Bone Marrow Fat Research Articles

Gender interactions between vertebral bone mineral density and fat content in the elderly: Assessment using fat-water MRI.

Adipose tissue is closely related to bone mass, bone quality, and bone fractures, but the connection between fat and bone is complex and gender-related. Fat-water magnetic resonance imaging (MRI) and MR spectroscopy (MRS) are very useful tools for identifying tissue fat. To assess gender interactions between bone mineral density (BMD), bone marrow fat, and body mass index (BMI) in the elderly using fat-water MRI and MRS. Prospective/cohort. Sixty-six women and 38 men (mean age, 62.3 years; range, 50-75 years), Asian. A 1.5T MR equipped with a body and spine array coil. STEAM MRS and T2 * Dixon were performed. Vertebral bone marrow fat ratio (MFR), BMI, and BMD were measured. Correlations between these variables and differences in bone density in MFR were assessed between participants, divided into three groups based on bone density. Multiple regression; Pearson tests; analysis of covariance; analysis of variance. Multiple regression analysis identified gender, vertebral bone MFR, and BMI as significant predictors of vertebral BMD (P < 0.001). Among the women, vertebral BMD was negatively correlated with vertebral MFR (P = 0.011), but among the men, it was positively correlated with BMI (P = 0.048), although this relationship was confounded by age and MFR. Moreover, vertebral bone marrow fat and BMI were indeed statistically uncorrelated in the elderly (P = 0.357 in women; P = 0.961 in men). We found gender interactions between fat and bone in the elderly. Higher bone marrow fat was correlated with lower trabecular BMD in older women but not in men. On the other hand, the positive correlation between BMI and BMD was more pronounced in men than in women. 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1382-1389.

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.

Osteosarcopenia: A case of geroscience.

Many older persons lose their mobility and independence due to multiple diseases occurring simultaneously. Geroscience is aimed at developing innovative approaches to better identify relationships among the biological processes of aging. Osteoporosis and sarcopenia are two of the most prevalent chronic diseases in older people, with both conditions sharing overlapping risk factors and pathogenesis. When occurring together, these diseases form a geriatric syndrome termed “osteosarcopenia,” which increases the risk of frailty, hospitalizations, and death. Findings from basic and clinical sciences aiming to understand osteosarcopenia have provided evidence of this syndrome as a case of geroscience. Genetic, endocrine, and mechanical stimuli, in addition to fat infiltration, sedentarism, and nutritional deficiencies, affect muscle and bone homeostasis to characterize this syndrome. However, research is in its infancy regarding accurate diagnostic markers and effective treatments with dual effects on muscle and bone. To date, resistance exercise remains the most promising strategy to increase muscle and bone mass, while sufficient quantities of protein, vitamin D, calcium, and creatine may preserve these tissues with aging. More recent findings, from rodent models, suggest treating ectopic fat in muscle and bone marrow as a possible avenue to curb osteosarcopenia, although this needs testing in human clinical trials.

High bone marrow fat in patients with Cushing’s syndrome and vertebral fractures

The evaluation of skeletal fragility in Cushing's syndrome (CS) is a clinical challenge, since dual-energy X-ray absorptiometry (DXA) does not capture abnormalities in bone microstructure induced by glucocorticoid excess. Hypercortisolism was shown to increase bone marrow adiposity, but it is still unknown whether high bone marrow fat (BMF) as measured by vertebral magnetic resonance spectroscopy may predict fracture risk in this clinical setting. In this cross-sectional study, we evaluated the association between BMF and vertebral fractures (VFs) in patients with CS. Twenty patients (5 M, age 44 ± 13 years) with active CS were evaluated for morphometric VFs, lumbar spine BMF, and bone mineral density (BMD). Fifteen healthy volunteers (4 M, age 43 ± 12 years) acted as control group for BMF evaluation. BMF was significantly higher in CS patients vs. controls (52.0% vs. 27.0%, p < 0.01), and was directly correlated with patients' age (p = 0.03), 24-hours urine-free cortisol (p = 0.03), midnight serum cortisol (p = 0.02), and serum CTX (p = 0.01). Patients with VFs (13 cases) showed significantly higher BMF vs. patients without VFs (65.0% vs. 24.0%, p = 0.03). Fractured patients with either normal BMD or osteopenia showed comparable BMF to fractured patients with either osteoporosis or low BMD for age (p = 0.71). When the analysis was restricted to patients with normal BMD or osteopenia, VFs were still significantly associated with higher BMF (p = 0.05). This study provides a first evidence that vertebral adiposity may be a marker of hypercortisolism-induced skeletal fragility and measurement of spine BMF could have a role in the diagnostic work-up for the assessment of fracture risk in CS.

Do Patients With Skin Psoriasis Show Subclinical Axial Inflammation on Magnetic Resonance Imaging of the Sacroiliac Joints and Entire Spine?

To explore potential subclinical involvement of the axial skeleton by magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the entire spine in patients with skin psoriasis without clinical evidence of peripheral or axial inflammation. Twenty patients with skin psoriasis but no clinical evidence of peripheral or axial inflammation and 22 healthy controls underwent standardized dermatologic and rheumatologic clinical examination and unenhanced 1.5T MRI of the SI joint and the entire spine. Two blinded readers globally assessed the presence or absence of SI joint inflammation simultaneously on T1-weighted and short tau inversion recovery MRI sequences with a confidence estimate. Bone marrow edema, fat metaplasia, erosion, and ankylosis of the SI joint, and vertebral corner inflammatory lesions and fat lesions were recorded using standardized modules. The prevalence of each lesion type was calculated in both groups, averaged across 2 readers. The number of subjects with lesions in the SI joint and spine (≥1, 2, 3, 4, or 5 lesions) as concordantly assessed by both readers was recorded. The median duration of skin psoriasis was 23.0 years, the median age of patients was 48.5 years, and 25.0% of patients and 9.1% of healthy controls were concordantly classified by both readers as having SI joint inflammation (P = 0.23). The prevalence of bone marrow edema and structural lesions was comparable across patients and controls, both on SI joint and spine MRI. In this controlled study, patients with skin psoriasis but no clinical arthritis or spondylitis showed limited evidence of concomitant subclinical axial involvement by SI joint and spine MRI. These findings do not support routine screening for subclinical axial inflammation in patients with longstanding skin psoriasis.

The glucocorticoid receptor in osteoprogenitors regulates bone mass and marrow fat.

Excess fat within bone marrow is associated with lower bone density. Metabolic stressors such as chronic caloric restriction (CR) can exacerbate marrow adiposity, and increased glucocorticoid signaling and adrenergic signaling are implicated in this phenotype. The current study tested the role of glucocorticoid signaling in CR-induced stress by conditionally deleting the glucocorticoid receptor (GR) in bone marrow osteoprogenitors (Osx1-Cre) of mice subjected to CR and ad libitum diets. Conditional knockout of the GR (GR-CKO) reduced cortical and trabecular bone mass as compared to wildtype (WT) mice under both ad libitum and CR conditions. No interaction was detected between genotype and diet, suggesting that the GR is not required for CR-induced skeletal changes. The lower bone mass in GR-CKO mice, and the further suppression of bone by CR, resulted from suppressed bone formation. Interestingly, treatment with the -adrenergic receptor antagonist propranolol mildly but selectively improved metrics of cortical bone mass in GR-CKO mice during CR, suggesting interaction between adrenergic and glucocorticoid signaling pathways that affects cortical bone. GR-CKO mice dramatically increased marrow fat under both ad libitum and CR-fed conditions, and surprisingly propranolol treatment was unable to rescue CR-induced marrow fat in either WT or GR-CKO mice. Additionally, serum corticosterone levels were selectively elevated in GR-CKO mice with CR, suggesting the possibility of bone-hypothalamus-pituitary-adrenal crosstalk during metabolic stress. This work highlights the complexities of glucocorticoid and β-adrenergic signaling in stress-induced changes in bone mass, and the importance of GR function in suppressing marrow adipogenesis while maintaining healthy bone mass.

Increased NF-kB activity in osteoprogenitor-lineage cells impairs the balance of bone versus fat in the marrow of skeletally mature mice.

"Senile osteoporosis" is defined as significant aging-associated bone loss, and is accompanied by increased fat in the bone marrow. The proportion of adipocytes in bone marrow is inversely correlated with bone formation, and is associated with increased risk of fracture. NF-κB is a transcription factor that functions as a master regulator of inflammation and bone remodeling. NF-κB activity increases during aging; furthermore, constitutive activation of NF-κB significantly impairs skeletal development in neonatal mice. However, the effects of NF-κB activation using a skeletally mature animal model have not been examined. In the current study, an osteoprogenitor (OP)-specific, doxycycline-regulated NF-κB activated transgenic mouse model (iNF-κB/OP) was generated to investigate the role of NF-κB in bone remodeling in skeletally mature mice. Reduced osteogenesis in the OP-lineage cells isolated from iNF-κB/OP mice was only observed in the absence of doxycycline in vitro. Bone mineral density in the metaphyseal regions of femurs and tibias was reduced in iNF-κB/OP mice. No significant differences in bone volume fraction and cortical bone thickness were observed. Osmium-stained bone marrow fat was increased in epiphyseal and metaphyseal areas in the tibias of iNF-κB/OP mice. These findings suggest that targeting NF-κB activity as a therapeutic strategy may improve bone healing and prevent aging-associated bone loss in aged patients.

Altered expression of leptin and leptin receptor in the development of immune-mediated aplastic anemia in mice.

The current study aimed to explore the levels of leptin (LEP) and LEP receptor (LEP-R) on the progression of aplastic anemia (AA) with bone marrow fat conversion. An AA model was developed by infusing C57BL/6 lymph node cells into BALB/c mice. At 0, 3, 6, 9, 12, 15 and 18 days after modeling, routine blood counts, bone marrow biopsy slides, lymphocyte subsets (CD4+ and CD8+ T cells) and cytokine levels [including interleukin (IL)-2, IL-4, IL-5 and interferon-γ] were assessed. LEP and LEP-R levels in peripheral blood serum, mesenchymal stem cells (MSCs) and bone marrow were also analyzed by enzyme-linked immunosorbent assay, polymerase chain reaction and immunohistochemistry. The relevance of LEP, LEP-R and other factors was analyzed by Pearson's correlation analysis. Peripheral pancytopenia (reduced count of white blood cells, red blood cells, hemoglobin and platelets), abnormal immune factor levels and histological changes in bone marrow sections were detected in the AA model mice, suggesting that these mice mimicked the pathological changes commonly observed in AA. In addition, following the establishment of AA, the LEP level was gradually increased and the LEP-R level was reduced in the mice over time (P<0.05). The expression of adipogenic genes, including CCAAT/enhancer-binding protein (C/EBP)α, C/EBPβ and peroxisome proliferator-activated receptor γ, was markedly increased, while the expression of the osteogenic gene runt-related transcription factor 2 was reduced compared with the levels in the control group (P<0.05). Taken together, damage to LEP-R may lead to dysregulation of LEP and the enhancement of MSCs to differentiate into adipocytes, resulting in excessive fat in bone marrow of AA patients.

PB2147 AL AMYLOIDOSIS IN THE CHILEAN PUBLIC HEALTH SYSTEM: A PENDING DEBT. MULTICENTER STUDY OF THE CHILEAN HEMATOLOGICAL COOPERATIVE GROUP (PANDA)

Background:Amyloidosis has an estimated incidence of 3‐14/1 million inhabitants/year is estimated, depending on the geographical area. While the whole world discusses about the new diagnostic and therapeutic tools, in Chile, and Latin America in general, we are far from that reality. There is little information about AL amyloidosis in Chile, consisting mainly on case reports. The largest report was in 2005, when where 11 cases were described.Aims:Characterize patients with AL amyloidosis in public health centers throughout the country.MethodsRetrospective and descriptive multicenter study. The public centers part of the Chilean hematological cooperative group (PANDA) were asked to search in their databases to find patients diagnosed with AL amyloidosis. In all centers, the diagnosis of AL amyloidosis was made with a positive Congo red stain on tissue biopsy. Affected organs were determined by biopsy or according to the definition of Gertz et al. Epidemiological, clinical and laboratory characteristics were evaluated.Results:Data was collected from 42 patients of eight public health centers. The median age was 65 years, ranging from 22 to 84 years. The male to female ratio was 1: 0.75. 24% of the patients were diagnosed with localized AL amyloidosis; 64% presented with a lambda light chain clone; 47% of cases were associated with multiple myeloma (MM) and a 9% with non‐Hodgkin lymphoma (NHL) (Figure 1): 2 MALT lymphomas, 1 lymphoplasmacytic lymphoma, and a non‐characterized low grade B cell lymphoma. The most frequently involved organ was the kidney (76%), followed by the heart (48%). The analysis by group: 1.‐ Primary amyloidosis, 2.‐ MM‐associated amyloidosis, and 3.‐NHL‐associated AL amyloidosis showed no statistical difference between them. Regarding diagnostic tests, 100% reported having performed serum protein electrophoresis (sPEP), 69% serum immunofixation (sIFE) and 43% urine IFE. Serum Free light chains (sFLC) were performed in 31% of the patients, and echocardiogram on 74%. The most frequently performed biopsies were bone marrow (52%) and subcutaneous fat tissue (38%), being these samples diagnostic in 45% and 44% of cases respectively. Renal biopsy was performed in 33% of the cases, with a positive diagnosis in all of them. Treatment was heterogeneous: 17% received only palliative care, 17% were treated with bortezomib based therapy, 21% with cyclophosphamide, thalidomide, and dexamethasone (CTD), and 40% with melphalan based therapy. No patient received a bone marrow transplant. The median OS of the group was 19 months. The 3‐year OS was 38%, and the 5‐year OS 28%. There was no difference between patients with or without associated MM (5‐year OS of 22% vs 24%; p= 0.8), with or without use of novel agents (5‐yr OS of 15% vs 38%; p = 0,09), localized versus systemic amyloidosis (5‐yr OS of 36% vs 27%; p = 0,6) or with or without cardiac involvement (5‐yr OS of 25% vs 31%; p = 0.31).Summary/Conclusion:This is to our knowledge, the biggest experience published in Chile and Latin‐America on this topic. The scarce number of patients may be due to registry deficiency on our healthcare system. This is further favored by lack of clinical suspicion and reduced access to diagnostic tools. There are shortfalls in the diagnostic study and treatment of amyloidosis AL in our public health centers. It is important to obtain realistic, national results to initiate strategies to improve both early diagnosis and management of this pathology. Improving awareness is therefore crucial.

Improved contrast for myeloma focal lesions with T2-weighted Dixon images compared to T1-weighted images

PurposeThe purpose of this study was twofold. First, to compare the contrast between spinal multiple myeloma (MM) focal lesions and surrounding bone marrow obtained on T2-weighted Dixon fat-only MR images to that obtained on T1-weighted spin-echo images. Second, to search for correlation between bone marrow fat fraction assessed by T2-weighted Dixon sequence and International Myeloma Working Group myeloma defining events. Materials and methodsA total of 39 patients with 112 focal MM lesions were included. There were 25 men and 14 women with a mean age of 68.8±9.8 [SD] years (range: 49-88 years). Contrast between focal MM lesions and surrounding bone marrow was calculated on T1-weighted spin-echo and T2-weighted Dixon (including water-only and fat-only) images. Contrast between focal MM lesions and bone marrow was compared using ANOVA and post-hoc Tukey tests. Correlation between bone marrow fat fraction and myeloma defining events was assessed using Spearman's correlation test. ResultsMM lesion contrast was greater on T2-weighted Dixon (F (2;93)=35.10) than on T1-weighted images (P<0.0001). Greatest MM lesion contrast was achieved with T2-weighted Dixon fat-only (0.63±0.21 [SD]; range: 0.06–0.91) compared to T2-weighted Dixon water-only (0.45±0.20 [SD]; range: 0.07–0.8) (P=0.0003) and T1-weighted (0.23±0.19 [SD]; range: 0.04–0.87) (P<0.0001) images. There were no significant correlations between myeloma defining events and fat fraction. ConclusionT2-weighted Dixon fat-only images provide greater contrast between MM lesions and adjacent bone marrow than T1-weighted images. The usefulness of a T1-weighted sequence associated to a T2-weighted Dixon sequence has to be determined.

Human Immune System Increases Breast Cancer-Induced Osteoblastic Bone Growth in a Humanized Mouse Model without Affecting Normal Bone.

Bone metastases are prevalent in many common cancers such as breast, prostate, and lung cancers, and novel therapies for treating bone metastases are needed. Human immune system-engrafted models are used in immuno-oncology (IO) studies for subcutaneous cancer cell or patient-derived xenograft implantations that mimic primary tumor growth. Novel efficacy models for IO compounds on bone metastases need to be established. The study was performed using CIEA NOG (NOG) mice engrafted with human CD34+ hematopoietic stem cells (huNOG) and age-matched immunodeficient NOG mice. Bone phenotyping was performed to evaluate baseline differences. BT-474 human breast cancer cells were inoculated into the tibia bone marrow, and cancer-induced bone changes were monitored by X-ray imaging. Bone content and volume were analyzed by dual X-ray absorptiometry and microcomputed tomography. Tumor-infiltrating lymphocytes (TILs) and the expression of immune checkpoint markers were analyzed by immunohistochemistry. Bone phenotyping showed no differences in bone architecture or volume of the healthy bones in huNOG and NOG mice, but the bone marrow fat was absent in huNOG mice. Fibrotic areas were observed in the bone marrow of some huNOG mice. BT-474 tumors induced osteoblastic bone growth. Bone lesions appeared earlier and were larger, and bone mineral density was higher in huNOG mice. huNOG mice had a high number of human CD3-, CD4-, and CD8-positive T cells and CD20-positive B cells in immune-related organs. A low number of TILs and PD-1-positive cells and low PD-L1 expression were observed in the BT-474 tumors at the endpoint. This study reports characterization of the first breast cancer bone growth model in huNOG mice. BT-474 tumors represent a “cold” tumor with a low number of TILs. This model can be used for evaluating the efficacy of combination treatments of IO therapies with immune-stimulatory compounds or therapeutic approaches on bone metastatic breast cancer.

1H-MRS of femoral red and yellow bone marrow fat composition and water content in healthy young men and women at 3 T

There is a discrepancy between studies suggesting that higher bone marrow fat saturation is associated with impaired health, and studies suggesting that erythropoiesis increases red bone marrow (RBM) fat saturation in young healthy individuals. Here, we seeked to elucidate these discrepancies by using long TE magnetic resonance spectroscopy (MRS) to study both yellow bone marrow (YBM) and RBM in the femur of healthy volunteers. Thirty-three young healthy volunteers (17 females), age range 20-31years, underwent long TE 1H MRS at 3.0 T of RBM and YBM fat composition in the left femur. The water content of the bone marrow depots was measured using short TE MRS. The female participants displayed a lower unsaturation in the sampled RBM volume (RBMV) than the males (P < 0.01) without displaying a concomitant difference in YBM (P = 0.42). They also showed a higher water content and broader spectral linewidths in RBM (P = 0.04). The water content in RBM strongly associated with broader spectral linewidths (R = 0.887, P ≪ 0.01) and inversely with RBMV fat unsaturation (R = - 0.365, P = 0.04). These results partly support the notion that females display higher rate of erythropoiesis and lower fat unsaturation in RBM.

Assessment of bone marrow fat by single-voxel vertebral magnetic resonance spectroscopy in cushing's syndrome with or without vertebral fractures

Assessment of bone marrow fat by single-voxel vertebral magnetic resonance spectroscopy in cushing's syndrome with or without vertebral fractures

Texture analysis of vertebral bone marrow using chemical shift encoding\u2013based water-fat MRI: a feasibility study

SummaryThis feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow using chemical shift encoding–based water-fat MRI. Acquired texture features like contrast and dissimilarity allowed for differentiation of pre- and postmenopausal women and may serve as imaging biomarkers in the future.IntroductionWhile the vertebral bone marrow fat using chemical shift encoding water-fat magnetic resonance imaging (MRI) has been extensively studied, its spatial heterogeneity has not been analyzed yet. Therefore, this feasibility study investigated the spatial heterogeneity of the lumbar vertebral bone marrow by using texture analysis in proton density fat fraction (PDFF) maps.MethodsForty-one healthy pre- and postmenopausal women were recruited for this study (premenopausal (n = 15) 30 ± 7 years, postmenopausal (n = 26) 65 ± 7 years). An eight-echo 3D spoiled gradient echo sequence was used for chemical shift encoding–based water-fat separation at the lumbar spine. Vertebral bodies L1 to L5 were manually segmented. Mean PDFF values and texture features were extracted at each vertebral level, namely variance, skewness, and kurtosis, using statistical moments and second-order features (energy, contrast, correlation, homogeneity, dissimilarity, entropy, variance, and sum average). Parameters were compared between pre- and postmenopausal women and vertebral levels.ResultsPDFF was significantly higher in post- than in premenopausal women (49.37 ± 8.14% versus 27.76 ± 7.30%, p < 0.05). Furthermore, PDFF increased from L1 to L5 (L1 37.93 ± 12.85%, L2 38.81 ± 12.77%, L3 40.23 ± 12.72%, L4 42.80 ± 13.27%, L5 45.21 ± 14.55%, p < 0.05). Bone marrow heterogeneity based on texture analysis was significantly (p < 0.05) increased in postmenopausal women. Contrast and dissimilarity performed best in differentiating pre- and postmenopausal women (AUC = 0.97 and 0.96, respectively), not significantly different compared with PDFF (AUC = 0.97).ConclusionConclusively, an increased bone marrow heterogeneity could be observed in postmenopausal women. In the future, texture parameters might provide additional information to detect and monitor vertebral bone marrow alterations due to aging or hormonal changes beyond conventional anatomic imaging.

Evaluation of disease chronicity by bone marrow fat fraction using sacroiliac joint magnetic resonance imaging in patients with spondyloarthritis: A retrospective study

This study investigated the use of fat fraction (FF) measurements in the sacroiliac (SI) joint to determine radiologic progression in patients with spondyloarthritis (SpA). A total of 138 patients who underwent pelvic magnetic resonance imaging (MRI) between September 2014 and March 2015 were retrospectively evaluated. The FF based upon fat deposition (%) using fat signaling on T1 and T2 weighted images in the sacroiliac joint was quantified using a 6-echo variant of the modified Dixon technique. We defined the normal bone marrow as normal FF, bone marrow edema as active inflammatory FF, and fat metaplasia as post-inflammatory FF. The mean FF of normal marrow was 52.0%±10.4% and 50.5%±10.1% in the left and right SI joints, respectively. The mean FF of post-inflammatory fat deposition was 81.9%±9.7% and 82.3%±9.6% in the left and right SI joints, respectively. The mean FF of active inflammatory fat deposition was 15.8%±5.9% and 13.5%±6.7% in the left and right SI joints, respectively. In multiple linear regression, post-inflammatory FF was found to be significantly associated with radiologic progression, such as symptom duration, SI joint grade, and modified Stoke Ankylosing Spondylitis Spine Score. Post-inflammatory FF indicates the chronicity of SpA. Evaluating FF using MRI in the SI joint will help to determine radiologic progression.

Associations between vertebral body fat fraction and intervertebral disc biochemical composition as assessed by quantitative MRI.

There is an interplay between the intervertebral disc (IVD) and the adjacent bone marrow that may play a role in the development of IVD degeneration and might influence chronic lower back pain (CLBP). To apply novel quantitative MRI techniques to assess the relationship between vertebral bone marrow fat (BMF) and biochemical changes in the adjacent IVD. Prospective. Forty-six subjects (26 female and 20 male) with a mean age of 47.3 ± 12.0 years. 3 T MRI; a combined T1ρ and T2 mapping pulse sequence and a 3D spoiled gradient recalled sequence with six echoes and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) reconstruction algorithm. Using quantitative MRI, the vertebral BMF fraction was measured as well as the biochemical composition (proteoglycan and collagen content) of the IVD. Furthermore, clinical Pfirrmann grading, Oswestry disability index (ODI), and visual analog scale (VAS) was assessed. Mixed random effects models accounting for multiple measurements per subject were used to assess the relationships between disc measurements and BMF. The relationships between BMF (mean) and T1ρ /T2 (mean and SD) were significant, with P < 0.05. Significant associations (P < 0.001) were found between clinical scores (Pfirrmann, ODI, and VAS) with T1ρ /T2 (mean and SD). BMF mean was significantly related to ODI (P = 0.037) and VAS (P = 0.043), but not with Pfirrmann (P = 0.451). In contrast, BMF SD was significantly related to Pfirrmann (P = 0.000) but not to ODI (P = 0.064) and VAS (P = 0.13). Our study demonstrates significant associations between BMF and biochemical changes in the adjacent IVD, both assessed by quantitative MRI; this may suggest that the conversion of hematopoietic bone marrow to fatty bone marrow impairs the supply of available nutrients to cells in the IVD and may thereby accelerate disc degeneration. 2 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2019;50:1219-1226.

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.

Clinicopathological prognostic indicators of survival and pathological findings in cold-stressed Florida manatees Trichechus manatus latirostris.

Cold-stress syndrome (CSS) is a leading natural cause of mortality in free-ranging Florida manatees Trichechus manatus latirostris, but comprehensive investigations into blood analyte derangements and prognostic indicators in CSS are lacking. The objectives of this study were to (1) compare admission blood analyte data of manatees pre and post rehabilitation for CSS to identify clinicopathological derangements, (2) identify blood analyte prognostic indicators for survival, and (3) correlate post-mortem anatomic pathological changes with clinicopathological findings to improve the understanding of CS pathophysiology. CSS manatees admitted to a rehabilitation facility between 2007 and 2017 were included: 59 manatees with data for clinicopathological analysis (7 non-survivors and 49 survivors) and 14 manatees with necropsy data (7 with and 7 without blood analyte data). Main interpretive clinicopathological findings indicated systemic inflammation, bone marrow damage, diuresis, malnutrition, tissue necrosis, fat mobilization, hepatic impairment, acid-base imbalances, and gastrointestinal ulceration. The best diagnostically performing prognostic indicators for survival included platelet concentration, aspartate aminotransferase, calcium, and blood urea nitrogen. The main anatomic pathological findings were cutaneous lesions (n = 14), lipid depletion (n = 12), upper gastrointestinal ulceration and/or hemorrhage (n = 9), and pneumonia (n = 5). Based on the identified blood prognostic indicators interpreted in the context of anatomic pathological findings, multi-organ tissue injury, gastrointestinal ulceration and/or hemorrhage, and hemodynamic and platelet derangements are the presumptive major factors of CSS manatee mortality. These results contribute to the understanding of the complex CSS pathophysiology and offer the use of blood analyte prognostic indicators as a clinically applicable tool for the medical care of manatees during rehabilitation, thereby contributing to increased rehabilitation success and conservation of the Florida manatee.

Decline in body condition and high drought mortality limit the spread of wild chital deer in north-east Queensland, Australia

Chital deer (Axis axis) were introduced to the Burdekin district of northern Queensland, Australia in 1886. Compared with most successful ungulate introductions they have been slow to expand their distribution and increase in abundance (Moriarty 2004). In this study we consider the possibility that forage shortages caused by periodic droughts have caused sufficient mortalities to limit the increase and spread of chital in the region. The Burdekin district experiences fluctuations in forage according to seasonal rainfall as well as multi-year droughts. This study recorded the decline in body condition, measured as kidney fat index (KFI) and bone marrow fat (BMF), over the wet and dry seasons of two successive years in two chital deer populations during a period when annual rainfall was ~40% below average. We relate the falls in mean KFI from ~45–15%, and mean BMF from ~80–50% to the surveyed decline in chital populations of ~80%. The extent of the decline implies increased mortalities in all age classes as well as reduced reproductive output. We propose that it is likely that chital populations have experienced several such drought mortality events since the 1890s which have contributed to their limited spread.

Bone Marrow Fat Physiology in Relation to Skeletal Metabolism and Cardiometabolic Disease Risk in Children With Cerebral Palsy.

Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with cerebral palsy have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance and how it relates to systemic energy metabolism among individuals with cerebral palsy are lacking. In this review, we highlight the skeletal status in children with cerebral palsy and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including the following: (1) Is the bone marrow fat in children with cerebral palsy metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with cerebral palsy? (4) If so, what are the mechanisms? In conclusion, although inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with cerebral palsy.