Bone marrow adipose tissue composition and glycemic improvements after gastric bypass surgery.

Fracture risk is increased in type 2 diabetes, which may in part be due to altered bone marrow adiposity. Cross sectional studies have reported that people with type 2 diabetes have lower unsaturated BMAT lipid levels than people without diabetes, although there are limited data on longitudinal changes. We hypothesized that Roux-en-Y gastric bypass (RYGB), which dramatically improves glycemic status, would have differential effects on BMAT composition, with increases in the unsaturated lipid index in people with diabetes. Given reports that axial BMAT is responsive to metabolic stimuli while appendicular BMAT is stable, we hypothesized that BMAT changes would occur at the spine but not the tibia. We enrolled 30 obese women, stratified by diabetes status, and used magnetic resonance spectroscopy to measure BMAT at the spine in all participants, and the tibia in a subset (n = 19). At baseline, BMAT parameters were similar between those with and without diabetes, except tibial marrow fat content was lower in women with diabetes (97.4 % ± 1.0 % versus 98.2 % ± 0.4 %, p = 0.04). Six months after surgery, both groups experienced similar weight loss of 27 kg ± 7 kg. At the spine, there was a significant interaction between diabetes status and changes in both marrow fat content and the unsaturated lipid index (p = 0.02, p < 0.01 for differences, respectively). Women with diabetes had a trend towards a decline in marrow fat content (-4.3 % ± 8.2 %, p = 0.09) and increase in the unsaturated lipid index (+1.1 % ± 1.5 %, p = 0.02). In contrast, BMAT parameters did not significantly change in women without diabetes. In all women, changes in the unsaturated lipid index inversely correlated with hemoglobin A1c changes (r = -0.47, p = 0.02). At the tibia, there was little BMAT change by diabetes status. Our results suggest that vertebral BMAT composition is responsive to changes in glycemic control after RYGB.

Dynamic heterogeneity in homogeneous polymer melts.

Chain entanglement behaviors were studied by 1H Hahn echo nuclear magnetic resonance (NMR) and 1H double-quantum (DQ) NMR experiments. Poly(ethylene oxide) (PEO) was chosen to investigate the chain entanglement behaviors. The 1H Hahn echo NMR results demonstrate that the critical molecular weight of PEO is approximately 6 kg mol-1. Above this critical molecular weight, chain entanglements start to occur in the melts resulting in anisotropic motions of polymer chain. The 1H DQ NMR observations establish that PEO melts with molecular weights above the critical value exhibit dynamical entanglements. The entangled networks, formed by PEO with a molecular weight of 480 kg mol-1 (PEO480), present slow mobility and rather homogeneously distributed chain entanglements, while the entangled networks, formed by PEO with a molecular weight of 255 kg mol-1 (PEO255), present fast mobility and obvious dynamic heterogeneity in the distribution of chain entanglement. Short chain PEOs like that with a molecular weight of 2 kg mol-1 are demonstrated to function like solvents when being added in an appropriate concentration to PEO480, and the dilution effect increases the chain mobility of PEO480. Moreover, properly diluted PEO480 networks exhibit dynamic heterogeneity similar to that observed in PEO255.

Serum FSH Is Associated With BMD, Bone Marrow Adiposity, and Body Composition in the AGES-Reykjavik Study of Older Adults.

CONTEXT: Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass. OBJECTIVE: To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Older adults from the AGES-Reykjavik Study, an observational cohort study. MAIN OUTCOME MEASURES: Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition. RESULTS: In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome. CONCLUSIONS: Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women.

Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between 1 H-MRS-based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg2 /cm4 /year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm3 /year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm3 /year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.

Chronic Kidney Disease Is Associated With Greater Bone Marrow Adiposity.

Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1 H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR <45 (n = 58) using linear regression models. Participants had a mean age of 81.5 (SD 4.1) years, mean eGFR of 64.3 (SD 16.1) mL/min/1.734 cm2 , mean BMAT of 54.5% (SD 8.5); 48.2% were women. In unadjusted and adjusted models (age, visit window, gender, diabetes and visceral adipose tissue), BMAT was higher in those with eGFR <45 (adjusted mean 58.5%; 95% CI, 56.2 to 60.7) compared with those with eGFR >60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR <45 versus >60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.

Sex hormones are negatively associated with vertebral bone marrow fat.

CONTEXT: Higher bone marrow fat (BMF)1 is associated with osteoporosis and reduced hematopoiesis. Exogenous estradiol reduces BMF in older women, but effects of endogenous sex hormones are unknown. OBJECTIVE: To determine if endogenous sex hormones are associated with BMF in older men and women. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Participants using medications that may affect BMF were excluded. MAIN OUTCOME MEASURES: Vertebral BMF was measured with magnetic resonance spectroscopy. Estradiol, testosterone and sex hormone binding globulin were measured on archived serum. Linear regression models were adjusted for age, total percent body fat and visit window. RESULTS: Analyses included 244 men and 226 women, mean age 81.5 (SD 4.1) years. Mean BMF was 54.1% (SD 8.6) (men) and 54.7% (SD 8.1) (women). In adjusted models, per 1pg/ml increase in total estradiol, there was a statistically significant 0.26% decrease in BMF in men (95% CI: -0.41, -0.11) and a non-significant 0.20% decrease in women (95% CI: -0.55, 0.15), with no evidence of interaction by gender (p=0.88). Per 10ng/dl increase in total testosterone, there was a significant 0.10% decrease in BMF in men (95% CI: -0.17, -0.03) and a non-significant 0.13% (95% CI: -0.79, 0.53) decrease in women, with no evidence of interaction by gender (p=0.97). CONCLUSION: Higher bone marrow fat is associated with lower total estradiol and testosterone levels in older men, with a similar but statistically non-significant association in older women. Sex hormone levels appear to play a role in the regulation of bone marrow fat in older adults.

Reliable quantification of marrow fat content and unsaturation level using in vivo MR spectroscopy.

PURPOSE: To develop a novel technique for reliable quantification of bone marrow fat content and composition using in vivo MR spectroscopy (MRS). METHODS: An MRS quantification method combining both advantages of Voigt line shape model and time-domain analysis was developed. The proposed method was tested using computer-simulated data and in vivo data acquired at lumbar vertebral bodies of 23 subjects (age, 83.8 ± 3.7 y; male, n = 13; female, n = 10) from L1 to L4. Reliability and reproducibility were calculated for the quantification results. Comparisons between the proposed method and some conventional methods were conducted. RESULTS: Low mean absolute percentage errors and low mean coefficients of variation for computer simulations suggest that the proposed method is accurate and precise. By using this method, marrow fat content can be quantified reliably, even for data with low spectral resolution and low signal-to-noise ratio (SNR). Unsaturation level can be reliably quantified for data with moderate spectral resolution and moderate SNR. Results obtained from in vivo data using the proposed method demonstrated better model fit than conventional methods. CONCLUSION: The method proposed in this study has better performance than conventional methods in the quantification of bone marrow MRS data and has great potential for wide applications of studying marrow fat content and composition. Magn Reson Med 79:1722-1729, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Unsaturation level decreased in bone marrow fat of postmenopausal women with low bone density using high resolution magic angle spinning (HRMAS) 1H NMR spectroscopy.

There are increasing evidences suggesting bone marrow adiposity tissue (MAT) plays a critical role in affecting both bone quantity and quality. However, very limited studies that have investigated the association between the composition of MAT and bone mineral density (BMD). The goal of this study was to quantify MAT unsaturation profile of marrow samples from post-menopausal women using ex vivo high-resolution magic angle spinning (HRMAS) proton nuclear magnetic resonance (1H NMR) spectroscopy, and to investigate the relationship between MAT composition and BMD. Bone marrow samples were obtained by iliac crest aspiration during surgical procedures from 24 postmenopausal women (65-89years) who had hip surgery due to bone fracture or arthroplasty. Marrow fat composition parameters, in particular, unsaturation level (UL), mono-unsaturation level (MUL) and saturation level (SL), were quantified using HRMAS 1H NMR spectroscopy. The patients were classified into three groups based on the DXA BMD T-scores: controls, osteopenia and osteoporosis. Marrow fat composition was compared between these three groups as well as between subjects with and without factures using ANOCOVA, adjusted for age. Subjects with lower BMD (n=17) had significantly lower MUL (P=0.003) and UL (P=0.039), and significantly higher SL (P=0.039) compared to controls (n=7). When separating lower BMD into osteopenia (n=9) and osteoporosis (n=8) groups, subjects with osteopenia had significantly lower MUL (P=0.002) and UL (P=0.010), and significantly higher SL (P=0.010) compared to healthy controls. No significant difference was observed between subjects with osteopenia and osteoporosis. Using HRMAS 1H NMR, significantly lower unsaturation and significantly higher saturation levels were observed in the marrow fat of subjects with lower BMD. HRMAS 1H NMR was shown to be a powerful tool for identifying novel MR markers of marrow fat composition that are associated with bone quality and potentially fracture, and other bone pathologies and changes after treatment. A better understanding of the relationship between bone marrow composition and bone quality in humans may identify novel treatment targets, and provide guidance on novel interventions and therapeutic strategies for bone preservation.

Bone Marrow Fat Changes After Gastric Bypass Surgery Are Associated With Loss of Bone Mass.

Bone marrow fat is a unique fat depot that may regulate bone metabolism. Marrow fat is increased in states of low bone mass, severe underweight, and diabetes. However, longitudinal effects of weight loss and improved glucose homeostasis on marrow fat are unclear, as is the relationship between marrow fat and bone mineral density (BMD) changes. We hypothesized that after Roux-en-Y gastric bypass (RYGB) surgery, marrow fat changes are associated with BMD loss. We enrolled 30 obese women, stratified by diabetes status. Before and 6 months after RYGB, we measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and vertebral marrow fat content by magnetic resonance spectroscopy. At baseline, those with higher marrow fat had lower BMD. Postoperatively, total body fat declined dramatically in all participants. Effects of RYGB on marrow fat differed by diabetes status (p = 0.03). Nondiabetic women showed no significant mean change in marrow fat (+1.8%, 95% confidence interval [CI] -1.8% to +5.4%, p = 0.29), although those who lost more total body fat were more likely to have marrow fat increases (r = -0.70, p = 0.01). In contrast, diabetic women demonstrated a mean marrow fat change of -6.5% (95% CI -13.1% to 0%, p = 0.05). Overall, those with greater improvements in hemoglobin A1c had decreases in marrow fat (r = 0.50, p = 0.01). Increases in IGF-1, a potential mediator of the marrow fat-bone relationship, were associated with marrow fat declines (r = -0.40, p = 0.05). Spinal volumetric BMD decreased by 6.4% ± 5.9% (p < 0.01), and femoral neck areal BMD decreased by 4.3% ± 4.1% (p < 0.01). Marrow fat and BMD changes were negatively associated, such that those with marrow fat increases had more BMD loss at both spine (r = -0.58, p < 0.01) and femoral neck (r = -0.49, p = 0.01), independent of age and menopause. Our findings suggest that glucose metabolism and weight loss may influence marrow fat behavior, and marrow fat may be a determinant of bone metabolism. © 2017 American Society for Bone and Mineral Research.

Determination of polymer crystallinity by the multivariable curve resolution method in 13C solid NMR spectrum.

Most of the polymers are composed of a crystal part, an amorphous part, and a transitional interfacial part. These components present disparate physical and chemical characteristics. However, it always suffers from peak overlapping in solid NMR spectrum in order to acquire polymer's crystallinity. The polyethylene oxide (PEO) sample was tested using the Torchia pulse sequence combined with the Multivariate Curve Resolution (MCR) method. A two dimensional CP/MAS spectrum containing spin-lattice relaxation time (T1) information was acquired. After the correction based on the reciprocity relation, the overlapped peaks were resolved and quantified together with their T1's. Crystallinity is therefore observed naturally according to components' content ratios associated with their T1 values.

Systematic bias in NMR diffusion measurements on polydisperse systems.

Least-squares fitting of the Stejskal-Tanner equation is a routine process in the measurement of molecular diffusion coefficient (MDC) using Nuclear Magnetic Resonance (NMR) Spectroscopy. It is simple and elegant. However, a bias of the MDC is noticed when the system is polydispersed. This is due to improper accounts of the diffusion coefficient distribution. Eventually, it leads to a discrepancy between the observed MDC and the statistical mean value of the distribution. To reveal the discrepancy, an analytical solution is derived when the diffusion data is taken a logarithmic linearization. Computer simulation is also applied to obtain a non-linear regression result. For a Gaussian distribution of the MDCs, the bias is proportional to the square of the distribution width (linear regression), but it is also inversely proportional to the statistical mean value of the distribution (non-linear regression). This indicates that the MDC derived from Stejskal-Tanner equation only holds well for narrow distribution of MDCs. Otherwise, molecular radius derived from the Stokes-Einstein equation needs to be reconsidered due to the incorrect estimation of the MDC.

Trust-region algorithm for the inversion of molecular diffusion NMR data.

Diffusion NMR experiments are very useful in studying structural and dynamical properties of molecules and in sorting out components from mixtures. A number of numerical approaches have been developed for the processing of diffusion NMR data. In this paper, numerical problems of the direct regularization methods such as CONTIN, MaxEnt, and the newly proposed ITAMeD approach are illustrated by analyzing simulated and experimental data. It allows us to further develop a new method to calculate the distribution of diffusion coefficients. Therefore, we present here an iterative regularization method based on the Trust-Region Algorithm for the Inversion (TRAIn) of molecular diffusion NMR data. It is demonstrated in this paper that our approach overcomes major numerical difficulties of the direct regularization methods mentioned above. Besides, this method reconstructs more reliable diffusion coefficient distributions, especially for real world samples of which the diffusion coefficients are nonsymmetrically distributed.