What causes myeloma bone pain? How can bone pain be managed?

[Music] what causes myeloma bone pain most of the patients have multiple myeloma bone pain due to lytic lesions we know that myeloma cells Express cytokines proteins that activate osteoclasts the osteoclasts are the bone-eating cells you have in your body osteoclasts bone-eating cells and osteoblasts those are the bone producing cells so in multiple myeloma we know that the myeloma cells directly secrete we'll protein cytokines growth factors that again as I said activate the osteoclasts but inhibit at the same time the osteoblasts so what you end up is that you have a hole in your bone we call that lytic lesions and this is because the over activity of the osteoclasts of the bone eating cells really cause that excessive resorption destruction of the bone you can have larger lytic lesions up to a centimeter several centimeters but those lytic lesions can be very small so the presentation of bone disease can vary from just an osteoporosis with many small I would say holes in your bones to a large lytic lesion that can cause a fracture so usually when you have osteoporosis you will not really feel any bone pain but when those lesions become larger they can be painful and when you develop a fracture for instance very often in your spine or in your ribs as a first symptom those lesions are very painful and very often patients come to the doctor with those fractures and this bone pain as I mentioned patients who have larger lytic lesions those lesions can directly cause bone pain due to instability of the bone and also the myeloma cells can cause directly pain if you have a large accumulation of myeloma cells and the bone how can bone pain be managed so if patients have myeloma bone pain the best thing to do is really to treat the myeloma as effectively and aggressively if possible so because it's the myeloma cells that are then impacting the bone cells but beyond that then it's really important to try to stabilize the skeleton as much as possible the way that's been most effective thus far is to try to slow down the activity of those scooping out cells and there's medications which we call anti resorbed of medications so they stop the bone resorption that's ongoing and there's two classes of those medications the first of the bisphosphonates so medications like primogenitor Aredia or zoledronic acid or Zometa the way that these medications is work as they get infused and they circulate around in the blood they ultimately land on the bone and then when they're laying on the bone then these osteoclasts try to dig up and scoop out some bone and in doing so they take up some of this bisphosphonate into the inside of the the osteoclast they internalize them and there's an enzyme within the osteo class called farnesyl pyrophosphate synthase these these bisphosphonates cause that enzyme to be blocked and when that enzyme is blocked then the cell basically can't survive anymore the other medication that has now been approved now for about the last year and a half is a medication called de no Sam AB or X jiva and that works a little bit differently so in order for an osteoclast to become a active bone resorbing cell it has to go through a maturation process and this medication Deneau somatic jiva it blocks the signal that the pre osteoclast needs to become an active osteoclast that works very well but the problem is if you ever discontinue that signal then all the the precursor cells that have built up are then rapidly able to become active osteoclasts and then they're able to quickly cause bone to be chewed up and lost and then there's really nothing to stop them so that's why if patients are started on a medication like to know some a Breck's jiva it really needs to be continued probably given at least once every six months thereafter whereas the bisphosphonates even after you have stopped taking them they're still lining the surface of the and so they'll continue to be active for several years likely they're after multiple myeloma you want to treat a for the destruction of the myeloma cells and B you want to inhibit the activity of the osteoclast bone eating cells to decrease the bone destruction bone resorption and bisphosphonates that has been shown help to reduce activities of the osteoclast so that's why each myeloma patient who starts treatment for multiple myeloma independent and that's important independent whether the patient has lytic lesions or not should be on a bisphosphonate and start with this kind of treatment we have a newer kid on the block DiNozzo map which is a rank ligand inhibitor and you know some app is very conveniently given it's given as a subcutaneous injection and in contrast to bisphosphonates bisphosphonates are given as an infusion so Dean also mapped rank ligand inhibitor also called X Jeeva this given subcutaneously monthly and the nice thing is you don't have to check the renal function so independent whether you have renal damage from the might of a myeloma to your kidneys you can get that in also map the promised in awesome up is it's very expensive and usually as a standard of care we recommend still so mara but for patients who have renal impairment or renal problems I think the nozzle map is a very nice alternative what I also want to mention and this is a very new result and it was published at Ash last year that in a large randomized trial there's 1,700 patients in which the patients were randomized to either receive Zometa or donoso map there was a ten point seven months increase in the progression free survival and patients who received t no soma we don't know exactly the mechanism of this but it's a very surprising and interesting result and I think in the future the myeloma experts have to think about what is the best treatment for bone disease is it a bisphosphonate or is it in our map bone pain is a very severe issue and especially at an early diagnosis of myeloma there are several things that we can do of course pain medicine should be use we don't like the non-steroidals like ibuprofen the clinic because they have they go through the kidneys and in myeloma patients the kidneys can be involved so we rather recommend acetaminophen which is tylenol instead of these these other drugs we recommend opioids if necessary for systemic treatments re also is bisphosphonates and they know some up because they provide also some pain relief sometimes for local treatment we can do either radiation we can in the spine we can do kyphoplasty or vertebroplasty because the bone cement that is going into the bone there can kind of help to numb the bone in this area because when it becomes hard it cooks the nerve endings more or less and so there's less pain in this area if necessary sometimes outside braces help to to stabilize that the patient doesn't do movements that could cause pain so we have a lot of options to to help with bone pain and still there's a lot of bone pain and we still have to get better but I think we already have a lot to to help the patients [Music]