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Multiple Myeloma Bone Health- Denosumab vs. Bisphophonates?

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“Prescribers are advised that zoledronic acid (bisphophonates) is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction…”

Hi David- I’m wondering your perception on the best modality to strengthen bones for a multiple myeloma bone health. I’ve heard about Denosumab, and would be interested in your thoughts on it.

Per CRAB acronym, only the Bone part has showed up in my blood work.

Thank You Abundantly! Monica

Hi Monica,
From your question I am assuming that you are interested in my experience as well as my reading on the subject of multiple myeloma bone health, bone strength and bone mineral density. I’m not trying to complicate my reply, I’m just trying to clarify where I’m coming from.
Denosumab and Bisphophonate therapies (zolendronic acid, aredia, pamidronate, etc.) have both been approved by the FDA as bone therapies for newly diagnosed MM patients. Even if newly diagnosed MM patients don’t have bone involvement or calcium increases in their blood upon diagnosis, oncology will prescribe bone therapy.
The challenge with Denosumab is that it is much more expensive than Bisphophonate therapy for multiple myeloma bone health.  Even if the patient has great health insurance, he/she may have a co-pay or deductible that can sting.
The question then, as a multiple myeloma bone health therapy, is Denosumab worth the money? Keep in mind this is all based on research. I don’t have personal experience with Denosumab.
I think the answer comes down to the patient and his/her kidney function. According to the second study linked and excerpted below, when comparing Denosumab to zoledronic acid, all side effects match up pretty equally.
So the main issue, the main adverse event is kidney damage.  Bisphophonates are excreted through the kidneys. Studies document that Bisphophonates can damage the kidneys.
Now, if you read the study I’ve excerpted below, it says that Bisphophonates will not cause LONG TERM kidney damage. I have a bias, am skeptical of studies like the one below mainly because:
  • MM patients may undergo bone therapies either for months initially, or repeatedly in their lives as MM patients.
  • MM patients are often older and my present with reduced kidney function to begin with.
  • Lastly, MM proteins themselves, MM as a disease, may cause kidney damage.
My apologies for this long-winded reply to your question…
So my answer is, if your kidney function testing, your
  • creatinine,
  • BUN,
  • eGFR


indicates that you have
  • kidney damage and
  • if your serum calcium is above the normal range indicating bone involvement, and
  • if you can afford Denosumab,
then yes, I would consider this therapy for strengthening your bones.
Conversely, if your kidney function is normal, if you have no pre-existing kidney damage,  and if you don’t want to pay for another expensive drug, Bisphophonates  should be just fine for you.
I have to give a plug for evidence-based but non-toxic bone health therapies. Everything from lifestyle therapies such as exercise to nutrition to nutritional supplementation such as vitamin D3, magnesium, curcumin, others are well-documented bone health therapies. Keep in mind that MM patients must be conscious of their bone health for the rest of their lives.
I hope I haven’t bored you too much. It is difficult to talk about MM therapies and their pros and cons in a sentence or two.
Let me know if you have any questions.
David Emerson
  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

“Bisphosphonates are widely used for the treatment of osteoporosis and are generally well tolerated. However, the United States Food and Drug Administration safety reports have highlighted the issue of renal safety in bisphosphonate-treated patients. All bisphosphonates carry labeled “warnings” or a contraindication for use in patients with severe renal impairment (creatinine clearance <30 or <35 mL/min)…
All bisphosphonate therapies have “warnings” for use in patients with severe renal impairment. Clinical trial results have shown that even in elderly, frail, osteoporotic patients with renal impairment, intravenous bisphosphonate therapy administration in accordance with the prescribing information did not result in long-term renal function decline. Physicians should follow guidelines for bisphosphonate therapies administration at all times.

Zoledronic acid associated with adverse effects on renal function

“Prescribers are advised that zoledronic acid is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction…”

Denosumab vs Zoledronic Acid in Newly Diagnosed Multiple Myeloma With Bone Disease

“In a phase III trial reported in The Lancet Oncology, Raje et al found that denosumab was noninferior to zoledronic acid in preventing skeletal-related events (SREs) in newly diagnosed multiple myeloma patients with bone disease…

Adverse Events-

The most common grade ≥ 3 adverse events in the denosumab vs zoledronic acid groups were

  • neutropenia (15% vs 15%),
  • thrombocytopenia (14% vs 12%),
  • anemia (12% vs 10%),
  • febrile neutropenia (11% vs 10%), and
  • pneumonia (8% vs 8%).

Renal toxicity was reported in 10% vs 17%. Any-grade hypocalcemia occurred in 17% vs 12%. Osteonecrosis of the jaw occurred in 4% vs 3% (P = .147). The most common serious adverse event in both groups was pneumonia (8% in both). One patient in the zoledronic acid group died of cardiac arrest that was considered treatment-related.


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