The rat study below suggests that you need to carefully watch your Vitamin D levels while on IV bisphosphonates.
Personally, I am being very cautious and only doing Aredia every three months, despite having had an L4 plasmacytoma and three other small lesions in my ribs and clavicle. I have a vitamin D receptor polymorphism that is associated with increased risk of myeloma. It's also important to remember that these drugs are hard on your kidneys and to stay very well-hydrated while using them.
A Hokugo et al, "Increased prevalence of bisphosphonate-related osteonecrosis of the jaw with vitamin D deficiency in rats", J Bone Miner Res. June 2010 (link to full text of article)
Abstract
Necrotic bone exposure in the oral cavity has recently been reported in patients treated with nitrogen-containing bisphosphonates as part of their therapeutic regimen for multiple myeloma or metastatic cancers to bone. It has been postulated that systemic conditions associated with cancer patients combined with tooth extraction may increase the risk of osteonecrosis of the jaw (ONJ).
The objective of this study was to establish an animal model of bisphosphonate-related ONJ by testing the combination of these risk factors. The generation of ONJ lesions in rats resembling human disease was achieved under the confluence of intravenous injection of zoledronate (ZOL; 35 microg/kg every 2 weeks), maxillary molar extraction, and vitamin D deficiency [VitD(-)]. The prevalence of ONJ in the VitD(-)/ZOL group was 66.7%, which was significantly higher (p < .05, Fisher exact test) than the control (0%), VitD(-) (0%), and ZOL alone (14.3%) groups.
Similar to human patients, rat ONJ lesions prolonged the oral exposure of necrotic bone sequestra and were uniquely associated with pseudoepitheliomatous hyperplasia. The number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end label-positive (TUNEL(+)) osteoclasts significantly increased on the surface of post-tooth extraction alveolar bone of the VitD(-)/ZOL group, where sustained inflammation was depicted by [(18)F]fluorodeoxyglucose micro-positron emission tomography (microPET). ONJ lesions were found to be associated with dense accumulation of mixed inflammatory / immune cells. These cells, composed of neutrophils and lymphocytes, appeared to juxtapose apoptotic osteoclasts.
It is suggested that the pathophysiologic mechanism(s) underpinning ONJ may involve the interaction between bisphosphonates and compromised vitamin D functions in the realm of skeletal homeostasis and innate immunity.
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KWeisman - Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 12/2012
- Age at diagnosis: 47
Re: Aredia & osteonecrosis of the jaw - what to do?
I developed ONJ while on Zometa and after going from dentist, to oral surgeon, to oncologists, I finally ended up in a periodentist's office. She treated my necrosis – successfully – with laser treatments to the necrosis. It took several months for it to heal, but I did heal without any complications luckily.
After being off Zometa for several years, I finally had the tooth in the necrosed area removed without any complications. I chose not to go back on Zometa, so I hopefully won't get this problem again.
Good luck with your treatments.
After being off Zometa for several years, I finally had the tooth in the necrosed area removed without any complications. I chose not to go back on Zometa, so I hopefully won't get this problem again.
Good luck with your treatments.
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Richard Beach
Re: Aredia & osteonecrosis of the jaw - what to do?
I too have a toothache and the tooth must come out and I am on a bisphosphonate (Zometa). I have to wait THREE months prior to having the tooth out, then wait until the hole and socket is FULLY sealed and healed before I go back on them - due to the very real danger of ONJ.
I would be looking very hard and asking lots of questions as to how this happened, as I would think the duty of care would have been to check the socket had healed properly prior to recommencing the bisphosphonate AND only a one month break prior is not what was recommended to me - all up should be about 5 months.
I would be looking very hard and asking lots of questions as to how this happened, as I would think the duty of care would have been to check the socket had healed properly prior to recommencing the bisphosphonate AND only a one month break prior is not what was recommended to me - all up should be about 5 months.
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Salzmav - Name: Salzmav
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2010
- Age at diagnosis: 52
Re: Aredia & osteonecrosis of the jaw - what to do?
I was on Aredia for a little less than 3 years and did not have any problems. Nevertheless, I was concerned about this side effect which, by the way, the oncologists never mentioned. Had I not been vigilant in checking out each medication, I would not have known. I had an extraction between starting Aredia and discovering the potential for this, so I'm doubly lucky not to exhibit this particular side effect.
Since you already have osteonecrosis, I would definitely stop taking it because you are obviously one of the small percentage where this happens. As in your case, it is most often triggered by some major dental procedure such as extractions.
For those who might take, or are taking, a bisphosphonate, there are a few things to be aware of. First, there are different dosing levels and oncologists typically use the highest dosage. You should switch to the lowest dosage because it has been proven to be just as effective as the highest dosage and, in my mind, the lower dosage would carry a lower chance of this side effect.
Secondly, the FDA has issued a guidance that taking a bisphosphonate carries no benefit beyond three years. One of the reasons for this advice is that the half-life of this drug is "10 years", so the effect carries on for a long period of time. So I followed that advice and discontinued mine. Instead, I switched to bone density testing and will only consider one of these meds if that testing shows that my bone density becomes critical. In my case, my bone density showed above normal, so I obviously no longer needed this potentially dangerous drug.
My heart goes out to you and Ian. I hope that the surgeon can help you work through this side effect and I suspect that bone grafts may be required once the necrosis process had abated. I thank you for sharing your story here, and please keep us posted on Ian's progress. Your story may prove helpful to many others of us who are potentially in the same boat.
John Benton
Since you already have osteonecrosis, I would definitely stop taking it because you are obviously one of the small percentage where this happens. As in your case, it is most often triggered by some major dental procedure such as extractions.
For those who might take, or are taking, a bisphosphonate, there are a few things to be aware of. First, there are different dosing levels and oncologists typically use the highest dosage. You should switch to the lowest dosage because it has been proven to be just as effective as the highest dosage and, in my mind, the lower dosage would carry a lower chance of this side effect.
Secondly, the FDA has issued a guidance that taking a bisphosphonate carries no benefit beyond three years. One of the reasons for this advice is that the half-life of this drug is "10 years", so the effect carries on for a long period of time. So I followed that advice and discontinued mine. Instead, I switched to bone density testing and will only consider one of these meds if that testing shows that my bone density becomes critical. In my case, my bone density showed above normal, so I obviously no longer needed this potentially dangerous drug.
My heart goes out to you and Ian. I hope that the surgeon can help you work through this side effect and I suspect that bone grafts may be required once the necrosis process had abated. I thank you for sharing your story here, and please keep us posted on Ian's progress. Your story may prove helpful to many others of us who are potentially in the same boat.
John Benton
Re: Aredia & osteonecrosis of the jaw - what to do?
Hi John,
I see you're new to the forum. Welcome.
I was wondering if you could clear something up for me. You mention an FDA warning about bisphosphonates. The warning that I'm aware of is the one that was issued in 2010. However, it did not apply to bisphosphonates used in the treatment of multiple myeloma. This is explained in this Beacon article,
"New FDA Warning About Bisphosphonates Does Not Apply To Multiple Myeloma," The Myeloma Beacon, Oct 15, 2010
and also in the FDA's own press release about the warning,
When it comes to issues such as how long to use a bisphosphonate, or whether or not regular doses or low doses should be used, I think it's worth looking at what myeloma experts say on the subjects, rather than general statements about bisphosphonates. The International Myeloma Working Group (IMWG) issued guidelines about bisphosphonate usage in 2013, and the guidelines discuss both treatment duration and does level (and other issues). Here's a summary of the guidelines,
"Experts Publish Treatment Recommendations For Multiple Myeloma-Related Bone Disease," The Myeloma Beacon, Jun 26, 2013
The complete text of the guidelines is available here:
E Terpos et al, "International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease," Journal of Clinical Oncology, June 20, 2013 (link to full text of article)
Those guidelines, according to the Beacon summary, say the following about the duration of bisphosphonate therapy
The guidelines also discuss evidence about the possibility of reducing bisphosphonates doses. They note that studies have investigated reduced dosing, but it's not possible to draw "final conclusions because of limitations of these studies."
I see you're new to the forum. Welcome.
I was wondering if you could clear something up for me. You mention an FDA warning about bisphosphonates. The warning that I'm aware of is the one that was issued in 2010. However, it did not apply to bisphosphonates used in the treatment of multiple myeloma. This is explained in this Beacon article,
"New FDA Warning About Bisphosphonates Does Not Apply To Multiple Myeloma," The Myeloma Beacon, Oct 15, 2010
and also in the FDA's own press release about the warning,
When it comes to issues such as how long to use a bisphosphonate, or whether or not regular doses or low doses should be used, I think it's worth looking at what myeloma experts say on the subjects, rather than general statements about bisphosphonates. The International Myeloma Working Group (IMWG) issued guidelines about bisphosphonate usage in 2013, and the guidelines discuss both treatment duration and does level (and other issues). Here's a summary of the guidelines,
"Experts Publish Treatment Recommendations For Multiple Myeloma-Related Bone Disease," The Myeloma Beacon, Jun 26, 2013
The complete text of the guidelines is available here:
E Terpos et al, "International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease," Journal of Clinical Oncology, June 20, 2013 (link to full text of article)
Those guidelines, according to the Beacon summary, say the following about the duration of bisphosphonate therapy
Treatment with Zometa should be administered until disease progression for patients who do not achieve a very good partial or complete response to their anti-myeloma therapy, and should be continued after relapse.
According to the experts, the evidence is less clear regarding the duration of therapy with Aredia. They therefore recommend that physician discretion determine the duration of treatment with Aredia, and that treatment be resumed at relapse.
The researchers add that the optimal treatment duration is not clear for patients who achieve a very good partial or complete response to their anti-myeloma therapy. The experts recommend, however, that these patients be treated for at least 12 months and up to 24 months and at their physicians' discretion thereafter.
The guidelines also discuss evidence about the possibility of reducing bisphosphonates doses. They note that studies have investigated reduced dosing, but it's not possible to draw "final conclusions because of limitations of these studies."
Re: Aredia & osteonecrosis of the jaw - what to do?
Just an update ...
What we thought was osteonecrosis of the jaw turns to be something far some serious.
As we were heading to the dental hospital on Monday (for a second opinion and xrays), we were fully expecting a confirmation that would eventually give the same result as the first dentist we saw (that is, the local dentist).
After the second dentist carefully examined the problem on the bottom right hand side of the jaw, where the problem seems to be, she said it's basically the root of the tooth left and if pulled out the gum will heal and seal properly (local dentist said the same thing, but asked a more detailed review of the jaw just to make sure things are ok).
In the waiting room , after 5 minutes and the first xray done, we were called in again, this time for a full scan of the jaw! Dentist said it looks quite interesting – it's a little puzzle for them.
The full scan revealed (it's initial results anyway) a hole (!!) of some sort that could be in the tooth or the jaw – nobody knows. This is the puzzle! It's in front of the teeth, bottom side, in below the gum. Results will come in a week.
Meanwhile, we have all types of scenarios in our heads and questions about what can it be. Osteonecrosis? Active multiple myeloma in the jawbone? Maintenance treatment for multiple myeloma?
Or something else ?
I guess anything else present apart from active multiple myeloma will be good news!
We have to wait and see. The end of the week cannot come soon enough!
What we thought was osteonecrosis of the jaw turns to be something far some serious.
As we were heading to the dental hospital on Monday (for a second opinion and xrays), we were fully expecting a confirmation that would eventually give the same result as the first dentist we saw (that is, the local dentist).
After the second dentist carefully examined the problem on the bottom right hand side of the jaw, where the problem seems to be, she said it's basically the root of the tooth left and if pulled out the gum will heal and seal properly (local dentist said the same thing, but asked a more detailed review of the jaw just to make sure things are ok).
In the waiting room , after 5 minutes and the first xray done, we were called in again, this time for a full scan of the jaw! Dentist said it looks quite interesting – it's a little puzzle for them.
The full scan revealed (it's initial results anyway) a hole (!!) of some sort that could be in the tooth or the jaw – nobody knows. This is the puzzle! It's in front of the teeth, bottom side, in below the gum. Results will come in a week.
Meanwhile, we have all types of scenarios in our heads and questions about what can it be. Osteonecrosis? Active multiple myeloma in the jawbone? Maintenance treatment for multiple myeloma?
Or something else ?
I guess anything else present apart from active multiple myeloma will be good news!
We have to wait and see. The end of the week cannot come soon enough!
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johanna - Name: Joanna
- Who do you know with myeloma?: Husband
- When were you/they diagnosed?: august 2012
- Age at diagnosis: 60
Re: Aredia & osteonecrosis of the jaw - what to do?
I have ONJ. I was on a monthly Zometa IV drip but hadn't been told about the dangers of having dental treatment at the same time.
However, I kept getting an abscess under a tooth on the bottom left and it had to come out.
The hole never healed. Fast forward awhile, and I had to have my chemo suspended so I could have most of my bottom teeth and half my top teeth extracted. I am left with my 8 top front ones so I can still smile
I am left with my back left wisdom tooth, which is next to the hole in my jaw, and I keep getting bone breaking through the gum.
The hospital is paying for me to have a new set of teeth to replace the ones I am missing. They are being made by a technician in Munich, Germany. I get my next fitting next week.
However, I kept getting an abscess under a tooth on the bottom left and it had to come out.
The hole never healed. Fast forward awhile, and I had to have my chemo suspended so I could have most of my bottom teeth and half my top teeth extracted. I am left with my 8 top front ones so I can still smile
I am left with my back left wisdom tooth, which is next to the hole in my jaw, and I keep getting bone breaking through the gum.
The hospital is paying for me to have a new set of teeth to replace the ones I am missing. They are being made by a technician in Munich, Germany. I get my next fitting next week.
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LeslieK - Name: LeslieK
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Nov 2006
- Age at diagnosis: 51
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