COMy 2025 | Advice for managing bone disease in multiple myeloma

Bone disease is the most common complication of multiple myeloma. During the last few years, we don’t have any new data on how to treat patients with bone disease because we have so many important antimyeloma drugs that the drugs that we are using, the bone-targeted agents, in order to manage bone disease in myeloma, I think they are enough. So we are using mainly the bisphosphonate zoledronic acid and the anti-RANK ligand monoclonal antibody named denosumab for the treatment of bone disease in myeloma, along with antimyeloma therapy. I think that the majority knows about that. 

The majority of the physicians give zoledronic acid at the dose of 4 mg or according to creatinine clearance every month or denosumab at the dose of 120 mg subcutaneously again every month. The two drugs have shown to be equal in terms of skeletal-related events based on a randomized trial that was published some years before. And also it seems that denosumab, because it’s not cleared through the kidneys, has very low adverse events of renal significance, and that’s why it is also a very good drug for those patients who have renal impairment. 

In general, the recommendation that I want to make to the doctors is that they would give zoledronic acid until the patients have a VGPR, and then they can either stop or give it every three or six months based on the risk profile for fracture of the patient. For example, if the patient has postmenopausal osteoporosis or receives a lot of dexamethasone. So these are important issues. And also to suggest that for patients who have stopped zoledronic acid, they may restart that at the time of biochemical relapse. Regarding denosumab, I would suggest the same thing, but if the doctors want to stop denosumab, then they have to take into consideration the rebound phenomenon that can happen with the stop of denosumab. And so six months after I would recommend to give a dose of zoledronic acid in order to stop this rebound phenomenon. For all these patients who receive either zoledronic acid or denosumab, I want to give the advice not to forget to give supplementation with calcium or vitamin D. I think that this is the most important issue and another issue regarding non-pharmaceutical interventions like surgery or balloon kyphoplasty. I want to say that balloon kyphoplasty or vertebroplasty can be used in patients with painful vertebral fractures if the antimyeloma therapy is not enough to reduce the pain. And also in the long bones, the surgery for plasmacytoma or in order to prevent a fracture there also has to be followed by radiation therapy in the area in order to sterilize, let’s say, from the myeloma cells the area. More or less, this is what I want to suggest to my colleagues who treat multiple myeloma regarding bone disease.

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