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Petryk, Anna, Tracy L. Bergemann, Kristen M. Polga, Kami J. Ulrich, Susan K. Raatz, David M. Brown, Leslie L. Robison, and Scott K. Baker. "Prospective Study of Changes in Bone Mineral Density and Turnover in Children after Hematopoietic Cell Transplantation." Blood 106, no. 11 (November 16, 2005): 1115. http://dx.doi.org/10.1182/blood.v106.11.1115.1115.
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Abstract Osteoporosis is common in adults after hematopoietic cell transplantation (HCT). The data on bone mineral density (BMD) in children after HCT are limited. The goals of this prospective study were to determine the incidence, timing, magnitude and possible predictors of bone loss in children following HCT. The study population included 49 patients (age 5–18 years) who were eligible to receive HCT at the University of Minnesota. The patients were evaluated at baseline, 100 days, 6 months, and 1 year after HCT. Lumbar BMD (BMDL) was assessed by dual-energy x-ray absorptiometry. The number of patients with osteopenia increased from 18% at baseline to 33% one year after HCT, and with osteoporosis from 16% to 19%. Mean areal BMDL z-score decreased from −0.56 to −1.1 by 6 months and at 1 year was −0.94, which was significant compared to standard normal distribution (p=0.004 and p=0.022, respectively). The absolute loss of bone mineral corresponded to 5.3% reduction in areal BMDL and 4.8% reduction in volumetric BMDL. The level of bone-specific alkaline phosphatase decreased by 30% by day 100 (p=0.009), followed by recovery toward baseline by 6 months. The level of osteocalcin >6.5 ng/mL at day 100 predicted recovery from the initial bone loss by 1 year. A reduction in BMDL at 6 months correlated with a cumulative dose of glucocorticoids. In conclusion, this study demonstrates that bone loss is common in children after HCT and is primarily due to suppression of bone formation. Further studies are necessary to validate osteocalcin as a predictive biomarker.
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Zarn, Jürg A., Ursina A. Zürcher, and H. Christoph Geiser. "Toxic Responses Induced at High Doses May Affect Benchmark Doses." Dose-Response 18, no. 2 (April 1, 2020): 155932582091960. http://dx.doi.org/10.1177/1559325820919605.
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To derive reference points (RPs) for health-based guidance values, the benchmark dose (BMD) approach increasingly replaces the no-observed-adverse-effect level approach. In the BMD approach, the RP corresponds to the benchmark dose lower confidence bounds (BMDLs) of a mathematical dose–response model derived from responses of animals over the entire dose range applied. The use of the entire dose range is seen as an important advantage of the BMD approach. This assumes that responses over the entire dose range are relevant for modeling low-dose responses, the basis for the RP. However, if part of the high-dose response was unnoticed triggered by a mechanism of action (MOA) that does not work at low doses, the high-dose response distorts the modeling of low-dose responses. Hence, we investigated the effect of high-dose specific responses on BMDLs by assuming a low- and a high-dose MOA. The BMDLs resulting from modeling fictitious quantal data were scattered over a broad dose range overlapping with the toxic range. Hence, BMDLs are sensitive to high-dose responses even though they might be irrelevant to low-dose response modeling. When applying the BMD approach, care should be taken that high-dose specific responses do not unduly affect the BMDL that derives from low doses.
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Migliaccio, Silvia, Davide Francomano, Roberto Bruzziches, Emanuela A. Greco, Rachele Fornari, Lorenzo M. Donini, Andrea Lenzi, and Antonio Aversa. "Trunk Fat Negatively Influences Skeletal and Testicular Functions in Obese Men: Clinical Implications for the Aging Male." International Journal of Endocrinology 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/182753.
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Osteocalcin (OSCA) seems to act as a negative regulator of energy metabolism and insulin sensitivity. Evidence from male rodents suggests that OSCA may also regulate testosterone (T) synthesis. Using a cross-sectional design, we evaluated OSCA, 25(OH) vitamin D, T, 17β-estradiol (E2), homeostasis model assessment of insulin resistance (HOMA-IR), and body composition in 86 obese (mean BMI = 34) male subjects (18–69 yr old). Independently from BMI, an inverse relationship between trunk fat percentage and plasma T (r2=−0.26,P<0.01) and between HOMA-IR and OSCA levels (r2=−0.22,P<0.005) was found. OSCA levels, as well as vitamin D, decreased significantly for higher BMI with significant differences above 35 (P<0.01). A direct correlation between T and bone mineral density at lumbar (BMDL) and neck (BMDH) (P<0.001,r2=−0.20;P<0.001,r2=−0.24) was found, independently from age. An inverse correlation between E2 levels, BMDL, and BMDH (P<0.001,r2=−0.20;P<0.001,r2=−0.19) was observed. These data provide new evidences that a relationship between trunk fat mass, insulin sensitivity, OSCA and T synthesis occurs. This new relationship with skeletal health has relevant implications for the aging male, suggesting OSCA as a novel marker of metabolic and gonadal health status.
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Monakhova, Yulia, Julien Jendral, and Dirk Lachenmeier. "The Margin of Exposure to Formaldehyde in Alcoholic Beverages." Archives of Industrial Hygiene and Toxicology 63, no. 2 (June 1, 2012): 227–37. http://dx.doi.org/10.2478/10004-1254-63-2012-2201.
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The Margin of Exposure to Formaldehyde in Alcoholic BeveragesFormaldehyde has been classified as carcinogenic to humans (WHO IARC group 1). It causes leukaemia and nasopharyngeal cancer, and was described to regularly occur in alcoholic beverages. However, its risk associated with consumption of alcohol has not been systematically studied, so this study will provide the first risk assessment of formaldehyde for consumers of alcoholic beverages.Human dietary intake of formaldehyde via alcoholic beverages in the European Union was estimated based on WHO alcohol consumption data and literature on formaldehyde contents of different beverage groups (beer, wine, spirits, and unrecorded alcohol). The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMD) for 10 % effect obtained from dose-response modelling of animal experiments.For tumours in male rats, a BMD of 30 mg kg-1 body weight per day and a "BMD lower confidence limit" (BMDL) of 23 mg kg-1 d-1 were calculated from available long-term animal experiments. The average human exposure to formaldehyde from alcoholic beverages was estimated at 8·10-5 mg kg-1 d-1. Comparing the human exposure with BMDL, the resulting MOE was above 200,000 for average scenarios. Even in the worst-case scenarios, the MOE was never below 10,000, which is considered to be the threshold for public health concerns.The risk assessment shows that the cancer risk from formaldehyde to the alcohol-consuming population is negligible and the priority for risk management (e.g. to reduce the contamination) is very low. The major risk in alcoholic beverages derives from ethanol and acetaldehyde.
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Rubio-Armendáriz, Carmen, Soraya Paz, Ángel J. Gutiérrez, Dailos González-Weller, Consuelo Revert, and Arturo Hardisson. "Human Exposure to Toxic Metals (Al, Cd, Cr, Ni, Pb, Sr) from the Consumption of Cereals in Canary Islands." Foods 10, no. 6 (May 21, 2021): 1158. http://dx.doi.org/10.3390/foods10061158.
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The Canary Islands is an archipelago that consumes cereals and derivatives imported from other regions of the world. The increase in contamination with toxic metals makes it necessary to assess the content of toxicological metals of interest to ensure quality and safety. The content of toxic metals (Al, Cd, Cr, Pb, Ni, Sr) was determined in 221 samples of cereals and derivatives (corn, wheat, gofio, corn gofio, barley gofio, roasted corn and flour) marketed in the Canary Islands using ICP-OES (inductively coupled plasma optical emission spectrometry) to assess dietary exposure. Al content recorded in barley gofio (29.5 mg/kg fresh weight) stands out. The estimated daily intake (EDI) of Pb is 52 µg/day if 100 g/day of barley gofio is consumed (121% and 240% of the BMDL nephrotoxicity limit set by the EFSA at 0.63 µg/kg body weight/day for adults and children, respectively). The EDI of PB is 16 µg/day if 30 g barley gofio/day is consumed by adults (36.2% of the abovementioned BMDL nephrotoxicity limit). The EDI of Pb is 7.8 µg/day if 15 g barley gofio/day is consumed by children (32.2% of the abovementioned BMDL nephrotoxicity limit). Gofio is a food of high nutritional value. It is necessary to establish monitoring programs for toxic metals in raw materials and processed products to reduce exposure levels.
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Kopylev, Leonid, and John Fox. "Parameters of a Dose-Response Model Are on the Boundary: What Happens with BMDL?" Risk Analysis 29, no. 1 (January 2009): 18–25. http://dx.doi.org/10.1111/j.1539-6924.2008.01125.x.
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Kim, Ah-Hyoun, Min-A. Ha, and Byung-Soo Kim. "Determining a BMDL of Blood Lead Based on ADHD Scores Using a Semi-Parametric Regression." Korean Journal of Applied Statistics 25, no. 3 (June 30, 2012): 389–401. http://dx.doi.org/10.5351/kjas.2012.25.3.389.
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Rubio-Armendáriz, Carmen, Soraya Paz, Ángel J. Gutiérrez, Verena Gomes Furtado, Dailos González-Weller, Consuelo Revert, and Arturo Hardisson. "Toxic Metals in Cereals in Cape Verde: Risk Assessment Evaluation." International Journal of Environmental Research and Public Health 18, no. 7 (April 6, 2021): 3833. http://dx.doi.org/10.3390/ijerph18073833.
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Consumption of cereals and cereal-based products represents 47% of the total food energy intake in Cape Verde. However, cereals also contribute to dietary exposure to metals that may pose a risk. Strengthening food security and providing nutritional information is a high-priority challenge for the Cape Verde government. In this study, toxic metal content (Cr, Ni, Sr, Al, Cd, and Pb) is determined in 126 samples of cereals and derivatives (rice, corn, wheat, corn flour, wheat flour, corn gofio) consumed in Cape Verde. Wheat flour samples stand out, with the highest Sr (1.60 mg/kg), Ni (0.25 mg/kg) and Cr (0.13 mg/kg) levels. While the consumption of 100 g/day of wheat would contribute to 13.2% of the tolerable daily intake (TDI) of Ni, a consumption of 100 g/day of wheat flour would contribute to 8.18% of the tolerable weekly intake (TWI) of Cd. Results show relevant Al levels (1.17–13.4 mg/kg), with the highest level observed in corn gofio. The mean Pb average content in cereals is 0.03–0.08 mg/kg, with the highest level observed in corn gofio. Al and Pb levels are lower in cereals without husks. Without being a health risk, the consumption of 100 g/day of wheat contributes to 17.5% of the European benchmark doses lower confidence limit (BMDL) of Pb for nephrotoxic effects; the consumption of 100 g/day of corn gofio provides an intake of 1.34 mg Al/day (13.7% of the TWI) and 8 µg Pb/day (20% of the BMDL for nephrotoxic effects). A strategy to minimize the dietary exposure of the Cape Verdean population to toxic metals from cereals should consider the continuous monitoring of imported cereals on arrival in Cape Verde, the assessment of the population’s total diet exposure to toxic metals and educational campaigns.
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Angerhofer, Richard A., Mark W. Michie, Glenn J. Leach, Mark S. Johnson, and Gunda Reddy. "Oral Toxicity Evaluation of Thiodiglycol in Sprague-Dawley Rats." International Journal of Toxicology 33, no. 5 (August 27, 2014): 393–402. http://dx.doi.org/10.1177/1091581814547541.
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Thiodiglycol (TDG) is the main product of sulfur mustard hydrolysis and is an environmental contaminant. Subacute and subchronic oral toxicity studies with TDG were conducted in Sprague-Dawley rats. Neat TDG was administered by gavage at doses of 157, 313, 625, 1250, 2500, 5000, and 9999 mg/kg/d, 5 days per week, for 14 days. In the 14-day study, decreased body weight and food consumption were observed at 5000 mg/kg/d. In the 90-day study, rats received neat TDG at doses of 50, 500, or 5000 mg/kg/d for 5 days per week. A fourth group served as a sham control. Individual body weight and food consumption were measured weekly. At termination of the experiment, urine, blood, and tissue samples were collected. Rats displayed significant decreased body weight with no effect on food consumption following administration of TDG at 5000 mg/kg/d. Both male and female rats showed significant increased kidney weights at 5000 mg/kg/d. The organ to body weight ratios increased significantly for liver, kidneys, testes, and brain in males and adrenals in females for 5000 mg/kg/d. At all doses of TDG, hematological and clinical parameters and tissue histopathology remained unaltered. The no observed adverse effect level (NOAEL) for oral subchronic toxicity was 500 mg/kg/d. Benchmark dose (BMD) was derived from the decreased gain in body weight that was seen in male rats. A BMD based on a 10% decrease in body weight was 1704 mg/kg/d, and the lower confidence limit on the dose BMD, the BMDL, was 372 mg/kg/d.
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Sakuragi, Sonoko, Ken Takahashi, Tsutomu Hoshuyama, Jiro Moriguchi, Fumiko Ohashi, Yoshinari Fukui, and Masayuki Ikeda. "Variation in benchmark dose (BMD) and the 95% lower confidence limit of benchmark dose (BMDL) among general Japanese populations with no anthropogenic exposure to cadmium." International Archives of Occupational and Environmental Health 85, no. 8 (January 24, 2012): 941–50. http://dx.doi.org/10.1007/s00420-012-0734-z.
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Zinovieva, M. L., P. G. Zhminko, and M. G. Prodanchuk. "Use of the benchmark dose approach for evaluation of dose and time-dependent response to 7-hydroxycoumarin 90-day exposure in rat females." Ukrainian Journal of Modern Toxicological Aspects 81, no. 1 (June 7, 2018): 17–24. http://dx.doi.org/10.33273/2663-4570-2018-81-1-17-24.
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Benchmark dose (BMD) analysis of existing data sets from experimental studies on animal for which NOAEL/LOAEL information is available allows to satisfy the need for quantifiable, scientifically justifiable approach to risk assessment. Previous study of 7-hydroxycoumarin (7-HOC) 3 months toxicity on rats revealed carbohydrates and lipids metabolism disturbance (blood glucose level (BGL) decrease, serum triglyceride level (STL) rise) as biologically relevant parameters to set up NOEL (20 mg/kg). Purpose. To conduct the dose and time of exposure effect dependence comparative analysis of BGL and STL published data set of 7-HOC subchronic toxicity in rats using BMD and NOAEL/LOAEL methodologies. Materials and methods. The available continuous data of STL and BGL from subchronic 7-HOC toxicity study data set for rat females were analyzed by means United States Environmental Protection Agency proposed software, BMDS 2.6.0.1. The response level was set as 10 %. Results. Hill’s model appropriately reflected BGL and STL dependence on 7-HOC dose. The BMDs estimates of STL rise were similar (46–49 mg/kg) in 1, 2, and 3 months of exposure. Coincident dependence was foundfor the lower-bound confidence limits on the BMDs (BMDLs) ranged 21–22 mg/kg at all the studied time points, whereas NOEL for this end point was defined as 50, 20, and 20 mg/kg in 1, 2, and 3 months respectively. BMDs of the BGL decrease were rising with time of exposure amounting 48, 93, 486 mg/kg after 1, 2, and 3 months respectively. BMDLs estimates were 24, 21, 207 mg/kg in 1, 2, and 3 months respectively, while NOEL for this end point were 50, 200, and 200 mg/kg at correspond time points. Conclusion. The benchmark dose method was more powerful statistical tool to analyze 7-HOC effects dose dependence in comparison to traditional approach. The observed BMDs and theirs derivatives changes indicated no enhancement of studied treatment related responses within the exposure time. Key words: benchmark dose approach, 7-hydroxycoumarin, subchronic toxicity.
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Johnson, David w., H. David Mclntyre, Alison Brown, Judy Freeman, and Russell J. Rigby. "The Role of Dexa Bone Densitometry in Evaluating Renal Osteodystrophy in Continuous Ambulatory Peritoneal Dialysis Patients." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 16, no. 1 (January 1996): 34–40. http://dx.doi.org/10.1177/089686089601600110.
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Objective The aims of this study were to assess the clinical utility of total and regional bone densitometry in a large continuous ambulatory peritoneal dialysis (CAPD) population and to determine the clinical, biochemical, and radiographic variables that best identified osteopenic CAPD patients. Design and Patients A cross-sectional study was performed on 45 CAPD patients (19 males, 26 females), comprising the total CAPD population at the Princess Alexandra Hospital. Main Outcome Measures Total body (TB), anteroposterior lumbar spine (APL), femoral neck (FN), Ward's triangle (WT), and skull bone mineral densities (BMDs) were measured using dual-energy x-ray absorptiometry (DEXA) and then correlated with clinical, biochemical, and radiographic indices of uremic osteodystrophy. Results BMDs were not significantly different from age and sex-matched reference population data. Considerable regional variation of BMD Z scores were noted between FN (-0.11 ± 0.23), WT (-0.11 ± 0.22), and APL (1.22 ± 0.04) (p = 0.003). APLZ scores were significantly reduced in patients with a previous history of fracture (-1.36 ± 1.07vs0.89 ± 0.31), bonepain(-0.72 ± 1.08vs 1.01 ± 0.31), or steroid treatment (-0.62 ± 0.39 vs 1.16 ± 0.35). Increased BMDZ scores for APL (1.82 ± 0.57 vs0.38 ± 0.29, p < 0.05), FN (0.32 ± 0.36vs-0.38 ± 0.29, p =0.014), and WT (0.45 ± 0.38vs-0.45 ± 0.26, p <0.05) were found in patients with radiographic hyperparathyroid bone disease. Both APL BMD Z scores and skull BMDs were weakly correlated with PTH (r = -0.33, p < 0.05 and r = -0.33, p < 0.05, respectively) and with CAPD duration (r = 0.30, p < 0.05 and r = -0.30, p < 0.05). Generally, however, total body and regional BMDs were poorly related to age, renal disease type, dialysis duration, renal failure duration, serum aluminum, calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone. Conclusions We conclude that the prevalence of osteopenia is not increased in CAPD patients. Clinical and biochemical parameters do not reliably predict BMD measurements, but prior steroids and bone symptoms are major risk factors for important bone loss. Although DEXA can reliably detect osteopenia in different skeletal regions, its usefulness in detecting osteodystrophy is limited by the confounding effects of superimposed hyperparathyroid osteosclerosis, which increases BMD.
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Curcic, Marijana, Sladjana Tanaskovic, Sanja Stankovic, Sasa Jankovic, Marko Antunovic, Snezana Djordjevic, Vesna Kilibarda, Slavica Vucinic, and Biljana Antonijevic. "Relationship of hepatotoxicity and the target tissue dose of decabrominated diphenyl ether in subacutely exposed Wistar rats." Vojnosanitetski pregled 72, no. 5 (2015): 405–13. http://dx.doi.org/10.2298/vsp1505405c.
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Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (?-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 x external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and ?-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely exposed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent substances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly.
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DiMeglio, L. A., Audrey Anna Bolyard, Tracy M. Marrero, Blanche P. Alter, Mary Ann Bonilla, Laurence A. Boxer, Dan Link, et al. "The Risk of Low Bone Mineral Density with Long-Term G-CSF Therapy for Severe Chronic Neutropenia." Blood 116, no. 21 (November 19, 2010): 1484. http://dx.doi.org/10.1182/blood.v116.21.1484.1484.
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Abstract Abstract 1484 Low bone mineral density (BMD) is a known risk factor for fractures. Low BMD has been reported in individuals with severe chronic neutropenia (SCN), and attributed both to the diseases causing neutropenia and to G-CSF therapy. However, given the rarity of SCN, few data exist regarding associations of BMD z-scores with disease characteristics such as type of neutropenia and duration of G-CSF therapy. We present data here obtained from BMD reports collected through the Severe Chronic Neutropenia International Registry (SCNIR). We reviewed BMDs on 128 subjects [40 children (< 21 years of age), 87 females] having sufficient information about lumbar spine BMD by dual-xray absorptiometry (DXA) for evaluation. For subjects with multiple BMD measurements available, the most recent one was used for analysis. Mean age was 32.0 years (range 0.6–85 years). 57 subjects had idiopathic SCN (mean age 40 years), 40 had congenital (mean age 15 years), 28 were cyclic (mean age 41 years) and 3 were autoimmune (mean age 18 years). 122 subjects had received G-CSF at the time of the BMD assessment (mean 8.8 years, range 0.1–19.9 years). 11 of the adults were on bisphosphonate therapy for low BMD at the time of the BMD assessment; no children were on anti-resorptive therapy. BMDs in these subjects were, on average, low. For the children, the BMD z-score (age matched mean ±1 standard deviation) was -1.0 ± 1.1, with 17.5% of children having BMDs that were low for age (Z-score < -2.0). For the adults the BMD t-score was -1.1 ± 1.4, with 46% of adults meeting t-score criteria for osteopenia (≤ -1.0) and 9% meeting criteria for osteoporosis (< -2.5). BMDs were lowest in those with congenital neutropenia, followed by those with cyclic neutropenia. For children, BMDs were lower in those who had received longer G-CSF therapy (r= -0.506, p=0.002). This association was not seen in adults (r= 0.074, p= 0.5). The low BMDs and the correlation of lower BMD with longer G-CSF treatment in children suggests there is an association of bone loss with the childhood diseases causing SCN. The data also suggest that regular assessments of bone health should be made in SCN patients, particularly those on long-term G-CSF therapy. Disclosures: Boxer: Amgen, Inc.: Equity Ownership. Dale:Amgen: Consultancy, Research Funding.
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Xu, Xuejuan, Nuo Xu, Ying Wang, Jinsong Chen, Lushi Chen, Shengjian Zhang, Jingxian Chen, Hongwen Deng, Xiaojun Luan, and Jie Shen. "The longitudinal associations between bone mineral density and appendicular skeletal muscle mass in Chinese community-dwelling middle aged and elderly men." PeerJ 9 (January 19, 2021): e10753. http://dx.doi.org/10.7717/peerj.10753.
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Background The present study aimed to investigate longitudinal associations between bone mineral densities (BMDs) and appendicular skeletal muscle (ASM) mass in different regions of the body using three different indicators, in Chinese community-dwelling middle-aged and elderly men. Methods A total of 1,343 men aged ≥ 40 years from a Chinese community were assessed at baseline (2014–2016), one-year follow-up (2016–2017; n = 648), two-year follow-up (2017–2018; n = 407), and three-year follow up (2018–2019; n = 208). At all the four time-points, measurements included ASM mass and BMDs for all regions of the body using dual-energy X-ray absorptiometry. A questionnaire was completed by patients and biochemical markers were assessed. We applied three different indicators to define ASM mass or lean mass respectively, including the appendicular skeletal muscle index (ASM adjusted by height, ASMI, according to the Asian Working Group for Sarcopenia), skeletal muscle index (ASM adjusted by weight, SMI, according to the International Working Group on Sarcopenia), and the appendicular skeletal muscle/body mass index (ratio of ASM and Body mass index (BMI), ASM/BMI, according to the Foundation for the National Institutes of Health). After adjusting for potential confounders, the generalized additive mixed model (GAMM) was used to analyze the trend in ASM mass over time, and to test the association between ASM mass and regional and whole-body BMDs. Results The incidence of low lean mass was 8.2% defined by ASMI, 16.3% defined by SMI, and 8.3% defined by ASM/BMI. There was a linear relationship between BMDs and ASM mass, and ASMI, ASM/BMI, and SMI gradually decreased with time. After adjusting for covariances, GAMM analysis determined longitudinal associations between BMDs and ASM mass by three indicators respectively: the skull BMD was negatively associated with ASM mass. For each unit increase in skull BMD, ASMI decreased by 0.28 kg/m2 (95% confidence interval (CI) [−0.39 to −0.16]), ASM/BMI decreased by 0.02 m2 (95% CI [−0.03 to −0.00]), and SMI decreased by 0.01% (95% CI[−0.01 to −0.00]). The remaining parameters (including whole-body mean BMD, thoracic spinal BMD, lumbar spinal BMD, hip BMD, femoral neck BMD, pelvic BMD, left arm BMD, right arm BMD, left leg BMD, right leg BMD) were positively correlated with ASM mass. The ASMI increased by 3.07 kg/m2for each unit increase in the femoral neck BMD (95% CI [2.31–3.84]). The ASM/BMI increased by 0.22 m2for each unit increase in the left arm BMD (95% CI [0.12–0.33]), and the SMI increased by 0.05% per unit increase in the left arm BMD (95% CI [0.02–0.08]). Conclusions Compared to ASMI and ASM/BMI, SMI was more sensitive to screen for the low lean mass. Skull BMD was negatively associated with ASM mass, while BMDs throughout the rest of the body were positively correlated with ASM mass among the middle-aged and elderly Chinese men.
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Serra, Angela, Laura Aliisa Saarimäki, Michele Fratello, Veer Singh Marwah, and Dario Greco. "BMDx: a graphical Shiny application to perform Benchmark Dose analysis for transcriptomics data." Bioinformatics 36, no. 9 (January 17, 2020): 2932–33. http://dx.doi.org/10.1093/bioinformatics/btaa030.
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Abstract Motivation The analysis of dose-dependent effects on the gene expression is gaining attention in the field of toxicogenomics. Currently available computational methods are usually limited to specific omics platforms or biological annotations and are able to analyse only one experiment at a time. Results We developed the software BMDx with a graphical user interface for the Benchmark Dose (BMD) analysis of transcriptomics data. We implemented an approach based on the fitting of multiple models and the selection of the optimal model based on the Akaike Information Criterion. The BMDx tool takes as an input a gene expression matrix and a phenotype table, computes the BMD, its related values, and IC50/EC50 estimations. It reports interactive tables and plots that the user can investigate for further details of the fitting, dose effects and functional enrichment. BMDx allows a fast and convenient comparison of the BMD values of a transcriptomics experiment at different time points and an effortless way to interpret the results. Furthermore, BMDx allows to analyse and to compare multiple experiments at once. Availability and implementation BMDx is implemented as an R/Shiny software and is available at https://github.com/Greco-Lab/BMDx/. Supplementary information Supplementary data are available at Bioinformatics online.
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Kawata, Eri, Benjamin Hedley, Benjamin Chin-Yee, Anargyros Xenocostas, Alejandro Lazo-Langner, Cyrus C. Hsia, Kang Howson-Jan, et al. "Reducing Cytogenetic Testing in the Era of Next Generation Sequencing (NGS); Are We Choosing Wisely?" Blood 136, Supplement 1 (November 5, 2020): 12–13. http://dx.doi.org/10.1182/blood-2020-138667.
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Background: The combination of automation and expanding panel of target genes has improved utility and reduced costs of Next Generation Sequencing (NGS), leading to its widespread adoption in the clinical laboratory. In most laboratories, NGS has been added without consideration for redundancy or relative value compared to traditional genomic assays such as G-band karyotyping and FISH. At our centre, most patients with suspected hematologic malignancies receive both conventional cytogenetics (CG) and NGS assessment in addition to bone marrow morphology and flow cytometry. Appropriate test utilization is a high priority highlighted by campaigns such as Choosing Wisely, which often disproportionally focus on appropriate utilization of "routine" high volume tests rather than new test modalities. We implemented NGS screening in patients with suspected hematologic malignancies (Levi et al. 2019), and demonstrated enhanced diagnostic and prognostic yield of NGS, supporting the efficacy and cost-effectiveness of an 'NGS first' approach with CG restricted to samples with morphologic abnormalities in MDS (Kawata et al. BJH 2020). In this follow up study, we further expanded our Morphologic Flow Triage/NGS first (MFT-NGS1) algorithm to investigate patients with suspected hematological diseases. The main objective of our study was to evaluate this rationalized molecular diagnostic testing "MFT-NGS1" algorithm for its feasibility, acceptability and cost impact. Methods: Using the results from morphologic interpretation of aspirate and flow cytometry, patient samples were triaged into 4 groups. Group 1: Patients with dysplastic features in the marrow or excess blasts were triaged to Bone Marrow Molecular Diagnostic 1 (BMD1) and had both NGS and G-band karyotyping. Group 2: Patients with no excess blasts or dysplasia (BMD2), had NGS only with CG sample held for 3 months in case testing was required in follow up. Group 3: Patients who had NGS and/or CG on a previous BM aspirate were triaged to (BMD3), with the comment that NGS and CG should not be repeated unless results will influence patient management. These samples were held for 4 weeks and testing was performed only if specifically requested. Group 4: Patients with suspected myeloma where the proportion of plasma cells was less than 5% were triaged to (BMD4), and FISH testing was cancelled. These samples were held for 3 months in case subsequent biopsy showed an increased proportion of plasma cells in keeping with myeloma. Results: Over a 9-month period between August 2019 to April 2020 a total of 599 adult BM samples were assessed; 549 (91.7%) were ordered by hematologists and 331 (60.1%) meeting study criteria for MFT-NGS1 algorithm. Of those, 115 (34.7%) samples showed morphologic abnormalities and triaged to BMD1; 61 (18.4%) samples showed no morphologic abnormalities and were triaged to BMD2; 116 (35%) had previous CG and/or NGS tested and triaged to BMD3; and 39 (11.8%) samples were from patients with suspected myeloma had less than 5% of plasma cells and were triaged into BMD4 group. (Figure 1) Overall the MFT-NGS1 algorithm decreases G band karyotyping or FISH analysis in 149/331 (45%) samples. Only 11 / 216 (5.5%) hematologist overruled triage comment and requested CG testing for a specific indication either suspected progression of known diseases or for a therapeutic decision (e.g. drug approval). CG and FISH were mistakenly performed without the necessary reconfirmation in 26/216 (12%). Conclusion: The proposed approach combining morphologic and flow triage and NGS as the primary genomic test (MFT-NGS) is both feasible and well accepted by clinical teams. We estimated that approximately 40% of all CG testing could be reduced primarily by reducing repeat testing which offsets a large proportion of the cost of implementation of NGS testing, while increasing both diagnostic and prognostic yield. Key factors for the success of this quality improvement project were involvement of clinical and genomic teams in developing the triage algorithm, rapid turnaround time (less than 24 to 48 hours) for aspirate interpretation and flow for triage and communication between laboratories within a fully integrated healthcare centre. Figure 1 Disclosures No relevant conflicts of interest to declare.
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Haba, Yvonne, Ralf Skripitz, Tobias Lindner, Martin Köckerling, Andreas Fritsche, Wolfram Mittelmeier, and Rainer Bader. "Bone Mineral Densities and Mechanical Properties of Retrieved Femoral Bone Samples in relation to Bone Mineral Densities Measured in the Respective Patients." Scientific World Journal 2012 (2012): 1–7. http://dx.doi.org/10.1100/2012/242403.
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The bone mineral density (BMD) of retrieved cancellous bone samples is compared to the BMD measuredin vivoin the respective osteoarthritic patients. Furthermore, mechanical properties, in terms of structural modulus (Es) and ultimate compression strength (σmax) of the bone samples, are correlated to BMD data. Human femoral heads were retrieved from 13 osteoarthritic patients undergoing total hip replacement. Subsequently, the BMD of each bone sample was analysed using dual energy X-ray absorptiometry (DXA) as well as ashing. Furthermore, BMDs of the proximal femur were analysed preoperatively in the respective patients by DXA. BMDs of the femoral neck and head showed a wide variation, from1016±166 mg/cm2to1376±404 mg/cm2. BMDs of the bone samples measured by DXA and ashing yielded values of315±199 mg/cm2and347±113 mg/cm3, respectively.Esandσmaxamounted to232±151 N/mm2and6.4±3.7 N/mm2. Significant correlation was found between the DXA and ashing data on the bone samples and the DXA data from the patients at the femoral head (r=0.85and 0.79, resp.).Escorrelated significantly with BMD in the patients and bone samples as well as the ashing data (r=0.79,r=0.82, andr=0.8, resp.).
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Dale, David C., Audrey Anna Bolyard, Linda A. DiMeglio, Tracy M. Marrero, and Laurence A. Boxer. "Bone Density Measurements in Patients with Severe Chronic Neutropenia On Long-Term G-CSF Therapy." Blood 114, no. 22 (November 20, 2009): 1362. http://dx.doi.org/10.1182/blood.v114.22.1362.1362.
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Abstract Abstract 1362 G-CSF is a very effective treatment for idiopathic, congenital and cyclic neutropenia (SCN). G-CSF also expands myeloid tissues that give rise to osteoclasts that resorb bone. For this reason, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data on fractures in this population for over 15 years. These data indicate that fractures are uncommon events. To expand information on bone health for patients on long-term G-CSF, we collected additional information from a patient survey and reviewed reports of bone mineral density measurements (BMD) in US children and adults in the SCNIR. Letters were sent to 680 patients; 367 responded. 17 of 367 patients reported fractures; 15 were related to accidents (11 extremities, 4 spine) and 2 were categorized as spontaneous (both spine). The frequency of fractures was 0.005 per patient year on G-CSF. 222 patients indicated that they had not had a BMD study. We received 266 BMDs on 145 subjects (45 children {<21 years of age} and 100 adults) having sufficient information in a standard report format for evaluation. There were 82 BMDs in the 45 children and 184 BMDs in the 100 adults. For adults, abnormal BMD was defined as a t score less than -2.5; for children abnormal was a z score of less than -2.0. 205 of 266 BMD reports were normal; BMDs for 34 of 45 children and 85 of 100 adults were normal. 11 BMDs prior to G-CSF treatment were normal (4 children, 5 adults – 2 adults had 2 normal BMDs) and 194 BMDs during G-CSF treatment were normal (30 children, 85 adults). The G-CSF median dose for children with normal scans was 5.1 mcg/kg/day (range 0.0 - 53) and for adults was 1.1 mcg/kg/day (range 0.0 - 38). 61 of 266 scans were abnormal in 11 children and 15 adults. 1 of 6 adult scans prior to G-CSF treatment was abnormal. During G-CSF treatment there were 60 abnormal BMDs in 11 children and 14 adults. The G-CSF median dose for children with abnormal BMDs was 3.6 mcg/kg/day (range 0.0 - 18) and for adults was 2.3 mcg/kg/day (range 0.0 - 37). 28 subjects (8 children, 20 adults) had three or more sequential BMD reports. Of these, 17 subjects (3 children, 14 adults) suggested a trend of decreasing BMD while on G-CSF, 11 subjects (5 children, 6 adults) had normal serial BMDs on G-CSF without trending toward decreased bone mineral density. 33 patients reported treatments with osteoporosis medications; 15(46%) calcium supplements, 12(36%) bisphosphonates, 3(9%) Vitamin D supplements, 2(6%) hormonal supplements, and 1(3%) calcitonin; the effectiveness of these therapies could not be evaluated. This survey confirms that overt fractures are low-frequency events for patients with SCN on many years of G-CSF therapy. The trend toward decreased BMD in approximately 60% of patients with serial assessments suggests that bone loss is a common effect of chronic G-CSF treatment. The data also suggest that baseline and follow-up BMD assessments are useful for determining bone health for SCN patients on long term G-CSF therapy. Disclosures Dale: Amgen Inc.: Consultancy, Honoraria, Research Funding, Speaker. Boxer:Amgen Inc.: Equity Ownership.
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Breukhoven, Petra E., Ralph W. J. Leunissen, Sandra W. K. de Kort, Ruben H. Willemsen, and Anita C. S. Hokken-Koelega. "Preterm birth does not affect bone mineral density in young adults." European Journal of Endocrinology 164, no. 1 (January 2011): 133–38. http://dx.doi.org/10.1530/eje-10-0573.
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ObjectivePrevious studies showed conflicting data on the effect of prematurity on bone mineral density (BMD) in infants and children. Only a few studies investigated the long-term effects of prematurity on BMD in early adulthood. The objective of our study was to assess the long-term effects of preterm birth on BMD of the total body (BMDTB), lumbar spine (BMDLS) and bone mineral apparent density of the LS (BMADLS).DesignCross-sectional study.MethodsIt consists of two hundred and seventy-six healthy subjects without serious postnatal complications, aged 18–24 years. The contribution of gestational age to the variance in BMD in young adulthood and the differences in BMD between 151 subjects born preterm (median gestational age 32.2 weeks (interquartile range (IQR) 30.3–34.0)) and 125 subjects born at term (median gestational age 40.0 weeks (IQR 39.0–40.0)) were investigated. BMD was determined by dual-energy X-ray absorptiometry.ResultsThere were no significant linear correlations between gestational age and BMDTB(r=0.063,P=0.30), BMDLS(r=0.062,P=0.31) and BMADLS(r=0.069,P=0.26). Also after adjustment for possible confounders, gestational age was no significant contributor to the variance in BMDTB(P=0.27), BMDLS(P=0.91) and BMADLS(P=0.87). No significant differences were found between preterm and term subjects with regard to BMDTB, BMDLSand BMADLS.ConclusionIn our cohort of 276 young adults, aged 18–24 years, gestational age was not a significant determinant in the variance of BMD. Preterm birth without serious postnatal complications is not associated with a lower BMD in young adulthood.
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Sapin, E., K. Briot, S. Kolta, P. Gravel, W. Skalli, C. Roux, and D. Mitton. "Bone mineral density assessment using the EOS® low-dose X-ray device: A feasibility study." Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine 222, no. 8 (November 1, 2008): 1263–71. http://dx.doi.org/10.1243/09544119jeim450.
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To predict bone strength in the case of osteoporosis, it could be a real benefit to assess the three-dimensional (3D) geometry and the bone mineral density (BMD) with a single low-dose X-ray device, such as the EOS system (Biospace Med, Paris, France). EOS 3D reconstructions of the spine have already been validated. Thus, this study aims at evaluating the accuracy of this low-dose system as a densitometer first ex vivo. The European Spine Phantom (ESP) (number 129) was scanned ten times using both the EOS and a Hologic device (Hologic, Inc., Massachusetts, USA). Accuracy was given by the sum of the systematic error (difference between BMDs assessed and true values given by the phantom manufacturer) and the random error (coefficient of variation). EOS BMDs and Hologic BMDs of 41 ex-vivo vertebrae were calculated and compared. The reproducibility of the method evaluating the EOS BMD was assessed giving the coefficient of variation of three measurements of the 41 vertebrae. The accuracy of the EOS system is below 5.2 per cent, versus 7.2 per cent for the Hologic system in the same conditions. EOS BMDs are significantly higher than Hologic BMDs, but they are strongly correlated. The reproducibility of the method of assessment is equal to 0.95 per cent. The EOS system is accurate for ex-vivo BMD assessments, which is promising regarding the use of this new system to predict vertebral strength.
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den Hoed, Marissa, S. M. F. Pluijm, Mariël L. Te Winkel, Hester A. de Groot-Kruseman, Marta Fiocco, Peter M. Hoogerbrugge, J. a. Leeuw, et al. "Aggravated Bone Density Decline after Symptomatic Osteonecrosis in Children with Acute Lymphoblastic Leukemia." Blood 124, no. 21 (December 6, 2014): 2260. http://dx.doi.org/10.1182/blood.v124.21.2260.2260.
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Abstract Background: Osteonecrosis (ON) and decline of bone mineral density (BMD) are serious side effects during and after treatment of childhood acute lymphoblastic leukemia (ALL). It is unknown whether ON and low BMD co-occur in the same patients, and whether these two osteogenic side effects can influence each other’s development during pediatric ALL treatment. Methods: BMD and the incidence of symptomatic ON were prospectively assessed in 466 patients with ALL (4-18 years of age) treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Symptomatic ON was defined as persistent pain in arms or legs not caused by vincristine administration, and confirmed by magnetic resonance imaging. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) were measured by dual X-ray absorptiometry at ALL diagnosis, after 32 weeks of treatment, at cessation of treatment (109 weeks) and 1 year after cessation of treatment. BMD was expressed as age-matched and gender-matched standard deviation scores (SDS; Z-score). Multivariate linear mixed models were adjusted for age at diagnosis. Results: Thirty patients (6.4%) suffered from ON. At cessation of treatment, mean BMDLS was -1.28 SDS (SD: 1.27, n=332; p<0.01) and BMDTB was -0.74 SDS (SD: 1.29, n=65; p<0.01) lower in ALL patients compared to their healthy peers. At baseline, BMDLS and BMDTB did not differ between patients who developed or who did not develop ON (mean BMDLS ON+: -0.90 vs. ON-: -1.14, p=0.36; mean BMDTB ON+: 0.07 vs. ON-: 0.25 p=0.65). At cessation of treatment, patients with ON seem to have a trend for a lower mean BMDLS (ON+: -1.68 vs. ON-: -1.31, p=0.18) and they have a lower mean BMDTB (ON+: -1.91 vs. ON-: -0.59, p=0.01) than patients without ON. Multivariate analyses showed that BMDTB change during follow-up was significantly different for patients with ON than without ON (interaction group time, p=0.04). Between BMD measurements before and after the diagnosis, patients with ON seemed to have a more rapid decline of BMDTB than in patients of the same age without ON (mean BMDTB difference -1.13 vs. -0.62, p=0.10). Conclusion: We conclude that symptomatic ON and low BMD during antileukemic treatment co-occur in pediatric ALL patients. BMD status at ALL diagnosis does not seem to precede ON. However, the development of ON seems to aggravate BMD decline during antileukemic treatment, most likely due to bone destruction and the advised physical immobilization. Disclosures No relevant conflicts of interest to declare.
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Gwinn, William M., Scott S. Auerbach, Fred Parham, Matthew D. Stout, Suramya Waidyanatha, Esra Mutlu, Brad Collins, et al. "Evaluation of 5-day In Vivo Rat Liver and Kidney With High-throughput Transcriptomics for Estimating Benchmark Doses of Apical Outcomes." Toxicological Sciences 176, no. 2 (June 3, 2020): 343–54. http://dx.doi.org/10.1093/toxsci/kfaa081.
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Abstract A 5-day in vivo rat model was evaluated as an approach to estimate chemical exposures that may pose minimal risk by comparing benchmark dose (BMD) values for transcriptional changes in the liver and kidney to BMD values for toxicological endpoints from traditional toxicity studies. Eighteen chemicals, most having been tested by the National Toxicology Program in 2-year bioassays, were evaluated. Some of these chemicals are potent hepatotoxicants (eg, DE71, PFOA, and furan) in rodents, some exhibit toxicity but have minimal hepatic effects (eg, acrylamide and α,β-thujone), and some exhibit little overt toxicity (eg, ginseng and milk thistle extract) based on traditional toxicological evaluations. Male Sprague Dawley rats were exposed once daily for 5 consecutive days by oral gavage to 8–10 dose levels for each chemical. Liver and kidney were collected 24 h after the final exposure and total RNA was assayed using high-throughput transcriptomics (HTT) with the rat S1500+ platform. HTT data were analyzed using BMD Express 2 to determine transcriptional gene set BMD values. BMDS was used to determine BMD values for histopathological effects from chronic or subchronic toxicity studies. For many of the chemicals, the lowest transcriptional BMDs from the 5-day assays were within a factor of 5 of the lowest histopathological BMDs from the toxicity studies. These data suggest that using HTT in a 5-day in vivo rat model provides reasonable estimates of BMD values for traditional apical endpoints. This approach may be useful to prioritize chemicals for further testing while providing actionable data in a timely and cost-effective manner.
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Sharma, Anurag, Elias Youssef, Meaghan Roche, and Michael Maroules. "Association of bone mineral density with breast cancer and histopathologic features of the tumor." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 16. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.16.
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16 Background: High bone mineral density (BMD) has been associated with increased incidence of breast cancer. We studied the differences in BMDs between females with and without breast cancer as well as the association between BMD and the histopathological features of breast cancer. Methods: Data on BMDs and Tscores of hip and spine were collected for 311 breast cancer patients from Dexa Scans available from 5 years before or within 1 year of diagnosis. The same information was collected for 1,047 females without breast cancer (age matched with study group). The following additional data was collected for breast cancer patients: TNM staging, Histology, Estrogen receptor (ER), Progesterone receptor (PR), Ki-67 and HER-2 percentages, Tumor size, and Tumor differentiation. Results: As expected, breast cancer patients were found to have higher hip/spine BMDs than women without breast cancer (p < 0.001). PR percentage was positively associated with hip BMD/Tscore and spine BMD/Tscore ([rsp=0.166/0.165, 0.145/0.164, respectively], p<0.05 for all [Spearman Correlation Analysis]). Tumor size was negatively associated with spine BMD/Tscore ([rsp=-0.134, p=0.06], [rsp=-0.136, p=0.04], respectively, [Spearman Correlation Analysis]). A negative trend was seen between Ki-67 percentages and BMD (although no significance was achieved). Patients with lymphovascular invasion had lower spine Tscores than patients without lymphovascular invasion (-1.22±1.45 vs. -0.84±1.37, p=0.04, [One-way ANOVA]). Conclusions: Amongst all women studied, women with breast cancer were likely to have a higher BMD. However, higher BMD in breast cancer patients was associated with favorable tumor characteristics. Higher BMD was also associated with higher percentage of PR while no significant association was seen with ER. Greater cumulative estrogen exposure in females with higher BMD might explain these results. Estrogens are known to affect proliferation of breast cancer cells and to alter their phenotypic and cytoarchitechtural features, including enhanced induction of PR and possible downregulation of ER. Future studies are needed to explore these underlying pathways, their effect on tumor behavior, and treatment implications.
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Klap, Bibi C., Mariël L. Te Winkel, Marjolein van Waas, Sebastiaan J. C. M. M. Neggers, Annemieke M. Boot, Rob Pieters, and Marry M. van den Heuvel-Eibrink. "Sequential Measurement of Bone Mineral Density Identifies Ongoing Recovery of Detrimental Bone Mass in Very Long Term Adult Survivors of Childhood Cancer." Blood 120, no. 21 (November 16, 2012): 4296. http://dx.doi.org/10.1182/blood.v120.21.4296.4296.
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Abstract Abstract 4296 Background Aim of this study was to investigate status and longitudinal evolvement of BMD in long-term adult survivors. Patients and methods A single-center cohort of 410 adult long-term survivors (171 females) was included in this retrospective study. Age at diagnosis was 6.6 years (0.0–16.8 yrs), and at follow up 24.5 years (18.0–49.3 yrs). Median follow-up time was 15.2 years (5.1–39.8 yrs). BMD of the lumbar spine (BMDLS) and total body (BMDTB) were measured. Results were compared with healthy age matched controls. Results Overall BMDTB and BMDLS were low in long-term survivors (median standard deviation score (SDS) −0.60, P < 0.001 and median SDS −0.40, P < 0.001 respectively). In ALL survivors both BMDTB (median SDS −0.65, P < 0.001) and BMDLS (median SDS −0.48, P < 0.001) were low. Backwards elimination of the multivariate linear regression analysis showed that both cranial irradiated and/or total body irradiated survivors were at significant risk for low BMDTB. BM(A)DLS was not different between survivors and controls and no risk factors were identified for low BM(A)DLS. In general, a slight but significant improvement of BMDTB and BMDLS was found in our sequential measurement. This BMD improvement was not found for ALL survivors alone. Conclusions Our study shows low BMD in childhood cancer survivors treated with cranial or total body irradiation. However, sequential DXA analysis shows ongoing recovery of bone mass, which suggests a potential for reaching peak bone mass later in life. Disclosures: No relevant conflicts of interest to declare.
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Kirchner, E. M., R. D. Lewis, and P. J. O'Connor. "Effect of past gymnastics participation on adult bone mass." Journal of Applied Physiology 80, no. 1 (January 1, 1996): 226–32. http://dx.doi.org/10.1152/jappl.1996.80.1.226.
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The purposes of this study were to determine bone mineral density (BMD) of former female college gymnasts (FG; n = 18) and controls (FC; n = 15) by using dual-energy X-ray absorptiometry (Hologic QDR 1000W) and to examine the relationships between current and former activity levels, diet, menstrual history and BMD. Current physical activity, dietary intake, and menstrual irregularity were assessed with the use of standardized questionnaires. A study-designed questionnaire was used to assess past physical activity. The BMDs of the FG were significantly higher (P < 0.001) than the BMDs of FC for the lumbar spine, femoral neck, Ward's triangle, and whole body, even when the influences of current and past physical activity levels were statistically controlled via analysis of covariance. FG and FC did not differ in nutrient intakes, and there were no BMD differences between FG who always had regular menstrual cycles vs. those who had an interruption (= or = 3 mo) of their menstrual cycle in the past. The higher BMD in FG compared with FC suggests that past participation in college gymnastics may provide a residual effect on adult BMD.
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Le Meignen, Marion, Pascal Auquier, Vincent Barlogis, Nicolas Sirvent, Audrey Contet, Marie-Claude Simeoni, Claire Galambrun, et al. "Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities." Blood 118, no. 6 (August 11, 2011): 1481–89. http://dx.doi.org/10.1182/blood-2011-01-332866.
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Abstract Femoral and lumbar bone mineral densities (BMDs) were measured in 159 adults enrolled in the Leucémies de l'Enfant et de l'Adolescent program, a French prospective multicentric cohort of childhood leukemia survivors. BMDs were expressed as Z-scores, and multivariate linear regression analyses were used to construct association models with potential risk factors. Mean age at evaluation and follow-up was 23 and 14.7 years, respectively. In the whole cohort, mean femoral Z-score was −0.19 ± 0.08. Two factors were associated with lower femoral BMD transplantation (−0.49 ± 0.15 vs −0.04 ± 0.10 in the chemotherapy group; P = .006) and female sex (−0.34 ± 0.10 vs −0.03 ± 0.13; P = .03). Among patients who received a transplant, the only significant risk factor was hypogonadism (−0.88 ± 0.16 vs −0.10 ± 0.23; P = .04). A slight reduction in lumbar BMD (mean Z-score, −0.37 ± 0.08) was detected in the whole cohort without difference between the transplantation and chemotherapy groups. Among patients who received a transplant, younger age at transplantation was correlated with a low lumbar BMD (P = .03). We conclude that adults who had received only chemotherapy for childhood leukemia have a slight reduction in their lumbar BMD and a normal femoral BMD. Patients who received a transplant with gonadal deficiency have a reduced femoral BMD which might increase the fracture risk later in life.
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Bielecka, Joanna, Renata Markiewicz-Żukowska, Patryk Nowakowski, Monika Grabia, Anna Puścion-Jakubik, Konrad Mielcarek, Krystyna Joanna Gromkowska-Kępka, Jolanta Soroczyńska, and Katarzyna Socha. "Content of Toxic Elements in 12 Groups of Rice Products Available on Polish Market: Human Health Risk Assessment." Foods 9, no. 12 (December 20, 2020): 1906. http://dx.doi.org/10.3390/foods9121906.
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Background: Rice is one of the most commonly consumed grains. It could be a good source of nutrients in a diet, but its consumption could also contribute to exposure to toxic elements. All rice products available on the Polish market are imported, which may pose a particular concern as to the safety of their consumption. The aim of our study was to estimate the content of As, Cd, Pb, and Hg in rice products and to assess the health risk indicators related to exposure to toxic elements consumed with rice products among the adult population in Poland. Methods: A total of 99 samples from 12 groups of rice products (basmati, black, brown, parboiled, red, wild, white rice and expanded rice, rice flakes, flour, pasta, and waffles) available in the Polish market were obtained. The content of Hg was determined using the atomic absorption spectrometry method (AAS). To measure As, Cd, and Pb, inductively coupled plasma-mass spectrometry (ICP-MS) was used. The health risk was assessed by calculating several indicators. Results: The average As, Cd, Pb, and Hg contents in all studied products were 123.5 ± 77.1 μg/kg, 25.7 ± 26.5 μg/kg, 37.5 ± 29.3 μg/kg, and 2.8 ± 2.6 μg/kg, respectively. Exceedance of the limit established by the Polish National Food Safety Standard was observed in one sample as regards the As content and exceedance of the European Commission standard in two samples for Hg. The samples of foods imported from European markets (n = 27) had statistically higher As content (p < 0.05) than those imported from Asian countries (n = 53). The values of health risk indicators did not show an increased risk for the Polish adult population. However, the daily intake of 55 g of rice corresponds to the benchmark dose lower confidence limit (BMDL) for Pb. Conclusion: The studied rice products could be regarded as safe for consumption by the Polish population as far as the content of As, Cd, Pb, and Hg is concerned.
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Zonunsanga, C., Hmingthanmawii LNU, Minggam Pertin, Chongreilen Chiru, Romi Singh Nongmaithem, and Yengkhom Jotin Singh. "Quality of Life in Postmenopausal Women and Its Correlation with Bone Mineral Density." Indian Journal of Physical Medicine and Rehabilitation 26, no. 3 (2015): 58–64. http://dx.doi.org/10.5005/ijopmr-26-3-58.
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Abstract Aim To evaluate the quality of life in postmenopausal women and its correlation with bone mineral density. Study design Cross-sectional study. Duration of the study October 2012 to September 2014. Settings Physical Medicine and Rehabilitation Department, Regional Institute of Medical Sciences, Imphal. Study population Postmenopausal women who attended the department during the study period. Materials and Methods Quality of life was assessed using WHOQOL-BREF questionnaire, a validated brief version of the WHOQOL-100. Bone mineral density (BMD) in the lumbar spine, femoral neck and trochanter were measured using dual energy x-ray absorptiometry (DEXA) scan – GE Lunar model. Results A total of 125 patients were studied. The mean t-scores in lumbar spine, femoral neck and trochanter were -2.550 ± 1.209, -1.831 ± 0.921 and -1.621 ± 1.064 respectively. The mean BMD (g/cm2) in lumbar spine, femoral neck and trochanter were 0.867 ± 0.144, 0.789 ± 0.131 and 0.682 ± 0.139 respectively. The mean overall WHOQOL score was 57.68±10.07. There were statistically significant positive association of WHOQOL score with the BMDs in lumbar spine, femoral neck and trochanter (p < 0.05). Multivariate regression showed significant relation of overall WHOQOL score with BMD lumbar spine (b=0.229; R2=0.119), BMD femoral neck (b=0.285; R2=0.129), and BMD trochanter (b=0.245; R2=0.119). Conclusion BMDs in the lumbar spine, femoral neck and trochanter had a positive correlation with quality of life scores. BMD also had a good predictive value in determining the quality of life in postmenopausal women.
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Brambila-Tapia, Aniel Jessica Leticia, Jorge Durán-González, Lucila Sandoval-Ramírez, Juan Pablo Mena, Mario Salazar-Páramo, Jorge Iván Gámez-Nava, Laura González-López, et al. "MTHFR C677T, MTHFR A1298C, and OPG A163G Polymorphisms in Mexican Patients with Rheumatoid Arthritis and Osteoporosis." Disease Markers 32, no. 2 (2012): 109–14. http://dx.doi.org/10.1155/2012/364894.
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MTHFR polymorphisms C677T and A1298C are associated with reduced MTHFR enzyme activity and hyperhomocysteinemia, which has been associated with osteoporosis. The A163G polymorphism inosteoprotegerin(OPG) has been studied in osteoporosis with controversial results. The objective of the present study was to investigate the association(s) among MTHFR C677T, MTHFR A1298C, and OPG A163G polymorphisms in Mexican patients with rheumatoid arthritis and osteoporosis. The femoral neck and lumbar spine bone mineral densities (BMDs) were measured in 71 RA patients, and genotyping for the three polymorphisms was performed via restriction fragment length polymorphism analysis. Patients with osteoporosis/osteopenia exhibited statistically significant differences in the genotype frequencies of MTHFR C677T as well as an association with femoral neck BMD; TT homozygotes had lower BMDs than patients with the CT genotype, and both of these groups had lower BMDs than patients with the CC genotype. The associations of the MTHFR C677T polymorphism with osteoporosis/osteopenia and femoral neck BMD suggest that these polymorphisms confer a risk of developing osteoporosis in patients with rheumatoid arthritis, a risk that may be reduced with folate and B complex supplementation.
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Zhu, Kun, Xueqin Du, Heather Greenfield, Qian Zhang, Guansheng Ma, Xiaoqi Hu, and David R. Fraser. "Bone mass in Chinese premenarcheal girls: the roles of body composition, calcium intake and physical activity." British Journal of Nutrition 92, no. 6 (December 2004): 985–93. http://dx.doi.org/10.1079/bjn20041278.
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The association of growth and anthropometric characteristics and lifestyle factors with bone mass and second metacarpal radiogrammetry parameters was evaluated in 373 healthy Chinese premenarcheal girls aged 9–11 years. Bone mineral content (BMC) and density (BMD) and bone area (BA) of distal forearm, proximal forearm and total body, bone mineral-free lean (BMFL) mass and fat mass were measured by dual-energy X-ray absorptiometry. Metacarpal bone periosteal and medullary diameters were measured. Dietary intakes were assessed by 7d food record and physical activity (PA) by questionnaire. BMFL and fat mass together explained 6·3 and 51·6% of the variation in total body BMC and BMD, respectively. BMFL mass contributed to a substantial proportion of the variation in forearm BMC and BMD and periosteal diameter (10·4–41·0%). The corresponding BA explained 14·8–80·4% of the variation in BMC. Other minor but significant predictors of total body bone mass were Ca intake, height, age and PA score (BMD only), and of forearm bone mass were PA score, bone age, height and fat mass. Nevertheless, after adjusting for bone and body size and for age or bone age, subjects with Ca intake above the median (417mg/d) had 1·8% greater total body BMC (P<0·001), and subjects with PA scores above the median had 2·4–2·5% greater distal and proximal forearm BMC (P<0·05) than those below. Vitamin D intake negatively associated with medullary diameter (partialR21·7%). The results indicate that premenarcheal girls should be encouraged to optimise nutrition and Ca intake and exercise regularly to achieve maximum peak bone mass.
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Rivera-Paredez, Berenice, Amado D. Quezada-Sánchez, Edgar Denova-Gutiérrez, Leticia Torres-Ibarra, Yvonne N. Flores, Jorge Salmerón, and Rafael Velázquez-Cruz. "Diet Modulates the Effects of Genetic Variants on the Vitamin D Metabolic Pathway and Bone Mineral Density in Mexican Postmenopausal Women." Journal of Nutrition 151, no. 7 (April 13, 2021): 1726–35. http://dx.doi.org/10.1093/jn/nxab067.
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ABSTRACT Background Macro- and micronutrients, such as proteins, vitamin D, and calcium (Ca), are important dietary factors that can modify bone mineral density (BMD). Genetic factors can interact with diet, affecting an individual's predisposition to osteoporosis. Objectives This study aimed to evaluate the associations between macro- and micronutrient intakes and BMD in Mexican postmenopausal women, and their interactions with genetic polymorphisms involved in the vitamin D metabolic pathway. Methods We analyzed data from 317 postmenopausal women from the Health Workers Cohort Study, a longitudinal cohort studied in Cuernavaca, Mexico. Postmenopausal women participated in 2 data collection waves (2004–2006 and 2010–2011), with a mean time of 6.4 years. Dietary intake was assessed with a semi-quantitative FFQ. BMD (femoral neck, hip, and lumbar spine) was measured by DXA. Hybrid mixed-effects regression models were used to assess the associations of dietary macro- and micronutrients on BMD, after adjusting for confounding factors and for diet and single nucleotide polymorphism interactions. Results At baseline, the median age was 57 years (IQR, 50–64). Mean femoral neck, hip, and lumbar spine BMDs decreased over time. We observed statistically significant longitudinal associations for diet (Ca, vitamin D, magnesium, phosphorus, and protein intake) and BMD. Increases of vitamin D, Ca, and protein intakes by 1 SD were associated with mean increases in the femoral neck BMD (0.083 SD, 0.064 SD, and 0.130 SD, respectively). Multiple significant interactions were identified between several loci (CYP2R1, CYP24A1, CYP27B1, VDR, and DHCR7/NADSYN1) and diet for BMDs (femoral neck, hip, and lumbar spine), mainly for protein intake. Conclusions Our data support associations of vitamin D, Ca, protein, phosphorous, and magnesium consumption with BMD in Mexican postmenopausal women and suggest possible gene-diet interactions. These results could facilitate future personalized nutrition recommendations to help prevent low BMD.
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Jensen, Signe M., Felix M. Kluxen, Jens C. Streibig, Nina Cedergreen, and Christian Ritz. "bmd: an R package for benchmark dose estimation." PeerJ 8 (December 17, 2020): e10557. http://dx.doi.org/10.7717/peerj.10557.
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The benchmark dose (BMD) methodology is used to derive a hazard characterization measure for risk assessment in toxicology or ecotoxicology. The present paper’s objective is to introduce the R extension package bmd, which facilitates the estimation of BMD and the benchmark dose lower limit for a wide range of dose-response models via the popular package drc. It allows using the most current statistical methods for BMD estimation, including model averaging. The package bmd can be used for BMD estimation for binomial, continuous, and count data in a simple set up or from complex hierarchical designs and is introduced using four examples. While there are other stand-alone software solutions available to estimate BMDs, the package bmd facilitates easy estimation within the established and flexible statistical environment R. It allows the rapid implementation of available, novel, and future statistical methods and the integration of other statistical analyses.
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te Winkel, Mariel L., Rob Pieters, Wim C. J. Hop, Jan C. Roos, Inge M. van der Sluis, Jos P. M. Bökkerink, Jan A. Leeuw, et al. "Bone Mineral Density At Diagnosis Determines Fracture Rate in Children Treated According to the DCOG-ALL9 Protocol." Blood 120, no. 21 (November 16, 2012): 1469. http://dx.doi.org/10.1182/blood.v120.21.1469.1469.
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Abstract Abstract 1469 Purpose As survival rates for pediatric acute lymphoblastic leukemia (ALL) have significantly improved, awareness of side effects such as skeletal toxicity becomes increasingly important. As BMD decrease over time might be associated with an increased risk of fractures, we performed repeated measurements of BMD in a large nation-wide study and studied the incidence of fractures in these children treated for ALL. Methods Prospectively, serial measurements (at diagnosis, after 32 weeks, after 2 years (at cessation of therapy) and after 3 years (1 year after cessation of therapy)) of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absorptiometry (DXA). Using logistic multivariate regression, we evaluated the following putative risk factors for a low BMDLS:age at diagnosis, gender, risk group of ALL treatment, weight and height at diagnosis. Moreover, Kaplan-Meier survival analysis was used to assess the cumulative incidence of fractures in 672 patients treated with the dexamethasone-based DCOG-ALL9 protocol. All reported fractures were symptomatic, and confirmed by X-ray. Cumulative incidences of fractures for different subgroups were compared with the Log-Rank test. Results At diagnosis, mean BMDLS of ALL patients was lower than that of healthy peers (mean BMDLS= −1.10 SDS, P< 0.001), and this remained significant lower during and after treatment (8 months: BMDLS = −1.10 SDS, P< 0.001; 24 months: BMDLS = −1,27 SDS, P< 0.001; 36 months: BMDLS = −0.95 SDS, P< 0.001). Multivariate linear regression analysis showed that after correction for weight, height and gender, treatment according to the HR treatment arm and older age at diagnosis had a significant negative effect on the decline of BMDLS during treatment (high-risk group: b = −0.50, P<0.001 and age at diagnosis: b = −0.15, P<0.001). The cumulative incidence of fractures at 3 years was 17.8%. Cumulative incidences of fractures between risk groups and age groups were not significantly different (NHR 18.8% vs. HR 15.7%, P = 0.18 and <10 years 17.7% vs. ≥10 years 17.6%, P = 0.85). Patients who developed fractures had a lower BMDLS during treatment than those without fractures. Treatment-related bone loss was similar in patients without fractures and patients with fractures (respectively: Δ BMDLS = −0.12 SDS vs. Δ BMDLS= −0.36 SDS; interaction group time, P = 0.295). Conclusion This large prospective study shows that the low value of BMDLS both at diagnosis and during treatment, rather than the treatment-related decline of BMDLS, determines the markedly increased fracture risk of 17.8%. Disclosures: No relevant conflicts of interest to declare.
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Ballard, Joyce E., Lorraine S. Wallace, David B. Holiday, Cassandra Herron, Liberty L. Harrington, Karen C. Mobbs, and Patricia Cussen. "Evaluation of Differences in Bone-Mineral Density in 51 Men Age 65–93 Years: A Cross-Sectional Study." Journal of Aging and Physical Activity 11, no. 4 (October 2003): 470–86. http://dx.doi.org/10.1123/japa.11.4.470.
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This study assessed differences in bone-mineral density (BMD) and lean and fat tissues between 5 age groups of White men age 65–93 years. Lean and fat tissues were measured with absorptiometry and anthropometry, and BMD, with dual-energy X-ray absorptiometry. Forearm, spinal, and femoral T scores were used to classify BMD as normal, osteopenic, or osteoporotic. A questionnaire evaluated previous physical activity, calcium intake, and bone fractures. Significantly lower values in body weight, lean tissue, and forearm BMD occurred in the older age groups. Significant, positive relationships were found between total lean tissue and radial, spinal, and hip BMDs. For the total group, osteopenic and osteoporotic T scores, respectively, were femoral neck 70.6% and 9.8%, radius 27.5% and 25.5%, and spine 25.5% and 7.8%. Differences in BMD values were found between levels of lifestyle factors (dietary calcium and history of previous fractures). In conclusion, elderly men should be encouraged to maintain adequate total lean tissue because of its association with BMD.
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den Hoed, Marissa, Bibi C. Klap, Mariël L. Te Winkel, Lisette Stolk, Rob Pieters, Marjolein van Waas, Sebastian J. C. M. M. Neggers, et al. "Determinants of Low Bone Mineral Density after Childhood Cancer." Blood 124, no. 21 (December 6, 2014): 933. http://dx.doi.org/10.1182/blood.v124.21.933.933.
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Abstract Purpose: Osteopenia is a potential complication of childhood cancer treatment, but the magnitude of this problem in survivors is unknown. We examined (determinants of) bone mineral density (BMD) status in long-term survivors of adult childhood cancer (CCS). Methods: This retrospective single-center cohort study included 346 subjects with the most common types of childhood cancer. Acute leukemia or lymphoma was diagnosed in 273 (81%) of the patients. All subjects had a median age at diagnosis of 7.0 years (range: 0.1-16.8 years) and a median follow-up time of 16.7 years (range 5.6-39.9 years). Total body BMD (BMDTB) and BMD of the lumbar spine (BMDLS) were measured by dual-X-ray absorptiometry. Osteopenia was defined as BMD standardized deviation score (SDS) below -1. Twelve candidate single nucleotide polymorphisms (SNPs) in 11 genes (COL1A1, TNFSF11, TNFRSF11, TNRFSA11B, VDR, ESR1,WLS, LRP5, MTHFR, MTRR, IL6) were investigated. Results: Survivors had a lower BMDTB and BMDLS (mean SDS: -0.55, p<0.001; and -0.30, p<0.001, respectively) as compared to healthy peers. This was similar in cancer survivors of leukemia and lymphoma (mean SDS: -0.49, p<0.001; and -0.32, p<0.001, respectively). Osteopenia (BMDTB and/or BMDLS) was present in 45% of the survivors (46% of the leukemia and lymphoma survivors). Multivariate logistic regression analyses identified age at diagnosis <12 years, age >30 years at follow-up, male gender, underweight at follow-up, carriers of the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and prednisone as independent prognostic factors for osteopenia. In survivors of leukemia and lymphoma, we identified low BMI at follow-up, carriers the minor allele of rs2504063 (LRP5), treatment with cranial-spinal radiotherapy and cyclophosphamide use as prognostic factors for osteopenia. Conclusions: This large cohort of childhood cancer survivors with the long follow-up identified osteopenia in 45% of CCS. This indicates that greater awareness for low BMD is warranted, especially in survivors who are older than 30 years, male, have underweight, have a genetic predisposition, and who were treated with cranial-spinal radiotherapy and/or steroids. Disclosures No relevant conflicts of interest to declare.
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Van Atteveld, Jenneke E., Saskia M. F. Pluijm, Kirsten K. Ness, Melissa M. Hudson, Wassim Chemaitilly, Sue C. Kaste, Leslie L. Robison, Sebastian J. C. M. M. Neggers, Marry M. Van den Heuvel-Eibrink, and Carmen L. Wilson. "Low and Very Low Bone Mineral Density Among Adult Survivors of Childhood Cancer Can be Predicted." Blood 132, Supplement 1 (November 29, 2018): 4840. http://dx.doi.org/10.1182/blood-2018-99-114631.
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Abstract Background: Although low bone mineral density (BMD) is prevalent among adult survivors of childhood cancer, evidence-based guidance for surveillance of low BMD among survivors by dual X-ray absorptiometry (DXA) is limited. Therefore, we aimed to develop and validate prediction models for low and very low BMD based on patient and treatment characteristics that identify adult survivors who require screening by DXA. Methods: Caucasian survivors (N=2412, median attained age, 30.9 [range: 18.1-65.9] years, 60% survivors of hematologic malignancies) enrolled in the St. Jude Lifetime Cohort (SJLIFE, development) and survivors previously treated at the Erasmus Medical Center (validation), the Netherlands (N=410, median age, 24.5 [range: 18.0-49.3] years, 73% survivors of hematologic malignancies) were evaluated with DXA to determine lumbar spine (BMDLS) and total body (BMDTB) BMD, with low and very low BMD defined as BMDLS and/or BMDTB Z-score ≤-1 or ≤-2, respectively. Backward multivariable logistic regression was used to build prediction models; performance was assessed using receiver operating characteristic curves. Diagnostic values were calculated at different probabilities. Diagnostic values were calculated at different probabilities. The formula PlowBMD=e^(β0+β1*x1+...+βn*xn)/(1+e^(β0+β1*x1+...+βn*xn)) was used to predict individual probability of low BMD (β0=intercept; βn=regression coefficient (β) of each predictor xn). Results: Low BMD was prevalent among 52% and 44% of SJLIFE and Dutch participants, and very low BMD among 20% and 10%, respectively. The model for low BMD included male sex (β=0.50), height (β=-0.05), weight (β=-0.03), age at cancer diagnosis (β=-0.02), current smoking (β=0.19) and cranial irradiation (β=0.31) as significant predictors. Areas under the curves (AUC's) were 0.72 (95%-CI 0.70-0.74) in SJLIFE and 0.70 (95%-CI 0.65-0.75) in the Dutch cohort. Sensitivity (69.6%), specificity (63.9%) and accuracy (66.9%) were optimized at a probability of 0.50. The model for very low BMD included male sex (β=0.55), height (β=-0.05), weight (β=-0.04), cranial (β=0.31) and abdominal (β=0.22) irradiation, yielding AUC's of 0.75 (SJLIFE cohort) and 0.72 (Dutch cohort). Conclusion: Validated models for low BMD including sex, age at cancer diagnosis, height, weight, smoking status, cranial irradiation and abdominal irradiation correctly identified BMD status in most Caucasian survivors through age 50 years. Clinical applicability can be warranted using our online calculator. Disclosures No relevant conflicts of interest to declare.
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Povoroznyuk, Vladyslav, Maryna Bystrytska, Nataliia Grygorieva, Iryna Karaban, and Nina Karasevich. "Bone Mineral Density, TBS, and Body Composition Indexes in Ukrainian Men with Parkinson’s Disease." Parkinson's Disease 2019 (February 7, 2019): 1–7. http://dx.doi.org/10.1155/2019/9394514.
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Introduction. Current research studies demonstrate the changes of bone mineral density (BMD) in subjects with Parkinson’s disease (PD); however, data about bone quality and body composition (BC) indexes are insufficient. The aim of the study was to assess the parameters of BMD, ВС, and trabecular bone score (TBS) in PD males. Materials and Methods. We performed a cross-sectional case-control research design and examined 76 males aged 50–77 years old, who were divided into two groups: first group including men without PD n=38 and the second group including subjects with PD n=38. Disease duration was at least 5 years; all PD participants were at levodopa therapy. BMD of lumbar spine, femoral neck, total femur, radius, and total body and TBS Ll−L4 were measured using the DXA method. Whole-body DXA measures were also used for the study of total, lean, and fat masses, skeletal muscle index (SMI), appendicular lean mass index (ALMI), and fat mass index (FMI). Results. Our study showed an increased incidence of osteoporosis and significantly lower total body BMD (respectively, 1.20 ± 0.13 and 1.26 ± 0.10 g/cm2, p=0.05), but not lumbar spine and femoral neck BMDs, and higher TBS value in PD men comparing to the control group (respectively, 1.33 ± 0.12 and 1.22 ± 0.18 un., p=0.005). Also, we established significantly decreased lower extremities BMD indexes, but not upper extremities, spine, and trunk BMDs in PD males. The femoral neck, proximal femur, and lower extremities BMD indexes in PD men were reliably lower at the side of predominance of clinical symptoms. Parameters of appendicular lean mass and ALMI in PD males were reliably higher, but fat mass values and FMI were lower compared to the control group in the absence of significant differences in lean mass values and SMI in weight-matched control. Conclusion. Due to low BMD values, changes in BC are present in PD males, and appropriate screening and preventive strategies should be instigated to maintain bone health in PD subjects.
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Susic, Gordana, Nada Pilipovic, and Roksanda Stojanovic. "Bone mineral density in patients with juvenile idiopathic arthritis." Srpski arhiv za celokupno lekarstvo 137, no. 7-8 (2009): 396–401. http://dx.doi.org/10.2298/sarh0908396s.
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Introduction. It is well known that juvenile idiopathic arthritis (JIA) as a chronic inflammatory disease with onset during the childhood, beside other complication, can lead to bone metabolism disturbance and osteoporosis. Objective. To assess bone mineral density (BMD) in children with JIA and to identify factors playing role in bone mineral disturbance. Methods. Seventy-five patients (26 male and 49 female) average disease duration 7.2 (2.4-16.8) years, and 73 age matched healthy control subjects (29 male and 44 female) participated in the study. Mean age of the groups was about 14.5 years. BMD was determined by dual x-ray absorptiometry (DEXA) of the lumbar spine (L2-L4). For further analysis we used the absolute value of BMD, expressed as g/cm2, Z score expressed as SD (relative value as standard deviation decline of normal BMD values of referent Italian population with identical age and gender), bone mineral content (BMC) as g/cm, and corrected BMD - BMDv as g/cm3. Results. Z score in the group of patients was significantly lower (-1.02?1.6) in comparison to the control group (-0.09?1.4; p<0.001). BMD, BMDv and BMC were also statistically lower in patients with JIA. The lowest Z score was found in patients with systemic onset (-2.63 SD). Z score showed a statistically significant positive correlation with arthritis course (polyarticular course had lower Z score), body mass index and standard deviation score for height and weight. Statistically significant negative correlation was detected in regard to Z score and glucocorticoid (GC) treatment duration, GC cumulative dose, number of joints with limited range of motion, radiological stage and functional class. Conclusion. The results showed a decreased BMD in patients with JIA in comparison to the control group. Systemic onset, polyarthritis, longer treatment with GC and higher cumulative dosage, as well as higher damage level (functional status and radiological stage) are factors playing negative role in bone metabolism in children with JIA.
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Kim, Keunyoung, Kyoungjune Pak, In-Joo Kim, Seong-Jang Kim, Dong Hyun Sohn, Aran Kim, and Seung-Geun Lee. "Association of Regional Bone Synthetic Activities of Vertebral Corners and Vertebral Bodies Quantified Using 18F-Fluoride Positron Emission Tomography with Bone Mineral Density on Dual Energy X-ray Absorptiometry in Patients with Ankylosing Spondylitis." Journal of Clinical Medicine 9, no. 8 (August 17, 2020): 2656. http://dx.doi.org/10.3390/jcm9082656.
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We investigated whether the bone-synthetic activities of vertebral bodies or vertebral corners quantified using 18F-fluoride positron emission tomography (PET) was associated with bone mineral density (BMD) at the corresponding lumbar vertebrae in ankylosing spondylitis (AS) at each vertebra level. We analyzed 48 lumbar vertebrae in 12 AS patients who underwent 18F-fluoride PET and dual energy X-ray absorptiometry (DXA). The mean standardized uptake values (SUVmean) of the vertebral body and corners from L1 to L4 were measured using the spatially separated region of interest (ROI). The L1–L4 BMDs were calculated based on the DXA (“conventional BMD”). The BMD of the internal vertebral bodies was measured by manually drawing ROIs to represent the trabecular BMD (“alternative BMD”). After adjusting the within-patient correlation, the 18F-fluoride SUVmean of the vertebral corners but not that of vertebral bodies was significantly related with the conventional BMD of the vertebra. Otherwise, the 18F-fluoride uptake of both the vertebral and vertebral bodies was significantly related with the alternative BMD. The bone-synthetic activities of the vertebral corners may be more closely related with BMD than those of the vertebral bodies, suggesting that the effects of regional bone metabolism at the vertebral corners and bodies on BMD differ in AS.
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Liu, Yung-Chun, Yung-Chieh Lin, Pei-Yin Tsai, Osuke Iwata, Chuew-Chuen Chuang, Yu-Han Huang, Yi-Shan Tsai, and Yung-Nien Sun. "Convolutional Neural Network-Based Humerus Segmentation and Application to Bone Mineral Density Estimation from Chest X-ray Images of Critical Infants." Diagnostics 10, no. 12 (November 30, 2020): 1028. http://dx.doi.org/10.3390/diagnostics10121028.
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Measuring bone mineral density (BMD) is important for surveying osteopenia in premature infants. However, the clinical availability of dual-energy X-ray absorptiometry (DEXA) for standard BMD measurement is very limited, and it is not a practical technique for critically premature infants. Developing alternative approaches for DEXA might improve clinical care for bone health. This study aimed to measure the BMD of premature infants via routine chest X-rays in the intensive care unit. A convolutional neural network (CNN) for humeral segmentation and quantification of BMD with calibration phantoms (QRM-DEXA) and soft tissue correction were developed. There were 210 X-rays of premature infants evaluated by this system, with an average Dice similarity coefficient value of 97.81% for humeral segmentation. The estimated humerus BMDs (g/cm3; mean ± standard) were 0.32 ± 0.06, 0.37 ± 0.06, and 0.32 ± 0.09, respectively, for the upper, middle, and bottom parts of the left humerus for the enrolled infants. To our knowledge, this is the first pilot study to apply a CNN model to humerus segmentation and to measure BMD in preterm infants. These preliminary results may accelerate the progress of BMD research in critical medicine and assist with nutritional care in premature infants.
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Souza, Marcio Leandro Ribeiro de, Ann Kristine Jansen, Luiz Oswaldo Carneiro Rodrigues, Darlene Larissa de Souza Vilela, Adriana Maria Kakehasi, Aline Stangherlin Martins, Juliana Ferreira de Souza, and Nilton Alves de Rezende. "Reduced bone mineral content and density in neurofibromatosis type 1 and its association with nutrient intake." Revista da Associação Médica Brasileira 66, no. 5 (May 2020): 666–72. http://dx.doi.org/10.1590/1806-9282.66.5.666.
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SUMMARY BACKGROUND Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disease characterized by multisystem involvement including low bone mineral density (BMD). OBJECTIVE To assess the bone phenotype of individuals with NF1 and verify its association with nutrient intake. METHODS Twenty-six adults with NF1 underwent bone phenotype assessments using dual-energy X-ray absorptiometry (DXA) and food intake evaluations. They were compared to 26 unaffected matched control patients. Weight, height, and waist circumference (WC) were measured. DXA provided total body, spine, and hip BMDs and bone mineral content (BMC) for all patients. Food intake was evaluated for energy, macro- and micro-nutrients. RESULTS Height (1.68 ± 0.1; 1.61 ± 0.1 cm; P = 0.003) and BMC (2.3 ± 0.4; 2.0 ± 0.5 kg; P = 0.046) were lower in the NF1 group. Individuals with NF1 also presented lower total body and spine BMDs (g/cm2) (1.1 ± 0.1, 1.0 ± 0.1, P = 0.036; 1.0 ± 0.1, 0.9 ± 0.1; P = 0.015, respectively). The frequency of total body bone mass below the expected level for patients’ ages was higher in the NF1 group (7.7%; 34.6%, P = 0.016). There were no differences in energy consumption. No correlations between BMC and BMD with nutrient intake were observed in the NF1 group. CONCLUSIONS The NF1 group presented lower BMCs and BMDs. Although a lower consumption of calcium, iron, and vitamin A, and a higher intake of sodium and omega-6 were observed, there was no relationship between bone phenotype and nutrient intake.
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Lee, Young Han, Jung Jin Kim, and In Gwun Jang. "Patient-Specific Phantomless Estimation of Bone Mineral Density and Its Effects on Finite Element Analysis Results: A Feasibility Study." Computational and Mathematical Methods in Medicine 2019 (January 3, 2019): 1–10. http://dx.doi.org/10.1155/2019/4102410.
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Objectives. This study proposes a regression model for the phantomless Hounsfield units (HU) to bone mineral density (BMD) conversion including patient physical factors and analyzes the accuracy of the estimated BMD values. Methods. The HU values, BMDs, circumferences of the body, and cross-sectional areas of bone were measured from 39 quantitative computed tomography images of L2 vertebrae and hips. Then, the phantomless HU-to-BMD conversion was derived using a multiple linear regression model. For the statistical analysis, the correlation between the estimated BMD values and the reference BMD values was evaluated using Pearson’s correlation test. Voxelwise BMD and finite element analysis (FEA) results were analyzed in terms of root-mean-square error (RMSE) and strain energy density, respectively. Results. The HU values and circumferences were statistically significant (p<0.05) for the lumbar spine, whereas only the HU values were statistically significant (p<0.05) for the proximal femur. The BMD values estimated using the proposed HU-to-BMD conversion were significantly correlated with those measured using the reference phantom: Pearson’s correlation coefficients of 0.998 and 0.984 for the lumbar spine and proximal femur, respectively. The RMSEs of the estimated BMD values for the lumbar spine and hip were 4.26 ± 0.60 (mg/cc) and 8.35 ± 0.57 (mg/cc), respectively. The errors of total strain energy were 1.06% and 0.91%, respectively. Conclusions. The proposed phantomless HU-to-BMD conversion demonstrates the potential of precisely estimating BMD values from CT images without the reference phantom and being utilized as a viable tool for FEA-based quantitative assessment using routine CT images.
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Lee, Young Ho, Jin-Hyun Woo, Seong Jae Choi, Jong Dae Ji, and Gwan Gyu Song. "Effects of Low-Dose Corticosteroids on the Bone Mineral Density of Patients With Rheumatoid Arthritis." Journal of Investigative Medicine 56, no. 8 (December 1, 2008): 1011–18. http://dx.doi.org/10.2310/jim.0b013e31818e82d7.
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BackgroundThe effects of long-term high-dose corticosteroids on bone mineral density (BMD) are clear, but the effects of low-dose corticosteroids in patients with rheumatoid arthritis (RA) remain controversial. The aim of this study was to assess the effects of low-dose corticosteroids on BMD in patients with RA.MethodsThe authors surveyed randomized controlled studies that examined the effects of low-dose corticosteroids on BMD in patients with RA using MEDLINE and the Cochrane Controlled Trials Register and by performing manual searches. Data were collected on BMD (end-of-period or change-from-baseline) after longest recorded treatment durations. Meta-analysis was performed using a random effects model; outcomes are presented as standardized mean differences (SMDs).ResultsSeven studies were included in this meta-analysis, which included 7 studies on lumbar BMD meta-analysis and 6 studies on femur BMD meta-analysis. Corticosteroids resulted in a moderate worsening in lumbar BMD compared with controls (SMD = −0.483; 95% confidence interval [CI], −0.815 to −0.151, P = 0.004), whereas the femoral BMD differences were not siginificant (SMD = −0.224; 95% CI, −0.663 to 0.215, P = 0.318). Subgroup analysis of BMD data performed on a change-from-baseline basis showed that corticosteroids had a clear effect on both lumbar and femoral BMDs (SMD = −0.354; 95% CI, −0.620 to −0.088, P = 0.009; SMD = −0.488; 95% CI, −0.911 to −0.065, P = 0.024, respectively).ConclusionsThis meta-analysis shows BMD loss after low-dose corticosteroid treatment in patients with RA. These findings have practical implications for the long-term management of patients with RA on low-dose corticosteroids.
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Jeong, Hyeon Jang, Joong Mo Ahn, and Joo Han Oh. "Trabecular Bone Score Could Not Predict the Bone Mineral Density of Proximal Humerus." Journal of Bone Metabolism 28, no. 3 (August 31, 2021): 239–47. http://dx.doi.org/10.11005/jbm.2021.28.3.239.
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Background: Osteoporosis is an important clinical factor for tendon healing after arthroscopic rotator cuff repair (ARCR). Conventional dual energy X-ray absorptiometry (DXA) of the hip and lumbar spine (LS) does not represent proximal humeral bone mineral density (BMD). Theoretically, direct measurement of the BMD of the proximal humerus is the best method; however, it is not popular and is non-standardized. Therefore, we evaluate whether the trabecular bone score (TBS) using LS DXA would represent proximal humeral BMD.Methods: Conventional hip and LS DXA and proximal humeral BMD were measured in 212 consecutive ARCR patients, and TBS was calculated using LS DXA. Comparative analysis between the affected and contralateral asymptomatic shoulders was done; moreover, correlation analysis was conducted to evaluate the representativity of TBS for proximal humeral BMD. Regression analysis was performed to elucidate the risk factor of intraoperative suture anchor failure (ISAF).Results: BMDs of the affected shoulder were significantly lower than those of the contralateral side (all P<0.05). TBS failed to present a strong correlation with proximal humeral BMD (correlation coefficients 0.155-0.506, all P<0.05), and the BMD of the greater tuberosity (GT) of the proximal humerus was revealed to be a sole risk factor for ISAF (odds ratio, 0.01, P=0.020).Conclusions: TBS and conventional hip and LS DXA did not represent proximal humeral BMD. Furthermore, among the various radiological measurements, the BMD of the GT was a sole risk factor of ISAF. Therefore, further research for the direct measurement of proximal humeral BMD is mandatory to predict proximal humeral focal osteoporosis.
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Odeh, Khalid, Alexander Rosinski, Jeremi Leasure, and Dimitriy Kondrashov. "Pedicle Screws Challenged: Lumbar Cortical Density and Thickness Are Greater in the Posterior Elements Than in the Pedicles." Global Spine Journal 11, no. 1 (November 22, 2019): 34–43. http://dx.doi.org/10.1177/2192568219889361.
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Study Design: Controlled laboratory study. Objective: To measure the total bone mineral density (BMD), cortical volume, and cortical thickness in seven different anatomical regions of the lumbar spine. Methods: Using computed tomography (CT) images, 3 cadaveric spines were digitally isolated by applying filters for cortical and cancellous bone. Each spine model was separated into 5 lumbar vertebrae, followed by segmentation of each vertebra into 7 anatomical regions of interest using 3-dimensional software modeling. The average Hounsfield units (HU) was determined for each region and converted to BMD with calibration phantoms of known BMD. These BMD measurements were further analyzed by the total volume, cortical volume, and cancellous volume. The cortical thickness was also measured. A similar analysis was performed by vertebral segment. St Mary’s Medical Center’s Institutional Review Board approved this study. No external funding was received for this work. Results: The lamina and inferior articular process contained the highest total BMD, thickest cortical shell, and largest percent volumes of cortical bone. The vertebral body demonstrated the lowest BMD. The BMDs of the L4 and L5 segments were lower; however, there were no statistically significant differences in BMD between the L1-L5 vertebral segments. Conclusion: Extrapedicular regions of the lumbar vertebrae, including the lamina and inferior articular process, contain denser bone than the pedicles. Since screw pullout strength relies greatly on bone density, the lamina and inferior articular processes may offer stronger fixation of the lumbar spine.
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Qin, Li’nan, Xiaopeng Guo, Lu Gao, Zihao Wang, Chenzhe Feng, Kan Deng, Wei Lian, and Bing Xing. "Preoperative and Postoperative Bone Mineral Density Change and Risk Factor Analysis in Patients with a GH-Secreting Pituitary Adenoma." International Journal of Endocrinology 2019 (November 3, 2019): 1–8. http://dx.doi.org/10.1155/2019/2102616.
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Purpose. This study analysed changes in bone mineral density (BMD) at different sites in patients with acromegaly and postoperative BMD changes and explored risk factors associated with BMD. Methods. Clinical data of 39 patients with growth hormone- (GH-) secreting pituitary adenomas and 29 patients with nonfunctioning pituitary adenomas who were newly diagnosed in neurosurgery from January 2016 to December 2018 were retrospectively analysed, including measurements of preoperative and postoperative BMD, serum GH glucose inhibition, random GH and IGF-1, and other anterior pituitary hormones. Results. The average patient age and disease duration were 43.74 (33.41–54.07) years and 72.15 (22.82–121.48) months, respectively. Compared with patients with nonfunctioning adenomas, patients with GH-secreting pituitary adenomas had significantly higher BMDs at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites (p<0.05). The BMD Z score at L1 and femoral neck sites significantly increased (p<0.05). Thirteen patients underwent re-examination of BMD 1 year postsurgery, and the BMD Z score was reduced to normal levels at L1, L2, L3, L4, L1-L4, and L2-L4 compared with preoperative levels (p<0.05). Postoperative BMD Z scores in the femoral neck and total hip were significantly increased (p<0.05). Disease duration was negatively correlated with the lumbar-spine BMD Z score. IGF-1 burden was negatively correlated with the BMD Z score at L1 and L1–L4. Multiple regression analysis showed that IGF-1 burden was a risk factor for a BMD Z score decrease at L1 and L1–L4. Conclusion. BMD in patients with GH-secreting pituitary adenomas (compared with nonfunctional adenomas) increased at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites. Lumbar-spine BMD Z score recovered to normal levels postsurgically when GH and IGF-1 levels were controlled. BMD Z score was negatively correlated with disease duration and IGF-1 burden in patients with GH-secreting pituitary adenomas, and IGF-1 burden was an independent risk factor for reduced lumbar-spine BMD Z score.
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Fujiyoshi, Akira, Lynda E. Polgreen, Daniel L. Hurley, Myron D. Gross, Stephen Sidney, and David R. Jacobs. "A Cross-Sectional Association Between Bone Mineral Density and Parathyroid Hormone and Other Biomarkers in Community-Dwelling Young Adults: The CARDIA Study." Journal of Clinical Endocrinology & Metabolism 98, no. 10 (October 1, 2013): 4038–46. http://dx.doi.org/10.1210/jc.2013-2198.
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Abstract Context: Most association studies of bone-related biomarkers (BBMs) with bone mineral density (BMD) have been conducted in postmenopausal women. Objective: We tested whether the following BBMs were cross-sectionally associated with BMD among young adults: serum 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25OHD), PTH, osteocalcin, bone-specific alkaline phosphatase (BAP), and urinary pyridinoline/urinary creatinine. Setting and Participants: We studied 319 individuals (134 women, 149 black, 24–36 years) recruited during 1992 through 1993 in Oakland, California. BMD was assessed with dual-energy x-ray absorptiometry. Linear regression models estimated the association between BMD and each BBM. Results: 1,25(OH)2D was inversely associated with all BMDs. 25OHD was positively, and PTH inversely, associated with lumbar spine, total hip, and whole-body BMD. BAP was inversely associated with left arm, right arm, and whole-body BMD but not with spine or hip BMD. Neither osteocalcin nor urinary pyridinoline/urinary creatinine was associated with BMD. When we placed all BBMs (including 1,25(OH)2D) in one model, the pattern and magnitude of association was similar except for PTH, which was attenuated. The association of BMD and BBMs did not differ significantly by race or sex. Conclusions: In this cross-sectional study of healthy young men and women who had PTH levels considered normal in clinical practice, higher PTH was associated with lower BMD, particularly in weight-bearing sites (ie, spine and hip). The inverse association of 1,25(OH)2D, together with the attenuation of PTH, suggests that the observed association of PTH is mediated by 1,25(OH)2D. BAP was inversely associated with arm BMD. BBMs can be important markers of skeletal activity in young adults, but their clinical role on bone health among this population is yet to be fully determined.
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Nordström, Anna, Tommy Olsson, and Peter Nordström. "Sustained Benefits from Previous Physical Activity on Bone Mineral Density in Males." Journal of Clinical Endocrinology & Metabolism 91, no. 7 (July 1, 2006): 2600–2604. http://dx.doi.org/10.1210/jc.2006-0151.
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Abstract Context: The effect of physical activity on bone mineral density (BMD) is not well investigated longitudinally after puberty in men. Objective: Our objective was to evaluate the effect of exercise and reduced exercise on BMD after puberty in men. Design: We conducted a longitudinal study. Participants: Sixty-three healthy young athletes and 27 male controls, both with a mean age of 17 yr at baseline, participated. Also, 136 of the participants’ parents were investigated to evaluate heritable influences. Main Outcome Measures: Total body, total hip, femoral neck, and humerus BMD (grams per square centimeter) were measured at baseline and after mean periods of 27, 68, and 94 months in the young cohort. Results: BMDs of control parents and athlete parents were equal, suggesting absence of selection bias. The 23 athletes that remained active throughout the study increased BMD at all sites when compared with controls (mean difference, 0.04–0.12 g/cm2; P < 0.05) during the study period. After an average of 3 yr, 27 athletes ended their active careers. Although this group initially lost BMD at the hip compared with active athletes, the former athletes still had higher BMD than controls at the femoral neck (0.12 g/cm2; P = 0.007), total hip (0.11 g/cm2; P = 0.02), and humerus (0.10 g/cm2; P = 0.02) at the final follow-up. Conclusions: High sensitivity to physical loading persists after puberty in men. Reduced physical activity is associated with BMD loss in the first 3 yr in weight-bearing bone. Sustained benefits in BMD are preserved 5 yr after intensive training ends.
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Huang, Jin-Feng, Xuan-Qi Zheng, Xiao-Lei Sun, Xiao Zhou, Jian Liu, Yan Michael Li, Xiang-Yang Wang, Xiao-Lei Zhang, and Ai-Min Wu. "Association between Bone Mineral Density and Severity of Chronic Kidney Disease." International Journal of Endocrinology 2020 (October 26, 2020): 1–11. http://dx.doi.org/10.1155/2020/8852690.
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Objective. We sought to evaluate the association between femoral neck (FN) and lumbar spine (LS) bone mineral densities (BMDs) with severity of chronic kidney disease (CKD) and prevalence of osteopenia or osteoporosis (OP) among the CKD group. Methods. Cross-sectional data from 11050 participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) were analyzed. Specifically, Pearson correlation was applied to analyze the relationship between BMD and estimated glomerular filtration rate (eGFR). General linear models (GLMs) were adjusted for potential confounders and used to analyze mean BMD, based on CKD and CKD stages. Results. FN BMD was positively correlated with the eGFR in the total and male CKD, but not in the female CKD population. LS BMD was not significantly associated with eGFR. After controlling for partial correlations, FN T-score was positively correlated with the eGFR in the total at-risk population. According to FN BMD, OP prevalence was positively associated with CKD stage. However, according to LS BMD, there was no significant association between OP and CKD stage. Conclusion. Our results may explain the higher prevalence of hip fracture, relative to that of the spine, among CKD patients and generate meaningful insights to guide care, prevention, and treatment regimens for CKD patients. However, the fact that this was a cross-sectional study may limit the possibility of drawing concrete conclusions. Nevertheless, these findings open up a new frontier for further studies to uncover the higher decrease of FN BMD compared to LS BMD among CKD cases.