# Correlation of Histopathological Profiles With Clinical and Radiological Risk Factors in Long-Bone Nonunion: A Prospective Cohort Study

## TL;DR

This study shows that examining tissue samples from non-healing bone fractures provides better insight into healing potential than imaging alone, helping guide treatment decisions.

## Contribution

The study demonstrates that histopathological evaluation adds critical biological insights beyond radiological classification in predicting healing outcomes for long-bone nonunions.

## Key findings

- Viable bone histology was strongly associated with complete healing in 83.3% of patients.
- Necrotic bone and chronic inflammation predicted persistent nonunion, with lower healing rates.
- Radiologically atrophic nonunions showed variable histological viability, indicating limitations of imaging alone.

## Abstract

Background

Fracture nonunion is a significant complication of orthopedic trauma, affecting a notable proportion of long bone fractures and contributing to prolonged disability and increased healthcare costs. Although radiological classification into hypertrophic, atrophic, and oligotrophic types is traditionally used to estimate biological activity at the fracture site, imaging alone may not accurately predict healing potential. Histopathological evaluation offers direct insight into tissue viability, cellular activity, and infection, potentially enhancing prognostication and guiding treatment strategies.

Methods

This prospective cohort study included 80 patients with long bone nonunions who underwent revision surgery at Stanley Medical College and Hospital between March 2024 and March 2025. Clinical risk factors such as age, comorbidities, smoking history, and prior infections, along with demographic data and fracture characteristics, were recorded. Radiological classification was performed for each case, and intraoperative samples from the nonunion site were subjected to detailed histopathological and microbiological examination. Healing outcomes were assessed at six months postoperatively and correlated with clinical, radiological, and histopathological parameters using appropriate statistical tests.

Results

Among the 80 patients, the majority were men and sustained diaphyseal fractures. Diabetes and prior infections were the most common comorbidities, and both were significantly associated with necrotic bone histology and poorer healing outcomes. Radiologically atrophic nonunions often showed variable histological viability, with viable bone or fibrocartilage present in more than 60% of cases, highlighting the limitations of radiological assessment alone. Histopathology revealed a spectrum of findings: viable bone in 24 (30%) patients, fibrous/fibrocartilage in 20 (37.5%) patients, necrotic bone in 14 (17.5%) patients, and chronic inflammation in 12 (15%) patients. Viable bone histology was strongly associated with complete healing in 20 (83.3%) patients, whereas necrotic bone and chronic inflammation predicted persistent nonunion. Culture-positive nonunions showed significantly lower healing rates (four (28.6%)) compared to culture-negative cases (46 (69.7%)).

Conclusion

Histopathological evaluation provides critical biological insights beyond radiological classification and strongly correlates with healing outcomes in long bone nonunions. Viable bone histology predicts favorable healing, while necrotic bone, chronic inflammation, diabetes, and culture-positive infections are associated with poor outcomes. Integrating clinical, radiological, microbiological, and histopathological data can improve risk stratification and help identify patients who would benefit from biological augmentation in addition to mechanical stabilization. Larger multicenter studies are warranted to validate these findings and develop standardized algorithms for the evaluation and management of fracture nonunions.