# Diabetic Neuropathy Is Associated With Lower Bone Mineral Density and Higher Fall Risk in Young Elderly Adults With Type 2 Diabetes

**Authors:** Luca D'Onofrio, Rocco Amendolara, Antonio Siena, Alessandro Latino, Renata Risi, Angela Balena, Simona Zampetti, Davide Masi, Marianna Alfonsi, Barbara La Scaleia, Mikiko Watanabe, Myrka Zago, Francesco Lacquaniti, Ernesto Maddaloni, Raffaella Buzzetti

PMC · DOI: 10.1002/dmrr.70135 · Diabetes/Metabolism Research and Reviews · 2026-02-08

## TL;DR

Diabetic neuropathy in type 2 diabetes is linked to lower bone density and higher fall risk in young elderly adults.

## Contribution

This study identifies a novel association between diabetic neuropathy, bone mineral density, and fall risk in type 2 diabetes patients.

## Key findings

- Diabetic neuropathy is associated with significantly lower bone mineral density at the femoral neck and total femur.
- Painful neuropathy at baseline increases the risk of falls over a 4-year follow-up.
- Insulin resistance markers are linked to decreased bone quality in patients with diabetic neuropathy.

## Abstract

Diabetic neuropathy (DN) is a recognised risk factor for fragility fractures. However, the mechanisms linking DN, bone health, and falling risk remain unclear. We aimed to assess bone health and risk of falls, with their contributing factors, in young elderly patients with type 2 diabetes (T2D) and mild‐to‐moderate DN.

We enrolled 144 subjects with T2D, excluding those with severe DN (neuropathy disability score ‐NDS‐ ≥ 9) or fracture history. Clinical and biochemical data were collected, including surrogate markers of insulin resistance, such as the triglycerides/HDL (TG/HDL) ratio and triglycerides/glucose (TyG) index. Bone mineral density (BMD) and trabecular bone score (TBS) were evaluated using DXA scans. Falls were self‐recorded prospectively over 4 years using diaries.

Subjects with DN (27%) had higher BMI (p = 0.036), fasting blood glucose (p = 0.04), serum triglycerides (p = 0.016), TG/HDL ratio (p = 0.012) and TyG index (p = 0.003) compared with those without DN. After adjustment for gender, age, BMI, HbA1c, TyG index and TG/HDL ratio, subjects with DN showed significantly lower BMD at the femoral neck (0.702 [0.638–0.850] g/cm2 vs. 0.789 [0.717–0.860] g/cm2, p = 0.015) and total femur (0.890 [0.820–1.055] g/cm2 vs. 0.983 [0.889–1.076] g/cm2, p = 0.027). No differences were observed in spine BMD or TBS. However, TBS was negatively correlated with the TG/HDL ratio (r = −0.215, p = 0.013) and visceral adipose tissue (r = −0.310, p < 0.001). After 4 years of follow‐up, subjects with painful neuropathy at baseline had a higher rate of falls (p = 0.011).

DN is associated with decreased BMD and increased risk of falls. Among factors associated with DN, insulin resistance was also associated with decreased bone quality.

## Linked entities

- **Diseases:** Diabetic neuropathy (MONDO:0006626), Type 2 diabetes (MONDO:0005148)

## Full-text entities

- **Genes:** INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** hypertriglyceridemia (MESH:D015228), blindness (MESH:D001766), stability (MESH:D043171), vertigo (MESH:D014717), pain (MESH:D010146), itching (MESH:D011537), impaired balance (MESH:D060825), central nervous system disorders (MESH:D002493), bone fractures (MESH:D050723), hypoesthesia (MESH:D006987), dizziness (MESH:D004244), diabetic vascular complications (MESH:D003925), muscle weakness (MESH:D018908), bone impairment (MESH:D001847), T1D (MESH:D003922), BD (MESH:D001528), Insulin resistance (MESH:D007333), Diabetes (MESH:D003920), fragility fractures (MESH:D005600), Falls (MESH:C537863), heart failure (MESH:D006333), allodynia (MESH:D006930), death (MESH:D003643), cancer (MESH:D009369), Painful neuropathy (MESH:C564945), Neuropathy (MESH:D009422), Anti (MESH:D006679), DN (MESH:D003929), dementia (MESH:D003704), T2D (MESH:D003924), foot ulceration (MESH:D016523), nystagmus (MESH:D009759), impairment in bone metabolism (MESH:D001851), bone fragility (MESH:C536063), TBS (MESH:D000236), neuropathic conditions (MESH:D009437), osteoporosis (MESH:D010024), loss of balance (MESH:D016388), stroke (MESH:D020521), obesity (MESH:D009765), reduced bone turnover (MESH:D001523), vestibular migraine (MESH:D008881), amputation (MESH:C565682), diabetic foot complications (MESH:D017719)
- **Chemicals:** Triglycerides (MESH:D014280), Fenofibrate (MESH:D011345), Exenatide (MESH:D000077270), TG (MESH:D013866), metformin (MESH:D008687), DN4 (-), creatinine (MESH:D003404), lipid (MESH:D008055), glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC12883200/full.md

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Source: https://tomesphere.com/paper/PMC12883200