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Myeloma and Osteonecrosis of the Jaw

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How often does osteonecrosis of the jaw (ONJ) occur in myeloma patients? The studies I’ve read document occurrences in the single digits. My problem with those studies is that they track MM patients for only a few years.

I am a long-term survivor of MM. I believe MM patients must take a balanced approach to MM treatment with both conventional and evidence-based non-conventional therapies. 

The study linked and excerpted below tracks the use of bisphosphonates (zometa, acedia, etc,) and denosumab for 10 years. Yes, the study is about the long-term use of bone strengthening drugs for prostate cancer patients with metastatic cancer but I’m using it to bring attention to the problems myeloma patients have with osteonecrosis of the jaw.

According to research between 1-10% of myeloma patients develop ONJ. I think that percentage is accurate if the MM patient is on bone-modifying agents (BMA) for only a year or two.

According to the study below, if a patient is one monthly BMA’s for 5-10 years, the occurrence of ONJ skyrockets to more than 60%.

What are the risks and benefits of bone modifying agents to myeloma patients?


  1. Reduction of Skeletal-Related Events (SREs):
    • BMAs significantly reduce the incidence of SREs, such as pathological fractures, spinal cord compression, and the need for radiation or surgery to bone.
  2. Bone Pain Relief:
    • These agents help in reducing bone pain, which is a common and debilitating symptom in myeloma patients.
  3. Improved Quality of Life:
    • By reducing the occurrence of SREs and alleviating bone pain, BMAs improve the overall quality of life for myeloma patients.
  4. Potential Anti-Tumor Effects:
    • Some studies suggest that BMAs may have direct anti-tumor effects, potentially inhibiting myeloma cell growth and survival.
  5. Preservation of Bone Density:
    • BMAs help in maintaining or improving bone density, which is often compromised in myeloma patients due to the disease and its treatment.


  1. Osteonecrosis of the Jaw (ONJ):
    • One of the most serious side effects, characterized by the death of jawbone tissue, often associated with dental procedures or poor oral hygiene.
  2. Hypocalcemia:
    • BMAs can cause low levels of calcium in the blood, necessitating careful monitoring and supplementation.
  3. Renal Toxicity:
    • Some BMAs, particularly bisphosphonates, can cause renal impairment or exacerbate existing renal issues, requiring dose adjustments or alternative treatments.
  4. Atypical Femur Fractures:
    • Long-term use of BMAs may be associated with atypical fractures of the femur, though this is relatively rare.
  5. Gastrointestinal Issues:
    • Patients may experience gastrointestinal side effects such as nausea, vomiting, and abdominal pain.
  6. Acute Phase Reactions:
    • Symptoms like fever, fatigue, and flu-like symptoms can occur, particularly with intravenous bisphosphonates, typically resolving within a few days.

Types of Bone Modifying Agents:

1. Bisphosphonates (e.g., Zoledronic Acid, Pamidronate):

  • Benefits: Effective in reducing SREs, improving bone density, and providing pain relief.
  • Risks: Higher incidence of ONJ, renal toxicity, hypocalcemia, acute phase reactions.

2. Denosumab:

  • Benefits: Effective in reducing SREs, especially beneficial for patients with renal impairment as it is not renally excreted.
  • Risks: ONJ, hypocalcemia, potential rebound bone loss upon discontinuation.

man hand holding his nutritional supplemets, healthy lifestyle background.

As you can see, there are many benefits of taking bone modifying agents for the newly diagnosed MM patient. My point is simply that less is more. Or I should say that the risks of BMA begin to outweigh the benefits the longer the MM patient takes BMA.

And remember that there are a host of nutritional supplements- vitamin d, magnesium, calcium, etc. shown to enhance bone health.

Are you a newly diagnosed MM patient? To learn more about both conventional and non-conventional MM therapies email me at David.PeopleBeatingCancer@gmail.com

Thank you,

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Cumulative incidence and risk factors for medication-related osteonecrosis of the jaw during long-term prostate cancer management

“Bone-modifying agents (BMA) are extensively used in treating patients with prostate cancer with bone metastases. However, this increases the risk of medication-related osteonecrosis of the jaw (MRONJ). The safety of long-term BMA administration in clinical practice remains unclear…

The 2-year, 5-year, and 10-year cumulative MRONJ incidence rates were 18%, 27%, and 61%, respectively. Multivariate analysis identified denosumab use as a risk factor for MRONJ, compared with zoledronic acid use (HR 4.64, 95% CI 1.93–11.1). Additionally, BMA use at longer than one-month intervals was associated with a lower risk of MRONJ (HR 0.08, 95% CI 0.01–0.64)…

The incidence of MRONJ in patients with prostate cancer (5–39%) has been reported to be higher than in patients with other cancers1,11,17,18

Cumulative incidence and risk factors for severe MRONJ

The cumulative incidence rates of severe MRONJ were 3%, 7%, 21%, and 51% at 1, 2, 5, and 10 years, respectively (Fig. 3A)..


This study focused on the cumulative incidence of MRONJ with long-term BMA use in prostate cancer patients with bone metastases. The cumulative incidence of MRONJ was approximately one-quarter at 5 years, but at 10 years, more than half of the patients had developed the disease.

Denosumab use was the risk factor for MRONJ of any stage, whereas BMA administration at longer than one-month intervals was associated with a lower risk of MRONJ. Thus, the null hypothesis that BMA type and dosing interval do not affect the occurrence of MRONJ has been rejected…

Recently, Nakai et al.1 reported an MRONJ incidence rate of 27.5% in patients with prostate cancer and bone metastases at 5 years, which is similar to our findings. However, the incidence at 10 years remained unknown.

In this study, the 10-year cumulative incidence of MRONJ was 61%. Although the majority of MRONJ cases occurred within the first 3 years, some MRONJ cases were observed even after long-term treatment. This highlights the substantial risk associated with long-term BMA use.

The association between prolonged BMA use and an increased incidence of MRONJ has been increasingly reported10,11,24,25, making the optimal duration of BMA administration a crucial issue for the future, especially in patients with prostate cancer who undergo prolonged BMA therapy…

Although denosumab is more effective than zoledronic acid in reducing the incidence of SREs, an analysis of eight RCTs found a significantly higher incidence of MRONJ with denosumab than with zoledronic acid administration7.

The incidence of MRONJ with denosumab use ranged from

  • 0.5–2.1% at 1 year,
  • 1.1–3.0% at 2 years,
  • and 1.3–3.2% at 3 years7.

Long-term denosumab use has been associated with an increased risk of MRONJ; however, observational studies on denosumab treatment beyond 3 years are limited. Our study identified denosumab use as an independent risk factor for MRONJ development compared with zoledronic acid use, even during long-term follow-up. The use of denosumab is expected to increase in the future because of its potential to mitigate nephrotoxicity and its non-requirement for intravenous infusion…


In conclusion, this study revealed a significantly increased cumulative incidence of MRONJ in patients with prostate cancer and bone metastases after long-term BMA treatment.

Denosumab use was identified as an independent risk factor for MRONJ, and BMA use at intervals longer than one month was associated with a lower risk of MRONJ. Diabetes mellitus and numerous bone metastases were also identified as risk factors for severe MRONJ. These findings advocate for considering extended BMA dosing intervals in patients with prostate cancer with bone metastases undergoing long-term therapy. Furthermore, the recognition of risk factors for severe MRONJ underscores the importance of early detection in patients with diabetes mellitus and multiple bone metastases as a preventive measure.”




Leave a Comment:

Deborah Rogow says last month

One oncologist I met with (Jim Berenson, in LA) told me that the risk of MRONJ is also affected by oral hygiene. I don’t know if that is true, but I figure it can’t hurt to improve one’s oral health, so I started being more careful/thorough with that.

    David Emerson says last month

    Hi Debbie-

    I’ve read that a person’s oral hygiene makes a difference so yes, I agree. The challenge is figuring out how much. But yes, we all should floss, brush, etc. Thanks.

    David Emerson

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