Clinical implications of bone marrow adiposity

Veldhuis-Vlug, Annegreet; Rosen, Clifford J.

doi:10.1111/joim.12718

Cited by 173 publications

(154 citation statements)

References 152 publications

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“…RANK is located in the cell membrane of osteoclasts and facilitates osteoclast activation and differentiation . RANKL was declared to accelerate bone resorption and depression of NF‐κB pathway represses osteoclast differentiation . All the above demonstrations provided evidence that the NF‐κB pathway plays an important role in OP progression and makes simulative effects on bone resorption and activation of OP.…”

Section: Discussionmentioning

confidence: 90%

“…3 RANKL was declared to accelerate bone resorption and depression of NF-κB pathway represses osteoclast differentiation. 36,37 All the above demonstrations provided evidence that the NF-κB pathway plays an important role in OP progression and makes simulative effects on bone resorption and activation of OP. In the present study, we found that the NF-κB pathway could be inhibited by CST5 up-regulation and by which mechanism the progression of OP was impeded.…”

Section: Discussionmentioning

confidence: 90%

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Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway

Wang

Zhang

et al. 2019

J Cellular Molecular Medi

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Here, we aim at exploring the effect of CST5 on bone resorption and activation of osteoclasts in osteoporosis (OP) rats through the NF‐κB pathway. Microarray analysis was used to screen the OP‐related differentially expressed genes. Osteoporosis was induced in rats by intragastric retinoic acid administration. The serum levels of tartrate‐resistant acid phosphatase (TRAP), bone alkaline phosphatase (BALP) and osteocalcin (OC) and the expression of CD61 on the surface of osteoclasts were examined. The number of osteoclasts and the number and area of resorption pits were detected. Besides, the pathological changes and bone mineral density in bone tissues of rats were assessed. Also, the relationship between CST5 and the NF‐κB pathway was identified through determining the expression of CST5, RANKL, RANK, OPG, p65 and IKB. Poorly expressed CST5 was indicated to affect the OP. CST5 elevation and inhibition of the NF‐κB pathway decreased serum levels of TRAP, BALP and OC and expression of CD61 in vivo and in vitro. In OP rats, CST5 overexpression increased trabecular bones and bone mineral density of bone tissues, but decreased trabecular separation, fat within the bone marrow cavities and the number of osteoclasts through inhibiting the NF‐κB pathway. In vivo experiments showed that CST5 elevation inhibited growth in number and area of osteoclastic resorption pits and restrained osteoclastic bone absorption by inhibiting the NF‐κB pathway. In summary, overexpression of CST5 suppresses the activation and bone resorption of osteoclasts by inhibiting the activation of the NF‐κB pathway.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway

Wang

Zhang

et al. 2019

J Cellular Molecular Medi

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“…T HE PROPORTION of bone marrow adipose tissue is thought to be related to the strength and remodeling capacity of the bone, 1 and quantitative changes in the bone marrow fat fraction have been examined in various pathologic states: first, bone marrow adiposity has been found to correlate with the bone loss pathophysiology in the course of osteoporosis and to increase the fracture risk in metabolic diseases such as diabetes mellitus. 2 Second, bone marrow adipose tissue has been shown to be replaced by malignant bone marrow processes, potentially providing a diagnostic instrument for the differentiation of benign and malignant bone marrow lesions. [3][4][5] Third, increased bone marrow fat fractions have been observed in patients with malignant disease and a positive treatment response to both chemotherapy and radiation.…”

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confidence: 99%

Proton density fat fraction MRI of vertebral bone marrow: Accuracy, repeatability, and reproducibility among readers, field strengths, and imaging platforms

Schmeel

Vomweg²,

Träber

et al. 2019

Magnetic Resonance Imaging

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Background Chemical shift‐encoding based water‐fat MRI is an emerging method to noninvasively assess proton density fat fraction (PDFF), a promising quantitative imaging biomarker for estimating tissue fat concentration. However, in vivo validation of PDFF is still lacking for bone marrow applications. Purpose To determine the accuracy and precision of MRI‐determined vertebral bone marrow PDFF among different readers and across different field strengths and imager manufacturers. Study Type Repeatability/reproducibility. Subjects Twenty‐four adult volunteers underwent lumbar spine MRI with one 1.5T and two different 3.0T MR scanners from two vendors on the same day. Field Strength/Sequence 1.5T and 3.0T/3D spoiled‐gradient echo multipoint Dixon sequences. Assessment Two independent readers measured intravertebral PDFF for the three most central slices of the L1–5 vertebral bodies. Single‐voxel MR spectroscopy (MRS)‐determined PDFF served as the reference standard for PDFF estimation. Statistical Tests Accuracy and bias were assessed by Pearson correlation, linear regression analysis, and Bland–Altman plots. Repeatability and reproducibility were evaluated by Wilcoxon signed rank test, Friedman test, and coefficients of variation. Intraclass correlation coefficients were used to validate intra‐ and interreader as well as intraimager agreements. Results MRI‐based PDFF estimates of lumbar bone marrow were highly correlated (r2 = 0.899) and accurate (mean bias, –0.6%) against the MRS‐determined PDFF reference standard. PDFF showed high linearity (r2 = 0.972–0.978) and small mean bias (0.6–1.5%) with 95% limits of agreement within ±3.4% across field strengths, imaging platforms, and readers. Repeatability and reproducibility of PDFF were high, with the mean overall coefficient of variation being 0.86% and 2.77%, respectively. The overall intraclass correlation coefficient was 0.986 as a measure for an excellent interreader agreement. Data Conclusion MRI‐based quantification of vertebral bone marrow PDFF is highly accurate, repeatable, and reproducible among readers, field strengths, and MRI platforms, indicating its robustness as a quantitative imaging biomarker for multicentric studies. Level of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1762–1772.

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“…It is likely that multiple body‐weight‐related alterations in metabolism are involved, including changes to the bone marrow microenvironment (Askmyr et al , ). Adipocytes are one of the most abundant cell types in bone marrow, and animal and in vitro studies suggest that bone marrow adipocytes may play a direct, active role in supporting leukemogenesis (Veldhuis‐Vlug & Rosen, ).…”

Section: Discussionmentioning

confidence: 99%

Anthropometric factors and risk of myeloid leukaemias and myelodysplastic syndromes: a prospective study and meta‐analysis

et al. 2019

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Summary There is insufficient evidence linking excess body weight to risk of myeloid malignancies. We investigated this association using data from the Cancer Prevention Study‐II (CPS‐II), and a meta‐analysis of published cohort studies. Among 152 090 CPS‐II participants, 387 acute myeloid leukaemias (AML), 100 chronic myeloid leukaemias (CML) and 170 MDS were identified over 21 years of follow‐up. In CPS‐II, body mass index (BMI) was weakly associated with risk of CML (hazard ratio [HR] = 1·04, 95% confidence interval [CI]: 0·99–1·09 per 1 unit increase in BMI), AML (HR = 1·01, 95% CI: 0·98–1·03) and MDS (HR = 1·03, 95% CI: 0·99–1·07). After controlling for other anthropometric factors, no clear association was observed for height, BMI at age 18 years or weight change. In the meta‐analysis (n = 7117 myeloid leukaemias), BMI 25–29·9 kg/m2 (HRpooled = 1·36, 95% CI: 1·12–1·59) and BMI ≥30 kg/m2 (HRpooled = 1·43, 95% CI: 1·18–1·69) were associated with higher risk of myeloid leukaemia overall, compared to a BMI <25 kg/m2. Likewise, BMI ≥25 kg/m2 was positively associated with both AML and CML risk individually in the meta‐analysis. These results underscore the need for large studies to detect associations with rare cancers, and show a modest, but positive association between excess body weight and myeloid malignancy risk.

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Clinical implications of bone marrow adiposity

Abstract: Abstract. Veldhuis-Vlug AG, Rosen CJ

Cited by 173 publications

References 152 publications

Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway

Up‐regulated CST5 inhibits bone resorption and activation of osteoclasts in rat models of osteoporosis via suppression of the NF‐κB pathway

Proton density fat fraction MRI of vertebral bone marrow: Accuracy, repeatability, and reproducibility among readers, field strengths, and imaging platforms

Anthropometric factors and risk of myeloid leukaemias and myelodysplastic syndromes: a prospective study and meta‐analysis

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