DIONJ Beyond Bisphosphonates: The Complete Drug Screening Framework

Your screening form could be missing five drug classes that can destroy the jawbone. Here’s how you can ensure you don’t miss them. 

The Bisphosphonate Blind Spot

Most implant clinicians have a bisphosphonate protocol down pat: 

Ask about alendronate. Check the duration of therapy. Consider CTX testing. Perhaps request a drug holiday.

You’re doing everything right. Except you’re screening for one pathway to osteonecrosis while missing five others.

Here’s what nobody tells you: bisphosphonates represent just one mechanism of drug-induced osteonecrosis of the jaw. The condition we should actually be calling DIONJ—Drug-Induced Osteonecrosis of the Jaw—has expanded well beyond its original medication associations.

And if your screening form only asks about bisphosphonates, you’re missing patients at significant risk.

Let me show you what’s changed and what you need to be screening for.

Why DIONJ Rather Than MRONJ?

The terminology evolution tells you everything about how our understanding has expanded.

BRONJ (Bisphosphonate-Related ONJ) was the original term, reflecting early identification with bisphosphonate use. Made sense at the time—that’s what we knew.

MRONJ (Medication-Related ONJ) expanded recognition to include denosumab and other antiresorptives. (Getting warmer.)

DIONJ (Drug-Induced ONJ) encompasses all pharmacological agents affecting jaw bone biology. This is the accurate term for current understanding.

The shift from BRONJ to MRONJ to DIONJ isn’t just semantic pedantry—it reflects a fundamental expansion of risk factors that changes how we should screen every implant patient.

The Five Additional Drug Classes (That Aren’t on Your Form)

Right. Let’s get into what you’re actually screening for.

Class 1: Antiangiogenic Agents

These are typically prescribed for metastatic cancer, particularly colorectal, lung, and renal cell carcinoma. Your patient might not volunteer this information unless you ask the right questions.

Examples:
Bevacizumab (Avastin), sunitinib, sorafenib

Mechanism:
VEGF inhibition—blocking vascular endothelial growth factor signalling. Here’s why that matters: VEGF is essential for angiogenesis during wound healing. Block the signalling, compromise the healing.

Jaw impact:
Without adequate angiogenesis, post-surgical bone healing is severely compromised. The tissue can’t rebuild the vascular network it needs.

Risk level: 

High when actively on therapy

Class 2: Tyrosine Kinase Inhibitors (TKIs)

These are commonly prescribed for chronic myeloid leukaemia and gastrointestinal stromal tumours. Again, not information that typically comes up when you ask “Are you on bisphosphonates?”

Examples:
Imatinib (Gleevec), dasatinib, nilotinib

Mechanism:
Targeted inhibition of specific cellular pathways, including those affecting bone metabolism. TKIs don’t just affect cancer cells—they affect normal cellular signalling, including in bone.

Jaw impact:
Multiple pathways of bone metabolism get disrupted. The specifics vary by agent, but the outcome is compromised bone healing and remodelling.

Risk level:
Moderate to high, depending on specific agent and duration

Class 3: Corticosteroids

Long-term steroid use is incredibly common—asthma, COPD, inflammatory bowel disease, rheumatoid arthritis, organ transplant patients. These patients are everywhere in general practice.

Examples:
Prednisone, prednisolone, dexamethasone

Mechanism:
Broad immunosuppression and effects on bone metabolism. Steroids affect virtually every aspect of bone biology—cell proliferation, differentiation, and mineralisation.

Jaw impact:
Suppressed bone formation, impaired healing, increased infection risk.

Critical note:
Corticosteroids invalidate CTX bone turnover testing. This is crucial. A patient on long-term steroids can have a “normal” CTX reading that provides completely false reassurance. The test is meaningless in this population.

Risk level:
Dose and duration dependent, but significant with long-term use

Class 4: mTOR Inhibitors

Typically prescribed for renal cell carcinoma and as immunosuppression in transplant patients. Often used in combination with other agents, which compounds risk.

Examples:
Everolimus (Afinitor), temsirolimus

Mechanism:
Inhibition of the mechanistic target of rapamycin, affecting cell proliferation and survival. mTOR is a critical regulator of cell growth and metabolism.

Jaw impact:
Impaired cellular response to surgical trauma, compromised healing cascade.

Risk level:
Moderate, but additive with other immunosuppressive agents

Class 5: Radiopharmaceuticals

Used specifically for bone metastases from prostate cancer. If your patient has been treated for metastatic prostate cancer, this should trigger immediate inquiry.

Examples:
Radium-223 (Xofigo)

Mechanism:
Delivering targeted radiation to bone tissue. The drug mimics calcium and deposits in areas of high bone turnover—which is exactly where metastases tend to form.

Jaw impact:
Similar considerations to head and neck radiation therapy. The jawbone receives ongoing radiation exposure that compromises its healing capacity and infection resistance.

Risk level:
High

CTX Testing: What It Can and Can’t Tell You

CTX (C-terminal telopeptide) testing measures bone turnover markers. It’s a useful tool when used correctly. But it has significant limitations that can provide false reassurance if you’re not aware of them.

Validity Conditions (When CTX Actually Works)

CTX is only valid when all of these conditions are met:

• The patient must be fasting
• The patient must not be on corticosteroids
• The patient must not be on methotrexate
• The patient must not have active cancer

Miss any of these, and the result is unreliable.

Interpreting Results

CTX below 100 pg/mL indicates severely suppressed bone turnover with high DIONJ risk. This is your red flag.

Critical limitation: CTX is invalid in patients on steroids, methotrexate, or with active cancer. A “normal” result in these populations provides false reassurance. You’re getting a number, but the number doesn’t mean what you think it means.

This matters because many of the patients on the five drug classes above will also be on steroids or have active cancer—exactly the populations where CTX is unreliable.

So what do you do? You rely on the drug history itself, not the biochemical marker. If the patient is on high-risk medications, treat them as high-risk regardless of CTX.

The Screening Form Revolution

Here’s the practical implementation that changes everything.

Current Approach (Inadequate)

“Are you on bisphosphonates?”

This question captures one drug class out of six. You’re screening for 17% of the risk.

Better Approach (Comprehensive)

“Are you taking any medications that affect your bones, blood vessels, or immune system?”

This opens the conversation to the full spectrum of relevant medications.

Specific Probes

Follow up with targeted questions:

• Are you being treated for osteoporosis?
• Are you receiving treatment for cancer, or have you been treated for cancer in the past?
• Have you had bone metastases?
• Are you on long-term steroids for any condition?
• Have you had an organ transplant?
• Have you received radiation treatment to the head or neck?

These questions capture the clinical scenarios where high-risk medications are prescribed.

Implementation in Practice

Update your medical history form. Train your reception staff on which responses trigger clinical review. Create a protocol for patients who screen positive.

This isn’t complicated. It’s just comprehensive.

The Question You Need to Answer

DIONJ risk assessment must extend beyond bisphosphonates.

Five additional drug classes affect jaw bone biology in ways that compromise surgical outcomes: antiangiogenics, tyrosine kinase inhibitors, corticosteroids, mTOR inhibitors, and radiopharmaceuticals.

Each class has distinct mechanisms, but all share the capacity to impair bone healing and increase osteonecrosis risk.

So here’s the question: How many of these drug classes appear on your current screening form?

If the answer is “none” or “just bisphosphonates,” you’re screening for historical understanding, not current evidence.

At the Academy iof Implant Excellence, we teach the biology behind the protocols. Understanding DIONJ pathophysiology across all relevant drug classes is one example of the depth that changes practice. Not because it’s complicated, but because most training providers are still teaching BRONJ protocols from 2010.

And once you understand the full scope of drug-induced osteonecrosis risk, you can’t go back to asking only about alendronate.

Ready to Understand the Biology Behind the Protocols?

The Academy of Implant Excellence teaches system-agnostic, biology-first implant training. From single implants to full-arch mastery. 80+ hours of depth that covers the invisible 10% where complications happen.

Because protocols work until they don’t.

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References

1. Marx RE. Oral and Maxillofacial Pathology. In: Hupp JR et al. Contemporary Oral and Maxillofacial Surgery. 7th ed. Elsevier, 2024.

2. Ruggiero SL et al. AAOMS Position Paper on MRONJ—2022 Update. J Oral Maxillofac Surg. 2022.

3. Resnik RR, Misch CE. Misch’s Avoiding Complications in Oral Implantology. Elsevier, 2018.