[MrPotatohead]

Where are the new treatments for myeloma bone damage?

by MrPotatohead on Fri Dec 18, 2015 2:15 am

Despite the fact that better than 70% of those with active multiple myeloma have bone damage caused by the disease, I have found very little concerning active research/clinical trials for new treatments to repair damaged bones or stop their destruction.

Bisphosphonates continue to be the treatment of choice to reduce fracture risk, but they are old news. Besides, they disrupt the normal remodeling of bone in an attempt to block the initial destruction of the remodeling process induced by the myeloma cells.

But this can create its own problems - e.g., deterioration in the old bone that can cause atypical fractures, as well as disastrous side effects like osteonecrosis of the jaw.

I found references to research in this area in neither the 2015 ASH, EHA, nor ASCO reports compiled by Beacon on this site.

I wonder what accounts for this paucity? As better treatments prolong survival, more and more of us are left with damaged bones that turn us into invalids, constantly fighting mobility and pain issues, even after the myeloma itself has been beaten back.

[goldmine848]

Re: Where are the new treatments for myeloma bone damage?

by goldmine848 on Fri Dec 18, 2015 7:35 pm

I know that there are ongoing clinical trials comparing Zometa to denosumab (Xgeva, Prolia). I don't know much about it, but I don't think it is a bisphosphonate. It is a monoclonal antibody.

[MrPotatohead]

Re: Where are the new treatments for myeloma bone damage?

by MrPotatohead on Fri Dec 18, 2015 10:20 pm

Thank you, goldmine848.

It is indeed a monoclonal antibody approved for preventing fractures in osteoporosis and for certain solid tumors that have spread to the bone. But it is not approved, interestingly enough, for multiple myeloma.

[Multibilly]

Re: Where are the new treatments for myeloma bone damage?

by Multibilly on Sat Dec 19, 2015 9:24 am

There is research being done in this field. As an example, there is one approach that uses the approach of binding a proteasome inhibitor to a bisphosphonate:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836429/

There were also a couple of papers delivered at ASH on new drug approaches to reducing bone loss in multiple myeloma patients:

https://myelomabeacon.org/resources/mtgs/ash2015/abs/119/
https://myelomabeacon.org/resources/mtgs/ash2015/abs/4241/

There was also an encouraging study presented at ASH that shows that lytic lesions can and do heal (there have been various disagreements on this topic on this forum over the years):

https://myelomabeacon.org/resources/mtgs/ash2015/abs/4193/

[JPC]

Re: Where are the new treatments for myeloma bone damage?

by JPC on Sat Dec 19, 2015 9:27 am

Hello Mr. PH:

I have no information or knowledge that I can share on your question, other than to say it is an excellent question. In one of the second opinions we had for my wife, the doctor insisted that all his patients go on Zometa, if they need it or not. My wife did not want to do this. She has multiple lesions on the spine, but they are too small to note a size, and they have started to heal based on induction, so, thank God it's not needed at this time.

But, if the bisphosphonate is supposed to support the bones, how can it deteriorate the jaw?? As you point out, there has got to be a better answer, but unfortunately at this time, I do not think there is. Hopefully a better answer will be developed on this important question in the near future. I can share with you that I have read that up to a certain level of size of the lesion, effective healing can occur. Above a certain size, the bone may heal, but is not as strong as original bone. Other posters have commented on the forum that the kyphoplasty procedure has worked very well in some cases for spinal issues.

Good luck to you.

[JPC]

Re: Where are the new treatments for myeloma bone damage?

by JPC on Sat Dec 19, 2015 9:54 am

Quick follow on MB's post:

As is usually the case, MB has posted some excellent references with some very good points. For a while, studies on bisphosphonates have shown somewhat better overall survival when used, as compared to the case of no bisphosphonates. The earlier literature seemed to indicate that the reason was simply better bone health, with a bad spinal injury or other bad injury leading to complications, etc. By avoiding or reducing or delaying this condition, overall survival was enhanced. Recently, I have read researchers have come to believe that the bisphosphonates actually have anti-myeloma effect, further enhancing overall survival. This was noted in MB's first post. There may be more optimal combinations and dosing strategies that are yet to be developed that can improve this effect.

Secondly, on the issue of bone healing, that I understand is noted in the PET/CT or spinal MRI report. The vocabulary is potentially somewhat confusing. The small focal lesions my wife had were noted as past osteoblastic activity (bone degradation). A subsequent report indicated increased osteoclastic (bone healing). On first reading the report, it sounded bad, but fortunately it was a good thing. (Anyone remember the difference between stalagmites and stalactites??). So healing can definitely occur, however, it is far better if it's caught earlier, and the more it progresses, the more difficult to get good healing, that is the problem.

[MrPotatohead]

Re: Where are the new treatments for myeloma bone damage?

by MrPotatohead on Sat Dec 19, 2015 4:23 pm

Multibilly,

Thanks very much indeed for posting the links. I apparently missed the ASH studies.

JPC,

Thanks for the additional information.

As I recall, during the remodeling process of healthy bone, the osteoclasts are responsible for tearing down worn bone, and the osteoblasts for building new bone to replace it. The bisphosphonates like Zometa bind to bone, and cause the osteoclasts to die, hence the accelerated osteoclast activity mediated by multiple myeloma is interrupted.

It is good news indeed that healing of lytic lesions can occur, since the consensus across the material I have read seemed to conclude otherwise.

It is also very interesting indeed that your wife's lesions have started to heal without bisphosphonate treatment! I hope that continues.

On why osteonecrosis of the jaw occurs, I think that question remains unanswered. I have read that the frequency of this side effect may be higher than originally thought, and that it in fact can occur in the absence of any dental work, contrary to earlier reports.

I do hope that the research Multibilly referred to soon leads to some new bone treatments, given how debilitating the bone destruction in myeloma can be.

I can vouch for kyphoplasty. I have had two vertebrae repaired, and my pain was reduced. Still, while that does address spinal fractures, it is not applicable to lytic lesions generally.

[JPC]

Re: Where are the new treatments for myeloma bone damage?

by JPC on Sun Dec 20, 2015 12:42 pm

Hello Mr. PH:

Thank you for the clarification on the issue osteo clast/blast mode of action. Your description I think was much more clear, concise and accurate.

One thought came to mind, just in case you have not looked into it already. Some patients have reported much better than expected response to physical therapy. A good PT has stretches and massages that can relieve pain and discomfort. Increasing strength and flexibility in the muscles enable them to support the problem areas of the skeleton. If you read the book earlier in the year by Tom Brokaw, he goes into detail on the benefits to him of PT (of course he has very strong financial resources that many other patients may not have to that degree). When his back muscles were still weak, he did no impact workouts in the swimming pool, for example. I know you said you are having pain/problems, so you would need to be cleared for such an activity. Another caveate is that not all PT's would be experienced in this type of recovery, so you would need to find someone who is experienced in working with degraded bone cases. I have posted before that this made a huge difference for my wife after her ASCT last February (admittedly, her case was slightly different, general reconditioning from the long period of inactivity from the ASCT, but she also had some bone pain).

Another thought: I am not personally a strong believer in acupuncture (as might be applied, for example, to myself), but I do hear that some patients have found that helpful, as well.

Good luck again. Regards,

[MrPotatohead]

Re: Where are the new treatments for myeloma bone damage?

by MrPotatohead on Sun Dec 20, 2015 11:31 pm

Hi JPC

I did try physical therapy, and did not have a very good experience. I think the problem was that the PT staff I worked with was familiar with addressing deconditioning and orthopedic issues, but not bone damage from cancer. I tried it for about three months, but was not able to achieve any improvement in the pain.

I actually don't see how PT could help. It seems to me that there needs to be some kind of treatment that reverses or repairs the bone damage in order for me, and others with myeloma bone damage, to get relief.

I do plan to try acupuncture.

Thanks very much for all of your suggestions.