Postmenopausal osteoporosis (PMOP) is a major health problem affecting millions of women worldwide. PMOP patients are often accompanied by abnormal accumulation of bone marrow adipose tissue (BMAT). BMAT is a critical regulator of bone homeostasis, and an increasing BMAT volume is negatively associated with bone mass reduction or fracture. BMAT regulates bone metabolism via adipokines, cytokines and the immune system, but the specific mechanisms are largely unknown. This review emphasizes the impact of estrogen deficiency on bone homeostasis and BMAT expansion, and the mechanism by which BMAT regulates PMOP, providing a promising strategy for targeting BMAT in preventing and treating PMOP.

Bone-fat balance is crucial to maintain bone homeostasis. As common progenitor cells of osteoblasts and adipocytes, bone marrow mesenchymal stem cells (BMSCs) are delicately balanced for their differentiation commitment. However, the exact mechanisms governing BMSC cell fate are unclear. In this study, we discovered that fibroblast growth factor 9 (Fgf9), a cytokine expressed in the bone marrow niche, controlled bone-fat balance by influencing the cell fate of BMSCs. Histomorphology and cytodifferentiation analysis showed that Fgf9 loss-of-function mutation (S99N) notably inhibited bone marrow adipose tissue (BMAT) formation and alleviated ovariectomy-induced bone loss and BMAT accumulation in adult mice. Furthermore, in vitro and in vivo investigations demonstrated that Fgf9 altered the differentiation potential of BMSCs, shifting from osteogenesis to adipogenesis at the early stages of cell commitment. Transcriptomic and gene expression analyses demonstrated that FGF9 upregulated the expression of adipogenic genes while downregulating osteogenic gene expression at both mRNA and protein levels. Mechanistic studies revealed that FGF9, through FGFR1, promoted adipogenic gene expression via PI3K/AKT/Hippo pathways and inhibited osteogenic gene expression via MAPK/ERK pathway. This study underscores the crucial role of Fgf9 as a cytokine regulating the bone-fat balance in adult bone, suggesting that FGF9 is a potentially therapeutic target in the treatment of osteoporosis.

To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping.
A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc.
VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05).
In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

OBJECTIVE: Low bone mineral density (BMD) significantly increases the risk of complications in patients undergoing spinal fusion. Existing evidence indicates that traditional dual-energy x-ray absorptiometry (DEXA) and quantitative CT (QCT) screening are underutilized in spine surgery. The MRI-based vertebral bone quality (VBQ) score provides a tool for primary screening of bone density. The validity of this score as a predictor across sexes has not been investigated. This study aimed to explore the effect of sex on the diagnostic efficacy of the VBQ in predicting osteopenia/osteoporosis and whether a sex-specific threshold exists.
METHODS: In this retrospective cohort study, patients who underwent lumbar fusion at a tertiary care center were reviewed. VBQ was obtained by noncontrast T1-weighted MRI. Patients were stratified according to sex and bone density. Data were analyzed between the groups. Pearson correlation analysis and linear regression were used to analyze the correlation between the VBQ and DEXA T values. Receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC) calculation, was used to evaluate the predictive performance of VBQ for low BMD in both sexes.
RESULTS: A total of 271 patients (92 male, 179 female patients) were analyzed. The correlation coefficient between VBQ and the lowest T value was -0.40 for male and -0.554 for female patients. In comparing the bone density subgroups, among male patients a significant difference in the VBQ scores was observed only between the normal and osteoporosis subgroups (p = 0.012). VBQ demonstrated statistically significant differences among female patients across all three subgroups (p < 0.001). The ROC analysis revealed that the predictive performance of VBQ in detecting low BMD was more consistent with the gold-standard DEXA results in female than in male patients (AUC 0.647 vs AUC 0.823, p = 0.02). The optimal thresholds were similar in both sexes.
CONCLUSIONS: Compared with male patients, VBQ has better discrimination between female patients with low BMD and those with normal bone density. Although the correlation between VBQ and bone density is weaker in male than in female patients, the optimal thresholds are similar in both sexes.

BACKGROUND: Accumulation of bone marrow adipose tissue (BMAT) is always seen in osteoporosis induced by estrogen deficiency. Herein, we aimed to investigate the mechanisms and consequences of this phenomenon by establishing a mouse model of osteoporosis caused by ovariectomy (OVX)-mimicked estrogen deficiency.
METHODS: Micro-CT, osmium tetroxide staining, and histological analyses were performed to examine the changes in bone microstructure, BMAT and white adipose tissue (WAT) in OVX mice compared to sham mice. The osteogenesis and adipogenesis of primary bone marrow stromal cells (BMSCs) isolated from sham and OVX mice were compared in vitro. The molecular phenotypes of BMAT and WAT were determined and compared by quantitative PCR (qPCR). Bone marrow adipocyte-conditioned medium (BMA CM) was prepared from sham or OVX mice for coculture assays, and BMSCs or bone marrow monocytes/macrophages (BMMs) were isolated and subjected to osteoblast and osteoclast differentiation, respectively. Cell staining and qPCR were used to assess the effects of BMAT on bone metabolism.
RESULTS: OVX-induced estrogen deficiency induced reductions in both cortical and trabecular bone mass along with an expansion of BMAT volume. At the cellular level, loss of estrogen inhibited BMSC osteogenesis and promoted BMSC adipogenesis, whereas addition of estradiol exerted the opposite effects. In response to estrogen deficiency, despite the common proinflammatory molecular phenotype observed in both fat depots, BMAT, unlike WAT, unexpectedly exhibited an increase in adipocyte differentiation and lipolytic activity as well as the maintenance of insulin sensitivity. Importantly, BMAT, but not WAT, presented increased mRNA levels of both BMP receptor inhibitors (Grem1, Chrdl1) and Rankl following OVX. In addition, treatment with BMA CM, especially from OVX mice, suppressed the osteoblast differentiation of BMSCs while favoring the osteoclast differentiation of BMMs.
CONCLUSIONS: Our study illustrates that OVX-induced estrogen deficiency results in bone loss and BMAT expansion by triggering imbalance between the osteogenesis and adipogenesis of BMSCs. Furthermore, expanded BMAT, unlike typical WAT, may negatively regulate bone homeostasis through paracrine inhibition of osteoblast-mediated bone formation and promotion of osteoclast-mediated bone resorption.

This study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders.
The study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated.
On average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253-0.263, p = 0.014-0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups (p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 (p = 0.038-0.040), 1.369 (p = 0.030-0.042), and 1.002 (p = 0.040-0.044) for each unit increase, respectively.
BMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders.

OBJECTIVE: To investigate the age and gender differences in vertebral bone marrow adipose tissue (BMAT) and volumetric bone mineral density (vBMD).
METHODS: A total of 427 healthy adults, including 175 males (41 %) and 252 females (59 %) with an age range of 21-82 years, underwent MRI and quantitative CT examinations of the lumbar spine (L2-L4), and the corresponding BMAT and vBMD values were measured. The age-related progressions of BMAT and vBMD in men and women were evaluated and compared.
RESULTS: In males, vertebral BMAT rose gradually throughout life, while in females, BMAT increased sharply between 41 and 60 years of age. In participants aged < 40 years, BMAT was greater in males compared to females (p ≤ 0.01), while after the age of 60, BMAT was higher in females (p < 0.05). In males, vBMD decreased gradually with age, while in females, there was a sharp decrease in vBMD after the age of 40 years. At age of 31-40 years, vBMD was higher in females (P < 0.002), while at age > 60 years, vBMD was higher in males (61-70 years, P < 0.01; > 70 years, P = 0.02).
CONCLUSIONS: We found significant age and gender differences in lumbar BMAT and vBMD. These findings will help to improve our understanding of the interaction between bone marrow fat content and bone mineral density in the ageing process.

Bone marrow (BM) is a heterogeneous niche where bone marrow stromal cells (BMSCs), osteoblasts, osteoclasts, adipocytes, hematopoietic cells, and immune cells coexist. The cellular composition of BM changes with various pathophysiological states. A reduction in osteoblast number and a concomitant increase in adipocyte number in aging and pathological conditions put bone marrow adipose tissue (BMAT) into spotlight. Accumulating evidence strongly supports that an overwhelming production of BMAT is a major contributor to bone loss disorders. Therefore, BMAT-targeted therapy can be an efficient and feasible intervention for osteoporosis. However, compared to blocking bone-destroying molecules produced by BMAT, suppressing BMAT formation is theoretically a more effective and fundamental approach in treating osteoporotic bone diseases. Thus, a deep insight into the molecular basis underlying increased BM adiposity during pathologic bone loss is critical to formulate strategies for therapeutically manipulating BMAT. In this review, we comprehensively summarize the molecular mechanisms involved in adipocyte differentiation of BMSCs as well as the interaction between bone marrow adipocytes and osteoclasts. More importantly, we further discuss the potential clinical implications of therapeutically targeting the upstream of BMAT formation in bone loss diseases.

Although a growing body of research shows that the bone marrow adipose tissue (BMAT) may play an essential role in bone inflammation and energy metabolism, available noninvasive methods for distinguishing different fatty acids in BMAT are still limited, in spite of their potential to provide novel biomarkers for bone related diseases.
To assess the ability of a localized intermolecular double quantum coherence (iDQC) spectroscopy sequence to resolve more fatty acid peaks than conventional MR spectroscopy (MRS), like polyunsaturated fatty acids (PUFA), from the human BMAT in the presence of trabecular bone; To preliminarily investigate whether the fatty acids composition is different between different regions and groups.
Compared with conventional MRS results, additional four fatty acids peaks were well resolved using the proposed method in human BMAT in the presence of trabecular bone. In addition, a different fat composition was found between distal femur and proximal tibia: fat was more unsaturated (vinyl, *p < 0.01; diallylic, *p < 0.01) in distal femur bone marrow than in proximal tibia, and this higher unsaturation level was caused by PUFA (r = 0.67, diallylic, *p < 0.01). No significant difference in fatty acid composition were found either between left and right legs, or between female and male in the healthy young subjects studied.
This study demonstrated that the unsaturated fatty acids information of human BMAT in the presence of trabecular bone can be clearly identified with the localized iDQC at 3 T. The resolved peaks, especially PUFA, may serve as additional diagnostic biomarkers for BMAT related diseases in the future.

The accuracy of QCT measurements of lumbar spine trabecular volumetric bone mineral density (vBMD) is decreased due to differences in the amount of bone marrow adipose tissue (BMAT).
To correct vBMD measurements for differences in marrow composition and investigate the true relationship between vBMD and BMAT.
Cross-sectional study.
University teaching hospital.
Healthy Chinese subjects (233 women, 167 men) aged between 21 and 82 years.
vBMD and BMAT were measured using QCT (120 kV) and chemical shift-encoded MRI of the L2-L4 vertebrae. vBMD measurements were standardized to the European Spine Phantom (ESP) and corrected for differences in BMAT. Linear regression was used to analyze BMAT, ESP adjusted vBMD (vBMDESPcorr) and BMAT corrected vBMD (vBMDBMATcorr) against age and corrected vBMD against BMAT.
BMAT in the L2-L4 vertebral bodies increased with age in both sexes, with a faster rate of change in women compared with men (0.54%/year vs. 0.27%/year, P < 0.0001). After vBMD measurements were corrected for BMAT there were statistically significant changes in the slope of the regression line with age in both sexes (women: -3.00 ± 0.13 vs. -2.57 ± 0.11 mg/cm3/year, P < 0.0001; men: -1.92 ± 0.15 vs. -1.70 ± 0.14 mg/cm3/year, P < 0.0001). When vBMDBMATcorr was plotted against BMAT, vBMD decreased linearly with increasing BMAT in both sexes (women: -3.30 ± 0.18 mg/cm3/%; men: -2.69 ± 0.25 mg/cm3/%, P = 0.048).
Our approach reveals the true relationship between vBMD and BMAT and provides a new tool for studying the interaction between bone and marrow adipose tissue.