Charcot neuroosteoarthropathy (CN) is a progressive destructive disorder of the foot and ankle most commonly associated with diabetic neuropathy [1-28]. Advanced disease stages may lead to severe deformity, joint instability, ulceration, and an increased risk of lower limb amputation [1-29].

• Charcot Neuroosteoarthropathy

• Diabetic Foot

• Arthrodesis

• Histopathology

• Bone Fusion

• Prognostic Factors

Mehlhorn AT, Huber V, Krenn V, Illgner U, Walther M. (2026) Histopathological Disease Activity Predicts Early Consolidation after Arthrod esis in Charcot Neuroosteoarthropathy: A Retrospective Cohort Study. Ann Sports Med Res 13(1): 1239.

Charcot neuroosteoarthropathy (CN) is a progressive destructive disorder of the foot and ankle most commonly associated with diabetic neuropathy [1-28]. Advanced disease stages may lead to severe deformity, joint instability, ulceration, and an increased risk of lower limb amputation [1-29].

Charcot neuroosteoarthropathy (CN) is a progressive destructive disorder of the foot and ankle most commonly associated with diabetic neuropathy [1-28]. Advanced disease stages may lead to severe deformity, joint instability, ulceration, and an increased risk of lower limb amputation [1-29].

However, clinical overlap between stages is frequently observed, and radiographic findings do not always reflect the underlying biological activity of the disease process [29-31]. Recent reviews emphasize the multifactorial pathophysiology of Charcot neuroosteoarthropathy and highlight the limited availability of objective biomarkers to guide surgical timing [30,31].

The histopathological Charcot Score (HCS) was introduced to quantify inflammatory, degenerative, and reparative tissue changes in intraoperative specimens [7]. The score evaluates histological features of bone, cartilage, synovial tissue, and inflammatory infiltration and provides a structured assessment of local tissue-level activity [7,8].

Although the HCS provides face validity as a histological activity marker, its potential prognostic value for postoperative outcomes has not yet been investigated.

The aim of the present study was therefore to determine whether histopathological activity quantified by the HCS correlates with early clinical and radiographic outcomes following hindfoot and ankle arthrodesis in patients with CN.

We hypothesized that lower histopathological activity would be associated with improved osseous consolidation and better functional outcome.

The optimal timing of reconstructive surgery in Charcot neuroosteoarthropathy (CN) remains controversial,particularly when clinical signs of disease activity overlap with later stages of consolidation. The histopathological Charcot Score (HCS) quantifies inflammatory and reparative tissue changes in intraoperative specimens; however, its prognostic relevance remains unestablished. This study investigated whether histopathological activity correlates with early clinical and radiographic outcomes following hindfoot and ankle arthrodesis for CN.

A retrospective cohort study including 62 patients undergoing corrective internal arthrodesis for CN between 2017 and 2023 was performed. Intraoperative tissue samples were analyzed using the HCS (range 0–21). Clinical outcome was assessed six months postoperatively using a modified Reinker–Carpenter grading system. Early osseous consolidation was evaluated by computed tomography at three months using a standardized fusion score (0–6 points). Associations between HCS and outcome parameters were analyzed using Spearman’s correlation. Multivariable regression analysis assessed potential confounding effects of age and sex.

Study design

A retrospective cohort study was conducted including consecutive patients who underwent corrective internal arthrodesis for Charcot neuroosteoarthropathy between 2017 and 2023. Institutional review board approval was obtained prior to data collection.

Patients

Inclusion criteria were:

• Confirmed diagnosis of Charcot neuroosteoarthropathy

• Eichenholtz stage II or III clinically and radiographically

• Corrective hindfoot or ankle arthrodesis

• Availability of intraoperative tissue specimen

• Minimum follow-up of six months

A total of 62 patients met the inclusion criteria. Mean patient age was 63.5 ± 11.6 years. Twenty-four patients were female and thirty-eight were male.

Because of the retrospective study design, detailed metabolic parameters such as HbA1c levels, smoking status, renal function, and vascular status were not consistently available for all patients and could therefore not be incorporated into multivariable adjustment.

Histopathological Charcot Score (HCS)

Intraoperative tissue samples were processed according to standardized histopathological protocols.

The histopathological Charcot Score (HCS) evaluates inflammatory, degenerative, and reparative tissue changes in intraoperative specimens and has previously been described by Illgner et al. [7]. The conceptual framework of semi-quantitative histopathological scoring systems has previously been applied in musculoskeletal pathology and osteomyelitis diagnostics [8,9].

The HCS evaluates seven histological parameters representing inflammatory, degenerative, and reparative tissue changes. Each parameter is scored from 0 to 3, resulting in a total score ranging from 0 to 21.

Activity levels were categorized as:

• 0–6 points: low activity

• 7–13 points: moderate activity

• 14–21 points: high activity

No patients in the present cohort demonstrated high activity scores.

It should be noted that the original HCS publication did not correlate histopathological findings with Eichenholtz stage. Therefore, HCS should be interpreted as a measure of tissue-level biological activity rather than a radiographic staging surrogate.

Clinical Outcome

Clinical outcome was assessed six months postoperatively using a modified Reinker–Carpenter grading system ranging from 0 to 3 points. This score evaluates pain, deformity correction, and functional capacity.

Radiographic Outcome

Computed tomography (CT) has been shown to provide a more reliable assessment of hindfoot fusion than conventional radiographs and is widely used for evaluating arthrodesis consolidation [11-13].

Computed tomography (CT) imaging was performed three months postoperatively according to institutional protocol.

Fusion was assessed at three joints:

• First tarsometatarsal joint

• Talonavicular joint

• Calcaneocuboid joint

Each joint was scored from 0 to 2 points depending on the degree of osseous bridging (>50%, 25–50%, <25%), resulting in a maximum fusion score of 6 points.

The three-month CT evaluation reflects early consolidation rather than definitive fusion.

Statistical Analysis

Clinical outcome scores were ordinal in nature; therefore, non-parametric statistics were applied. Spearman correlation coefficients were calculated to assess monotonic associations between HCS and outcome parameters. To contextualize effect size, the proportion of explained variance (r²) was calculated.

Multivariable linear regression model were constructed to evaluate whether HCS remained associated with outcome measures after adjustment for age and sex. Statistical significance was defined as p < 0.05.

Patient Characteristics

Median HCS was 7 (range 4–13). Twenty-nine patients demonstrated low histopathological activity (HCS ≤6), while thirty-three patients demonstrated moderate activity (7–13). Median clinical score at six months was 1 (range 0–3). Median CT consolidation score at three months was 4 (range 0–6).

Correlation Analysis

HCS demonstrated a significant negative correlation with clinical outcome (r = −0.33, p = 0.01) (Figure 1A-1B). A similar negative correlation was observed between HCS and CT consolidation score (r = −0.34, p = 0.008) (Figure 2A-2B).

Figure 1 1A-1B. Lower Histopathological Charcot Scores were associated with better clinical outcomes as measured using the modified Reinker-Carpenter score in patients with Charcot Neuroosteoarthropathy treated with arthrodesis.

Figure 2 2A-2B. Lower Histopathological Charcot Scores were associated with better bony consolidation as measured on CT scans 3 months postoperatively in patients with Charcot Neuroosteoarthropathy treated with arthrodesis.

The corresponding explained variance (r² ≈ 0.11–0.12) indicates that histopathological activity represents a measurable contributor to variability in early postoperative outcomes.

Subgroup Analysis

Patients with low histopathological activity demonstrated significantly higher median clinical scores (p = 0.007) and CT consolidation scores (p = 0.044) compared with patients with moderate activity.

Regression Analysis

Age and sex were not significant predictors of clinical or radiographic outcome (p > 0.05).

The present study evaluated whether histopathological disease activity quantified by the Histopathological Charcot Score is associated with early clinical and radiographic outcomes following hindfoot and ankle arthrodesis for Charcot neuroosteoarthropathy.

Charcot neuroosteoarthropathy represents a complex complication of diabetic neuropathy characterized by progressive joint destruction, deformity, and a high risk of ulceration and amputation [1-29]. Despite advances in diabetic foot care, surgical decision-making in Charcot reconstruction remains challenging, particularly regarding the optimal timing of surgery.

Current treatment algorithms are primarily based on the Eichenholtz staging system, which relies on clinical and radiographic findings [2]. However, several recent studies and reviews have highlighted the limitations of purely radiographic staging and emphasized the importance of biological disease activity [30,31].

The present findings suggest that histopathological activity may represent such a biological parameter. Higher HCS values were associated with inferior clinical outcome and reduced early osseous consolidation.

The observed correlation coefficients (r ≈ −0.33 to −0.34) correspond to moderate associations according to conventional interpretation standards. Bone healing in Charcot neuroosteoarthropathy is influenced by multiple interacting factors, including metabolic control, vascular status, neuropathy severity, and mechanical stability [30,31]. In this multifactorial context, the observed explained variance of approximately 11–12% suggests that histopathological activity represents a measurable and clinically relevant contributor to early postoperative outcome variability.

Subgroup analysis further demonstrated superior clinical and radiographic outcomes in patients with lower histopathological activity. This observation supports the hypothesis that ongoing inflammatory activity at the tissue level may impair early consolidation.

Radiographic assessment in the present study was performed using CT imaging at three months postoperatively. CT has previously been shown to provide superior reliability in assessing hindfoot arthrodesis compared with conventional radiographs [11-13]. Although this time point reflects early consolidation rather than definitive fusion, early osseous bridging is clinically relevant in this high-risk patient population.

Several limitations must be acknowledged. First, the retrospective study design introduces potential selection bias. Second, important systemic factors influencing bone healing in Charcot neuroosteoarthropathy - such as glycemic control, smoking status, renal function, and vascular status - were not consistently available. These factors have previously been identified as relevant determinants of surgical outcome in Charcot reconstruction [30,31].

Despite these limitations, the present study provides preliminary evidence that histopathological disease activity correlates with early postoperative healing dynamics following arthrodesis for Charcot neuroosteoarthropathy.

From a clinical perspective, histopathological evaluation of intraoperative tissue samples may provide additional biological information when determining surgical timing. Future prospective studies integrating standardized metabolic assessment, validated patient reported outcome measures, and longer-term imaging follow-up are required to further clarify the prognostic value of histopathological disease activity.

Higher histopathological disease activity was associated with inferior early consolidation and functional outcome following arthrodesis for Charcot neuroosteoarthropathy. Although the effect size was moderate, histopathological assessment may provide additional information regarding biological disease activity at the time of surgery. Further prospective studies are required to confirm the prognostic role of histopathological activity in surgical decision making for Charcot neuroosteoarthropathy.

The authors thank the histopathology laboratory staff for their technical assistance in specimen processing.

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