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Low bone morphogenic protein-2 in diabetes patients with peripheral neuropathy is a correlated risk factor for the
Jean Cassuto1,2, Agnetha Folestad3, Martin Ålund4
1Orthopedic Research Unit, Department of Orthopedic Surgery, Sahlgrenska University Hospital, Mölndal, 43180, Sweden. jean.cassuto@aniv.gu.se.
Aims:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Low bone morphogenic protein-2 (BMP-2) levels are linked to Charcot foot fractures in diabetes patients. BMP-7 may help bone repair, but suppressed BMP-2 indicates a higher fracture risk.
Area of Science:
- Orthopedics and Sports Medicine
- Endocrinology and Metabolism
- Bone Biology and Regenerative Medicine
Background:
- Diabetes patients with peripheral neuropathy face an elevated risk of Charcot arthropathy (Charcot), often leading to foot fractures.
- Bone morphogenic proteins (BMPs) are crucial for bone homeostasis and fracture healing, yet their role in Charcot pathophysiology remains unexplored.
Purpose of the Study:
- To investigate the role of various Bone Morphogenic Proteins (BMPs) in the development and progression of Charcot arthropathy in diabetes patients.
Main Methods:
- A 24-month observational study involving 16 active Charcot patients treated with total contact casting (TCC).
- Regular monitoring via plain radiographs and MRI, with plasma BMP levels (BMP-1, -2, -3, -4, -6, -7, -9) analyzed at 9 intervals.
- Comparison with 15 diabetes patients with neuropathy (no Charcot) and 15 healthy controls.
Main Results:
- Charcot patients exhibited pathologically low BMP-2 levels at baseline, remaining suppressed throughout the 2-year follow-up compared to both control groups (p < 0.001).
- BMP-2 levels did not differ between healthy and diabetes-with-neuropathy control groups.
- A significant increase in BMP-7 levels was observed in Charcot patients between 6-12 months post-TCC treatment; other BMPs showed no significant group differences.
Conclusions:
- Suppressed BMP-2 levels in diabetes patients with neuropathy are associated with an increased risk of Charcot fractures, highlighting BMP-2's critical role in initiating bone repair.
- BMP-7 may play a compensatory role in fracture repair in Charcot patients, potentially mitigating the effects of other osteogenic BMP deficiencies.
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