DW: Why are patients with MM at risk for bone disease?
Dr. Raje: Bone disease is a very common problem associated with multiple myeloma. It is in fact one of the pathognomonic features of myeloma. You know, when you think about CRAB criteria, the B in the CRAB stands for bone disease, and really it is present, I would argue, in the majority of myeloma patients. And the question is, how hard do we look for bone disease in patients with myeloma?
The reason for patients to have bone-related problems in the context of multiple myeloma is … and this is data which has gone back now years, wherein we’ve shown that bone metabolism is significantly impacted in the context of myeloma. You have two different cell types: osteoclasts, which are the bone destroying cells; and osteoblasts, which are the bone forming cells, which are at complete odds in the context of myeloma. And we also know that the myeloma tumor cells, or the myeloma cells, feed into this vicious cycle wherein they cause an increase in osteoclastogenesis—that is the bone destroying cells—and there’s very little, if any osteoblastic activity, that is the bone healing part of it. And there’s a whole bunch of proteins and cytokines which we’ve identified as factors which could be contributing to this. And this is that interaction between the tumor cell and the bone microenvironment, which then results in osteolytic disease, which is very classic of multiple myeloma. And, you know, if you want to think about osteolytic disease simplistically, it is an extreme form of osteoporosis wherein you can actually get those bony lesions that I’m talking about.
And the reason it’s really important to try and identify this and treat this proactively is because this can result in pretty significant morbidity in the way of bone pain fractures, and some of the acute sort of emergencies that we know of in oncology, such as hypercalcemia and cord compression can be a consequence of bone disease.
DW: How do you address bone disease in patients with MM?
Dr. Raje: We should start out by thinking about, how do you diagnose bone disease in patients with multiple myeloma? And the International Myeloma Working Group has now come up with imaging modalities. Up until recently, we were using x-rays to diagnose bony-related problems, so scale surveys was part of routine workup for multiple myeloma patients. That has changed with the new guidelines and our recommendation is really to use either a whole body low-dose CAT scan, or a PET CT scan, or an MRI as an initial diagnostic tool. And the reason for that is x-rays are able to pick up bone disease in patients where you have more than 50% of bone loss, so the bone loss is pretty extreme by the time it shows up on an x-ray. And therefore it’s important to use more sensitive criteria to pick up on bone disease, and this is sort of incorporated into the new working diagnosis of symptomatic multiple myeloma. So you don’t necessarily have to have symptoms, but if on imaging modalities you have evidence of bone disease, that’s enough for us to warrant treatment for myeloma and the associated bone disease as well. So imaging is really important. We’ve completely replaced scale surveys, at least at my center, and we’re doing whole body low-dose CAT scans. It’s an easy test. It takes about a minute and a half. It does not expose a patient to that much more radiation, and it has a sensitivity of nearly 90%, so you’re able to pick up bone disease in a lot of patients.
The other thing I will say is, you know, diagnosing is important, but trying to prevent some of the complications that I’ve talked about with bone disease already very important to diminish the morbidity. And we also know that if you have the morbidity associated with bone disease, it is associated with worsening outcomes in terms of mortality as well. So it’s critical that we pick up on it and critical that we proactively treat it. So the best treatment for bone disease for myeloma is treat the underlying myeloma. Once you treat the underlying myeloma, patients are going to have lot less in terms of bony-related complications. And the other things we have now for years is the use of minor bisphosphonates. So we use either pamidronate or zoledronic acid for the treatment of bone disease. And we now have a new monoclonal antibody, which is a RANK ligand inhibitor called Denosumab, which is also used for the treatment of myeloma related bone.