Do bone strengtheners help ease bone pain? How often should they be administered?

Do bone strengtheners help ease bone pain? The bone kind of modifying agents like I have to say bisphosphonates, antinosomal, I don't think that they directly treat bone pain. I think what I see in my patients, when I treat patients for multiple myeloma and they go into a fast remission, I decrease substantially the burden of the myeloma cells. And by decreasing the burden of the myeloma cells, I also decrease the osteoclast activating factors. So I mentioned already osteoclasts are the bone-resorbing cells. So I take the factors away that activate the osteoclasts. And this reduced osteoclast activity by less myeloma cells in addition to the bone-modifying agents, patients experience less pain. So it's amazing that patients who go into complete remission have almost no pain need anymore. So I see that in, I would say, 90% of my patients, a drastic reduction of the bone pain. It takes a while. So very often it takes six months. But it's amazing how well we can treat pain by just bringing the myeloma into a remission. I'm not sure whether we can really state that the bone-modifying agents are modifying the pain directly. I think by reducing the bone destruction, patients experience less pain. How often should bone strengtheners be administered? There are so many studies out that there is substantial confusion even among experts how often and how long bone-modifying agents should be given. Let's talk about Zomera. The recommendations from ESCO are monthly for two years. But there's also a study out that giving Zomera every three months is as good as giving it monthly. So there's substantial disorientation to be very polite to give it. What I do is, first of all, I put all my patients on bisphosphonates. Then they are diagnosed with multiple myeloma. And then they have the need of a systemic treatment against multiple myeloma, period. I usually do that with Zomera. I start a monthly treatment for at least a year. I want to have a saturation of the skeleton with Zomera. And then in the second year, I either stop Zomera already. If patients have no bone disease or no major problem with their bones, or in case I think that there is a need for continuation of Zomera, I spread the interval to every three months. So why is that? So first of all, we know that Zomera has a very long half-life time, eight years. So Zomera binds to the skeleton. And even if you stop Zomera, you still have it in your skeleton. And then osteoclasts do bone resorption. They are inhibited by Zomera. So we know that the drug lasts for a longer time. So that's why we give it for a limited time. And I think it's relatively safe to stop Zomera after a year or absolutely after two years when patients are in complete remission. Then you do not have any myeloma cells that activate the osteoclasts. And you have your saturation of the skeleton with Zomera. You can stop it. Why do we stop it? We learned that patients, the longer patients are on Zomera, the higher is the risk for the osteonecrosis of the jaw. Once you have, we call that ONJ, you have to stop the bisphosphonates for good. So what I want to make sure, I want to make sure that patients do not develop ONJ, osteonecrosis of the jaw. And in case they have a relapse, that I can restart the bisphosphonates for potential protection of the bones. There is no clear answer on the dosing of bisphosphonates. Myeloma specialists may have varying opinions. It is best to discuss your unique situation with your myeloma specialist to come up with a treatment protocol that's right for you.