# Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the development of Charcot arthropathy

## TL;DR

Low levels of BMP-2 in diabetic patients with neuropathy are linked to a higher risk of developing Charcot arthropathy, a condition involving foot fractures.

## Contribution

This study identifies BMP-2 as a novel risk factor for Charcot arthropathy in diabetes patients with peripheral neuropathy.

## Key findings

- Charcot patients had consistently low BMP-2 levels compared to controls for 24 months.
- BMP-7 levels increased in Charcot patients after treatment, possibly compensating for low BMP-2.
- Low BMP-2 is associated with impaired bone repair and increased fracture risk in these patients.

## Abstract

Diabetes patients with peripheral neuropathy run increased risk of developing Charcot arthropathy (Charcot), often associated with foot fractures. Bone morphogenic proteins (BMPs) are among the most important regulators of bone homeostasis and fracture repair but have not been investigated in the pathophysiology of Charcot. The current study aims to address this issue.

Sixteen patients diagnosed with active Charcot were treated with total contact cast (TCC) and monitored during 24 months (M) with repeated plain radiographs and magnetic resonance imaging (MRI). Plasma was sampled at 9 occasions and analyzed for BMP-1, BMP-2, BMP-3, BMP-4, BMP-6, BMP-7 and BMP-9 as well as for basal laboratory data. Fifteen diabetes patients with peripheral neuropathy and fifteen healthy participants without diabetes served as controls.

All Charcot patients had pathologically low BMP-2 level at inclusion which remained suppressed throughout the 2-year follow-up as defined by being lower than 2 standard deviations (SD) of BMP-2 in healthy controls (p < 0.001) and in diabetes patients with neuropathy without Charcot (p < 0.002). BMP-2 did not differ between the control groups. BMP-7 in Charcot patients increased significantly 6–12 months following TCC treatment. Other BMPs showed no significant differences between the groups at any point during the follow-up.

Low BMP-2 in diabetes patients with neuropathy is associated with increased risk of developing Charcot fractures due to the critical role of BMP-2 for the initiation of bone repair. BMP-7 appears to partly compensate for the lack of response by other osteogenic BMPs during fracture repair in Charcot patients.

The online version contains supplementary material available at 10.1007/s00592-025-02573-5.