What is bone strengthening therapy?

What is bone strengthening therapy? Should bone strengthening therapy be restarted at relapse?

 
The idea behind bone strengthening therapy is that I really think of this as sort of the icing on the cake to myeloma therapy. Now, what I what I mean by that is that we know that myeloma likes causing bone damage. Not in everyone. Not everyone with myeloma has bone damage, but one of the cardinal signs and symptoms of myeloma is bone damage.

Myeloma likes chewing on the bones. When I talk to patients about this, I refer to this as sort of like bone or sort of like termites in wood, where the termites are the myeloma, the wood is the bone. So termites like chewing on the wood. Myeloma likes chewing on the bone. eventually the bone in myeloma can get soft.

It can even break if those termites or if the myeloma cells chew on the bone enough to cause significant enough damage. The best way to control bone damage in myeloma is to control the myeloma. So all the medications that we use to treat myeloma as they kill off those myeloma cells, they indirectly help the bones because it means the termites are no longer chewing.

You know, when myeloma cells have stopped chewing on the bones and then the bones have a remarkable ability to heal. So once the myeloma stops beating up on the bones and the bones can actually heal themselves. So again, key to controlling bone damages in myeloma is control the myeloma. But then we know in addition that there are bone strengthening medications, that can actually be helpful in specifically strengthening the bone such that they're proven to reduce the risk of bones fracturing.

And then there is even some data that they can help with bone pain in myeloma. even some interesting data showing that these drugs sometimes can help keep myeloma under control for longer, which is not something that we would think of for that class of that medication. But it seems to work. so needless to say that bone strengthening medications in myeloma can be extremely helpful.

And so the ones that we most often use are zoledronic acid, which is zometa or the other. The other one is denosumab, which is xgeva. these medications have, they're both highly effective. They both have their individual space for when we use them. and so they both are highly appropriate for people with myeloma. In terms of how we use them at relapse,

 
There's really not a whole lot of science to inform this discussion. and a lot of that is driven by the fact that as these medicines are given, they often stay in the bones for years, if not forever. So bisphosphonates, especially this zoledronic acid, you get it once ten years ago you especially if you've gotten it for some length of time years past that medicine basically gets incorporated into the bones as bones are growing, building, remodeling, and then it sticks around so it does not get clear from the body.

 
Which is to say that that medicine is pretty much in you forever. and as a result of that, it's hard to know, okay, if myeloma comes back, is the old Zometa or the old zoledronic acid that's in there still going to be helpful, or do we need to boost it? Do we need to give more? there have really not been great studies to inform that discussion, but what I'd say is that what most of us do, or that if myeloma has come back, we have a discussion about restarting those medications, assuming a person's not currently on them.

if they have bone trouble with their myeloma, then it's probably especially important to do it. So we recommend that for almost everyone with bone issues related to their myeloma, if they don't have bone issues, still recommend it, but it's probably less critical. and then the other thing that we need to think about with those agents is not only, you know, benefits for bone health, but also side effects, and so if the side effects are likely to be excessive

 
then a lot of times we'll skip those medications. and so the side effects that we think about or that the bisphosphates can sometimes cause kidney trouble. Most often they don't. But we need to think about that. Low blood calcium levels can sometimes be an issue with those medications. But then the most feared complication with those medications is this thing called osteonecrosis of the jaw.

 
We call it ONJ for short. And so this is an unusual side effect that we don't completely understand biologically. But what happens is that when people receive bisphosphonates. So again typically zoledronic acid or denosumab can happen with either of those medications. that those medicines sometimes can cause damage to the teeth and the jaw. Usually it's relatively minor, but when it happens it can be more severe or even up to the point of teeth falling out, gums peeling back.

It's rare, but it can be pretty awful. that's those side effects happen in a small minority of people, but it's most often people that either they get the medication and they either don't have great teeth to begin with, or they get major dental work after they've received those medications for a while. With major, major dental work referring to not cleanings, not fillings.

 
Any routine dental care is fine, but it's more often things that are more invasive in the jaw. So things like extractions when people have teeth pulled, of course, that gets into the socket or implants, you know, when they put the screws in that false teeth attached to those screws, of course, go into the jaw. and so people that have dental issues or they're likely to need procedures like that, or if they've had procedures like that recently, we typically avoid those bone strengthening medications at least until the dental issues are resolved.

so to sum up, I'd say that most people with relapsed refractory myeloma probably should be on those medications, but it's not a it's not a uniform recommendation for everyone. But we think about it. So how long do we do it for us. So there's really no research on how long we should do that for. I'd say that most often we do it for one year or two years, often giving it once every three months.

And then as the myeloma gets back under control, we feel like the bones are doing okay. Often stop the medication. But sometimes if somebody's myeloma is not in great remission, if we feel like the myeloma is still active, we'll keep it going. but that's really a sort of individualized discussion, largely because we have very little data to inform us on what the best, the best way is to use those medications and that specific circumstance.

 
In multiple myeloma, we know that the bones are affected. First of all, we do have the bone lesions in a lot of patients at diagnosis and then in general the myeloma can also cause osteoporosis. In the supportive care guidelines, we do have a recommendation to treat everyone with bone strengthening medications, at least for the two years after diagnosis.

We have two different options. We have the bisphosphonates, the zometa or zoledronic acid. We have the denosumab or Xgeva as the other option. And these are also the recommendation is for two years for xgeva either continue at every six months after that or you give one dose of zometa to prevent, rebound.

so this helps prevent both fractures and bone lesions going forward. At relapse depends a little bit. There's not any strict kind of guidelines on when and if to start. Depends a little bit on how the patient prevents and how long it was ago that you had the initial bone strengthening. So for someone, for instance, if there's an unfortunate relapse after a year, maybe you don't need to restart because these especially the bisphosphonates, they have an effect over a long period of time.

 
If someone relapses after many years and again with a compression fracture, then yes, I would restart that again. The important thing to think about there was both of these medications. They are usually very well tolerated, but they can have some dental side effects, something called osteonecrosis of the jaw. So we always have our patients see a dentist and clear them for this before starting.

 
So I mean there's a guideline statement around that, you know, from Asco and other guidelines, statements as well. it's, you know, currently when patients present, and if they have bone lesions or osteopenia osteoporosis it's indicated to use anti resorptive therapy. assuming that they, they've had all necessary restorative dental care performed. So dental evaluation prior to that is important.

so it's, folks can get anti resorptive therapy generally for two years is what the recommendation is. There's some data to support giving anti resorptives for a longer period of time. but that's perhaps, you know, open to physician and patient choice. The current recommendation is to resume antiresorptive therapy at the time of disease relapse.

But I think that you know there the data is less well developed. And so I think it's really a patient choice. And physician choice, individuals presenting with hypercalcemia for example, at relapse. Well, it would make sense to treat with an antiresorptive therapy because it'll mitigate that. type of side effect or that issue, and others, you know, on a case by case basis, depending on the way they present.