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The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity
Open accessAbstract
Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.
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“As aging-related osteoporosis typically features low bone mass, microarchitectural alterations and bone marrow adipose tissue expansion40–42, our findings suggest that AD mice at a younger age recapitulate an aged skeletal phenotype.”
From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [40]
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Aging-related metabolic dysregulation in osteoporosis: mechanisms and therapeutic strategies
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Epigenetic transcriptional regulation of skeletal aging: The emerging role of m6A methylation
Song, C., Song, G., Zhang, S., Zhao, H., Wen, Z., Chen, Y., Chen, X., Liu, B., Ni, Q., & Fan, D.-P. (2026) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2026.101088 · Cited by 1
“While excessive adipose tissue can exert mechanical loading on bones, potentially inducing a compensatory increase in BMD, it concurrently promotes chronic low-grade inflammation and hormonal dysregulation which exert deleterious effects on bone homeostasis [6,7].”
Gong, M., Cao, T., Feng, X.-M., Ding, J., Fan, N., He, Y., & Yan, Y.-X. (2026) · NMCD. Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2026.104704 · Cited by 1
The Broken Cradle: Bone Marrow Stem Cell Niche Remodelling in Diabetes
Kum, J. J. Y., Howlett, C. J., & Khan, Z. A. (2025) · Stem Cell Reviews and Reports · doi:10.1007/s12015-025-11038-9 · Cited by 1
“Recent work has expanded this paradigm, as bone marrow adiposity is now recognized as a shared pathogenic mechanism linking osteoporosis, diabetes, and obesity, with marrow adipocytes actively secreting pro-inflammatory cytokines and adipokines that impair bone remodeling [ 104].”
Li, L.-W., Ma, Y., He, X., Cao, M.-Y., Zheng, E., & Leng, J. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-06826-4 · Cited by 1
“Obesity can lead to alterations in the cellular structure and molecular networks of the bone microenvironment, causing changes in the volume of trabeculae and bone cortex, while increasing the mass of bone marrow adipose tissue, which has a deleterious impact on bone mass and strength [29].”
Diabetes Burnout Among the Elderly With Type 2 Diabetes
Muntamah, U., Siyamti, D., & Sianturi, M. (2025) · Window of Health : Jurnal Kesehatan · doi:10.33096/woh.vi.2615 · Cited by 1
“25 These biomedical mechanisms, when combined with cultural expectations and gendered roles, highlight the multifactorial nature of diabetes burnout in elderly women in Indonesia.”
The association between body roundness index and lumbar marrow fat content in postmenopausal women.
Luo, P., Miao, Z.-Y., Guo, M.-Y., Qin, L., Xu, R., Lu, L., Wang, Y., & Li, G.-W. (2025) · Bone · doi:10.1016/j.bone.2025.117684 · Cited by 1
Polypharmacy and Bone Health in Patients with Type 2 Diabetes Mellitus: A Narrative Review
Kashmoola, I. O., Mohammad, S. H., & Alsaaty, M. (2025) · Journal of Bone Metabolism · doi:10.11005/jbm.25.975 · Cited by 1
“[22] Likewise, in patients with T2DM, CKD disturbs homeostasis of minerals resulting in bone and mineral disorders.”
Li, W., Wang, W., Zhang, M., Chen, Q., Li, F., & Li, S. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1518656 · Cited by 1
Xu, L., & Cao, Y. (2025) · Archives of Dermatological Research · doi:10.1007/s00403-025-03805-y · Cited by 1
Liu, X., Lou, Y., Chang, Z., Gu, C.-Y., Du, B., & Sun, G.-Q. (2025) · Clinics · doi:10.1016/j.clinsp.2025.100674 · Cited by 1
“7,27 In fact, osteoporosis and fracture risk increases along with age, independently from body weight, and, in menopause, the abrupt decrease of estrogen is the primary cause of osteoporosis.”
Opportunistic Computed Tomography
Reid, J., Tobin, J., McCrosson, M., Rivas, G., Rothwell, S., Ravinsky, R., & Lawrence, J. (2024) · Clinical Spine Surgery · doi:10.1097/bsd.0000000000001710 · Cited by 1
HDL levels modulate the impact of type 2 diabetes susceptibility alleles in older adults
Sullivan, S. O. ’., Hageh, C. A., Henschel, A., Chacar, S., Abchee, A., Zalloua, P., & Nader, M. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02039-7 · Cited by 1
“Indeed several chronic diseases and ageing share pathophysiological processes under-pinned by disruption of signal pathways at the molecular and cellular level [19–21].”
BackgroundAnalysis of Shared Mechanisms and Chinese Herbal Medicines Between Osteoporosis and Type 2 Diabetes
Yang, H., Luo, F., & Xiong, Z. (2023) · Pharmacognosy Magazine · doi:10.1177/09731296231215568 · Cited by 1
“Several factors, including hyperglycemia, oxidative stress, alterations in relevant cytokines and hormone levels, and the use of antidiabetic medications, have been implicated in the development of OP in individuals with T2D (Ali et al., 2022; Mo et al., 2022).”
BackgroundResearch Progress of Irisin in Obesity and Related Metabolic Diseases
张, 怡. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.13122830 · Cited by 1
Lai, C.-H., LI, Y.-T., Wu, T.-S., & Wu, C.-T. (2026) · Archives of Osteoporosis · doi:10.1007/s11657-026-01785-8
Barreno-Avila, J. D., Toapanta, K. E. S., Barreno, C. I. S., & Laura, G. G. I. (2026) · Impact Research Journal · doi:10.63380/irj.v4n2.2026.423
Peng, D.-C., Liang, C.-T., Li, Y.-X., Tan, J.-Q., Jiang, K.-L., Song, Z.-Y., Guo, X.-Y., & Wang, H.-K. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1927444
Bach, U., Uslar, T., Fünning, C., Tombak, G., Frenes, K., Walter, J., Gerber, P. A., Beuschlein, F., Konukoglu, E., Frauenfelder, T., et al. (2026) · Skeletal Radiology · doi:10.1007/s00256-026-05381-2
Yuan, R., Cui, Y.-J., Sun, J., Liu, H.-R., Guo, J., Qi, Y.-P., Du, J., & Li, M.-Q. (2026) · Cellular Signalling · doi:10.1016/j.cellsig.2026.112946
Zhan, Z., Zheng, K., Tu, Y., Lan, C., & Zheng, L. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1847739
Xia, Z.-H., Wei, L.-L., Ji, J.-J., Wu, S.-B., Sun, Y., Zong, G.-Y., Li, X.-Y., Ye, Y.-X., Zhang, Y., & Huang, D.-G. (2026) · Cell Biology and Toxicology · doi:10.1007/s10565-026-10223-x
“The influence of obesity on the skeleton is context dependent and not uniformly protective (Ali et al. 2022).”
Zhang, S., Wang, H., Zhao, C., Zhu, C., Li, X., Su, Z., Zou, J., Wang, C., Zhang, L., Yuan, Y., et al. (2026) · Stem Cell Research & Therapy · doi:10.1186/s13287-026-05068-4 · Cited by 1
“…observations indicate a significant positive correlation between increased bone marrow fat content, visceral fat accumulation, and decreased bone mineral density as well as bone loss, a phenotypic association that is a typical clinical feature of age-related and postmenopausal osteoporosis [32–34].”
Cao, H., Zhong, L.-J., Zhong, F.-T., Lin, R.-Y., Chen, H.-J., Huang, J.-Q., & Wei, W. (2026) · Journal of Endocrinological Investigation · doi:10.1007/s40618-026-02899-z
Impact of Clinical Factors on Bone Microarchitecture in Patients with Turner Syndrome
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“For instance, osteoporosis, the most prevalent bone remodeling disorder globally, often exhibits heightened marrow fat content [17,18].”
“One-stop-shop” medical imaging for osteoporosis and obese patients: a narrative review
Zhang, L., Lei, H., Li, Y., Yang, H., & Zhao, H. (2026) · Journal of Endocrinological Investigation · doi:10.1007/s40618-026-02810-w
“Obesity also regulates the expression of bone anabolic molecules and disrupts intracellular signaling cascades in bone tissue [12, 41].”
Zhu, Q., Wang, T., Lou, N., Yu, Z., Wang, Z., Guo, H., & Li, X. (2026) · Medicine · doi:10.1097/md.0000000000048107
“[47] A similar complex, nonlinear interaction was also indicated between age and weight in our study.”
循环炎症蛋白成纤维细胞生长因子21与骨质疏松以及骨折的关系研究
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“Specifically, increased bone marrow adiposity is a common feature of several bone disorders and has been associated with poor bone quality and a higher risk of fractures [20].”
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Çavuşoğlu, E., & Gün, M. (2025) · Nurse Education in Practice · doi:10.1016/j.nepr.2025.104559
Wang, J.-J., Hu, J., Xu, Y.-F., Dai, W., Wu, J.-C., & Cao, Y.-H. (2025) · Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy · doi:10.2147/dmso.s524654
“35 Glycated hemoglobin (HbA1c) has long been the gold standard for glycemic control and shown to be associated with various chronic complications of DM, such as diabetic retinopathy, diabetic nephropathy, and diabetic peripheral neuropathy.”
Metadata
- Authors
- Ali, D., Tencerova, M., Figeac, F., Kassem, M., & Jafari, A.
- Affiliations
- University of Southern Denmark (DK)
- University of Copenhagen (DK)
- Corresponding author
- Ali, Dalia
- Jafari, Abbas
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2022-09-15
- Volume
- 13
- Pages
- 981487-981487
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC9520254
- OpenAlex
- W4295942629
- Cited by
- 122
- References
- 220
- Citations by year
- 2026: 25 · 2025: 42 · 2024: 43 · 2023: 10 · 2022: 2
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, cc-by)
- Funders
- Olav Thon Stiftelsen
- Grantová Agentura České Republiky
- Novo Nordisk Fonden
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- osteoporosis, bone marrow adipose tissue, bone marrow adiposity, obesity, type 2 diabetes, aging, bone fragility, bone homeostasis, bone formation, fracture risk, postmenopausal women, older men
- MeSH terms
- Aged, Aging, Bone Marrow, Diabetes Mellitus, Type 2, Female, Humans, Male, Obesity, Osteoporosis, Adiposity, Fractures, Bone
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