ONJ-GUARD: Transparent Medication-Related Osteonecrosis of the Jaw Risk-Context Stratification Before or During Antiresorptive Therapy

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

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is uncommon in routine osteoporosis care, but when it occurs it is clinically disruptive, difficult to reverse, and often amplified by avoidable dental and host-level cofactors. The bedside problem is not simply identifying exposure to bisphosphonates or denosumab; it is recognizing when the oral context makes standard antiresorptive treatment unsafe, when invasive dental work should be coordinated before therapy, and when nonhealing exposed bone or infection should trigger urgent specialist evaluation. We present ONJ-GUARD, an executable Python skill for transparent MRONJ risk-context stratification before or during antiresorptive therapy. The model integrates antiresorptive exposure type, therapy duration, planned or recent invasive dental procedures, active periodontitis or poor oral hygiene, ill-fitting dentures or repetitive oral trauma, glucocorticoids or major immunosuppression, diabetes or microvascular disease, current smoking, antiangiogenic or chemotherapy exposure, prior MRONJ or nonhealing exposed bone, and active jaw pain, swelling, or oral infection. Outputs include visible component scores, categorical risk classes, recommended actions, alerts, and explicit limitations. In demonstration scenarios, a short-course oral bisphosphonate user without dental triggers is LOW risk, a denosumab candidate with extraction plus periodontitis and systemic cofactors is VERY HIGH risk, and a patient with prior exposed jaw bone plus active infection during potent antiresorptive therapy is CONTRAINDICATED / CRITICAL. ONJ-GUARD is designed as an auditable medication-safety aid rather than a validated probability calculator.

Keywords: osteonecrosis of the jaw, MRONJ, bisphosphonate, denosumab, osteoporosis, dental extraction, glucocorticoids, clinical decision support, DeSci

1. Clinical problem

Antiresorptive therapy is central to osteoporosis care, including glucocorticoid-induced bone disease, postmenopausal osteoporosis, and fracture prevention in medically complex patients. The clinical trap is that a patient may have a legitimate skeletal indication while simultaneously carrying an unstable oral environment: planned extraction, active periodontitis, poor oral hygiene, denture trauma, diabetes, smoking, immunosuppression, or a prior nonhealing lesion. MRONJ remains uncommon in low-dose osteoporosis regimens, but its morbidity is substantial enough that prevention matters more than retrospective explanation.

In routine practice, clinicians often know the medication but do not systematically structure the dental context. A transparent executable tool is useful if it makes those hidden triggers explicit before dosing and escalates appropriately when exposed bone or infection is already present.

2. Methodology

2.1 Design principles

ONJ-GUARD follows five practical principles:

1. The oral environment matters. Dental extractions, implants, periodontitis, and trauma are the common trigger contexts that convert a tolerated drug exposure into a wound-healing failure state.
2. Potency and duration matter. Intravenous bisphosphonates, denosumab, and prolonged oral bisphosphonate exposure raise concern beyond short-course oral therapy.
3. Host-level healing factors matter. Glucocorticoids, diabetes, smoking, and major immunosuppression reduce reserve.
4. Nonhealing bone is a red flag, not a nuance. Once exposed bone or a nonhealing socket is present, the clinical problem changes from prevention to urgent assessment.
5. Transparency matters. Users should be able to see which triggers drove escalation.

2.2 Model structure

The implementation computes four visible components:

• Exposure component — current/planned antiresorptive therapy, drug class potency, and prolonged oral exposure
• Oral-trigger component — invasive dental procedures, active periodontitis, denture/oral trauma, and active jaw pain/swelling/infection
• Host-factor component — glucocorticoids or immunosuppression, diabetes or microvascular disease, smoking, antiangiogenic/chemotherapy exposure, and older age
• Red-flag component — prior MRONJ or nonhealing exposed bone

Interaction terms increase concern for antiresorptive exposure plus invasive dental procedures, periodontitis plus diabetes, smoking plus immunosuppression, and prior exposed bone combined with ongoing therapy or infection.

2.3 Output logic

The skill returns:

• Total score
• Risk class: LOW, HIGH, VERY HIGH, or CONTRAINDICATED / CRITICAL
• Recommended actions
• Safety alerts
• Explicit limitations

3. Executable skill

3.1 Implementation

The implementation is standalone Python using only the standard library and is stored locally at:

skills/onj-guard/onj_guard.py

3.2 Demo output summary

Short-course oral bisphosphonate user without dental triggers -> LOW
Denosumab candidate with planned extraction, periodontitis, steroids, and diabetes -> VERY HIGH
Prior exposed jaw bone with infection during potent antiresorptive therapy -> CONTRAINDICATED / CRITICAL

Representative critical output:

total_score: 95.5
risk_class: CONTRAINDICATED / CRITICAL
alert: Prior or current exposed nonhealing jaw bone is not a minor precaution; it is a major red flag for active or recurrent MRONJ.

4. Why this solves a real problem

The question clinicians face is usually operational: can treatment proceed now, should dental disease be corrected first, or has the patient already crossed into a jaw-safety state that makes further routine dosing unsafe? ONJ-GUARD addresses that practical problem. It does not overclaim to predict an exact probability. Instead, it makes the modifiable oral triggers, potency context, and red flags explicit in a form an agent or clinician can inspect line by line.

5. Limitations

1. This is an evidence-informed heuristic tool, not a prospectively calibrated probability calculator for MRONJ.
2. Weights are derived from guideline statements, observational studies, and bedside oral-surgery risk logic rather than a single regression-derived cohort.
3. The tool does not diagnose osteonecrosis of the jaw and cannot replace dental examination, imaging, or lesion staging.
4. Cancer-dose antiresorptives, head and neck radiation, and complex oncologic exposures may carry different absolute risks than routine osteoporosis care.
5. Use only as a transparent clinical decision-support aid alongside clinician, dental, and oral surgery judgment.

6. Demo output

Running python3 skills/onj-guard/onj_guard.py produces three structured demonstration cases with JSON output. Expected classifications:

• Short-course oral bisphosphonate user without dental triggers: LOW
• Denosumab candidate with planned extraction, periodontitis, steroids, and diabetes: VERY HIGH
• Prior exposed jaw bone with infection during potent antiresorptive therapy: CONTRAINDICATED / CRITICAL

References

1. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update. J Oral Maxillofac Surg. 2022;80(5):920-943. DOI: 10.1016/j.joms.2022.02.008
2. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus. J Bone Miner Res. 2015;30(1):3-23. DOI: 10.1002/jbmr.2405
3. Yamada S, Kurita H, Kondo E, et al. A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients. Sci Rep. 2022;12:7991. DOI: 10.1038/s41598-022-11615-9
4. Yarom N, Shapiro CL, Peterson DE, et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(25):2270-2290. DOI: 10.1200/JCO.19.01186
5. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177-187. DOI: 10.1016/j.ctrv.2018.06.007

skill_md

#!/usr/bin/env python3
"""
ONJ-GUARD — Medication-related osteonecrosis of the jaw risk-context stratification.

Transparent clinical skill for estimating concern before or during antiresorptive therapy.

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

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


@dataclass
class OnjGuardInput:
    age: int
    indication: str
    antiresorptive_exposure: str = 'oral_bisphosphonate'
    therapy_duration_years: float = 0.0
    current_or_planned_antiresorptive: bool = True
    invasive_dental_procedure_planned_or_recent: bool = False
    active_periodontitis_or_poor_oral_hygiene: bool = False
    ill_fitting_dentures_or_repetitive_oral_trauma: bool = False
    glucocorticoids_or_major_immunosuppression: bool = False
    diabetes_poor_control_or_microvascular_disease: bool = False
    current_smoking: bool = False
    antiangiogenic_or_chemotherapy_exposure: bool = False
    prior_mronj_or_nonhealing_exposed_bone: bool = False
    jaw_pain_swelling_or_oral_infection: bool = False


def exposure_component(inp: OnjGuardInput) -> float:
    score = 0.0
    if inp.current_or_planned_antiresorptive:
        score += 1.0
    if inp.antiresorptive_exposure == 'oral_bisphosphonate':
        score += 0.4
        if inp.therapy_duration_years >= 4:
            score += 0.8
    elif inp.antiresorptive_exposure == 'denosumab':
        score += 1.2
    elif inp.antiresorptive_exposure == 'iv_bisphosphonate':
        score += 1.4
    elif inp.antiresorptive_exposure == 'sequential_or_multiple_antiresorptives':
        score += 1.8
    return score


def oral_trigger_component(inp: OnjGuardInput) -> float:
    score = 0.0
    if inp.invasive_dental_procedure_planned_or_recent:
        score += 2.2
    if inp.active_periodontitis_or_poor_oral_hygiene:
        score += 1.8
    if inp.ill_fitting_dentures_or_repetitive_oral_trauma:
        score += 0.9
    if inp.jaw_pain_swelling_or_oral_infection:
        score += 2.2
    return score


def host_factor_component(inp: OnjGuardInput) -> float:
    score = 0.0
    if inp.glucocorticoids_or_major_immunosuppression:
        score += 1.0
    if inp.diabetes_poor_control_or_microvascular_disease:
        score += 0.9
    if inp.current_smoking:
        score += 0.7
    if inp.antiangiogenic_or_chemotherapy_exposure:
        score += 1.0
    if inp.age >= 70:
        score += 0.3
    return score


def red_flag_component(inp: OnjGuardInput) -> float:
    score = 0.0
    if inp.prior_mronj_or_nonhealing_exposed_bone:
        score += 3.4
    return score


def total_score(inp: OnjGuardInput) -> float:
    score = (
        exposure_component(inp)
        + oral_trigger_component(inp)
        + host_factor_component(inp)
        + red_flag_component(inp)
    )
    if inp.current_or_planned_antiresorptive and inp.invasive_dental_procedure_planned_or_recent:
        score += 1.6
    if inp.active_periodontitis_or_poor_oral_hygiene and inp.diabetes_poor_control_or_microvascular_disease:
        score += 0.8
    if inp.glucocorticoids_or_major_immunosuppression and inp.current_smoking:
        score += 0.5
    if inp.prior_mronj_or_nonhealing_exposed_bone and inp.current_or_planned_antiresorptive:
        score += 2.2
    if inp.jaw_pain_swelling_or_oral_infection and inp.prior_mronj_or_nonhealing_exposed_bone:
        score += 1.8
    return round(max(score, 0.0) * 5.0, 1)


def classify(inp: OnjGuardInput, score: float) -> str:
    if inp.prior_mronj_or_nonhealing_exposed_bone and inp.jaw_pain_swelling_or_oral_infection:
        return 'CONTRAINDICATED / CRITICAL'
    if score >= 75:
        return 'CONTRAINDICATED / CRITICAL'
    if score >= 45:
        return 'VERY HIGH'
    if score >= 20:
        return 'HIGH'
    return 'LOW'


def recommendations(inp: OnjGuardInput, score: float, risk_class: str) -> List[str]:
    out: List[str] = []
    if risk_class == 'LOW':
        out.append('Current context is compatible with antiresorptive therapy using routine dental prevention, oral-hygiene reinforcement, and follow-up.')
    elif risk_class == 'HIGH':
        out.append('High-risk context: optimize dental health, review timing of invasive dental procedures, and avoid rushed antiresorptive exposure.')
    elif risk_class == 'VERY HIGH':
        out.append('Very high concern: obtain dental or oral surgery review before continuing or initiating standard antiresorptive therapy.')
    else:
        out.append('Exposure is contraindicated or clinically critical until nonhealing bone, active infection, or suspected MRONJ is urgently assessed and managed.')
        out.append('Arrange urgent oral surgery or dental specialist evaluation and avoid additional routine antiresorptive dosing until the jaw lesion is clarified.')

    if inp.invasive_dental_procedure_planned_or_recent:
        out.append('Extractions and implants are major trigger contexts for MRONJ and require coordinated timing with dental care.')
    if inp.active_periodontitis_or_poor_oral_hygiene:
        out.append('Periodontal stabilization and oral-hygiene improvement are modifiable risk reducers before elective antiresorptive treatment.')
    if inp.glucocorticoids_or_major_immunosuppression:
        out.append('Immunosuppression can impair wound healing and should raise the threshold for proceeding without dental optimization.')
    if inp.diabetes_poor_control_or_microvascular_disease:
        out.append('Poor glycemic control is a modifiable cofactor and should be improved when feasible.')
    return out


def alerts(inp: OnjGuardInput, risk_class: str) -> List[str]:
    out: List[str] = []
    if inp.prior_mronj_or_nonhealing_exposed_bone:
        out.append('Prior or current exposed nonhealing jaw bone is not a minor precaution; it is a major red flag for active or recurrent MRONJ.')
    if inp.jaw_pain_swelling_or_oral_infection:
        out.append('Jaw pain, swelling, purulence, or oral infection during antiresorptive therapy should trigger direct examination, not watchful waiting alone.')
    if inp.antiresorptive_exposure in {'iv_bisphosphonate', 'denosumab', 'sequential_or_multiple_antiresorptives'}:
        out.append('Potent antiresorptive exposure increases MRONJ concern relative to short-course oral bisphosphonate use.')
    if risk_class != 'LOW':
        out.append('This tool is a transparent triage aid, not a substitute for direct dental examination or specialist management.')
    return out


def run_onj_guard(inp: OnjGuardInput) -> Dict[str, Any]:
    score = total_score(inp)
    risk_class = classify(inp, score)
    return {
        'input_summary': asdict(inp),
        'exposure_component': round(exposure_component(inp), 2),
        'oral_trigger_component': round(oral_trigger_component(inp), 2),
        'host_factor_component': round(host_factor_component(inp), 2),
        'red_flag_component': round(red_flag_component(inp), 2),
        'total_score': score,
        'risk_class': risk_class,
        'recommended_actions': recommendations(inp, score, risk_class),
        'alerts': alerts(inp, risk_class),
        'limitations': [
            'Evidence-informed heuristic model, not a prospectively calibrated probability calculator for MRONJ.',
            'Weights are derived from guideline statements, observational studies, and bedside oral-surgery risk logic rather than a single regression-derived cohort.',
            'The tool does not diagnose osteonecrosis of the jaw and cannot replace dental examination, imaging, or lesion staging.',
            'Cancer-dose antiresorptives, head and neck radiation, and complex oncologic exposures may carry different absolute risks than routine osteoporosis care.',
            'Use as a transparent clinical decision-support aid alongside clinician, dental, and oral surgery judgment.'
        ]
    }


if __name__ == '__main__':
    demos = [
        (
            'Short-course oral bisphosphonate user without dental triggers',
            OnjGuardInput(age=64, indication='Glucocorticoid-induced osteoporosis', therapy_duration_years=1.0),
        ),
        (
            'Denosumab candidate with planned extraction, periodontitis, steroids, and diabetes',
            OnjGuardInput(
                age=72,
                indication='Postmenopausal osteoporosis',
                antiresorptive_exposure='denosumab',
                invasive_dental_procedure_planned_or_recent=True,
                active_periodontitis_or_poor_oral_hygiene=True,
                glucocorticoids_or_major_immunosuppression=True,
                diabetes_poor_control_or_microvascular_disease=True,
            ),
        ),
        (
            'Prior exposed jaw bone with infection during potent antiresorptive therapy',
            OnjGuardInput(
                age=76,
                indication='Severe osteoporosis after vertebral fracture',
                antiresorptive_exposure='iv_bisphosphonate',
                therapy_duration_years=4.0,
                invasive_dental_procedure_planned_or_recent=True,
                active_periodontitis_or_poor_oral_hygiene=True,
                ill_fitting_dentures_or_repetitive_oral_trauma=True,
                glucocorticoids_or_major_immunosuppression=True,
                diabetes_poor_control_or_microvascular_disease=True,
                current_smoking=True,
                prior_mronj_or_nonhealing_exposed_bone=True,
                jaw_pain_swelling_or_oral_infection=True,
            ),
        ),
    ]

    print('=' * 78)
    print('ONJ-GUARD — Medication-Related Osteonecrosis of the Jaw Risk-Context Stratification')
    print('Authors: Dr. Erick Zamora-Tehozol, DNAI, RheumaAI')
    print('=' * 78)
    for label, demo in demos:
        result = run_onj_guard(demo)
        print(f'\n--- {label} ---')
        print(json.dumps(result, indent=2))

SKILL.md

ONJ-GUARD

Medication-related osteonecrosis of the jaw risk-context stratification before or during antiresorptive therapy

What it does

ONJ-GUARD is a transparent clinical skill that estimates concern for medication-related osteonecrosis of the jaw (MRONJ) before antiresorptive therapy, around dental extractions or implants, or when warning signs such as exposed nonhealing bone, jaw pain, swelling, or oral infection appear.

Inputs

• Age and indication
• Antiresorptive exposure type (oral bisphosphonate, denosumab, intravenous bisphosphonate, or sequential/multiple antiresorptives)
• Therapy duration
• Current or planned antiresorptive exposure
• Planned or recent invasive dental procedure
• Active periodontitis or poor oral hygiene
• Ill-fitting dentures or repetitive oral trauma
• Glucocorticoids or major immunosuppression
• Diabetes with poor control or microvascular disease
• Current smoking
• Antiangiogenic or chemotherapy exposure
• Prior MRONJ or nonhealing exposed bone
• Jaw pain, swelling, or oral infection

Outputs

• Exposure component
• Oral-trigger component
• Host-factor component
• Red-flag component
• Total score
• Risk class: LOW / HIGH / VERY HIGH / CONTRAINDICATED-CRITICAL
• Recommended actions
• Safety alerts
• Explicit limitations

Why it matters

MRONJ is uncommon in routine osteoporosis care, but when it occurs it is clinically disruptive, slow to heal, and often triggered by a preventable mismatch between antiresorptive exposure and poor dental context. Clinicians need a transparent way to identify when routine treatment can proceed, when dental optimization should come first, and when exposed bone or infection makes further dosing unsafe.

Run

python3 onj_guard.py

Demo scenarios

1. Short-course oral bisphosphonate user without dental triggers
2. Denosumab candidate with planned extraction, periodontitis, steroids, and diabetes
3. Prior exposed jaw bone with infection during potent antiresorptive therapy

References

1. Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws—2022 Update. J Oral Maxillofac Surg. 2022;80(5):920-943. DOI: 10.1016/j.joms.2022.02.008
2. Khan AA, Morrison A, Hanley DA, et al. Diagnosis and Management of Osteonecrosis of the Jaw: A Systematic Review and International Consensus. J Bone Miner Res. 2015;30(1):3-23. DOI: 10.1002/jbmr.2405
3. Yamada S, Kurita H, Kondo E, et al. A 5-year retrospective cohort study of denosumab induced medication related osteonecrosis of the jaw in osteoporosis patients. Sci Rep. 2022;12:7991. DOI: 10.1038/s41598-022-11615-9
4. Yarom N, Shapiro CL, Peterson DE, et al. Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(25):2270-2290. DOI: 10.1200/JCO.19.01186
5. Otto S, Pautke C, Van den Wyngaert T, Niepel D, Schiødt M. Medication-related osteonecrosis of the jaw: Prevention, diagnosis and management in patients with cancer and bone metastases. Cancer Treat Rev. 2018;69:177-187. DOI: 10.1016/j.ctrv.2018.06.007