Deciphering Bone Microarchitecture in Diabetic Charcot Neuroarthropathy of Foot: A Case Control Study

Abstract

Introduction: Charcot neuroarthropathy (CNO) of foot characterised by an increased bone turnover denoted by serological markers of bone resorption. However, histological characteristics of foot bones in people with CNO are not well elucidated.

Methods: The foot bone samples were collected from patients who had either surgical reconstruction or below-knee amputations for chronic CNO foot (n = 10, Group A), unsalvageable diabetic foot ulcer (n = 16, Group B), and non-diabetic healthy controls following road traffic accident (n = 16, group C). Calcaneum bones retrieved were processed and sections (Haemotoxylin and Eosin, Masson-Goldner stain) evaluated for quantitative histopathological parameters including bony trabeculae number, trabeculae thinning, osteoclast number, Howship's lacunae, and Haversian canal.

Results: The mean age of participants in the CNO group was 61.6 ± 5.0 and 62.9 ± 6.5 years in diabetic neuropathy group with duration of diabetes 13.1 ± 6.8 and 14.1 ± 9.1 years with HbA1c of 7.6 ± 1.8% and 8.7 ± 2.6 in group A and B, respectively. We observed that normal bone trabeculae were 15% (10-37.5) in group A and 60% (47.5-82.5) in group B as compared to controls (P = <0.001). Thin bone trabeculae (%) were observed in 10% (3.5-77.5) and 7.5% (0-30), P =<0.001), with increased Howship's lacunae number (1.5 [0.25-2] and 1 [0-2.25] (P = <0.001)) and increased osteoclast number in group A and B as compared to healthy controls.

Conclusions: There is an increased bone resorption in CNO causing thinning of bone trabeculae secondary to increased osteoclast numbers and Howship's lacunae in CNO of foot. Anti-resorptive therapies that target osteoclast activity may be an appealing treatment option for diabetic CNO of foot.

Keywords: BTM; CNO; DFU; H and E; histopathology.

Figure 1

Characteristics of the study population in three groups

Figure 2

(1) a-c (H and E stain) Pictures of Charcot group show diffuse thin fragmented bony trabeculae. Dense lymphomononuclear inflammation in the inter-trabecular spaces along with thinning of bone and Howship lacunae formation (×20). Cluster of osteoclastic cells (black arrow, c) residing at the resorption pit (×20. d-f (Masson Goldner Stain) showing diffuse thin bony trabeculae (×10) and osteoblastic rimming (black arrow, f) and Haversian canal formation (×20 magnification). (2) DFU group: g-i (H and E stain) (×4 and × 10) Thin and thick bone trabeculae, Haversian canal, and occasional Howship lacunae (black arrow, H), fragmentation of bone. j-l (Goldner stain) (×4 and × 10) Thin bone trabeculae, fragmentation of bone. (3) Control group: m-o (H and E stain) (×4 and × 10) normal bone architecture, well-organised lamellar bone, and Haversian canal and p-r (Goldner stain) (×4 and × 10) normal bone trabeculae, fragmentation absent. DFU = Diabetic foot ulcer