# Fat Mass Influences Femur Bone Strength and Geometry Parameters, but Not Bone Mineral Density, in Autoimmune Diabetes: A Pilot Study

**Authors:** Renata Risi, Rocco Amendolara, Vahideh Abedi, Francesco De Vita, Federica Barbaro, Angela Balena, Mikiko Watanabe, Daniela Luverà, Angelo Lauria Pantano, Luca D'Onofrio, Raffaella Buzzetti, Ernesto Maddaloni

PMC · DOI: 10.1002/dmrr.70149 · Diabetes/Metabolism Research and Reviews · 2026-03-19

## TL;DR

Excess fat in people with autoimmune diabetes weakens femur bone strength and geometry, even though bone mineral density remains unaffected.

## Contribution

This pilot study identifies the negative impact of fat mass on bone geometry and strength in autoimmune diabetes, beyond bone mineral density.

## Key findings

- Total Fat% negatively correlates with bone strength and geometry parameters at femur sites after adjusting for confounders.
- Visceral adipose tissue independently predicts worse bone geometry markers at IT and NN femur sites.
- Lean mass positively associates with bone structural parameters at IT and FS femur sites.

## Abstract

Autoimmune diabetes (AD) increases fracture risk. Overweight worsens bone health despite increasing bone mineral density (BMD). This study examines how adiposity influences BMD and Dual X‐Ray Absorptiometry (DXA)‐derived parameters of bone geometry and strength in AD.

DXA scan was used to assess body mass composition, BMD, trabecular bone score (TBS), and hip structural analysis (HSA)‐derived parameters at narrow neck (NN), intertrochanteric (IT) and femur shaft (FS) in 52 normal weight adults with AD and 51 with AD and overweight. Multilinear regression models were used to adjust the associations for age, sex, BMI, HbA1c%, lean mass % and physical activity.

Total Fat% was negatively associated with markers of bone strength and geometry at different femur sites, including cross‐sectional moment of inertia (CSMI) and section modulus (Z) at IT site, cross‐sectional area (CSA), CSMI and Z at the FS site and CSMI, buckling ratio (BR) and Z at the NN site, after adjustment for confounders. Visceral adipose tissue emerged as a negative independent predictor of BR at IT and NN. Lean mass % was positively associated with TBS, CSA, CSMI and Z at the IT and FS sites. Negative predictors of bone health were female sex and age.

In adults with AD, excess fat mass, including visceral adiposity, is independently associated with impaired hip bone strength and geometry at the femur shaft. These findings highlight the limitations of BMD alone in evaluating bone health in people with AD and overweight, emphasising the negative skeletal effects of adiposity.

## Full-text entities

- **Genes:** SLC30A8 (solute carrier family 30 member 8) [NCBI Gene 169026] {aka ZNT8, ZnT-8}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, ADIPOQ (adiponectin, C1Q and collagen domain containing) [NCBI Gene 9370] {aka ACDC, ACRP30, ADIPQTL1, ADPN, APM-1, APM1}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, FAT1 (FAT atypical cadherin 1) [NCBI Gene 2195] {aka CDHF7, CDHR8, FAT, ME5, hFat1}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, ERCC8 (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) [NCBI Gene 1161] {aka CKN1, CSA, UVSS2}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, SOST (sclerostin) [NCBI Gene 50964] {aka CDD, DAND6, SOST1, VBCH}, LEP (leptin) [NCBI Gene 3952] {aka LEPD, OB, OBS}
- **Diseases:** Fat mass excess (MESH:C536030), insulin deficiency (MESH:D007333), CSMI (MESH:D014593), OW (MESH:D050177), hip fractures (MESH:D006620), bone (MESH:D001847), type 2 diabetes (MESH:D003924), obesity (MESH:D009765), cancer (MESH:D009369), osteoporosis (MESH:D010024), fatty (MESH:D008067), AD (MESH:D003922), BMD (MESH:D001851), psychiatric illnesses (MESH:D001523), Diabetes (MESH:D003920), frailty (MESH:D000073496), hepatic cirrhosis (MESH:D008103), visceral adiposity (MESH:D007418), adiposity (MESH:D018205), smoker (MESH:C000719328), inflammation (MESH:D007249), bone fractures (MESH:D050723), end-stage renal disease (MESH:D007676)
- **Chemicals:** TG (MESH:D013866), denosumab (MESH:D000069448), bisphosphonates (MESH:D004164), BR (-), Cholesterol (MESH:D002784), teriparatide (MESH:D019379), creatinine (MESH:D003404), AGEs (MESH:D017127), C peptide (MESH:D002096), TC (MESH:D013667), Vitamin D. (MESH:D014807), Triglycerides (MESH:D014280), FFA (MESH:D005230), romosozumab (MESH:C557282), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13000683/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC13000683/full.md

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Source: https://tomesphere.com/paper/PMC13000683