Effects of implant precoating and fat contamination on the stability of the tibial baseplate.

BACKGROUND: Approximately 5% of primary total knee arthroplasty patients require revision within 10 years, often due to distal component loosening. Application of a thin layer of PMMA cement as precoating on the tibial component aims to prevent aseptic loosening. This study investigates the impact of precoating and fat contamination on tibial baseplate stability. METHODS: Two groups of NexGen® stemmed tibial implants (size 4) were studied: Option implants (N = 12) and PMMA Precoat implants (N = 12). Each implant design was divided into two subgroups, (N = 6), with one subgroup featuring bone marrow fat at the implant-cement interface and the other without contamination. In a mechanical testing machine, the implants underwent uniaxial loading for 20,000 cycles, while recording vertical micromotion and migration of the tibial baseplates. Subsequently, a push-out test assessed fixation strength at the cement interfaces. Results were compared using non-parametric statistics and presented as median and min-to-max ranges. RESULTS: Option implants exhibited higher micromotion in dry conditions compared to precoated implants (p = 0.03). Under contamination, both designs demonstrated similar micromotion values. Fixation strength did not significantly differ between designs under dry, uncontaminated conditions (p > 0.99). However, under contaminated conditions, the failure load for the non-coated Option implant was nearly half that of the uncontaminated counterparts (3517 N, 2603-4367 N vs 7531 N, 5163-9000 N; p = 0.002). Precoat implants displayed less susceptibility to fat contamination (p = 0.30). CONCLUSION: NexGen® implant PMMA precoating might reduce the risk of aseptic loosening and revision surgery in case of eventual bone-marrow fat contamination.

Marrow Adipocyte Senescence in the Pathogenesis of Bone Loss.

PURPOSE OF REVIEW: Beyond aging, senescent cells accumulate during multiple pathological conditions, including chemotherapy, radiation, glucocorticoids, obesity, and diabetes, even earlier in life. Therefore, cellular senescence represents a unifying pathogenic mechanism driving skeletal and metabolic disorders. However, whether senescent bone marrow adipocytes (BMAds) are causal in mediating skeletal dysfunction has only recently been evaluated. RECENT FINDINGS: Despite evidence of BMAd senescence following glucocorticoid therapy, additional evidence for BMAd senescence in other conditions has thus far been limited. Because the study of BMAds presents unique challenges making these cells difficult to isolate and image, here we review issues and approaches to overcome such challenges, and present advancements in isolation and histological techniques that may help with the future study of senescent BMAds. Further insights into the roles of BMAd senescence in the pathogenesis of skeletal dysfunction may have important basic science and clinical implications for human physiology and disease.

Comparison of the value of adipose tissues in abdomen and lumbar vertebra for predicting disease activity in Crohn's disease: A preliminary study based on CSE-MRI.

BACKGROUND: To compare the value of adipose tissues in abdomen and lumbar vertebra for predicting Crohn's disease (CD) activity based on chemical shift encoded magnetic resonance imaging (CSE-MRI). METHODS: 84 CD patients were divided into remission, mild, and moderate-severely groups based on CD activity index (CDAI). Differences in different adipose parameters [subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), mesenteric fat index (MFI), and bone marrow fat fraction (BMFF)] and blood inflammatory indicators among three groups, as well as the correlation of above parameters and CDAI were analyzed. The areas under the receiver-operating characteristic curves (AUCs) for the parameters selected by multivariate logistic regression analysis for predicting active CD were calculated. RESULTS: There were no significant differences in VAT and MFI among three groups (both P > 0.05). The cross-sectional areas of SAT in moderate-severe group were significantly lower than those in remission group (P = 0.014). BMFF values of remission group were significantly higher than those in the mild and moderate-severe groups (both P < 0.001). BMFF was negatively correlated with CDAI (r = -0.595, P < 0.001). SAT exhibited no significant correlation with CDAI. Erythrocyte sedimentation rate (ESR) and BMFF were the independent predictors of CDAI. Both combined had a higher diagnostic efficacy for active CD with an AUC of 0.895. CONCLUSIONS: BMFF is the best marker for predicting CD activity in fat parameters of abdomen and lumbar vertebra based on CSE-MRI. The model based on BMFF and ESR has a high efficiency in predicting active CD. TRIAL REGISTRATION: No. 22 K164 (Registered 18-07-2022).

Assessment of Calcaneal Spongy Bone Magnetic Resonance Characteristics in Women: A Comparison between Measures Obtained at 0.3 T, 1.5 T, and 3.0 T.

BACKGROUND: There is a growing interest in bone tissue MRI and an even greater interest in using low-cost MR scanners. However, the characteristics of bone MRI remain to be fully defined, especially at low field strength. This study aimed to characterize the signal-to-noise ratio (SNR), T2, and T2* in spongy bone at 0.3 T, 1.5 T, and 3.0 T. Furthermore, relaxation times were characterized as a function of bone-marrow lipid/water ratio content and trabecular bone density. METHODS: Thirty-two women in total underwent an MR-imaging investigation of the calcaneus at 0.3 T, 1.5 T, and 3.0 T. MR-spectroscopy was performed at 3.0 T to assess the fat/water ratio. SNR, T2, and T2* were quantified in distinct calcaneal regions (ST, TC, and CC). ANOVA and Pearson correlation statistics were used. RESULTS: SNR increase depends on the magnetic field strength, acquisition sequence, and calcaneal location. T2* was different at 3.0 T and 1.5 T in ST, TC, and CC. Relaxation times decrease as much as the magnetic field strength increases. The significant linear correlation between relaxation times and fat/water found in healthy young is lost in osteoporotic subjects. CONCLUSION: The results have implications for the possible use of relaxation vs. lipid/water marrow content for bone quality assessment and the development of quantitative MRI diagnostics at low field strength.

Assessing osteoporosis in postmenopausal women: preliminary results using a novel lumbar spine phantom-based MRI scoring method.

OBJECTIVE: To develop a novel magnetic resonance imaging (MRI) phantom for producing F-score (for fat) and W-score (for water) and to evaluate the performance of these scores in assessing osteoporosis and related vertebral fractures. MATERIALS AND METHODS: First, a real-time phantom consisting of oil and water tubes was manufactured. Then, 30 female volunteers (age: 62.3 ± 6.3 years) underwent lumbar spine examination with MRI (using a novel phantom) and dual-energy X-ray absorptiometry (DXA), following ethical approval. MRI phantom-based F-score and W-score were defined by normalizing the vertebral signal intensities (SIs) by the oil and water SIs of the phantom on T1- and T2-weighted images, respectively. The diagnostic performances of the new scores for assessing osteoporosis and vertebral fractures were examined using receiver operating characteristic analysis and compared with DXA-measured areal bone mineral density (DXA-aBMD). RESULTS: The F-score and W-score were greater in the osteoporotic patients (3.93 and 2.29) than the non-osteoporotic subjects (3.05 and 1.79) and achieved AUC values of 0.85 and 0.74 (p < 0.05), respectively, when detecting osteoporosis. Similarly, F-score and W-score had greater values for the fracture patients (3.94 and 2.53) than the non-fracture subjects (3.14 and 1.69) and produced better AUC values (0.90 for W-score and 0.79 for F-score) compared to DXA-aBMD (AUC: 0.27, p < 0.05). In addition, the F-score and W-score had a strong correlation (r = 0.77; p < 0.001). CONCLUSION: A novel real-time lumber spine MRI phantom was developed, based upon which newly defined F-score and W-score were able to detect osteoporosis and demonstrated an improved ability over DXA-aBMD in differentiating patients with vertebral fractures.

Linking bone marrow fat with decreased bone mineral density among Indian patients with osteoporotic fracture.

Osteoporosis is a systemic skeletal disorder with low-bone mass causing micro-architectural deterioration and an increase in bone fragility and susceptibility to fractures. According to a worldwide report by IOF, 1 in 3 females and 1 in 5 males will experience fractures due to the osteoporotic changes in their bones. Fractures may be the first clinical manifestation of the disease. They have been causes for morbidity and mortality imposing economic burden to osteoporosis. Bone marrow fat is a negative regulator of bone-turnover and a key integrator of bone and energy metabolism. Hence we assess the bone marrow fat and BMD in patients with osteoporotic bone fractures. This cross-sectional study was conducted in 30 patients from the department of orthopaedic surgery. Biopsy samples were received from excised bone during surgery. Biochemical parameters and bone marrow fat were quantified by established methods. A negative correlation between BMD versus serum adiponectin, FGF21 and similar observation with BMD versus bone marrow fat is seen. Therefore, increased bone-marrow fat and adiponectin, FGF21 levels and decreased BMD in osteoporosis. This observation might be useful for prevention, management and therapeutic potential of osteoporosis. Based on our study findings, understand the bone-fat relationship to implications with low BMD in patients with osteoporosis.

Fat as a Friend or Foe of the Bone.

PURPOSE OF REVIEW: The objective of this review is to summarize the literature on the prevalence and diagnosis of obesity and its metabolic profile, including bone metabolism, focusing on the main inflammatory and turnover bone mediators that better characterize metabolically healthy obesity phenotype, and to summarize the therapeutic interventions for obesity with their effects on bone health. RECENT FINDINGS: Osteoporosis and fracture risk not only increase with age and menopause but also with metabolic diseases, such as diabetes mellitus. Thus, patients with high BMI may have a higher bone fragility and fracture risk. However, some obese individuals with healthy metabolic profiles seem to be less at risk of bone fracture. Obesity has become an alarming disease with growing prevalence and multiple metabolic comorbidities, resulting in a significant burden on healthcare and increased mortality. The imbalance between increased food ingestion and decreased energy expenditure leads to pathological adipose tissue distribution and function, with increased secretion of proinflammatory markers and harmful consequences for body tissues, including bone tissue. However, some obese individuals seem to have a healthy metabolic profile and may not develop cardiometabolic disease during their lives. This healthy metabolic profile also benefits bone turnover and is associated with lower fracture risk.

A novel deep learning method for large-scale analysis of bone marrow adiposity using UK Biobank Dixon MRI data.

Background: Bone marrow adipose tissue (BMAT) represents > 10% fat mass in healthy humans and can be measured by magnetic resonance imaging (MRI) as the bone marrow fat fraction (BMFF). Human MRI studies have identified several diseases associated with BMFF but have been relatively small scale. Population-scale studies therefore have huge potential to reveal BMAT's true clinical relevance. The UK Biobank (UKBB) is undertaking MRI of 100,000 participants, providing the ideal opportunity for such advances. Objective: To establish deep learning for high-throughput multi-site BMFF analysis from UKBB MRI data. Materials and methods: We studied males and females aged 60-69. Bone marrow (BM) segmentation was automated using a new lightweight attention-based 3D U-Net convolutional neural network that improved segmentation of small structures from large volumetric data. Using manual segmentations from 61-64 subjects, the models were trained to segment four BM regions of interest: the spine (thoracic and lumbar vertebrae), femoral head, total hip and femoral diaphysis. Models were tested using a further 10-12 datasets per region and validated using datasets from 729 UKBB participants. BMFF was then quantified and pathophysiological characteristics assessed, including site- and sex-dependent differences and the relationships with age, BMI, bone mineral density, peripheral adiposity, and osteoporosis. Results: Model accuracy matched or exceeded that for conventional U-Nets, yielding Dice scores of 91.2% (spine), 94.5% (femoral head), 91.2% (total hip) and 86.6% (femoral diaphysis). One case of severe scoliosis prevented segmentation of the spine, while one case of Non-Hodgkin Lymphoma prevented segmentation of the spine, femoral head and total hip because of T2 signal depletion; however, successful segmentation was not disrupted by any other pathophysiological variables. The resulting BMFF measurements confirmed expected relationships between BMFF and age, sex and bone density, and identified new site- and sex-specific characteristics. Conclusions: We have established a new deep learning method for accurate segmentation of small structures from large volumetric data, allowing high-throughput multi-site BMFF measurement in the UKBB. Our findings reveal new pathophysiological insights, highlighting the potential of BMFF as a novel clinical biomarker. Applying our method across the full UKBB cohort will help to reveal the impact of BMAT on human health and disease.

Demonstration of magnetic resonance Z-spectral imaging for fatty acid characterization of bone marrow at 3 T.

Magnetic resonance Z-spectral imaging (ZSI) has emerged as a new approach to measure fat fraction (FF). However, its feasibility for fat spectral imaging remains to be elucidated. In this study, a single-slice ZSI sequence dedicated to fat spectral imaging was designed, and its capability for fatty acid characterization was investigated on peanut oil samples, a multiple-vial fat-water phantom with varied oil volumes, and vertebral body marrow in healthy volunteers and osteoporosis patients at 3 T. The peanut oil spectrum was also recorded with a 400-MHz NMR spectrometer. A Gaussian-Lorentzian sum model was used to resolve water and six fat signals of the pure oil sample or four fat signals of the fat-water phantom or vertebral bone marrow from Z spectra. Fat peak amplitudes were normalized to the total peak amplitude of water and all fat signals. Normalized fat peak amplitudes and FF were quantified and compared among vials of the fat-water phantom or between healthy volunteers and osteoporosis patients. An unpaired student's t-test and Pearson's correlation were conducted, with p less than 0.05 considered statistically significant. The results showed that the peanut oil spectra measured with the ZSI technique were in line with respective NMR spectra, with amplitudes of the six fat signal peaks significantly correlated between the two methods (y = x + 0.001, r = 0.996, p < 0.001 under a repetition time of 1.6 s; and y = 1.026x - 0.003, r = 0.996, p < 0.001 under a repetition time of 3.1 s). Moreover, ZSI-measured FF exhibited a significant correlation with prepared oil volumes (y = 0.876x + 1.290, r = 0.996, p < 0.001). The osteoporosis patients showed significantly higher normalized fat peak amplitudes and FF in the L4 vertebral body marrow than the healthy volunteers (all p < 0.01). In summary, the designed ZSI sequence is feasible for fatty acid characterization, and has the potential to facilitate the diagnosis and evaluation of diseases associated with fat alterations at 3 T.

Assessment of Osteoporosis at the Lumbar Spine Using Ultrashort Echo Time Magnetization Transfer (UTE-MT) MRI.

BACKGROUND: Bone collagen-matrix contributes to the mechanical properties of bone by imparting tensile strength and elasticity, which can be indirectly quantified by ultrashort echo time magnetization transfer ratio (UTE-MTR) to assess osteoporosis. PURPOSE: To evaluate osteoporosis at the human lumbar spine using UTE-MTR. STUDY TYPE: Prospective. POPULATION: One hundred forty-eight-volunteers (age-range, 50-85; females, N = 90), including 81-normal bone density, 35-osteopenic, and 32-osteoporotic subjects. Ten additional healthy volunteers were recruited to study the intrasession reproducibility of the UTE-MT. FIELD STRENGTH/SEQUENCE: 3T/UTE-MT, short repetition-time adiabatic inversion recovery prepared UTE (STAIR-UTE), and iterative decomposition of water-and-fat with echo-asymmetry and least-squares estimation (IDEAL-IQ). ASSESSMENT: Fracture risk was calculated using Fracture-Risk-Assessment-Tool (FRAX). Region-of-interests (ROIs) were delineated on the trabecular area in the maps of bone-mineral-density, UTE-MTR, collagen-bound water proton-fraction (CBWPF), and bone-marrow fat fraction (BMFF). STATISTICAL TESTS: Linear-regression and Bland-Altman analysis were performed to assess the reproducibility of UTE-MTR measurements in the different scans. UTE-MTR and BMFF were correlated with bone-mineral-density using Pearson's regression and with FRAX scores using nonlinear regression. The abilities of UTE-MTR, CBWPF, and BMFF to discriminate between the three patient subgroups were evaluated using receiver-operator-characteristic (ROC) analysis and area-under-the-curve (AUC). Decision-curve-analysis (DCA) and clinical-impact curves were used to evaluate the value of UTE-MTR in clinical diagnosis. The DeLong test was used to compare the ROC curves. P-value <0.05 was considered statistically significant. RESULTS: Excellent reproducibility was obtained for the UTE-MT measurements. UTE-MTR strongly correlated with bone-mineral-density (r = 0.76) and FRAX scores (r = -0.77). UTE-MTR exhibited higher AUCs (≥0.723) than BMFF, indicating its superior ability to distinguish between the three patient subgroups. The DCA and clinical-impact curves confirmed the diagnostic value of UTE-MTR. UTE-MTR and CBWPF showed similar performance in correlation with bone-mineral-density and cohort classification. DATA CONCLUSION: UTE-MTR strongly correlates with bone-mineral-density and FRAX and shows great potential in distinguishing between normal, osteopenic, and osteoporotic subjects. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

The effects of PPARγ inhibitor on bones and bone marrow fat in aged glucocorticoid-treated female rats.

Progressive bone marrow (BM) fat accumulation is a common bone loss characteristic in older populations and glucocorticoid (GC)-induced skeletal destruction that is inversely associated with bone synthesis and directly associated with increased peroxisomal proliferator-activated receptor gamma (PPARγ) expression. PPARγ inhibition is an efficient therapeutic strategy for aged- and GC-related skeletal disorders. This study aimed to evaluate the effect of PPARγ inhibition on aged GC-treated female rats. It was hypothesised that bisphenol A diglycidyl ether (BADGE) could inhibit marrow adiposity and improve osteogenesis by inhibiting PPARγ, thereby preventing GC-induced osteoporosis (GIO). Female Sprague-Dawley rats (n = 32, age = 18 months) were randomly allocated to one of the following groups: (1) control, (2) BADGE (30 mg/kg/day, intraperitoneal), (3) methylprednisolone (MP; 30 mg/kg/day, subcutaneous), and (4) MP + BADGE. After eight weeks of treatment, bone density (BD) and trabecular bone microarchitectures were quantified by micro-computed tomography (CT), and BM adipocytes were quantified by histopathology. Additionally, mRNA and protein expression of adipogenic and osteogenic markers were quantified by reverse transcription-quantitative polymerase chain reaction. Furthermore, serum bone turnover biomarker levels were quantified by enzyme-linked immunosorbent assay. MP treatment led to marrow adipogenesis and bone deterioration. However, rats treated with MP + BADGE showed lower marrow adipogenesis, as indicated by smaller marrow adipocyte diameter, decreased density and area percentages, reduced expression of marrow adipogenic genes and proteins, improved BD and trabecular microarchitectures, increased expression of osteogenic genes and proteins, and higher levels of serum bone formation markers. These results were consistent with the differences observed between control and BADGE mono-treated rats. In conclusion, BADGE treatment attenuates BM adiposity and improves bone formation in aged GC-treated female rats by inhibiting PPARγ. Therefore, PPARγ might be a potential target for treating GIO in older populations.

Liver Fat, Bone Marrow Adipose Tissue, and Bone Mineral Density in Children With Overweight.

CONTEXT: Hepatic steatosis is associated with decreased bone mineral density (BMD). Bone marrow fat fraction (BMFF) could play a role in this relationship in children with obesity. OBJECTIVE: The objectives of this work were (i) to examine the relationship between the lumbar spine (LS) BMFF and BMD, and (ii) to explore the mediating role of LS-BMFF on the relationship between percentage hepatic fat with LS-BMD in preadolescent children with overweight/obesity. METHODS: Hepatic fat and LS-BMFF (magnetic resonance imaging) and areal LS-BMD (LS-aBMD, dual-energy x-ray absorptiometry) were measured in 106 children (aged 10.6 ± 1.1 years, 53.8% girls) with overweight/obesity. RESULTS: LS-BMFF was inversely associated with LS-aBMD (r = -0.313; P = .001) and directly related with percentage hepatic fat (r = 0.276; P = .005). LS-BMFF was significantly greater in children with than without hepatic steatosis (P = .003; Cohen's d: 0.61; 95% CI, -0.21 to 1.0), while no significant difference was seen between children with overweight and those with obesity (P = .604; Cohen's d: 0.16; 95% CI, -0.21-0.55). Mediating analysis indicated that LS-BMFF is an important mediator (50%) in the association of hepatic fat with lower LS-aBMD (indirect effect: ß = -.076; 95% CI, -0.143 to -0.015). CONCLUSION: These findings suggest that hepatic steatosis, rather than overall excess adiposity, is associated with greater bone marrow adipose tissue in preadolescent children with overweight/obesity, which in turn, is related to lower BMD. Hepatic steatosis could be a potential biomarker of osteoporosis risk, and a therapeutic target for interventions that aim to reduce not only hepatic steatosis, but for those designed to improve bone health in such children.

Associations between vertebral bone marrow fat and sagittal spine alignment as assessed by chemical shift-encoding-based water-fat MRI.

BACKGROUND: The relationship between sagittal spine alignment and vertebral bone marrow fat is unknown. We aimed to assess the relationship between vertebral bone marrow fat and sagittal spine alignment using chemical shift-encoding-based water-fat magnetic resonance imaging (MRI). METHODS: A total of 181 asymptomatic volunteers were recruited for whole spine X-ray and lumbar MRI. Spine typing was performed according to the Roussouly classification and measurement of vertebral fat fraction based on the chemical shift-encoding-based water-fat MRI. One-way analysis of variance (ANOVA) was used to analyze the differences in vertebral fat fraction between spine types. The post hoc least significant difference (LSD) test was utilized for subgroup comparison after ANOVA. RESULTS: Overall, the vertebral fat fraction increased from L1 to L5 and was the same for each spine type. The vertebral fat fraction was the highest in type 1 and lowest in type 4 at all levels. ANOVA revealed statistically significant differences in fat fraction among different spine types at L4 and L5 (P < .05). The post hoc LSD test showed that the fat fraction of L4 was significantly different (P < .05) between type 1 and type 4 as well as between type 2 and type 4. The fat fraction of L5 was significantly different between type 1 and type 3, between type 1 and type 4, and between type 2 and type 4 (P < .05). CONCLUSION: Our study found that vertebral bone marrow fat is associated with sagittal spine alignment, which may serve as a new additional explanation for the association of sagittal alignment with spinal degeneration.

Differences in specific abdominal fat depots between metabolically healthy and unhealthy children with overweight/obesity: The role of cardiorespiratory fitness.

OBJECTIVES: Fat depots localization has a critical role in the metabolic health status of adults. Nevertheless, whether that is also the case in children remains under-studied. Therefore, the aims of this study were: (i) to examine the differences between metabolically healthy (MHO) and unhealthy (MUO) overweight/obesity phenotypes on specific abdominal fat depots, and (ii) to further explore whether cardiorespiratory fitness plays a major role in the differences between metabolic phenotypes among children with overweight/obesity. METHODS: A total of 114 children with overweight/obesity (10.6 ± 1.1 years, 62 girls) were included. Children were classified as MHO (n = 68) or MUO. visceral (VAT), abdominal subcutaneous (ASAT), intermuscular abdominal (IMAAT), psoas, hepatic, pancreatic, and lumbar bone marrow adipose tissues were measured by magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20 m shuttle run test. RESULTS: MHO children had lower VAT and ASAT contents and psoas fat fraction compared to MUO children (difference = 12.4%-25.8%, all p < 0.035). MUO-unfit had more VAT and ASAT content than those MUO-fit and MHO-fit (difference = 34.8%-45.3%, all p < 0.044). MUO-unfit shows also greater IMAAT fat fraction than those MUO-fit and MHO-fit peers (difference = 16.4%-13.9% respectively, all p ≤ 0.001). In addition, MHO-unfit presented higher IMAAT fat fraction than MHO-fit (difference = 13.4%, p < 0.001). MUO-unfit presented higher psoas fat fraction than MHO-fit (difference = 29.1%, p = 0.008). CONCLUSIONS: VAT together with ASAT and psoas fat fraction, were lower in MHO than in MUO children. Further, we also observed that being fit, regardless of metabolic phenotype, has a protective role over the specific abdominal fat depots among children with overweight/obesity.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

OBJECTIVE: Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. DESIGN: Cross-sectional. METHODS: Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. RESULTS: Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). CONCLUSIONS: TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. SIGNIFICANCE STATEMENT: Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Impact of arm position on vertebral bone marrow proton density fat fraction in chemical-shift-encoded magnetic resonance imaging: a preliminary study.

Arm positions employed during magnetic resonance imaging (MRI) can affect magnetic field distribution, which may result in variability in proton density fat fraction (PDFF) measurements. This study evaluated the effect of arm position on lumbar PDFF measured using chemical-shift-encoded MRI (CSE-MRI). Fifteen healthy volunteers from a single-center underwent lumbar CSE-MRI at two different arm positions (side and elevated) using a single 3T scanner. Scans were performed twice in each position. PDFFs of the L1-L5 vertebrae were independently measured by two readers, and reader measurements were compared by calculating intraclass correlation coefficients (ICC). We compared PDFF measurements from two arm positions and from two consecutive scans using the Wilcoxon test and Bland-Altman analysis. Measurements from the two readers were in high agreement [ICC =0.999; 95% confidence interval (CI), 0.998-0.999]. No significant difference was observed between PDFFs from the first and second scans of all vertebrae for each reader (all P>0.05); however, PDFF for the elevated arm position was significantly higher than that for the side arm position (37.9-44.8% vs. 37.0-43.8%; all P<0.05), except at the L2 level by reader 2. The mean differences in PDFF measurements from the first and second scans [0.1%; 95% limits of agreement (LoA), -1.8% to 1.9%] and from the side arm and elevated arm positions (0.8%; 95% LoA, -1.6% to 3.2%) were small. In conclusion, these preliminary data suggest that different arm positions during CSE-MRI can slightly affect lumbar PDFF; however, the mean absolute differences were very small.

Changes in Vertebral Marrow Fat Fraction Using 3D Fat Analysis & Calculation Technique Imaging Sequence in Aromatase Inhibitor-Treated Breast Cancer Women.

Aromatase inhibitor (AI) is a cornerstone drug for postmenopausal women with estrogen receptor-positive early-stage breast cancer. Fat-bone interactions within the bone marrow milieu are growing areas of scientific interest. Although AI treatment could lead to deterioration of the skeleton, the association between AI medication and subsequent marrow adiposity remains elusive. A total of 40 postmenopausal, early-staged, and hormone receptor-positive breast cancer patients who underwent treatment with adjuvant AIs and 40 matched controls were included. Marrow proton density fat fraction (PDFF) at the L1-L4 vertebral bodies using 3D Fat Analysis & Calculation Technique imaging (FACT) sequence at 3.0T, bone mineral density (BMD) by dual-energy X-ray absorptiometry, and serum bone turnover biomarkers were determined at baseline and at 6 and 12 months. We found that, in comparison to baseline, an increase of type I collagen cross-linked telopeptide was detected at 12 months (P <0.05). From baseline to 12 months, the PDFF measured using FACT was greatly increased. At 12 months, the median percent change of PDFF (4.9% vs. 0.9%, P <0.05) was significantly different between the AI treatments and controls. The same trend was observed for the marrow PDFF at 6 months relative to the respective values at baseline. Although BMD values were significantly reduced after 12 months in AI-treated women, changes in BMD vs. baseline condition were not significantly different between the AI-treated and control groups [Δ BMD -1.6% to -1.8% vs. -0.3% to -0.6%, respectively, P > 0.05]. In the AI-treated group, Δ PDFF was associated with Δ BMD at the lumbar spine (r = -0.585, P < 0.001), but not in the controls. Taken together, over a 12-month period, spinal marrow fat content assessed with FACT sequence significantly increased in postmenopausal women with hormone-receptor-positive breast cancer receiving AI treatment.

A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis.

Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.

Gender- and Age-Associated Differences in Bone Marrow Adipose Tissue and Bone Marrow Fat Unsaturation Throughout the Skeleton, Quantified Using Chemical Shift Encoding-Based Water-Fat MRI.

Bone marrow adipose tissue (BMAT) is a dynamic tissue which is associated with osteoporosis, bone metastasis, and primary bone tumors. The aim of this study is to determine region-specific variations and age- and gender-specific differences in BMAT and BMAT composition in healthy subjects. In this cross-sectional study, we included 40 healthy subjects (26 male: mean age 49 years, range 22-75 years; 14 female: mean age 50 years, range 29-71) and determined the bone marrow signal fat fraction and bone marrow unsaturation in the spine (C3-L5), pelvis, femora, and tibiae using chemical shift encoding-based water-fat imaging (WFI) with multiple gradient echoes (mGRE). Regions of interest covered the individual vertebral bodies, pelvis and proximal epimetaphysis, diaphysis, and distal epimetaphysis of the femur and tibia. The spinal fat fraction increased from cervical to lumbar vertebral bodies (mean fat fraction ( ± SD or (IQR): cervical spine 0.37 ± 0.1; thoracic spine 0.41 ± 0.08. lumbar spine 0.46 ± 0.01; p < 0.001). The femoral fat fraction increased from proximal to distal (proximal 0.78 ± 0.09; diaphysis 0.86 (0.15); distal 0.93 ± 0.02; p < 0.001), while within the tibia the fat fraction decreased from proximal to distal (proximal 0.92 ± 0.01; diaphysis 0.91 (0.02); distal 0.90 ± 0.01; p < 0.001). In female subjects, age was associated with fat fraction in the spine, pelvis, and proximal femur (ρ = 0.88 p < 0.001; ρ = 0.87 p < 0.001; ρ = 0.63 p = 0.02; ρ = 0.74 p = 0.002, respectively), while in male subjects age was only associated with spinal fat fraction (ρ = 0.40 p = 0.04). Fat fraction and unsaturation were negatively associated within the spine (r = -0.40 p = 0.01), while in the extremities fat fraction and unsaturation were positively associated (distal femur: r = 0.42 p = 0.01; proximal tibia: r = 0.47, p = 0.002; distal tibia: r = 0.35 p = 0.03), both independent of age and gender. In conclusion, we confirm the distinct, age- and gender-dependent, distribution of BMAT throughout the human skeleton and we show that, contradicting previous animal studies, bone marrow unsaturation in human subjects is highest within the axial skeleton compared to the appendicular skeleton. Furthermore, we show that BMAT unsaturation was negatively correlated with BMAT within the spine, while in the appendicular skeleton, BMAT and BMAT unsaturation were positively associated.