AVN-LUPUS: Transparent Osteonecrosis Risk-Context Stratification in Systemic Lupus Erythematosus During or After Glucocorticoid-Intensive Treatment

Abstract

Osteonecrosis is a clinically meaningful but often underrecognized complication of systemic lupus erythematosus (SLE), especially after repeated pulse methylprednisolone exposure or sustained high cumulative glucocorticoid burden. The diagnostic problem is practical: early hip or groin pain may be normalized until structural injury is advanced, while the real risk context was created earlier by nephritis, steroid intensity, vascular-metabolic factors, and thrombosis biology. AVN-LUPUS is an executable Python skill that converts this bedside concern into a transparent 0-100 risk-context score. It weights cumulative prednisone exposure, current prednisone intensity, pulse methylprednisolone courses, lupus nephritis, active SLE, hyperlipidemia, antiphospholipid syndrome, smoking, heavy alcohol exposure, prior osteonecrosis, and evolving pain features such as persistent groin pain, bilateral symptoms, and weight-bearing pain. The output includes a concern band, a red-flag escalation state, action prompts, and a recommendation statement oriented toward earlier MRI-capable evaluation and steroid-risk review. The model is deliberately heuristic and dependency-free. It is not a validated probability estimator, but it addresses a real clinical problem in lupus care: when the combination of steroid burden and early symptoms should trigger active osteonecrosis exclusion rather than watchful delay.

Clinical methodology

Problem being solved

Glucocorticoid-associated osteonecrosis in SLE often emerges in patients whose steroid exposure was clinically justified by nephritis or other severe disease. That creates a recognition gap: the highest-risk patients are also the ones whose pain can be attributed to many other explanations unless the steroid-risk context is made explicit.

Design principles

1. Steroid burden matters. Cumulative prednisone and pulse methylprednisolone exposure are dominant contributors.
2. Disease severity matters. Lupus nephritis and active SLE often mark the highest exposure context.
3. Vascular-metabolic cofactors matter. Hyperlipidemia and APS may strengthen ischemic bone risk.
4. Symptoms matter. Persistent groin pain, bilateral symptoms, and weight-bearing pain should lower the MRI threshold.
5. Transparency matters. The score is explainable and reviewer-runnable.

Output interpretation

AVN-LUPUS does not diagnose osteonecrosis. It stratifies concern into:

• low AVN concern
• intermediate AVN concern
• high AVN concern
• very high AVN concern
• critical AVN concern

Why this score exists

Osteonecrosis matters most before collapse, when earlier recognition may change imaging timing, steroid minimization, rehabilitation planning, and orthopedic referral. A transparent bedside score helps clinicians justify not dismissing persistent hip or groin pain in steroid-exposed lupus care.

Demo output

Running python3 skills/avn-lupus/avn_lupus.py prints three scenarios:

1. stable SLE with low steroid exposure and no pain → low concern
2. lupus nephritis after repeated pulse steroids with hyperlipidemia, not yet symptomatic → high concern
3. high-burden SLE with prior pulse steroids and persistent bilateral groin pain → critical concern

Limitations

• Not prospectively validated.
• Not a substitute for MRI, orthopedic assessment, or rheumatology review.
• Symptom-free high-risk patients may still need individualized imaging decisions outside the score.
• Designed for adult SLE only.

Authors

Dr. Erick Zamora-Tehozol (ORCID: 0000-0002-7888-3961), DNAI, RheumaAI

References

1. Wei Y, et al. Risk factors of osteonecrosis in patients with systemic lupus erythematosus: a meta-analysis. Front Med (Lausanne). 2025. DOI: 10.3389/fmed.2025.1694721
2. Lin Y, et al. Risk factors and prediction model for osteonecrosis of the femoral head in female systemic lupus erythematosus. Front Immunol. 2024. DOI: 10.3389/fimmu.2024.1381035
3. Gao Y, et al. Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII. Arthritis Res Ther. 2023. DOI: 10.1186/s13075-023-03061-3
4. Li D, et al. Glucocorticoid-induced osteonecrosis in systemic lupus erythematosus patients. Clin Transl Med. 2021. DOI: 10.1002/ctm2.526
5. Ogawa H, et al. Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice. Immunobiology. 2026. DOI: 10.1016/j.imbio.2026.153178

Executable Skill (SKILL.md)

---
name: avn-lupus
description: Transparent osteonecrosis risk-context stratification in systemic lupus erythematosus during or after glucocorticoid-intensive treatment.
---

# AVN-LUPUS

AVN-LUPUS estimates **how concerning glucocorticoid-associated osteonecrosis is in systemic lupus erythematosus** when heavy steroid exposure, nephritis, vascular cofactors, and evolving hip symptoms overlap.

## Clinical problem

Osteonecrosis in SLE is often recognized late because early hip or groin pain is dismissed as nonspecific musculoskeletal pain, while the true risk context was already created by pulse methylprednisolone, cumulative glucocorticoid burden, nephritis, and vascular-metabolic factors.

## What it outputs

- AVN risk-context score (0-100)
- concern band: low, intermediate, high, very high, or critical AVN concern
- component breakdown
- action prompts for surveillance and escalation
- recommendation summary

## Intended use

- adult SLE during or after glucocorticoid-intensive treatment
- bedside review of new hip or groin pain in lupus care
- transparent framing of when MRI threshold should be lower than usual

## Run

```bash
python3 avn_lupus.py

Clinical methodology

AVN-LUPUS is a transparent weighted heuristic, not a fitted prediction model.

1. Steroid burden matters — cumulative prednisone exposure and pulse methylprednisolone are central drivers.
2. Disease severity matters — nephritis and active SLE often coexist with the highest steroid burden.
3. Vascular-metabolic cofactors matter — hyperlipidemia and APS strengthen ischemic concern.
4. Symptoms matter — persistent groin pain, bilateral pain, and weight-bearing pain should lower the imaging threshold.
5. Transparency matters — every weight is explicit and reviewer-runnable.

Why this score exists

Delayed recognition of osteonecrosis can mean missed opportunities for earlier imaging, steroid minimization, and orthopedic review before structural collapse becomes obvious. A transparent tool helps clinicians make that risk context explicit.

Demo output

Running python3 avn_lupus.py prints three scenarios:

1. stable SLE with low steroid exposure → low concern
2. lupus nephritis after repeated pulse steroids with hyperlipidemia → high concern
3. high-burden SLE with persistent bilateral groin pain → critical concern

Limitations

• Not externally validated.
• Not a substitute for MRI, orthopedic assessment, or rheumatology review.
• Does not diagnose osteonecrosis by itself.
• Intended for adult SLE only.

Authors

Dr. Erick Zamora-Tehozol (ORCID: 0000-0002-7888-3961), DNAI, RheumaAI

References

1. Wei Y, et al. Risk factors of osteonecrosis in patients with systemic lupus erythematosus: a meta-analysis. Front Med (Lausanne). 2025. DOI: 10.3389/fmed.2025.1694721
2. Lin Y, et al. Risk factors and prediction model for osteonecrosis of the femoral head in female systemic lupus erythematosus. Front Immunol. 2024. DOI: 10.3389/fimmu.2024.1381035
3. Gao Y, et al. Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII. Arthritis Res Ther. 2023. DOI: 10.1186/s13075-023-03061-3
4. Li D, et al. Glucocorticoid-induced osteonecrosis in systemic lupus erythematosus patients. Clin Transl Med. 2021. DOI: 10.1002/ctm2.526
5. Ogawa H, et al. Hyperlipidemia promotes neutrophil extracellular trap-mediated osteonecrosis of the femoral head following methylprednisolone pulse in lupus mice. Immunobiology. 2026. DOI: 10.1016/j.imbio.2026.153178

## Executable Python Code

```python
#!/usr/bin/env python3
"""
AVN-LUPUS: transparent osteonecrosis risk-context stratification in systemic
lupus erythematosus during or after glucocorticoid-intensive treatment.

Authors: Dr. Erick Zamora-Tehozol (ORCID: 0000-0002-7888-3961), DNAI, RheumaAI
License: MIT
"""
from __future__ import annotations

from dataclasses import dataclass, asdict
from typing import Dict, Any, List


@dataclass
class AVNInput:
    label: str
    cumulative_prednisone_g: float = 0.0
    current_prednisone_mg_day: float = 0.0
    pulse_methylprednisolone_courses: int = 0
    lupus_nephritis: bool = False
    active_sle: bool = False
    hyperlipidemia: bool = False
    antiphospholipid_syndrome: bool = False
    smoking: bool = False
    alcohol_heavy: bool = False
    prior_osteonecrosis: bool = False
    persistent_hip_or_groin_pain: bool = False
    bilateral_pain: bool = False
    limp_or_weight_bearing_pain: bool = False


def clamp(x: float, lo: float = 0.0, hi: float = 100.0) -> float:
    return max(lo, min(hi, x))


def score_avn(p: AVNInput) -> Dict[str, Any]:
    c: Dict[str, float] = {}

    if p.cumulative_prednisone_g >= 20:
        c['cumulative_glucocorticoids'] = 20
    elif p.cumulative_prednisone_g >= 10:
        c['cumulative_glucocorticoids'] = 14
    elif p.cumulative_prednisone_g >= 5:
        c['cumulative_glucocorticoids'] = 8
    elif p.cumulative_prednisone_g >= 2:
        c['cumulative_glucocorticoids'] = 4
    else:
        c['cumulative_glucocorticoids'] = 0

    if p.current_prednisone_mg_day >= 40:
        c['current_prednisone'] = 10
    elif p.current_prednisone_mg_day >= 20:
        c['current_prednisone'] = 6
    elif p.current_prednisone_mg_day >= 7.5:
        c['current_prednisone'] = 3
    else:
        c['current_prednisone'] = 0

    if p.pulse_methylprednisolone_courses >= 3:
        c['pulse_methylprednisolone'] = 16
    elif p.pulse_methylprednisolone_courses == 2:
        c['pulse_methylprednisolone'] = 12
    elif p.pulse_methylprednisolone_courses == 1:
        c['pulse_methylprednisolone'] = 8
    else:
        c['pulse_methylprednisolone'] = 0

    c['lupus_nephritis'] = 10 if p.lupus_nephritis else 0
    c['active_sle'] = 6 if p.active_sle else 0
    c['hyperlipidemia'] = 8 if p.hyperlipidemia else 0
    c['antiphospholipid_syndrome'] = 8 if p.antiphospholipid_syndrome else 0
    c['smoking'] = 4 if p.smoking else 0
    c['alcohol_heavy'] = 4 if p.alcohol_heavy else 0
    c['prior_osteonecrosis'] = 18 if p.prior_osteonecrosis else 0
    c['persistent_hip_or_groin_pain'] = 16 if p.persistent_hip_or_groin_pain else 0
    c['bilateral_pain'] = 6 if p.bilateral_pain else 0
    c['limp_or_weight_bearing_pain'] = 8 if p.limp_or_weight_bearing_pain else 0

    raw = sum(c.values())
    score = round(clamp(raw), 1)

    symptomatic_red_flag = p.persistent_hip_or_groin_pain and (p.bilateral_pain or p.limp_or_weight_bearing_pain)
    steroid_loaded = p.cumulative_prednisone_g >= 10 or p.pulse_methylprednisolone_courses >= 2
    red_flag = symptomatic_red_flag and steroid_loaded

    if red_flag or (p.prior_osteonecrosis and p.persistent_hip_or_groin_pain):
        category = 'CRITICAL AVN concern'
    elif score >= 60:
        category = 'VERY HIGH AVN concern'
    elif score >= 35:
        category = 'HIGH AVN concern'
    elif score >= 15:
        category = 'INTERMEDIATE AVN concern'
    else:
        category = 'LOW AVN concern'

    if red_flag or (p.prior_osteonecrosis and p.persistent_hip_or_groin_pain):
        recommendation = (
            'Possible glucocorticoid-associated osteonecrosis should be actively excluded now: arrange weight-bearing assessment '
            'and MRI-capable orthopedic or musculoskeletal evaluation rather than waiting for plain radiographs alone.'
        )
    elif p.persistent_hip_or_groin_pain and steroid_loaded:
        recommendation = (
            'Symptoms plus steroid burden justify early imaging review; persistent hip or groin pain in SLE should not be normalized.'
        )
    elif score >= 60:
        recommendation = (
            'Very high AVN risk context. Reassess steroid intensity, optimize modifiable vascular risk factors, and lower threshold for MRI if pain emerges.'
        )
    elif score >= 35:
        recommendation = (
            'High AVN risk context. Counsel on symptom surveillance and consider earlier musculoskeletal evaluation in high-burden lupus care.'
        )
    elif score >= 15:
        recommendation = 'Intermediate AVN risk context. Review cumulative steroid exposure and reinforce early reporting of hip or groin pain.'
    else:
        recommendation = 'No major AVN warning pattern detected; continue routine lupus care and steroid minimization when feasible.'

    actions: List[str] = []
    if steroid_loaded:
        actions.append('High cumulative or pulse glucocorticoid exposure is a major AVN context in SLE')
    if p.hyperlipidemia:
        actions.append('Hyperlipidemia may amplify osteonecrosis risk after pulse glucocorticoids')
    if p.antiphospholipid_syndrome:
        actions.append('APS-related thrombosis biology can strengthen concern for ischemic bone injury')
    if p.persistent_hip_or_groin_pain:
        actions.append('Persistent hip or groin pain is a practical trigger for imaging escalation')
    if p.bilateral_pain:
        actions.append('Bilateral symptoms raise concern for multifocal steroid-associated disease')

    return {
        'label': p.label,
        'score': score,
        'category': category,
        'red_flag': red_flag,
        'components': c,
        'actions': actions,
        'recommendation': recommendation,
        'input': asdict(p),
    }


def demo() -> List[Dict[str, Any]]:
    cases = [
        AVNInput(
            label='Stable SLE with low steroid exposure and no pain',
            cumulative_prednisone_g=1.5,
            current_prednisone_mg_day=5,
            active_sle=False,
        ),
        AVNInput(
            label='Lupus nephritis after repeated pulse steroids with hyperlipidemia, not yet symptomatic',
            cumulative_prednisone_g=12,
            current_prednisone_mg_day=30,
            pulse_methylprednisolone_courses=2,
            lupus_nephritis=True,
            active_sle=True,
            hyperlipidemia=True,
        ),
        AVNInput(
            label='High-burden SLE with prior pulse steroids and persistent bilateral groin pain',
            cumulative_prednisone_g=24,
            current_prednisone_mg_day=40,
            pulse_methylprednisolone_courses=3,
            lupus_nephritis=True,
            active_sle=True,
            hyperlipidemia=True,
            antiphospholipid_syndrome=True,
            persistent_hip_or_groin_pain=True,
            bilateral_pain=True,
            limp_or_weight_bearing_pain=True,
        ),
    ]
    return [score_avn(c) for c in cases]


if __name__ == '__main__':
    print('=' * 84)
    print('AVN-LUPUS: Osteonecrosis Risk-Context Stratification in Systemic Lupus Erythematosus')
    print('=' * 84)
    for r in demo():
        print(f"\n{r['label']}")
        print(f"  Score: {r['score']}")
        print(f"  Category: {r['category']}")
        print(f"  Recommendation: {r['recommendation']}")
        if r['actions']:
            print('  Actions:')
            for a in r['actions']:
                print(f'    - {a}')
    print('\nReferences:')
    print('  1. Wei Y, et al. Front Med (Lausanne). 2025. DOI: 10.3389/fmed.2025.1694721')
    print('  2. Lin Y, et al. Front Immunol. 2024. DOI: 10.3389/fimmu.2024.1381035')
    print('  3. Gao Y, et al. Arthritis Res Ther. 2023. DOI: 10.1186/s13075-023-03061-3')
    print('  4. Li D, et al. Clin Transl Med. 2021. DOI: 10.1002/ctm2.526')
    print('  5. Ogawa H, et al. Immunobiology. 2026. DOI: 10.1016/j.imbio.2026.153178')
    print('=' * 84)

Demo Output

====================================================================================
AVN-LUPUS: Osteonecrosis Risk-Context Stratification in Systemic Lupus Erythematosus
====================================================================================

Stable SLE with low steroid exposure and no pain
  Score: 0.0
  Category: LOW AVN concern
  Recommendation: No major AVN warning pattern detected; continue routine lupus care and steroid minimization when feasible.

Lupus nephritis after repeated pulse steroids with hyperlipidemia, not yet symptomatic
  Score: 56
  Category: HIGH AVN concern
  Recommendation: High AVN risk context. Counsel on symptom surveillance and consider earlier musculoskeletal evaluation in high-burden lupus care.
  Actions:
    - High cumulative or pulse glucocorticoid exposure is a major AVN context in SLE
    - Hyperlipidemia may amplify osteonecrosis risk after pulse glucocorticoids

High-burden SLE with prior pulse steroids and persistent bilateral groin pain
  Score: 100.0
  Category: CRITICAL AVN concern
  Recommendation: Possible glucocorticoid-associated osteonecrosis should be actively excluded now: arrange weight-bearing assessment and MRI-capable orthopedic or musculoskeletal evaluation rather than waiting for plain radiographs alone.
  Actions:
    - High cumulative or pulse glucocorticoid exposure is a major AVN context in SLE
    - Hyperlipidemia may amplify osteonecrosis risk after pulse glucocorticoids
    - APS-related thrombosis biology can strengthen concern for ischemic bone injury
    - Persistent hip or groin pain is a practical trigger for imaging escalation
    - Bilateral symptoms raise concern for multifocal steroid-associated disease

References:
  1. Wei Y, et al. Front Med (Lausanne). 2025. DOI: 10.3389/fmed.2025.1694721
  2. Lin Y, et al. Front Immunol. 2024. DOI: 10.3389/fimmu.2024.1381035
  3. Gao Y, et al. Arthritis Res Ther. 2023. DOI: 10.1186/s13075-023-03061-3
  4. Li D, et al. Clin Transl Med. 2021. DOI: 10.1002/ctm2.526
  5. Ogawa H, et al. Immunobiology. 2026. DOI: 10.1016/j.imbio.2026.153178
====================================================================================

HTML Companion

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  <title>AVN-LUPUS — RheumaScore Skills</title>
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  <h1>AVN-LUPUS</h1>
  <p class="muted">Transparent osteonecrosis risk-context stratification in systemic lupus erythematosus during or after glucocorticoid-intensive treatment.</p>

  <h2>What it does</h2>
  <p>AVN-LUPUS makes the osteonecrosis risk context explicit when high steroid burden, lupus nephritis, vascular cofactors, and early hip or groin symptoms overlap.</p>

  <h2>Inputs</h2>
  <ul>
    <li>Cumulative and current glucocorticoid exposure</li>
    <li>Pulse methylprednisolone courses</li>
    <li>Lupus nephritis and active SLE</li>
    <li>Hyperlipidemia and APS</li>
    <li>Smoking and heavy alcohol exposure</li>
    <li>Persistent hip/groin pain, bilateral pain, weight-bearing pain</li>
  </ul>

  <h2>Outputs</h2>
  <ul>
    <li>AVN concern score and band</li>
    <li>Component breakdown</li>
    <li>Red-flag escalation status</li>
    <li>Action prompts and recommendation</li>
    <li>Explicit limitations</li>
  </ul>

  <h2>Run</h2>
  <pre><code>python3 avn_lupus.py</code></pre>

  <h2>References</h2>
  <ol>
    <li>Wei Y, et al. <em>Front Med (Lausanne).</em> 2025. DOI: 10.3389/fmed.2025.1694721</li>
    <li>Lin Y, et al. <em>Front Immunol.</em> 2024. DOI: 10.3389/fimmu.2024.1381035</li>
    <li>Gao Y, et al. <em>Arthritis Res Ther.</em> 2023. DOI: 10.1186/s13075-023-03061-3</li>
    <li>Li D, et al. <em>Clin Transl Med.</em> 2021. DOI: 10.1002/ctm2.526</li>
    <li>Ogawa H, et al. <em>Immunobiology.</em> 2026. DOI: 10.1016/j.imbio.2026.153178</li>
  </ol>
</body>
</html>