(Guest Lecture): Impact of Myeloma on Bone Health | MCRT Webcast: Making Sense of Myeloma Bone Issues

[Music] when we think about the bone i'd like to have you think about buying a soup bone in the supermarket and if you pick up a soup bone you'll see it really has two separate components one is a thick white shell that's the cortical bone it's very very strong if you take that bone you could jump on it and you wouldn't harm the bone you'd need a hammer in order to break and then inside that cortical bone is that brown spongy bone marrow where your blood producing organ resides and where myeloma initiates itself myeloma cells have the ability to do two things one is they will grow outside the bone marrow into the cortical bone and it replaces the very hard cortical bone with the very little soft clusters and islands of myeloma cells that we refer to as small little plasmacytomas when you look at the bones on x-ray the hard calcium-containing bone will show white and where the little clusters of myeloma cells that replace the blow bone integrate they don't stop the extra so they look dark and because they're little islands of myeloma cells they grow in almost perfectly round shapes and so it's gained the misnomer of holes in the bone but that of course is not correct they're not really holes the hard bone structure calcium is being replaced by the soft gelatinous material of myeloma cells that produce these replaced lytic lesions that are so often incorrectly referred to as holes in the bones but in any case when these small little areas of replacement occur the bone becomes structurally less sound the ability to withstand the pressures of daily life is reduced because the bone is structurally unsound and on top of this myeloma cells produce chemicals and these chemicals actually leech bone mineral out of the bone it takes the calcium out of the bone which softens and weakens them this actual extraction of calcium from the bone into the bloodstream is why about 10 percent of newly diagnosed myeloma patients have high levels of calcium in the blood these high levels of calcium are derived from the calcium being extracted from the bone this bone mineral loss is a natural process of aging and when it occurs to a significant degree it's referred to as osteoporosis but in multiple myeloma the process is accelerated so you have two problems going on with the bone the first problem represents the loss of bone mineral osteoporosis the second is the invasion into the cortical bone producing the lytic lesion so-called holes that make the bone structurally weak and when you look at myeloma unfortunately 70 of myeloma patients come to attention due to some type of bone pain usually in the bones of the spine or in the ribs occasionally the long bones with fractures of an arm or a leg but typically back pain and rib pain and this often is not diagnosed rapidly there'll be a number of you in the audience where you will have had back pain for a number of weeks or months and your diagnosis will have been delayed because on x-ray of the spine what you see are compression fractures the spine actually is made up of children's building blocks they're the shape they're cubes essentially and in an adult spine there are 24 of these building blocks one on top of another the vertebrae and the vertebrae that are subjected to a lot of mechanical stress which is the lower vertebrae predominantly if they get weakened by myeloma they will collapse they'll compress which of course will cause very exquisite pain it's a fracture and the pain that they produce is like a typical fracture if you lie perfectly still and don't move the affected part be that a rib an arm or your back there's no pain at all but as soon as you try to move we'll just say your spine due to a compression fracture rotation getting out of bed moving your center of gravity forward trying to get off the toilet will cause exquisite pain because you're moving flexing rotating that damaged part and that's the fracture pain that leads to diagnosis unfortunately if you do a plain x-ray of the bone itself what you'll find is compression fracture and it won't obviously look like a malignancy so it's possible to do x-rays c fractures and ascribe it off to plane osteoporosis leading to delays and diagnosis so frequently patients won't present until they develop multiple spinal fractures these fractures which represent collapse of these child building blocks many patients recognize by loss of height the vertebrae roughly are about an inch to an inch and a half in vertical height and if you will compress four of them fifty percent you'll end up losing two to three inches in height and this is very common in the myeloma population to report significant height loss one thing we should all be aware of is that these fractures occur due to the activity of the myeloma and with modern techniques with much much deeper responses and much more prolonged responses the reality is the frequency of these skeletal events in my practice over 40 years has declined sharply when people develop very very low levels of myeloma no matter how you measure the myeloma is under very deep control the likelihood of developing a subsequent skeletal event is very small so skeletal events these fractures usually are either part of diagnosis or very many years down the line if the disease can't be well controlled they'll come again but during the main course of the disease what i've seen over the last 40 years has been that the frequency of these events have declined sharply and this has led to a lot of changes in the way in which medications used to prevent these skeletal events are administered when i first started there really was no treatment other than calcium and vitamin d which of course is recommended for all patients but there are other medications that we'll be discussing that will help prevent bone damage and what we've found over the years because of the deep durable responses where we used to for example give some treatments monthly now we'll give them for every three months because the likelihood of developing a skeletal fracture when your disease is under such good control is actually small secondly we've also for patients with very very deep responses we used to give monthly treatments indefinitely now for people with very deep responses we'll treat patients for two years and we will completely discontinue treatment because the risk of an event is so low that the risk of a complication of treatment see the risk of withholding treatment so we stop treatment for many bactivates the way in which we understand the bone that bone is not a static organ bone is living and it's vital and that's a good thing because as you all know bones grow and of course if bones were not living things they wouldn't repair themselves after referring [Music] and hip happens in the bonuses there's this dynamic between continuous ball so there's this dynamic equal resorption and as a consequence the bonus spins with many of the treatments that are used what they do is they begin to inhibit they block the resorption of bone which is accelerated in myeloma but don't have an impact on the continued production of bone and thereby overall improving bone or skeletal mineralization over time there's this balance that occurs now in terms of the treatments that become available to us there are a number at the time of diagnosis of course there are three approved medications that are used to help maintain bone health in addition to both calcium and phosphorus vitamin d but it's also important to know that there are a number of supportive treatments that are available one of which is vertebroplasty or kyphoplasty in both of those techniques a fractured bone can be injected with a bony cement and this results in significant pain reduction for a high proportion of patients so this is a technique we use quite frequently in patients where after chemotherapy with control of the myeloma and persistent pain due to spinal fractures will have an interventional radiologist inject cement for pain control it's important to keep in mind that the role of vertebroplasty or kyphoplasty is solely limited to pain control it isn't going to make you taller and these injections are not done simply because fractures are present it has to be fractures that are provide causing significant pain that aren't controlled with non-opioid analgesics and after the myeloma is responsive and controlled if there's one i would say major problem with non-myeloma experts in newly diagnosed myeloma patients that i think is overly abused it's spinal radiotherapy spinal radiation for non-myeloma malignancies like lung cancer or breast cancer that are not particularly responsive to chemotherapy spinal involvement with those cancers can be responsive and the pain can be controlled with radiation therapy but in multiple myeloma the disease is highly responsive more importantly when spinal fractures occur the pain is not due to the cancer cells themselves it's due to the fractures and what i found is that patients get extensive and inappropriate radiation to the spine thinking it will control pain but they're fractures and they take time to heal and so even with effective myeloma therapy bone pain can persist two to three months before adequate healing occurs but it does occur and when it doesn't occur typically the answer still shouldn't be radiation but reconsideration of vertebroplasty or kyphoplasty i would say that in multiple myeloma reconstructive spine surgery i think also is overused i think it would be an unusual patient that actually would need spine rods placed those patients usually can be managed much less invasively with much less risk i would say that there are occasional times when radiation therapy for bone disease is appropriate one would be either after surgical fixation of a long bone to prevent any further erosion of the bone occasionally if there is a very high risk of fracture in an affected bone radiation therapy in a very localized area to prevent fracture but almost never to the spine this would be given to an arm or a leg or rarely a postage stamp size treatment to a rib would be indicated the only time we would consider spinal radiation for a bony event is if we thought there was significant encroachment either on the spinal cord or a nerve root in those cases localized radiation can prevent neurological complications but by and large we don't use radiation therapy we rely on effective therapy of the myeloma and the three approved medications that are regularly used to help reduce the bone turnover the bone resorption that allows for strengthening of the bone and thereby reducing the risk of a subsequent skeletal events many patients ask on a regular basis whether these so-called holes if you will fill in or disappear they do not and so effective therapy doesn't mean that the bone x-rays or imaging studies normalize it what actually happens is these replaced areas of myeloma once the myeloma is destroyed those little areas fill up with scar tissue and although scar tissue doesn't have the structural integrity of normal bone it's much much stronger than myeloma replacement it's the difference between something gelatinous like raw liver and something tough like gristle on meat which is very strong difficult to tear through and so the bone clearly gets stronger when the myeloma is destroyed and is replaced by the scar tissue so the skeletal x-rays of the spine the vertebra don't grow back the so-called holes don't disappear but clearly get stronger and again i think my primary message is that after initial diagnosis during the bulk of the course of myeloma the number of skeletal events have declined substantially and the risk of a skeletal event with deep responses that we see now over 60 percent of the time are very very low and so in many instances the need for ongoing supportive therapy of the bone is less than the risk of a complication of these treatments and i think i used up my 15 minutes jenny so i'll put myself back on mute for professor rajay [Music] you