Alicia Morgans: Hi. I'm so excited to be here at SOGUG 2022, where I have the chance to speak with Dr. Miguel Ángel Climent. And we are speaking about bone health. Wonderful to see you today.

Miguel Ángel Climent Durán: Thank you very much. It's a pleasure to be here.

Alicia Morgans: Wonderful. So Dr. Ángel Climent, I know that you practice in Valencia, a beautiful place, and really came to SOGUG to talk about bone health in prostate cancer and how we have to have different considerations across the spectrum of disease states. So can you share a little bit about what you discussed?

Miguel Ángel Climent Durán: Of course, you're right because this different... the approach to patients with castration-resistant prostate cancer and hormone-sensitive prostate cancers. The patients who are castration-resistant prostate cancer, we should prevent the bone events that they will have in the future, the need for radiotherapy, the fractures and so on, with bone protecting agents. And in hormone-sensitive patients, the problem is osteoporosis that is provoked by hormonal treatments. And the approach is different, and the doses and the management of the patient is different in this way.

Alicia Morgans: It absolutely is. And many times, with the patients being treated for osteoporosis, I see a bit of a disconnect that we don't as doctors always remember the purpose and the dosing. And this even applies to patients who might be on long-term hormonal treatments with their radiation for localized disease. How should we treat patients who are on long-term hormonal treatments, whether they're localized with long-term ADT or metastatic hormone sensitive? What is the approach there?

Miguel Ángel Climent Durán: The first thing is lifestyle. We should improve the movement and the exercise in the patients. They should have a correct dose of calcium intake in the day and of vitamin D. Here in Spain, we have the sun. And we think that the patients, that's a D vitamin. But most of the time, we are not in the sun. We are covered, and the deficiency of vitamin D is very spread in all the population. So we have to take care of this.

And of course, not to smoke, not abusing alcohol and make exercise. Walking, dancing, tai chi, whatever activities work for the patients to prevent osteoporosis and to prevent fractures in the future. After that, if the patient is osteoporotic, let's say if we make a densitometry and the patients is in osteoporosis range, then he will need a bisphosphonate or denosumab dose that is different from the dose for prevention of osseous events in castration-resistant prostate cancer.

Alicia Morgans: Yes. I think that's so important, and I just want to call out your comments on lifestyle and activity. These weightbearing activities are so important. That stress on the bones helps to encourage the bones to rebuild, and I love that you recommend dancing to your patients. I will have to add that into my list. That's a lovely activity.

Miguel Ángel Climent Durán: Here in Spain, in all people associations, the veterans' associations, there is always music and they dance in the afternoons. They have time for dancing, and I think that is important too. And it's, of course, more joyful for the patients to do this kind of exercise.

Alicia Morgans: Absolutely, and it does get you out there and gets you moving in a way that's safe and also collegial with other people. That's wonderful.

So just to emphasize, too, the zoledronic acid dose that we usually use is a once a year dose really for this fragility fracture prevention. Denosumab dosing is at 60 milligrams once every six months. So these are lower doses than we use in metastatic castration-resistant prostate cancer. And in metastatic CRPC, obviously we're, as you said, trying to prevent skeletal-related events or symptomatic skeletal events. What is the approach there?

Miguel Ángel Climent Durán: The approach there is that the patients, we have to prevent that skeletal events and the dose is higher. The dose of zoledronic acid is four milligrams every month, although there is some works that maybe giving the same dose every 12 months is exactly the same that giving it monthly. And denosumab also in 120 milligrams, then, every month is useful to prevent the bone skeletal events.

Of course, we have to give them calcium and vitamin D to prevent the hypocalcemia and to prevent the osteoporosis and the bone health and to do all this kind of thing. And that's it. That is what we should do.

We don't have enough evidence if we have to maintain this treatment for longer than two years. The zoledronic acid trial was for two years. The comparison with zoledronic acid and denosumab were longer because of the risk of mandibular osteonecrosis. That is something that is not very usual, very common. Less than 1-2% of the patients, that is very, life-limiting toxicity. So we have to take care of the teeth and so on with the dentist and so on in these patients.

Alicia Morgans: Absolutely. Do you recommend for your patients to see a dentist to get clearance or an evaluation before they start these medications? We do now. I think this is something that's evolved in our practices, at least in the US, over years where we didn't necessarily always do that when these medicines were first available. But now, it's quite commonplace to do that collaboration with the dentist.

Miguel Ángel Climent Durán: I recommend the patients to go to the dentist before starting treatment.

Alicia Morgans: Yes.

Miguel Ángel Climent Durán: Of course, normally it's not an urgent treatment to give, so we can wait for going to the dentist. And if they have something... They have to take away a teeth or whatever, we can wait because maybe it's one month, two months and we can wait to start treatment. And it's good that they have a good teeth health before starting treatment because it's a way of prevention of this complication in the future.

Alicia Morgans: Absolutely. And of course, it helps them with their nutrition and everything as well to have a good set of teeth. And that's great.

So one thing that I also more recently learned about and wanted to pick your brain about is the rapid loss of bone density when we stop denosumab in particular, which I think is really interesting and is not something that we commonly review and talk about in our circles. How has that affected you in your practice? And what I'm referring to, for anyone who isn't so aware, usually after, say, six to 12 months after we stopped denosumab, there's actually a reversion, a loss of bone mineral density, and patients have... essentially lose all the bone density that they gained during their routine treatment.

Miguel Ángel Climent Durán: That's right, and this had been seen most in osteoporosis prevention patients. Here in Spain, we have the problem that although denosumab is approved for treatment in castration-resistant to prevent skeletal events, because of the price we have not been using quite normally. And I don't use it. I use always zoledronic acid, so I have not really experience of the thing you are talking about, that the suppression of the treatment makes the patients to lose the bone density. But it has been described, and we have to take care about that when we stop the treatment for the first months to watch if something happens with the patients or to change for a bisphosphonate.

Alicia Morgans: Absolutely. And that is the guidance, that if you are going to stop your denosumab, to switch over to a bisphosphonate which really integrates-

Miguel Ángel Climent Durán: Yes.

Alicia Morgans: ... into the bone and is longstanding in the bone. But I think it is interesting, and it's something that I especially think about now in my younger patients who are getting denosumab for fragility fracture prevention and how I want to consider their treatment not just now, but over time and counseling that. That is important.

Miguel Ángel Climent Durán: It's important.

Alicia Morgans: So very good. So what would, I guess, your summary be to folks who are treating patients with prostate cancer and need to pay very close attention, of course, to the bone health as well?

Miguel Ángel Climent Durán: The message is that we have to take care of the bone health of our patients with prostate cancer. The hormonal treatment is getting longer and longer, and that means that the osteoporosis will grow in the future. So we have to take care of that and to prevent the problems with osteoporosis in the future. That means lifestyle, as we were talking, and of course treatment with bisphosphonates or denosumab if it is necessary.

Alicia Morgans: Absolutely. Well, thank you so much for going through this review and talking to us about how we can really pay attention to this critical part of our patients' holistic care while we also, of course, are taking care of the prostate cancer. I appreciate your time and your expertise.

Miguel Ángel Climent Durán: Thank you very much.