index (BMI) increased from 19.5 to 31.3kg/m(2). In contrast, there was no discernable impact of BMI on the LSC for any of the proximal femur regions. The LSC at the spine is determined by the patient, whereas the LSC at the femur is determined by the technologist. Use of a single value for the LSC will lead to misinterpretations of the significance of BMD changes at both the spine and the proximal femur.

Is Thyroid Screening Necessary for Nuclear Medicine Personnel Receiving and Administering Capsules Containing Large Doses of 131I?

The cost-effectiveness of a thyroid screening procedure for the detection of internal contamination of personnel working with large doses of encapsulated iodine-131 (131I) was examined by reviewing the results of screening measurements performed during 1 year. Thyroid burdens were measured by self-assessment using a sodium iodide (NaI) probe. Of 113 screening measurements, 101 indicated a negative thyroid content of 131I. The largest burden observed was statistically not different from zero. The count rate corresponding to the largest observed burden would represent an 131I content of 23 Bq, which is approximately 0.2% of the level at which results have to be reported to the Canadian Nuclear Safety Commission. Negative count rates arose because of a small overestimation of the background contribution that was measured with a neck phantom positioned in front of the thyroid probe. The cost of a thyroid screening program for personnel who handle encapsulated 131I is considerable, especially when the need for such measurements is questionable.

Reproducibility of DXA measurements of bone mineral density and body composition in children.

BACKGROUND: The technique of X-ray-based dual photon absorptiometry (DXA) is frequently used in children for the detection of changes in bone mass or body composition. Such changes can only be considered real if the uncertainties arising from the measurement technique are exceeded. OBJECTIVE: Our objectives were twofold: (1) to determine the reproducibility of bone mineral density (BMD) measurements in children at the spine and the hip and from the whole body, as well as of whole-body measurements of mineral mass, lean body mass and fat mass in children; and (2) to estimate, from the measured precision, the time interval that needs to elapse before a statistically significant change in a DXA variable can be detected. MATERIALS AND METHODS: The reproducibility of techniques for the measurement of BMD and body composition using DXA was measured in 15 young children (9 girls and 6 boys) and 17 older children (9 girls and 8 boys). RESULTS: Reproducibility was derived from the standard deviation of three repeated measurements of spine BMD, total hip BMD, whole-body BMD (WBBMD), whole-body bone mineral content (WBBMC), lean mass and fat mass. Technique precision was better than 0.01 g cm(-2) for spine BMD and for WBBMD. Hip BMD measurements were slightly less precise, particularly in younger children (0.013 g cm(-2)). For body composition variables, technique precision was 13 g for WBBMC, 201 g for lean body mass and 172 g for fat mass in younger children. Technique precision for older children was 18 g, 251 g and 189 g for the corresponding variables. Predictions showed that the absence of a normal increase in WBBMC in a small-for-age girl could be established after 12 months. For spine BMD, a significant increase should be observable after 6 months for boys over the age of 11 years. For younger boys, more than 12 months has to elapse before anticipated changes can be detected with confidence. CONCLUSION: The time intervals required to elapse before decisions can be made concerning the significance of observed differences between successive measurements of BMD or body composition in children depend upon the age of the child.