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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.

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.

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 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.

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

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.X-ray-based dual-photon absorptiometry (DXA) was used to perform measurements of lumbar spine BMD, proximal femur BMD, and VF assessment (VFA).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 (p0.001) in women with at least one VF whereas spine BMD only tended to be less (0.10p0.05). 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.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.

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 as25% deformity (nonfracture) and as25% deformity (fracture).

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 (r2 = 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.

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

The nutritional status of children with cancer is clinically important. In an effort to separate the influences of disease and treatment, we studied children at the time of diagnosis. A total of 99 children underwent assessment by 24 hours dietary recall, measurement of body mass index (BMI), and analysis of body composition by dual energy x-ray absorptiometry (DXA scan). The group averages for calorie intake and BMI were close to the median population norms but ranged widely among individuals. As a group the study participants exceeded the Dietary Reference Intake for protein. Nine children (9%) had a BMIfifth percentile. There were statistically significant but at best moderate correlations between dietary intake and body composition by DXA scan. Twenty-four hours dietary recall may not provide accurate assessment of nutritional status in individual children with cancer at diagnosis. However, DXA scans cannot be undertaken in a timely fashion on all children at this point. Alternative methods of assessment are being explored.

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.

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.

On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of (131)I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98 +/- 64 microSv. The maximum penetrating dose was 283 microSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of (131)I with three distinct phases. The corresponding clearance half-times were

Background Osteopenia has been reported in children surviving acute lymphoblastic leukemia and brain tumors, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a role in the development of this complication. In order to explore that possibility, we examined survivors of brain tumors treated with and without radiation in childhood to investigate associations between radiation, osteopenia, physical activity, health status and overall health-related quality of life (HRQL). Procedure Subjects were survivors of posterior fossa tumors (astrocytoma or medulloblastoma) or optic glioma, 1 year off treatment. Measurements of growth velocity, body composition, bone densitometry, physical activity and HRQL were undertaken. Results Twenty-five (62.5%) of the 40 eligible patients participated in the study. Of the 25 patients, 12 (48%) received radiation therapy (R group) while 13 received no radiation (NR group). Growth hormone (GH) deficiency had been detected in three subjects, one had completed GH therapy while two were still on hormone replacement. The prevalence of osteopenia was 44% in the entire group, and 67% versus 27% in the R and NR groups. Florid osteoporosis was present in 20% of the entire group, more than 40% of the R group but none of the NR group. A significant correlation (P

Since there is almost no information on whether the concomitant use of diagnostic radioisotopes and radiographic contrast media interferes with dual-energy X-ray absorptiometry (DXA), we investigated these potentially confounding effects. At routine scheduled radiographic follow-up, 40 patients previously treated for malignant lymphomas or solid tumors in Hamilton and Ottawa, Canada were evaluated, 10 in each of the following 4 categories of diagnostic procedure: (1) computed tomography (CT) with intravenous, iodine-based contrast (+/-oral contrast), (2) magnetic resonance imaging (MRI) with gadolinium-based contrast, (3) gallium scan (GS), and (4) technetium bone scan (TBS). Whole body bone mineral content (WB-BMC) and lumbar spine bone mineral density (LS-BMD), total fat mass (TFM), and lean body mass (LBM) were measured by DXA immediately before and after the other radiological studies (on the same day) and then 7 days later. No statistically significant differences were found among WB-BMC, LS-BMD, TFM, and LBM Z-scores immediately before and after MRI, GS, TBS, and 7 days later. The DXA measurements performed immediately before and after CT showed statistically significant differences in WB-BMC (100% vs 124.5%, p

Summary Objective To investigate the relationships between bone mineral density (BMD) in the hip, spine, distal femur and proximal tibia and minimum joint space width (mJSW) in the knees of healthy women. Methods Women 22–68 years old without a history of knee pain, bone or joint disease or injury underwent a single, fixed-flexion knee X-ray. Radiographs were graded according to the Kellgren–Lawrence scale and analyzed for mJSW using a computer algorithm. Dual X-ray absorptiometry scans of the spine, hip, distal femur and proximal tibia were also acquired for each participant. Femur and tibia scans were acquired and analyzed using a modified version of the lumbar spine software. Results Forty-five females, mean [standard deviation (SD)] age and body mass index (BMI) of 40.1 (13.9) years and 24.6 (4.5)kg/m 2 , respectively, participated. The mean (SD) mJSW was 4.64 (0.68)mm. Linear regression analyses controlling for age and BMI revealed that BMD in the femoral trochanter and the central two regions of the tibia (T2 and T3) was significantly related to mJSW in the knee. A backwards regression analysis performed to determine which region of interest is most significantly related to mJSW revealed that femoral trochanter BMD ( β -value=0.416) is the most significant. Conclusions In contrast to the suggestion that BMD is negatively correlated with mJSW in the knees of osteoarthritic individuals, these results suggest that increasing BMD in the femoral trochanter and tibia is significantly associated with increasing mJSW in healthy females. Further investigation of this relationship is warranted.

Bone mineral density (BMD), bone geometry, and muscle cross-sectional area (CSA) were investigated in two sets of monozygotic female twins, where one of each pair had sustained a spinal cord injury (SCI). Twin pair 1 (TP1) and twin pair 2 (TP2) were 32 and 47 yr old and were 7 and greater than 20 yr postinjury, respectively. BMD was measured using dual-energy X-ray absorptiometry. Computed tomography was used to measure volumetric BMD, bone geometry, and muscle CSA of the thigh and calf. For the SCI twin of TP1, BMDs of hip, distal femur, proximal tibia, and spine were 59.5, 46.6, 53.1, and 93.3%, respectively, of values of the noninjured twin. For TP2, corresponding values in the SCI twin were 36.2, 35.9, 39.2, and 62.2%, respectively, of the non-SCI twin. Average muscle CSAs of the SCI twins were 31.2 ± 2.3% and 31.0 ± 6.1% of the values for their non-SCI twin, indicating that muscle CSAs were reduced by 70%. Among the SCI twins, volumetric BMDs were 83.4 ± 2.4% and 87.0 ± 3.45% of the non-SCI twins' values. Moments of inertia in the SCI twins ranged from 62.4 to 97.9% of the non-SCI twins' values at mid-femur and calf. This study reveals that in addition to the declines in muscle CSA and BMD, important changes in bone geometry occur in women after SCI.

Summary Objective To estimate the prevalence of bone and soft tissue abnormalities in asymptomatic knees using peripheral magnetic resonance imaging (pMRI) and to examine the relationship between these abnormalities and Kellgren-Lawrence (K-L) graded X-rays. Method Volunteers (20–68 years) with no history of knee pain, injury or bone or joint disease were recruited. Individuals underwent a single MRI scan and radiograph of their non-dominant knee. pMR images were acquired in sagittal plane using a 3-D gradient-echo protocol. Two radiologists graded the presence and severity of cartilage degeneration, osteophytosis, meniscal and ligamentous abnormalities, bone marrow edema and subchondral cysts. X-rays were acquired using a fixed-flexion technique and graded using the K-L scale. Results Forty-four individuals, mean age (SD) 41.1 (14.2) years, participated. K-L grading of X-rays revealed 29 individuals were grade 0, 12 were grade 1 and 3 were grade 2. Five individuals showed evidence of cartilage lesions, the femoral trochlea, medial femur and patella being those regions most commonly affected. Twelve individuals (27.3%) showed evidence of osteophytosis, nine of whom did not show evidence on X-ray. Forty-three individuals showed evidence of at least one meniscal abnormality while 27 individuals (61.4%) had abnormalities in at least three of the four regions of the knee. Conclusion Our results suggest that osteophytes may be more prevalent in this population than radiographic data suggests due to the limitations of two-dimensional imaging. Meniscal degeneration or tears, a risk factor for knee osteoarthritis, are highly prevalent in asymptomatic individuals with the medial anterior and posterior horns being the most commonly affected regions.

In 1994, 207 women participated in a study designed to examine the effects of occupational exposure and various lifestyle factors on bone and blood lead levels. In vivo measurements of Pb concentrations in tibia were performed by X-ray fluorescence. All 108 former smelter employees and 99 referents provided blood samples and answered a questionnaire on lifestyle characteristics and the relevant medical history. Lead concentrations in tibia and blood were significantly higher in the exposed group. The difference in mean bone Pb concentrations of the two groups is markedly greater than the difference in the mean blood Pb concentrations, supporting the view that bone Pb measurements are a more reliable determinant of Pb body burden. Chronic exposure did not result in any statistically significant differences in adverse pregnancy outcomes. A significantly lower age at the onset of menopause in occupationally exposed women may suggest that Pb causes adverse changes in the pattern of estrus and menses. The exposed women had lower bone Pb concentrations than those found in most studies on predominantly male workers. Blood Pb concentrations remain increased in women long after the cessation of occupational exposure, reflecting the importance of the endogenous exposure. The endogenous exposure relation found for postmenopausal exposed women is consistent with data on male smelter workers, whereas the relation found for premenopausal women is significantly lower. This suggests that sex plays an important role in the metabolism of lead, and current models of exposure extrapolated from male data may be inappropriate for use on women.

Dual energy X-ray absorptiometry (DXA) is presently considered the standard technique for diagnosis of osteoporosis. It has been suggested that the presence of lead interferes with the accurate measurement of bone mineral density (BMD) by DXA because of the increased attenuation and that an accurate measurement of BMD cannot be determined unless the patient’s bone lead content of patients is known. We performed DXA measurements on plaster of Paris phantoms and a Hologic Spine phantom in combination with polyester resin doped with various concentrations of lead. At lead levels which correspond to bone concentrations in occupationally exposed individuals, the suggested increase in densitometric BMD was not detected. Numerical calculations show that the effect of the lead depends upon the two energies of the X-ray beam of a particular device. The discrepancy between the actual and the densitometric BMD increases linearly and is about 0.3% at 100 ppm. Such change cannot be detected by the Hologic QDR 4500A, the device used for this experiment.

Twenty-one of 46 postmenopausal women were assigned to a home-based exercise program consisting of 60 min of exercise, 3 d/wk. The 25 nonexercisers continued usual daily activities. Each woman had at least one prevalent vertebral fracture and suffered from osteoporosis as defined by the application of WHO criteria to lumbar spine bone mineral density. Vertebral heights were measured using bone densitometry at baseline and 12 mo later. Vertebrae T9 to L4 were all identified for each of the 46 subjects in both the baseline and end-of-study lateral scans. The change in mean vertebral height over the course of the study was –0.3 mm anteriorly, –0.7 mm at the mid-location, and –0.4 mm posteriorly for the nonexercisers. For the exercisers, the corresponding changes were +0.1 mm anteriorly, –0.3 mm at the mid-location, and +0.2 mm posteriorly. The benefit of exercise in preserving vertebral morphometry in patients with osteoporosis deserves further investigation.

Hormone replacement therapy (HRT) produces a small increase in bone mineral density (BMD) when measured by dual energy X-ray absorptiometry (DXA). The corresponding decrease in fracture risk is more impressive, implying that other factors that contribute to bone strength are favourably modified by HRT. We investigated, using peripheral quantitated computed tomography (pQCT), the changes produced by HRT in both the distribution of mineral between cortical and trabecular bone and the changes produced by HRT in the apparent structure of trabecular bone, expressed as average hole area and apparent connectivity. Twenty-one postmenopausal women starting HRT and 32 control women were followed for 2 years, with distal radius pQCT measurements every 6 months. HRT prevented the loss of total bone mass seen in controls (p < 0.02). HRT also produced an apparent rapid loss of trabecular bone mass within the first 6 months of the study (p < 0.02), with an associated rapid loss in the apparent connectivity (p = 0.034). Average hole area also increased but not to a statistically significant extent. Exogenous estrogen apparently fills small marrow pores close to the endocortical surface, such that the pQCT-defined boundary between trabecular and cortical bone is shifted in favour of cortical bone. Trabecular bone structure indices are adversely affected, as the central, poorly interconnected trabecular bone with greater than average marrow spaces constitutes a greater fraction of the remaining trabecular bone. This study suggests that the improvements in fracture risk resulting from HRT are explained by a reversal of net endocortical resorption of bone.Key words: average hole area, connectivity, distal radius, endocortical resorption, hormone replacement therapy, peripheral quantitated computed tomography, trabecular structure.

This randomized controlled trial was designed to investigate the effect of a 6-month home-based exercise program versus control (usual activities) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture. Twelve-month assessments of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained. The home exercise program followed a "lifestyle exercise" approach where participants completed exercises 60 min per day, 3 days a week and could complete exercises in small periods of time throughout the day. Exercise activities included stretching, strength training and aerobics (i.e. walking). Participants were assessed at baseline, 6 months, and 12 months using the Osteoporosis Quality of Life Questionnaire (OQLQ), the Sickness Impact Profile (SIP), a balance test, and the Timed Up And Go test. Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck. Quality of life (OQLQ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms (P=0.003), emotion (P=0.01) and leisure (P=0.03). Results from the balance test indicated a greater effect in the exercise group over 12 months (P

The purpose of this cross-sectional case-control study was to determine whether indices of bone structure at the 4% site of the radius discriminate women who have sustained a recent low-energy fracture of the contralateral distal radius (n = 21) from women with similar bone density and no history of fracture (n = 21). Images of the distal forearm were acquired using peripheral quantitative computed tomography (pQCT) and were analyzed using in-house-developed software to determine indices of trabecular bone structure (average hole size [H(A)], maximum hole size, and connectivity index). The same images were analyzed using commercial software to determine bone density, mass, geometry, and torsional strength. The fracture group had significantly larger H(A) (p = 0.03). No other bone variable differed between groups. Individual H(A) values were compared to the mean value for young adult women (n = 42). The odds ratio (95% confidence interval) associated with an H(A) >2 SDs above the young adult mean was 5.4 (1.2-24.3). Thus, estimation of in vivo trabecular bone porosity by measuring the average diameter of the pQCT-imaged marrow spaces in the ultradistal radius identifies individuals with low bone mass most at risk for osteoporotic fracture.

The aim of this paper was to assess the endogenous release of lead from bone to blood, in 204 exposed subjects. resuming their duties after a 10-month strike in a primary lead smelter in 1991. In vivo 109Cd K X-ray Fluorescence (109Cd K XRF) was used to measure the bone lead concentration in tibia and calcaneus in the smelter, in 1994 and five years later. The 1994 data were used to derive the post-strike bone lead concentrations retrospectively from the significant association between bone lead and the cumulative blood lead index (CBLI). When a linear model was used to predict the current blood lead upon the level of lead in bone, structural analysis of the data produced slopes for tibia (2.0, 95% CI 1.66-2.54) and calcaneus (0.19, 95% CI 0.16-0.23) that were significantly higher than those predicted by the commonly used simple linear regression method, for tibia (0.73, 95%, CI 0.58-0.88) and calcaneus (0.08, 95% CI 0.06-0.09). This suggests that more lead than previously predicted by regression is released from bone to blood. Furthermore, the structural analysis of the data produced an estimation of the contribution of the bone lead stores to the bloodstream that was more consistent with the 1999 epidemiological data than did the regression estimation. Moreover, a non-linear relationship between tibia lead and blood lead was suggested from the assumption checking procedures for regression. When a non-linear regression model was fit to the data, the method produced estimates of important parameters in human lead kinetics, namely the blood lead saturation constant, showing a good agreement with current knowledge of lead metabolism. Finally, the likelihood of a non-linear bone lead release seems to be supported by the recently described dependence of the half-life of lead in bone on age and intensity of occupational exposure.

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 200μm 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±9yr and body mass index of 26.84±4.77kg/m 2 , 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.

In vivo peripheral quantitative computed tomography (pQCT) and peripheral magnetic resonance imaging (pMRI) modalities can measure apparent bone microstructure at resolutions 200 mm 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 mm) and pQCT (200 mm). This study examined 67 women with a mean age of 74 � 9 yr and body mass index of 27.65 � 5.74 kg/m 2 , 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.

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. 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. 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. This trial has been registered at ClinicalTrials.gov: NCT00808496 (registered on 12 December 2008).

Cast immobilization of injured forearms is common clinical practice yet little is known about the effect of reduced skeletal loading in the absence of pathology. This study reports the changes in the forearms of nine healthy young adults owing to six weeks in a plaster cast followed by 1 year of either habitual activity or a strengthening program. Both groups exhibited similar patterns of change in wrist mobility, forearm muscle strength, and bone variables. Because of small sample size and poor compliance with the exercise protocol, no conclusions can be drawn about the effect of exercise. In all subjects, reduced loading caused a decrease in wrist mobility (p < 0.02) and grip strength (p = 0.01) with full recovery following 3 months of remobilization. Six months after removing the cast, bone size was reduced in the middle region of the radius (p = 0.02) and recovered after 1 year of remobilization. Given that radial bone mass tended to decrease while bone density was unchanged, we conclude that the effect of casting was modulated by changes in gross bone morphology rather than in material characteristics.Key words: bone mass, muscle strength, physical loading, radius, young adults.

In this study, 539 occupationally exposed subjects received in vivo bone lead measurements using 109Cd excited K X-ray fluorescence (109Cd K XRF). Of these subjects, 327 had previously been measured five years earlier. Measurements were made from both tibia and calcaneus samples, taken to reflect cortical and trabecular bone, respectively. Changes in tibia lead concentration related negatively to initial tibia lead concentration and positively to both lead exposure between the measurement dates and initial calcaneus lead concentration. This finding confirmed and strengthened the interpretation of an earlier study involving fewer subjects. With the larger data set it was possible to examine subgroups of subjects. This showed that people aged less than 40 years had a shorter half-life for the release of lead from the tibia (4.9, 95% CI 3.6-7.8 years) than did those older than 40 (13.8, 95% CI 9.7-23.8 years). Similarly, less intensely exposed subjects (lifetime average blood leador = 25 micrograms dL-1) had a shorter tibia lead half-life (6.2, 95% CI 4.7-9.0 years) than those with a lifetime average blood lead25 micrograms dL-1 (14.7, 95% CI 9.7-29.9 years). Age and measures of lead exposure were strongly correlated; nevertheless, age matched subgroups with high and low intensity exposures showed clearance rates that were significantly different at the 10% level, with the lower exposure intensity again being associated with the faster clearance. These findings imply that current models of human lead metabolism should be examined with a view to adjusting them to account for kinetic rates varying with age and probably also with exposure level.

Bone mineral density is higher in dominant vs. nondominant limbs, implying that the greater use of dominant limbs in everyday activities results in the deposition of more bone or that the dominant limb is genetically larger. The objective of the present study was to determine whether bone mineral density differences between dominant and nondominant arms were greater in older vs. younger women. To determine whether this was due to a greater lifetime of preferential loading of the dominant arm, differences between dominant and nondominant arms were compared to accumulated amounts of physical activities which emphasized use of the dominant arm. Bone mineral density of dominant and nondominant arms was assessed by dual-energy X-ray absorptiometry in groups of younger (n = 35; age = 20.9) and older (n = 53; age = 57.4) women. The difference between arms was greater in the older vs. the younger group (5.2% vs. 1.9%, respectively, P < 0.01). Within the older group, total lifetime energy expenditure during activities emphasizing loading of the dominant arm correlated with the bone mineral difference between dominant and nondominant arms (r = 0.47, P < 0.01). This implies that a greater lifetime of preferential loading of the dominant arm in the older group resulted in a greater difference between arms. Am. J. Hum. Biol. 12:633-637, 2000. Copyright 2000 Wiley-Liss, Inc.

This cross-sectional study identifies differences in distal radial trabecular bone structure related to habitual loading patterns in the upper extremities using high-resolution peripheral quantitative computed tomography. As well, it determines whether measurements of these indices in one limb serve as satisfactory surrogates for the contralateral limb. The dominant and nondominant forearms of 106 adult volunteers (mean age [SD], 44.3[17.5] yr) were scanned and indices of trabecular bone structure (connectivity index [CI], maximum hole size [H(M)], and mean hole size [H(A)]) were determined at the distal radius. The images were also analyzed to determine bone density. For all subjects, H(M) is significantly smaller in the dominant radius (p0.01). Right-handed subjects (n = 96) have greater CI (p0.05) and smaller H(M) (p0.01) in the dominant radius. For the total group, the dominant limb has a greater mass (total and cortical bone mineral content, p0.01 and p0.05, respectively) and greater total bone volumetric density (p0.05). There are no significant differences between limbs for the group of left-handed subjectslapr;n = 10). As expected, significant associations exist between side-to-side measurements of bone structure and density (p0.001). The correlation coefficients for connectivity index, H(M), and H(A) are 0.86, 0.85, and 0.87, respectively. For bone density, the between-limb associations are 0. 90, 0.73, and 0.92 for the total, cortical, and trabecular bone compartments at the distal radius. Differences in the structure of the trabecular bone network suggest that differential loading of the dominant limb preserves bone strength.

This cross-sectional study determines gender differences in the age-dependent patterns in radial trabecular bone structure using high-resolution peripheral quantitative computed tomography. The nondominant forearms of 145 adult volunteers (57 men) were scanned and indices of trabecular structure (connectivity index [CI]; mean hole size [H A ]; and maximum hole size [H M ]) were determined at the ultradistal radius. The images were also analyzed to determine bone density. Men had significantly higher values for CI ( p H A ( p p p p p A (+2.2%/yr) and H M (+1.1%/yr) was significant in women ( p

Although intrapulmonary fibrin deposition is a pathognomonic feature of acute lung injury, it remains uncertain whether thrombin inhibitors affect clinically important outcomes. We hypothesized that both heparin and antithrombin (AT) concentrate improve gas exchange during experimental respiratory distress syndrome. We also tested whether combination therapy is more beneficial than monotherapy. Forty-eight newborn piglets were randomized within 12 litters to one of four groups in a factorial design: (1) AT; (2) heparin; (3) AT plus heparin; (4) untreated control animals. After lung lavage and 4 h of barovolutrauma, mechanical ventilation was continued for 24 h during which ventilator pressures and inspired oxygen were adjusted to maintain normal blood gases. The arterial/ alveolar oxygen tension ratio (a/A ratio) and the ventilator efficiency index (VEI) at 18 and 24 h were compared by repeated measures analysis of variance (ANOVA). In contrast to our hypothesis, only heparin improved gas exchange, and we found little evidence of an interaction with AT. The a/A ratio was 0.48 +/- 0.27 (mean +/- SD) in the presence of heparin versus 0.33 +/- 0.26 in its absence; p = 0.01. Corresponding VEI was 0.30 +/- 0.12 versus 0.25 +/- 0.14; p = 0.04. Hyaline membrane formation was also decreased in heparin-treated animals (p = 0.02).

Osteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as a consequence of therapy. It has been suggested that cranial irradiation may play a crucial role in this disorder. To explore that possibility, survivors of brain tumours in childhood, all of whom had received radiotherapy, were examined for evidence of bone mineral loss. 19 children were assessed, on average at 7 years after treatment. Measurements of growth velocities, plain radiography of the skeleton, bone densitometry, health-related quality of life and physical activity were undertaken. Growth hormone (GH) deficiency had been detected in 6 children and 5 had received GH replacement, for a minimum of more than 3 years. 9 children were radiographically osteopenic (including the 5 who had received GH). Z scores for bone mineral density (BMD) were negative in the majority of children. Health-related quality of life was less and pain more frequent in those with low BMD scores. Pain was correlated negatively with both free-time activity and seasonal activity (P < 0.01). Osteopenia is a common sequel of therapy in children with brain tumours. Those with osteopenia have more pain and more compromised, health-related quality of life than those who are not osteopenic, and pain significantly limits physical activity. The pathogenesis of osteopenia in these children is still uncertain, but is likely to be multifactorial.

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.

Lean body mass (LBM), total body bone mineral mass (BMC), total body bone areal density (BMD), and body fat mass (FM) were measured in rats by dual photon absorptiometry (DXA), using two different instruments. The coefficients of variation for repeated measurements of LBM and FM were about 0.4 and 2.5%, respectively, over an animal body weight range of 150 to 600 g. For BMC and BMD, the coefficients of variation were less than 2%. The correlation coefficients for LBM, FM, BMC, and BMD measured on the two densitometers were all greater than 0.94. The slope of the regression line relating LBM measured by DXA and LBM measured by carcass analysis was 0.999, and the correlation coefficient was 0.99. For FM the slope was 1.05, and the correlation coefficient was 0.98. BMC measures by DXA were falsely low in small animals. For larger animals, the correlation between BMC and ash weight was 0.93, but the slope of the regression line was 0.78. DXA measures of LBM and FM were accurate and reproducible for rats weighing between 150 and 600 g. There was a size-dependent error in BMC, which will be significant in longitudinal measurements of bone mass.

X-ray fluorescence (XRF) has been demonstrated to be an extremely useful technique for measuring trace quantities of heavy metals in various tissues within the body. This study investigates the applicability of XRF to the measurement of bone uranium concentration. The factors affecting the accuracy and minimal detectable concentration of bone uranium in vivo are discussed. The system chosen employs a 57Co source to excite the uranium K x-rays, with the source and detector in an approximate 180 degrees backscatter geometry relative to the sample position. It is demonstrated, with experiment and Monte Carlo simulation, that the x-ray to coherent peak ratio is linearly related to concentration and is independent of variations in source-sample geometry, thickness of overlying tissue and tibia size. Preliminary in vivo measurements indicate that this system has a minimum detectable concentration of approximately 20 micrograms U/g bone mineral which may not be sufficiently precise for a monitoring system for occupational workers. Future work will involve attempts to enhance this precision through the use of alternative sources for the excitation of uranium x-rays as well as possible modifications to the detector and electronics.

In this study a method of assessing trabecular bone structure at the distal end of the radius from high-resolution magnetic resonanceimages is described. Trabecular bone is segmented from the marrow and soft tissue background using an adaptive threshold, a region growth, and a skeletonization step. From the processed image we measured the connectivity and orientation of the trabecular bone network. Connectivity was assessed by a proposed connectivity index (CI) and marrow space was quantitated by a mean hole area (H A ). Significant age-related changes in CI and H A were observed in a mixed group of normal volunteers. CI decreased at a rate of 0.18 yr −1 (r=0.72, n=14, p and H A increased at a rate of 0.018 mm 2 yr −1 (r=0.69, n=14, p Gradient analysis was used to examine trabecular orientation, and revealed that the individual trabeculae at the distal end of the radius are organized anisotropically along the bone. These findings suggest that clinical magnetic resonancescanners can be used to assess trabecular bone structure in vivo.

Bone lead content of the mid-tibia was measured by in vivo fluorescence excitation in 90 females and 59 males aged between 6 and 81. The cross-sectionally derived rate of increase of tibia lead content was 0.24 +/- 0.03 microgram [g mineral]-1 yr-1. In 93 adult women, the corresponding rate of increase for calcaneus lead content was 0.12 +/- 0.11 microgram [g mineral]-1 yr-1. Comparison with European values show that, in Canada, the rates of lead accumulation are greater than those found in N. Sweden and Finland, similar to those of S. Sweden and less than values measured in England.

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.

We conducted a 2-year (42 weeks of consecutive training in each year, separated by 10 weeks of testing and vacation time) randomized, controlled trial of weight training in 142 healthy male and female subjects, aged 60 to 80 years. Measurements included dynamic strength, symptom-limited endurance in cycling, treadmill walking and stair climbing, muscle size, and bone mineral density and content of the lumbar spine and whole body. One hundred and thirteen subjects completed the study (57 exercise, 56 control), with a mean attendance of 85% among the exercisers. Muscle strength was unchanged in the control subjects but increased (collapsed across age and gender) from 32% (leg press) to 90% (military press) in the exercisers. Symptom-limited endurance in cycling, treadmill walking, and stair climbing increased in the exercisers by (mean +/- SE) 6.2 +/- 0.8%, 29.2 +/- 7.3%, and 57 +/- 12%, respectively; the only change in the controls was an unanticipated 33% increase in stair climbing performance during the first year. These values were unchanged in the controls. Cross-sectional area of the knee extensors increased by 8.7 +/- 0.9% in the trained subjects and was unchanged in controls. Measures of whole body, lumbar spine bone mineral density, and lumbar spine bone mineral content were unchanged in the exercisers, but whole body bone mineral content decreased by 1%. In contrast, there were small increases (< 4.0%) in bone mineral density among the controls. Long-term weight training proved to be a safe and well-tolerated mode of exercise for the elderly. Increased strength was associated with muscle hypertrophy in each year, and with increased endurance in cycling, walking, and stair climbing. There were no changes in bone mineral density but a small reduction in whole body bone mineral content.

Twenty young women (20.3 +/- 1.0 years) participated in a weight training program in which upper and lower body exercises were done twice per week for 20 weeks. Ten other women (20.2 +/- 0.4 years) served as a control group. Training resulted in significant (p < 0.05) increases in arm curl (73%), bench press (33%), and leg press (23%) lifting performance. Whole body (3.7%), trunk (3.0%), arm (9.7%), and leg (3.3%) lean tissue mass also increased significantly, based on measurements made by dual energy x-ray absorptiometry (DEXA). Changes in the control group were small and nonsignificant. In contrast, training did not increase DEXA-measured bone mineral content (BMC) and density (BMD) in a whole body measure nor in arm, leg, ribs, thoracic and lumbar spine, and pelvis segments. Similarly, hip BMC and BMD at femoral neck, trochanter, intertrochanter, and Ward's triangle sites, and total hip did not increase with training. The data indicate that a resistance training program that effectively increases strength and lean tissue mass in young women may fail to increase BMC or BMD over a 20-week training period.

Postmenarcheal adolescent girls performed resistance training (RT) for 26 weeks, which consisted of 4 sets of 13 exercises of varying and progressive intensity performed 3 times weekly on hydraulic resistance machines. Bone mineral was assessed by dual photon absorptiometry. Resistance training resulted in significant increases (pre-post) in biceps curl (21.4%), triceps press (21.5%), knee extension (25.1%), knee flexion (52.8%), and squat press (21.5%) strength. There were no significant differences between RT and control (C) groups initially, and no significant effects of training (pre-post) for total body (TB) or lumbar spine (LS) bone mineral content (BMC) or bone mineral density (BMD). The largest increases in LS bone mineral occurred during the first 13 weeks, and although not significant, the increases in LS BMC (g) (3.9 vs. 5.9%), LS BMC (g.cm-1) (2.6 vs. 5.9%), LS areal BMD (g.cm-2) (1.48 vs. 4.75%), and LS bone mineral apparent density (BMAD, g.cm-3) (0.47 vs. 4.13%) were greater in the RT compared with the C group during this period. In conclusion, resistance training resulted in a trend towards a transient increase in LS bone mineral during the first 13 weeks, but despite significant strength gains, there were no significant changes in TB or LS bone mineral after 26 weeks of training.

The lead content of bones that were surface scattered about a purported campsite of the 1845 Franklin expedition was measured using a fluorescence excitation technique based on a109Cd radioisotope source. The lead concentrations are considerably greater than values observed in modern populations and the ratio of the lead content in the calcaneus to that in the tibia is greater than that observed in subjects currently exposed occupationally. The pattern of distribution of lead between bones indicates excessive intake of lead during the period of the expedition. Predictions of blood lead levels based on the measured bone lead concentrations, suggest that the current upper limit for occupational exposure recommended to prevent neurological changes was exceeded.

Serum lead, whole blood lead, and lead in both tibia and calcaneus were measured in each of 49 active lead workers. Serum lead correlated more strongly with both in vivo bone lead measurements than did whole blood lead. The ratio of serum lead to whole blood lead varied from 0.8% to 2.5% and showed a positive correlation with tibia, and an even stronger correlation with calcaneus lead. This implies that lead released from bone (endogenous exposure) results in a higher proportion of whole blood lead being in serum than is the case for exogenous exposure. This observation needs to be confirmed, and the relationships amongst the parameters must be studied further, particularly in former or retired lead workers. If confirmed, since at least a portion of lead in serum is readily diffusible and thus toxicologically more immediately significant than lead bound to red cells, the health implications of endogenous exposure may have to be reassessed. © 1996 Wiley-Liss, Inc.

The effects of three years of low dose or moderate dose hormone replacement on bone mass and serum cardiovascular risk factor were measure in post-menopausal women. After six months of calcium supplementation, women chose to add hormone replacement therapy (HRT) or to remain on calcium. Those choosing hormones were randomized either to a law dose or moderate dose group. The low dose regimen was 0.3 mg/d equine estrogen and 2.5 mg/d medroxyprogesterone for three years. The moderate dose group rook 0.625 mg/d equine estrogen (days 1-25) and 5 mg/d medroxyprogesoerone (days 16-25) for the first two years, after which the cyclical regimen was replaced with a continuous regimen of 0.625 mg/d dequine estrogen and 2.5 mg/d medroxyprogesterone. Low dose HRT prevented the loss of radius bone mass observed in subjects taking calcium only. Moderate dose HRT also protected radius bone mass, increased lumbar spine bone mass, and improved the ratio of serum high density to low density lipoproteins.

A dedicated computed tomography system was used to acquire transaxial images of the distal radius to assess trabecular bone structure in vivo. We segmented trabecular bone from the marrow and soft tissue background by postprocessing the image with a region grow and skeletonization step. From the processed image we assessed the integrity of the bone by examining the continuity of its trabecular network and by determining the area of the holes comprising its marrow space. The continuity of the bone imaged was assessed by a proposed connectivity index (CI) and the size of the marrow spaces was assessed by calculating a mean hole area (H(A)) in the bone cross-section. Repeat measurements revealed that the intra-subject variability in CI and H(A) was small (CV6%). Both CI and H(A) were sensitive enough to reflect differences in structure at the head of the radius and at several sites along its shaft. We tested the diagnostic value of assessing bone structure at the distal end of the radius by measuring trabecular bone density, CI and H(A) in a mixed group of 26 subjects, nine of whom had suffered a wrist fracture. We found that a trabecular bone density threshold of 116 mg cm-3, corresponding to two standard deviations below the mean density in the 17 non-fractured subjects, separated fractured from non-fractured subjects with a sensitivity of 22% and a specificity of 100%. A CI threshold of -4.7 doubled the sensitivity (44%) and maintained the 100% specificity. An H(A) threshold of 4.5 mm2 achieved a sensitivity of 89% and a specificity of 94%. This increased sensitivity achieved by our indices suggests that an in vivo assessment of trabecular bone structure can contribute significantly to the identification of persons at risk of fracture.

SummaryWe performed a prospective matched cohort study to investigate the effects of long-term (>1 month) heparin therapy on lumbar spine bone density. Twenty-five women who received heparin during pregnancy, and 25 matched controls underwent dual photon absorptiometry of the lumbar spine in the post-partum period. Zero of 25 heparin-treated patients developed fractures. Heparin-treated patients had a 0.082 g/cm2 lower bone density compared to untreated controls, which is clinically and statistically significant (p = 0.0077). There were 6 matched pairs in which only the heparin-treated patient had a bone density below 1.0 g/ cm2, compared to only one pair in which only the control patient had a bone density below this level (p = 0.089). The correlation coefficients of the difference .in bone density in each matched pair, and the duration of heparin therapy, the mean daily dose, and the total dose of heparin were 0.042, -0.015, and 0.021, respectively; none of these values is statistically significant. We conclude: 1) long-term heparin therapy was associated with a significant reduction in bone density, although fractures are uncommon, 2) there was no significant correlation between lumbar bone density and the dose or duration of heparin.