Marrow Fat Content Research Articles

Whole-Body Functional MRI and PET/MRI in Multiple Myeloma.

Simple SummaryWhole-body magnetic resonance imaging (MRI) is recognized as the most sensitive imaging technique for the detection of bone marrow infiltration, and was therefore, recently included in the new diagnostic myeloma criteria, as proposed by the International Myeloma Working Group. The use of diffusion-weighted MRI further improved the performances of whole-body MRI in the setting of multiple myeloma, and its systematic implementation in general clinical practice is now recommended. Whole-body, dynamic, contrast-enhanced MRI might provide further information on lesions vascularity and might help evaluate response to treatment. Hybrid PET/MRI might act as the optimal imaging modality, owing to the association of the best techniques for both detecting bone marrow involvement and evaluating treatment response, providing one-stop-shop imaging in a whole-body scale. This review provides an overview on the value of whole-body MRI, including diffusion-weighted and dynamic contrast-enhanced MRI and whole-body 18F-FDG PET/MRI in diagnosis, staging, and response evaluation in multiple myeloma.Bone disease is one of the major features of multiple myeloma (MM), and imaging has a pivotal role in both diagnosis and follow-up. Whole-body magnetic resonance imaging (MRI) is recognized as the gold standard for the detection of bone marrow involvement, owing to its high sensitivity. The use of functional MRI sequences further improved the performances of whole-body MRI in the setting of MM. Whole-body diffusion-weighted (DW) MRI is the most attractive functional technique and its systematic implementation in general clinical practice is now recommended by the International Myeloma Working Group. Whole-body dynamic contrast-enhanced (DCE) MRI might provide further information on lesions vascularity and help evaluate response to treatment. Whole Body PET/MRI is an emerging hybrid imaging technique that offers the opportunity to combine information on morphology, fat content of bone marrow, bone marrow cellularity and vascularization, and metabolic activity. Whole-body PET/MRI allows a one-stop-shop examination, including the most sensitive technique for detecting bone marrow involvement, and the most recognized technique for treatment response evaluation. This review aims at providing an overview on the value of whole-body MRI, including DW and DCE MRI, and combined whole-body 18F-FDG PET/MRI in diagnosis, staging, and response evaluation in patients with MM.

Fat fraction quantification of lumbar spine: comparison of T1-weighted two-point Dixon and single-voxel magnetic resonance spectroscopy in diagnosis of multiple myeloma.

We aimed to investigate the value of T1-weighted two-point Dixon technique and single-voxel magnetic resonance spectroscopy (MRS) in diagnosis of multiple myeloma (MM) through quantifying fat content of vertebral marrow. A total of 30 MM patients and 30 healthy volunteers underwent T1-weighted two-point Dixon and single-voxel MRS imaging. The fat fraction map (FFM) was reconstructed from the Dixon images using the equation FFM = Lip/In, where Lip represents fat maps and In represents in-phase images. The fat fraction (FF) of MRS was calculated by using the integral area of Lip peak divided by the sum of integral area of Lip peak and water peak. FF values measured by the Dixon technique and MRS were significantly decreased in MM patients (45.99%±3.39% and 47.63%±4.38%) compared with healthy controls (64.43%±0.96% and 76.22%±1.91%) (P < 0.001 with both methods). FF values measured by Dixon technique were significantly positively correlated to those measured by MRS in MM (r = 0.837, P < 0.001) and healthy control group (r = 0.735, P < 0.001), respectively. There was no significant difference between area under the curve (AUC) obtained by the Dixon technique (0.878±0.047; range, 0.785 to 0.971; optimal cutoff, 56.35 for healthy controls vs. MM) and MRS (0.883±0.047; range, 0.791 to 0.974; optimal cutoff, 61.00 for healthy controls vs. MM). The ability of Dixon technique to differentiate MM group from healthy controls was equivalent to single-voxel MRS. Regarding detection of fat contents in vertebral bone, T1-weighted two-point Dixon technique exhibited equivalent performance to single-voxel MRS in the diagnosis of multiple myeloma. Moreover, two-point Dixon is a more convenient and stable technique for assessing bone marrow changes in MM patients than single-voxel MRS.

Marrow Fat Content and Composition in β-Thalassemia: A Study using 1 H-MRS.

β-thalassemia is a genetic disease that causes abnormal production of red blood cells (ineffective erythropoiesis, IE). IE is a condition known to change bone marrow composition. To evaluate the effect of IE on the marrow fat content and fat unsaturation levels in the proximal femur using 1 H-MRS. Prospective. Twenty-three subjects were included in this study, seven control and 16 β-thalassemia subjects. 3.0T; stimulated echo acquisition Mode (STEAM); magnetic resonance spectroscopy (MRS) sequence. Multiecho MRS scans were performed in four regions of the proximal left femur of each subject, that is, diaphysis, femoral neck, femoral head, and greater trochanter. The examined regions were grouped into red (diaphysis and femoral neck) and yellow marrow regions (femoral head and greater trochanter). The Jonckheere-Terpstra test was used to evaluate the impact of increasing disease severity on bone marrow fat fraction (BMFF), marrow conversion index, and fat unsaturation index (UI). Pairwise comparison analysis was performed when a significant trend (P < 0.05) was found. K-means clustering analysis was used to examine the clusters observed when BMFF in the red and yellow regions were studied (diaphysis against greater trochanter). BMFF showed a significant decreasing trend with increasing disease severity in both red (TJT = 109.00, z = -4.414, P < 0.05) and yellow marrow regions (TJT = 108.00, z = -4.438, P < 0.05). The opposite trend was observed in UI in both bone marrow regions (red marrow: TJT = 180.5, z = 3.515, P < 0.05; yellow marrow: TJT = 155.0, z = 2.282, P = 0.05). Three distinct forms of marrow adipogenesis were found when plotting BMFF diaphysis against BMFF greater trochanter: 1) normal (centroid: 80.4%, 66.6%), 2) partial disruption (centroid: 51.1%, 16.6%), and 3) total disruption (centroid: 2.6%, 1.6%). β-thalassemia is associated with decreased marrow fat, and increased marrow fat unsaturation level. 2 TECHNICAL EFFICACY STAGE: 3.

Changes in Bone Marrow Fat upon Dietary-Induced Weight Loss.

Background: Bone marrow fat is implicated in metabolism, bone health and haematological diseases. Thus, this study aims to analyse the impact of moderate weight loss on bone marrow fat content (BMFC) in obese, healthy individuals. Methods: Data of the HELENA-Trial (Healthy nutrition and energy restriction as cancer prevention strategies: a randomized controlled intervention trial), a randomized controlled trial (RCT) among 137 non-smoking, overweight or obese participants, were analysed to quantify the Magnetic Resonance Imaging (MRI)-derived BMFC at baseline, after a 12-week dietary intervention phase, and after a 50-week follow-up. The study cohort was classified into quartiles based on changes in body weight between baseline and week 12. Changes in BMFC in respect of weight loss were analysed by linear mixed models. Spearman’s coefficients were used to assess correlations between anthropometric parameters, blood biochemical markers, blood cells and BMFC. Results: Relative changes in BMFC from baseline to week 12 were 0.0 ± 0.2%, −3.2 ± 0.1%, −6.1 ± 0.2% and −11.5 ± 0.6% for Q1 to Q4. Across all four quartiles and for the two-group comparison, Q1 versus Q4, there was a significant difference (p < 0.05) for changes in BMFC. BMFC was not associated with blood cell counts and showed only weaker correlations (<0.3) with metabolic biomarkers. Conclusion: Weight loss is associated with a decrease of BMFC. However, BMFC showed no stronger associations with inflammatory and metabolic biomarkers.

Analysis of muscle, hip, and subcutaneous fat in osteoporosis patients with varying degrees of fracture risk using 3T Chemical Shift Encoded MRI

Osteoporosis (OP) is a major disease that affects 200 million people worldwide. Fatty acid metabolism plays an important role in bone health and plays an important role in bone quality and remodeling. Increased bone marrow fat quantity has been shown to be associated with a decrease in bone mineral density (BMD), which is used to predict fracture risk. Chemical-Shift Encoded magnetic resonance imaging (CSE-MRI) allows noninvasive and quantitative assessment of adipose tissues (AT). The aim of our study was to assess hip or proximal femoral bone marrow adipose tissue (BMAT), thigh muscle (MUS), and subcutaneous adipose tissue (SAT) in 128 OP subjects matched for age, BMD, weight and height with different degrees of fracture risk assessed through the FRAX score (low, moderate and high). Our results showed an increase in BMAT and in MUS in high compared to low fracture risk patients. We also assessed the relationship between fracture risk as assessed by FRAX and AT quantities. Overall, the results of this study suggest that assessment of adipose tissue via 3T CSE-MRI provides insight into the pathophysiology fracture risk by showing differences in the bone marrow and muscle fat content in subjects with similarly osteoporotic BMD as assessed by DXA, but with varying degrees of fracture risk as assessed by FRAX.

The effect of metformin on vertebral marrow fat in postmenopausal women with newly diagnosed type 2 diabetes mellitus.

To determine the effect of metformin on marrow adiposity in postmenopausal women with newly diagnosed type 2 diabetes mellitus (T2DM). We enrolled 25 postmenopausal T2DM women who satisfied the requirement of having been on 1 year of metformin therapy and 26 age-matched healthy women receiving a placebo. All participants were analyzed for marrow fat fraction (FF) by magnetic resonance spectroscopy, vertebral volumetric bone mineral density (vBMD) by quantitative computed tomography, blood glucose, lipid profiles, and bone biomarkers to compare values before and after the interventions. Differences between groups were assessed using a Student's t test and chi-square test or an analysis of covariance adjusted for covariates. Twelve-month change in within-group difference was assessed using paired t tests. Correlations were determined by Pearson's correlation. Vertebral vBMD was lower in T2DM than in nondiabetic controls (105.6 ± 13.8 vs 112.8 ± 15.2 mg/cm; P = 0.029). T2DM women had a higher marrow FF than those without diabetes (66.3 ± 7.2% vs 58.9 ± 7.5%; P < 0.001), even after adjusting for covariates. From baseline to month 12 in the T2DM group, metformin was associated with a reduction in marrow FF (-12.0%; P < 0.001) and an increase in vBMD (3.7%; P = 0.020). For metformin-treated T2DM women, the 12-month change in marrow FF was inversely associated with change in vBMD (r = -0.771, P < 0.001), but not with changes in bone biomarkers, whereas change in vBMD or FF was not significant in the control group. Postmenopausal women with newly diagnosed T2DM have a higher marrow fat content compared with nondiabetic women. Metformin treatment reduced marrow adiposity in T2DM.

Bone marrow fat fraction assessment in regard to physical activity: KORA FF4-3-T MR imaging in a population-based cohort.

To establish the effect of different degrees and kinds of physical activity on bone marrow fat (BMAT) content at different anatomical locations in a population-based cohort study undergoing whole-body MR imaging. Subjects of the KORA FF4 study without known cardiovascular disease underwent BMAT fat fraction (FF) quantification in L1 and L2 vertebrae and femoral heads/necks (hip) via a 2-point T1-weighted VIBE Dixon sequence. BMAT-FF was calculated as mean value (fat image) divided by mean value (fat + water image). Physical activity was determined by self-assessment questionnaire regarding time spent exercising, non-exercise walking, non-exercise cycling, and job-related physical activity. A total of 385 subjects (96% of 400 available; 56 ± 9.1years; 58% male) were included in the analysis. Exercise was distributed quite evenly (29% > 2h/week; 31% ~ 1h/week (regularly); 15% ~ 1h/week (irregularly); 26% no physical activity). BMAT-FF was 52.6 ± 10.2% in L1, 56.2 ± 10.3% in L2, 87.4 ± 5.9% in the right hip, and 87.2 ± 5.9% in the left hip (all p < 0.001). Correlation of BMAT-FF between spine and hip was only moderate (r 0.42 to 0.46). Spinal BMAT-FF, but not hip BMAT-FF, was inversely associated with exercise > 2h/week (p ≤ 0.02 vs. p ≥ 0.35, respectively). These associations remained significant after adjusting for age, gender, waist circumference, and glucose tolerance. No coherent association was found between BMAT-FF and physical activity in the less active groups. In our study, exercise was inversely correlated with vertebral BMAT-FF, but not hip BMAT-FF, when exercising for more than 2h per week. Physical activity seems to affect the spine at least preferentially compared to the hip. • In our population-based cohort, at least 2h of physical activity per week were required to show lower levels of bone marrow adipose tissue fat fraction in MRI. • Physical activity seems to affect bone marrow adipose tissue at least preferentially at the spine in contrast to the proximal femur.

Proximal femur fat fraction variation in healthy subjects using chemical shift-encoding based MRI

The objective of this study was to describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.

Increased BMPR1A Expression Enhances the Adipogenic Differentiation of Mesenchymal Stem Cells in Patients with Ankylosing Spondylitis.

Objective To investigate the adipogenic differentiation capacity of mesenchymal stem cells (MSCs) from ankylosing spondylitis (AS) patients and explore the mechanism of abnormal MSC adipogenesis in AS. Methods MSCs from patients with AS (ASMSCs) and healthy donors (HDMSCs) were cultured in adipogenic differentiation medium for up to 21 days. Adipogenic differentiation was determined using oil red O (ORO) staining and quantification and was confirmed by assessing adipogenic marker expression (PPAR-γ, FABP4, and adiponectin). Gene expression of adipogenic markers was detected using qRT-PCR. Protein levels of adipogenic markers and signaling pathway-related molecules were assessed via Western blotting. Levels of bone morphogenetic proteins 4, 6, 7, and 9 were determined using enzyme-linked immunosorbent assays. Lentiviruses encoding short hairpin RNAs (shRNAs) were constructed to reverse abnormal bone morphogenetic protein receptor 1A (BMPR1A) expression and evaluate its role in abnormal ASMSC adipogenic differentiation. Bone marrow fat content was assessed using hematoxylin and eosin (HE) staining. BMPR1A expression in bone marrow MSCs was measured using immunofluorescence staining. Results ASMSCs exhibited a greater adipogenic differentiation capacity than HDMSCs. During adipogenesis, ASMSCs expressed BMPR1A at higher levels, which activated the BMP-pSmad1/5/8 signaling pathway and increased adipogenesis. BMPR1A silencing using an shRNA eliminated the difference in adipogenic differentiation between HDMSCs and ASMSCs. Moreover, HE and immunofluorescence staining showed higher bone marrow fat content and BMPR1A expression in patients with AS than in healthy donors. Conclusion Increased BMPR1A expression induces abnormal ASMSC adipogenic differentiation, potentially contributing to fat metaplasia and thus new bone formation in patients with AS.

Vertebral bone marrow fat fraction changes in postmenopausal women with breast cancer receiving combined aromatase inhibitor and bisphosphonate therapy

BackgroundQuantification of vertebral bone marrow (VBM) water–fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period.MethodsTwenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP).All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject.All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4.ResultsBaseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05).ConclusionsOver a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.

Bone marrow adiposity is inversely associated with bone mineral density in postmenopausal females.

Aim To evaluate vertebral bone marrow adiposity (BMA) using magnetic resonance spectroscopy (MRS) in postmenopausal women and to determine an association of bone density with bone marrow fat content. Methods This cross-sectional study included 120 postmenopausal women referred for osteoporosis screening. All women underwent assessment of bone mineral density by dual X-ray absorptiometry (DXA), who were divided based on T scores into osteoporosis (OST; n=60) and control group (CG; n=60). MRS was used to measure fat fraction (FF), lipid/water ratio (LWR) and fat content (FC) at vertebral spine (L1-L4). Results Mean age, menopause or reproductive period duration was not significantly different between women in OST and control group. Median LWR in OST group was significantly higher compared to CG, 31.5 (22.9-38.8) vs. 28.7 (13.7-37.3) (p=0.039). Median FC was significantly higher in OST compared to the control group, 47.0 (46.3-78.8) and 46.4 (44.3-48.6), respectively (p=0.011). FC was significantly negatively associated with BMD at lumbar spine (Rho=-0.042; p<0.001) and with BMD at hip (Rho=-0.64; p<0.001). In logistic regression model, FC remained independently associated with osteoporosis after controlling for confounders (age, menopause duration, reproductive period duration and body mass index) (OR=1.3; 95% CI 1.1-1.6). Conclusion Bone marrow adiposity is an independent predictor of low bone mass in postmenopausal women suggesting its role as a therapeutic target in postmenopausal osteoporosis management.

Osteoarthritis as an organ disease: from the cradle to the grave.

Considered for decades as a cartilage disease, recent studies of osteoarthritis (OA) take us back to the concepts discussed at the naming of the disorder as "bone-joint-inflammation". By describing the joint as an organ, can OA be called an organ disease - similar to heart disease? Is there a systemic (which system?) involvement? Would this help with diagnosis or therapy? Hyperplasia of the joint tissues is one of the most notable early features of the disease: articular cartilage thickens, chondrocytes proliferate and increase matrix biosynthesis, but not its incorporation; the subchondral bone densifies but is hypomineralised and there is an increase in bone marrow fat content. Associations between OA and hypertension, hypercholesterolaemia and blood glucose suggest systemic and metabolic components are involved. The source of pain is still unknown but here is evidence for peripheral and central sensitisation. Joint deformity is difficult to quantify, but statistical shape modelling provides a tool to use as an imaging biomarker. A genome-wide association study meta-analysis has identified novel genes associated with hip shape with many genes related to tissue growth and development. There are associations between hip shapes and age of first walking as well as with obesity through adulthood. These life-course events and a recapitulation in old age of developmental processes suggest that the cradle may affect our path to the grave. These observations suggest that tissue regeneration approaches, treating only the cartilage in OA joints, may only be of limited benefit.

Active cushing syndrome patients have increased ectopic fat deposition and bone marrow fat content compared to cured patients and healthy subjects: a pilot 1H-MRS study.

Glucocorticoid excess is one of the most important causes of bone disorders. Bone marrow fat (BMF) has been identified as a l new mediator of bone metabolism. Cushing syndrome (CS), is a main regulator of adipose tissue distribution but its impact on BMF is unknown. The objective of the study was to evaluate the effect of chronic hypercortisolism on BMF. This was a cross-sectional study. Seventeen active and seventeen cured ACTH-dependent CS patients along with seventeen controls (matched with the active group for age and sex) were included. the BMF content of the femoral neck and L3 vertebrae were measured by 1H-MRS on a 3-Tesla wide-bore magnet. BMD was evaluated in patients using dual-energy X-ray absorptiometry. Active CS patients had higher BMF content both in the femur (82.5±2.6%) and vertebrae (70.1±5.1%) compared to the controls (70.8±3.6%, p=0.013 and 49.0±3.7% p=0.005, respectively). In cured CS patients (average remission time of 43 months), BMF content was not different from controls at both sites (72.3±2.9% (femur) and 46.7%±5.3% (L3)). BMF content was positively correlated with age, fasting plasma glucose, HbA1c, triglycerides and visceral adipose tissue in the whole cohort and negatively correlated with BMD values in the CS patients . Accumulation of BMF is induced by hypercortisolism. In remission patients BMF reached values of controls. Further studies are needed to determine whether this increase in marrow adiposity in CS is associated with bone loss.

Reliability of measuring the fat content of the lumbar vertebral marrow and paraspinal muscles using MRI mDIXON-Quant sequence.

We aimed to assess the reliability of measuring the fat content of the lumbar vertebral marrow and the paraspinal muscles using magnetic resonance imaging (MRI) mDIXON-Quant sequence. Thirty-one healthy volunteers were included. All participants underwent liver mDIXON-Quant imaging on a 3.0 T Philips MRI scanner by observer A. Within two weeks, observer B repeated the scan. After the examination, each observer independently measured the fat content of the third lumbar vertebra (L3), and the psoas (PS), erector spinae (ES), and multifidus (MF) muscles on central L3 axial images. After two weeks, each observer repeated the same measurements. They were blinded to their previous results. Reliability was estimated by evaluating the repeatability and reproducibility. The repeatability of the fat content measurements of L3, PS, ES, and MF was high. The intraclass correlation coefficients of the fat content of L3, PS, ES, and MF were 0.997, 0.984, 0.997, and 0.995 for observer A and 0.948, 0.974, 0.963, and 0.995 for observer B, respectively. The reproducibility of the measurement of the fat content of L3, PS, ES, and MF was high, and the interclass correlation coefficients were 0.984, 0.981, 0.977, and 0.998, respectively. Using mDIXON-Quant imaging to measure the fat content of the lumbar vertebral marrow and paraspinal muscles shows high reliability and is suitable for use in clinical practice.

Magnetic Resonance Spectroscopy for Evaluating the Effect of Pulsed Electromagnetic Fields on Marrow Adiposity in Postmenopausal Women With Osteopenia.

Pulsed electromagnetic fields (PEMFs) could promote osteogenic differentiation and suppress adipogenic differentiation in bone mesenchymal stem cells ex vivo. However, data on the effect of PEMF on marrow adiposity in humans remain elusive. We aimed to determine the in vivo effect of PEMF on marrow adiposity in postmenopausal women using magnetic resonance spectroscopy. Sixty-one postmenopausal women with osteopenia, aged 53 to 85 years, were randomly assigned to receive either PEMF treatment or placebo. The session was performed 3 times per week for 6 months. All women received adequate dietary calcium and vitamin D. Bone mineral density (BMD) by dual-energy x-ray absorptiometry, vertebral marrow fat content by magnetic resonance spectroscopy, and serum biomarkers were evaluated before and after 6 months of treatment. A total of 27 (87.1%) and 25 (83.3%) women completed the treatment schedule in the PEMF and placebo groups, respectively. After the 6-month treatment, lumbar spine and hip BMD increased by 1.46% to 2.04%, serum bone-specific alkaline phosphatase increased by 3.23%, and C-terminal telopeptides of type 1 collagen decreased by 9.12% in the PEMF group (P < 0.05), whereas the mean percentage changes in BMD and serum biomarkers were not significant in the placebo group. Pulsed electromagnetic field treatment significantly reduced marrow fat fraction by 4.81%. The treatment difference between the 2 groups was -4.43% (95% confidence interval, -3.70% to -5.65%; P = 0.009). Pulsed electromagnetic field is an effective physiotherapy in postmenopausal women, and this effect may, at least in part, regulate the amount of fat within the bone marrow. Magnetic resonance spectroscopy may serve as a complementary imaging biomarker for monitoring response to therapy in osteoporosis.

Vertebral bone marrow fat content in normal adults with varying bone densities at 3T magnetic resonance imaging.

Sex-related differences of vertebral bone marrow fat in relation to varying bone densities have not yet been evaluated although some studies have reported an inverse association of bone marrow fat and bone mineral density (BMD). To evaluate the relationship between bone marrow fat and BMD and to demonstrate the sex-related differences of the vertebral bone marrow fat in normal adults with varying bone densities. A total of 123 normal adult volunteers were enrolled in this study. 1H-MRS of the lumbar spine was performed. The fat fraction (FF) values of vertebral bone marrow were measured. Volumetric BMD measurement was performed by quantitative computed tomography (QCT). All participants were divided into three groups according to BMD (normal, osteopenia, osteoporosis). The differences in the FF and body mass index (BMI) values of the three groups were compared, and partial correlation analysis was used to evaluate the correlation between FF values and BMD/BMI. The FF values increased with decreasing BMD in both male and female participants. There were significant sex differences for the FF values in the normal bone density group ( P < 0.001). The FF values of the normal bone density group in male participants were significantly higher than those of the female participants ( P < 0.001). The FF values were significantly negative correlated with BMD for all participants (r = -0.820, P < 0.001). The FF values of vertebral bone marrow correlated inversely with BMD. Sex-related differences of FF values was related to BMD.

Bone disorders associated with diabetes mellitus and its treatments.

Both type 1 and type 2 diabetes mellitus are associated with bone disorders, albeit via different mechanisms. Early studies in patients with type 1 diabetes suggested a 10-fold increase in the hip fracture risk compared to non-diabetic controls. Meta-analyses published more recently indicate a somewhat smaller risk increase, with odds ratios of 6 to 7. Diminished bone mineral density is among the contributors to the increased fracture risk. Both types of diabetes are associated with decreased bone strength related to low bone turnover. The multiple and interconnected pathophysiological mechanisms underlying the bone disorders seen in type 1 diabetes include insulin deficiency, accumulation of advanced glycation end products, bone microarchitecture alterations, changes in bone marrow fat content, low-grade inflammation, and osteocyte dysfunction. The bone alterations are less severe in type 2 diabetes. Odds ratios for hip fractures have ranged across studies from 1.2 to 1.7, and bone mineral density is higher than in non-diabetic controls. The odds ratio is about 1.2 for all bone fragility fractures combined. The pathophysiological mechanisms are complex, particularly as obesity is very common in patients with type 2 diabetes and is itself associated with an increased risk of fractures at specific sites (humerus, tibia, and ankle). The main mechanisms underlying the bone fragility are an increase in the risk of falls, sarcopenia, disorders of carbohydrate metabolism, vitamin D deficiency, and alterations in cortical bone microarchitecture and bone matrix. The medications used to treat both types of diabetes do not seem to play a major role. Nevertheless, thiazolidinediones and, to a lesser extent, sodium-glucose cotransporter inhibitors may have adverse effects on bone, whereas metformin may have beneficial effects. For the most part, the standard management of bone fragility applies to patients with diabetes. However, emphasis should be placed on preventing falls, which are particularly common in this population. Finally, there is some evidence to suggest that anti-fracture treatments are similarly effective in patients with and without diabetes.

Marrow adiposity and bone: Review of clinical implications.

There is growing interest in the relationship between bone marrow fat (BMF) and skeletal health. Progress in clinical studies of BMF and skeletal health has been greatly enhanced by recent technical advances in our ability to measure BMF non-invasively. Magnetic resonance imagery (MRI) with or without spectroscopy is currently the standard technique for evaluating BMF content and composition in humans. This review focuses on clinical studies of marrow fat and its relationship with bone. The amount of marrow fat is associated with bone mineral density (BMD). Several studies have reported a significant negative association between marrow fat content and BMD in both healthy and osteoporotic populations. There may also be a relationship between marrow fat and fracture (mostly vertebral fracture), but data are scarce and further studies are needed. Furthermore, a few studies suggest that a lower proportion of unsaturated lipids in vertebral BMF may be associated with reduced BMD and greater prevalence of fracture. Marrow fat might be influenced by metabolic diseases associated with bone loss and fractures, such as diabetes mellitus, obesity and anorexia nervosa. An intriguing aspect of bariatric (weight loss) surgery is that it induces bone loss and fractures, but with different impacts on marrow fat depending on diabetic status. In daily practice, the usefulness for clinicians of assessing marrow fat using MRI is still limited. However, the perspectives are exciting, particularly in terms of improving the diagnosis and management of osteoporosis. Further studies are needed to better understand the regulators involved in the marrow fat-bone relationship and the links between marrow fat, other fat depots and energy metabolism.

A study on dynamic monitoring, components, and risk factors of embolism during total knee arthroplasty.

Background:Fat embolism is a common complication of orthopedic surgery. However, the exact component and risk factor responsible for this complication remains unelucidated. This study aimed to detect the origin of the pulmonary embolus and identify relevant risk factors of pulmonary embolism in total knee replacement.Methods:A total of 40 osteoarthritis patients who underwent primary unilateral TKA were recruited into this study. Transesophageal echocardiography (TEE) was utilized to dynamically monitor the embolism. Pulmonary arterial pressure was recorded and biopsies were obtained from the medullary cavity during surgery.Results:After tourniquet release, the arterial embolism was observed by TEE to have a peak signal at 30 seconds when pulmonary arterial pressure was increased by 25% to 40% (P = .002). The pathology study of the embolism revealed its bone marrow origin. Total embolus quantity was positively correlated with age (P = .021), body mass index (BMI, P = .041), and fat content of the bone marrow (P = .003). Logistic regression analysis revealed that the fat content of the marrow (OR: 1.432, 95% CI: 1.335–1.592), age (OR: 1.632, 95% CI: 1.445–1.832), and BMI (OR: 1.231, 95% CI: 1.032–1.381) were risk factors for pulmonary hypertension.Conclusion:This study revealed that the embolus detected in the right atrium was derived from bone marrow tissues, and this led to pulmonary arterial pressure fluctuations after tourniquet release. Therefore, elderly patients who have high BMI or bone marrow fat content are at high-risk for pulmonary fat embolism during TKA.

Assessment of alveolar bone marrow fat content using 15 T MRI

Bone marrow fat is inversely correlated with bone mineral density. The aim of this study is to present a method to quantify alveolar bone marrow fat content using a 15 T magnetic resonance imaging (MRI) scanner. A 15 T MRI scanner with a 13-mm inner diameter loop-gap radiofrequency coil was used to scan seven 3-mm diameter alveolar bone biopsy specimens. A 3-D gradient-echo relaxation time (T1)-weighted pulse sequence was chosen to obtain images. All images were obtained with a voxel size (58 µm3) sufficient to resolve trabecular spaces. Automated volume of the bone marrow fat content and derived bone volume fraction (BV/TV) were calculated. Results were compared with actual BV/TV obtained from micro-computed tomography (CT) scans. Mean fat tissue volume was 20.1 ± 11%. There was a significantly strong inverse correlation between fat tissue volume and BV/TV (r = -0.68; P = .045). Furthermore, there was a strong agreement between BV/TV derived from MRI and obtained with micro-CT (interclass correlation coefficient = 0.92; P = .001). Bone marrow fat of small alveolar bone biopsy specimens can be quantified with sufficient spatial resolution using an ultra-high-field MRI scanner and a T1-weighted pulse sequence.