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- Pham, T. T., et al.
(författare)
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Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot
- 2020
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 105:7, s. 2300-2310
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. OBJECTIVE: Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). DESIGN: This was a cross-sectional and longitudinal study. SETTING: The study was conducted in a clinical research center. PATIENTS OR OTHER PARTICIPANTS: Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. INTERVENTION(S): Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. MAIN OUTCOME MEASURE: We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. RESULTS: Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. CONCLUSIONS: Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism. © Endocrine Society 2020.
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- Cheng, Sulin, et al.
(författare)
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Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.
- 2005
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 82:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period. OBJECTIVE: The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10-12 y. DESIGN: This placebo-controlled intervention trial randomly assigned 195 healthy girls at Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4 groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000 mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine, and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography. RESULTS: With the use of intention-to-treat or efficacy analysis, calcium supplementation with cheese resulted in a higher percentage change in cortical thickness of the tibia than did placebo, calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004, respectively) and in higher whole-body bone mineral density than did placebo treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical linear model with random effects to control for growth velocity, these differences disappeared. CONCLUSIONS: Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium. Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty.
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- Ivaska, KK, et al.
(författare)
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Identification of novel proteolytic forms of osteocalcin in human urine
- 2003
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Ingår i: Biochemical and Biophysical Research Communications. - 1090-2104. ; 306:4, s. 973-980
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we report the isolation and characterization of osteocalcin in human urine using mass spectrometry and N-terminal sequencing. Multiple proteolytic forms of osteocalcin were found, which consisted of 16-27 residues from the middle region of the molecule. Several fragments had residue Gly7 at the N-terminus and the most predominant was fragment 7-31. Additional fragments starting from residue Asp14 were detected in the samples of children and young adults. Immunochemical detection of urine osteocalcin fragments had a statistically significant negative correlation to bone mineral density in evaluation of urine samples from 75-year-old women. Thus, the measurement of osteocalcin fragments in urine may have potential applications in diagnostics related to disorders of bone metabolism.
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| 16. |
- Ivaska, Kaisa K., et al.
(författare)
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Bone Turnover Marker Profiling and Fracture Risk in Older Women : Fracture Risk from Age 75 to 90
- 2022
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Ingår i: Calcified Tissue International. - : Springer Science and Business Media LLC. - 0171-967X .- 1432-0827. ; 111:3, s. 288-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A major challenge in osteoporosis is to identify individuals at high fracture risk. We investigated six bone turnover markers (BTMs) to determine association with specific fracture types; the time-frame for risk prediction and whether these are influenced by age at assessment. Methods: Population-based OPRA cohort (n = 1044) was assessed at ages 75, 80, 85 and fractures documented for up to 15 years. Six BTMs were analyzed at each time-point (N-terminal propeptide of type I collagen, PINP; total osteocalcin, OC; bone-specific alkaline phosphatase, BALP; C-terminal telopeptide of type I collagen, CTX; tartrate-resistant acid phosphatase 5b, TRAcP5b; urinary osteocalcin). Hazard ratios (HR) for any, major osteoporotic, vertebral and hip fractures were calculated as short (1, 2, 3 years) and long-term risk (5, 10, 15 years). Results: At 75 year, high CTX levels were associated with an increased risk of all fractures, including major osteoporotic fractures, across most time-frames (HRs ranging: 1.28 to 2.28). PINP was not consistently associated. Urinary osteocalcin was consistently associated with elevated short-term risk (HRs ranging: 1.83–2.72). Other BTMs were directionally in accordance, though not all statistically significant. BTMs were not predictive for hip fractures. Association of all BTMs attenuated over time; at 80 year none were associated with an increased fracture risk. Conclusion: CTX, urinary OC and TRAcP5b are predictive for fracture in a 1 to 3 year, perspective, whereas in the long-term or above age 80 years, BTMs appear less valuable. Resorption markers, particularly CTX, were more consistently associated with fracture risk than formation markers in the very elderly.
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- Ivaska, KK, et al.
(författare)
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Urinary osteocalcin as a marker of bone metabolism
- 2005
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 51:3, s. 618-628
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteocalcin (OC) is produced by osteoblasts during bone formation, and circulating OC has been used in clinical investigations as a marker of bone metabolism. OC is excreted into urine by glomerular filtration and can be found in urine as midmolecule fragments. Methods: We developed and evaluated three immunoassays (U-MidOC, U-LongOC, and U-TotalOC) for the detection of various molecular forms of urine OC (U-OC. We evaluated the association of U-OC with other markers of bone turnover and with bone mass in 1044 elderly women and studied seasonal and circadian variation of U-OC. Results: U-OC correlated with other bone turnover markers [Spearman correlation (r), 0.30-0.57; P <0.0001], demonstrating the association between U-OC and skeletal metabolism. There was also a significant association between bone metabolism assessed by U-OC quartiles and bone mass assessed by total body bone mineral content (P <0.0001). The seasonal effects appeared to be rather small, but we observed A significant circadian rhythm similar to the one reported for serum OC with high values in the morning and low values in the afternoon. Conclusions: The three immunoassays had unique specificities toward different naturally occurring U-OC fragments. U-OC concentrations measured with any of these assays correlated with bone turnover rates assessed by conventional serum markers of bone metabolism. The measurement of OC in urine samples could be used as an index of bone turnover in monitoring bone metabolism.
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- Jahnukainen, K, et al.
(författare)
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Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia
- 2015
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 84:2, s. 108-115
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> We evaluated the body composition and its association with hypogonadism in adult male long-term acute lymphoblastic leukemia (ALL) survivors. <b><i>Methods:</i></b> The cohort included 49 long-term male ALL survivors and 55 age-matched healthy controls. Fat and lean mass was assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for adipokines and testicular endocrine markers. <b><i>Results:</i></b> As compared with controls, the ALL survivors (median age 29 years, range 25-38), assessed 10-28 years after ALL diagnosis, had higher percentages of body (p < 0.05) and trunk fat mass (p < 0.05), and a lower body lean mass (p < 0.001). Survivors had significantly higher levels of leptin and adiponectin and lower levels of insulin-like growth factor-binding protein 3. Body fat mass and percent fat mass correlated with serum leptin and sex hormone-binding globulin (SHBG) levels. Altogether, 15% of the ALL survivors and 9% of age-matched controls were obese (BMI ≥30). Obese survivors more often had hypogonadism, had received testicular irradiation, and needed testosterone replacement therapy compared to nonobese survivors. <b><i>Conclusion:</i></b> At young adulthood, long-term male ALL survivors have significantly increased body adiposity despite normal weight and BMI. Potential indicators of increased adiposity included high leptin and low SHBG levels. Serum testicular endocrine markers did not correlate with body adiposity.
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| 22. |
- Vaisanen, V, et al.
(författare)
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Development of sensitive immunoassays for free and total human glandular kallikrein 2
- 2004
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 50:9, s. 1607-1617
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free and total human kallikrein 2 (hK2) might improve the discrimination between prostate cancer and benign prostatic hyperplasia. Concentrations of hK2 are 100-fold lower than concentrations of prostate-specific antigen (PSA); therefore, an hK2 assay must have a low detection limit and good specificity. Methods: PSA- and hK2-specific monoclonal antibodies were used in solid-phase, two-site immunofluorometric assays to detect free and total hK2. The total hK2 assay used PSA-specific antibodies to block nonspecific signal. The capture antibody of the free hK2 assay did not cross-react with PSA. To determine the hK2 concentrations in the male bloodstream, total hK2 was measured in a control group consisting of 426 noncharacterized serum samples. Free and total hK2 were measured in plasma from 103 patients with confirmed prostate cancer. Results: All 426 males in the control group had a total hK2 concentration above the detection limit of 0.0008 mug/L. The median total hK2 concentration was 0.022 mug/L (range, 0.0015-0.37 mug/L). hK2 concentrations were 0.1-58% of total PSA (median, 3.6%). hK2 concentrations were similar in men 41-50 and 51-60 years of age. The ratio of hK2 to PSA steadily decreased from 5-30% at PSA <1 mug/L to 1-2% at higher PSA concentrations. In 103 patients with prostate cancer, the median hK2 concentration in plasma was 0.079 mug/L (range, 0.0015-16.2 mug/L). The median free hK2 concentration was 0.070 (range, 0.005-12.2) mug/L. The proportion of free to total hK2 varied from 17% to 131% (mean, 85%). Conclusions: The wide variation in the free-to-total hK2 ratio suggests that hK2 in blood plasma is not consistently in the free, noncomplexed form in patients with prostate cancer. The new assay is sufficiently sensitive to be used to study the diagnostic accuracies of free and total hK2 for prostate cancer.
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