Hello, again. You have by now heard my colleague, Dr. Kelly, talk about anabolic drug therapy, and in this new section, I'm going to touch upon management strategies for our patients with osteoporosis. We have now heard about what drugs we have in our armamentarium, but what we are going to talk about is what drug to choose and how long to use that drug for in our patients where we have embarked them upon osteoporosis treatment. Next we are going to go over an algorithmic approach to patients who are at low to moderate risk. So this is a patient who has no prior fragility fracture. They're considered at moderate risk, for instance, for osteoporosis. So any of these agents would be fine to use. You can use an oral bisphosphonate, you can use denosumab, or you can use an IV bisphosphonate depending on the patient's risk and their choices after you talk to the patient. An important thing is to assess response to therapy at least yearly, and it does not mean that you have to get a bone density test every year, but what you want to do is to have the patient come into the clinic and look at their adherence to medication. We know that osteoporosis therapies tend to fall off after a period of use because patients do not really perceive the importance of taking a medication, or they may develop side effects and patients don't generally tell you that they have stopped taking a medication. So a yearly check is a good point at that time to review how they are taking the medication, are they experiencing any side effects, is cost a barrier, are they continuing to take their calcium and vitamin D, are they doing the other non-pharmacological things like exercising regularly, those kind of things. So if the patient has a stable or increasing bone density and has not had any fractures, well that right there is a response to therapy, which is good. So in this kind of a patient, you may consider giving them a bisphosphonate holiday after they have had five years of oral bisphosphonate, or if they have had three years of IV bisphosphonate treatment. As I mentioned in my previous slide about bisphosphonate potency, for alendronate and zoledronic acid, which are potent bisphosphonates, bisphosphonate holidays can be given for a longer period of time. For drugs like resedronate, which is a less potent or short-acting bisphosphonate, drug holidays should not be very long. And then you resume treatment after you see that their next bone density shows a decline, or if you are using their bone turnover markers like CTX and you see that their bone turnover is going up, at that point you may want to reinstitute medication. On the other hand, if you notice that after taking the medication appropriately and doing all the right things, there is a decrease in bone density or the patient sustains a fracture. Now, one fracture while on therapy does not mean that therapy failed, but if the patient is having multiple fractures while on therapy, that might be a worrisome feature. At that point, you may consider that this patient is not doing well on the current treatment that you have them on. At this point, you want to make sure that they're taking the medication correctly, and you also want to look for secondary causes of osteoporosis. What does that mean? Patients may have another reason for bone loss other than menopausal bone loss or related to aging. They may have underlying primary hyperparathyroidism. They may have underlying celiac disease, which prevents absorption of calcium and vitamin D. These are patients who are taking the medication appropriately, and despite that, have either fractures or decline in bone density, so a secondary cause workup should be done. You may also want to screen them for other endocrine issues like Cushing's, which they may have, or they may have hyperthyroidism, which needs to be corrected. After you've done the assessment for osteoporosis secondary causes, then if they have been on an oral bisphosphonate before, you may want to switch them over to an IV bisphosphonate, which will have better potency and the adherence is also better, or you may want to switch them over from a bisphosphonate to an anabolic agent if their fracture risk is high, or you may want to switch them over from an oral bisphosphonate to denosumab therapy, which is more potent. So this is the kind of algorithmic approach that you may have to a patient who is at initial low risk for fracture or moderate risk for fracture. This next algorithm applies to a patient who is at high risk for fracture, for instance somebody who has had a prior fragility fracture. This person you would like to use anabolic therapy first. So patients with a recent fracture are at a very high risk of more fractures over the next two years, and this risk is independent of baseline T-score, we talked about that. The treatment goal for these patients is to rapidly and maximally reduce their fracture risk. So osteoanabolic agents reduce fracture risk faster and to a greater extent than anti-resorptive agents. So osteoanabolic therapy is a better choice or the better first choice for patients at imminent fracture risk. So you would choose teriparatide, abelaparatide, romososumab first, and then after that therapy is complete then you would switch them over to either denosumab or zoledronic acid preferentially. You could use, after you've used the osteoanabolic therapy, you can still use oral bisphosphonates if the patient so chooses to do so, but it would be better to use a more potent anti-resorptive agent to seal the bone gains that you have made with the anabolic agents. Then you have to assess response to therapy. For most of the patients who are on anabolic therapy, we can use bone turnover markers for the teriparatide and abelaparatide. With romososumab, they're not as useful. You can use bone density data if bone density is due for that patient to see if they're responding appropriately. If the patient is on zoledronic acid, you can continue the medication if they are stable and doing well. You can give them a drug holiday after six years. The data on this is not very clear, or you can switch to an anabolic agent if bone mineral density declines or another fracture occurs. If the patient is on denosumab, you continue the therapy because with denosumab, you cannot abruptly stop taking the medication. It causes rebound bone loss. After you want to switch the patient from denosumab to another medication, you have to bridge them over with a bisphosphonate, preferably an intravenous bisphosphonate. If the patient is on teriparatide, abelaparatide, or romososumab, that patient needs sequential therapy with either an IV bisphosphonate or denosumab. Again, you can use an oral bisphosphonate if the patient has contraindications or it's a patient's choice, but it's better to use a potent medication like IV bisphosphonate or denosumab after you have given them osteoanabolic therapy. As I mentioned in my previous slide, it is very important to monitor patients at regular intervals to determine the efficacy of treatment and whether any adjustments are needed. So how do we monitor our patients? We repeat their bone density every one to two years until findings are stable. If a patient has issues where their lumbar spine and hip bone density are not evaluable, we can use the one-third radius. One-third radius should also be checked in patients who have primary hyperparathyroidism or men who have been treated with androgen deprivation therapy because those sites are preferentially involved. Monitor serial changes in lumbar spine, total hip, or femoral neck bone density. Again, if the lumbar spine, hip, or both are not evaluable, monitoring the one-third radius is acceptable. Ideally, follow-up bone densities should be on the same machine to prevent discrepancies. This is a big issue with patients where they sometimes go from medical center to medical center to get their bone densities done, and this should be avoided. Bone density evaluation is very, very important for the patient, and sometimes we can use bone turnover markers to assess patient adherence as well as efficacy of therapy. So bone turnover markers can be sometimes difficult to evaluate, especially in primary care settings where physicians may not be used to interpreting that data, and a lot of states in the country do not reimburse for bone turnover marker testing. So a good rule of the thumb is that with antiresorptive therapy, significant reductions in bone turnover markers are seen, and they are associated with fracture reduction initially. And if you have a patient who's on anabolic therapy like the teriparatide or rubellaparatide, you can see that the bone turnover markers are higher, which indicates good response to treatment. A reduction in bone turnover markers after starting antiresorptive therapy is a good indication that the medication is being efficacious. How do we know that therapy is successful? So if we have stable or increasing bone density with no evidence of new fractures or vertebral fracture progression, that's a good sign. If you have bone turnover markers at or below the median value for premenopausal women as a target for response to therapy for patients taking antiresorptive agents, that's also a good outcome. Now alternative therapy or reassessment for causes of secondary osteoporosis should be considered in patients who have recurrent fractures or significant bone loss while on therapy. And remember, one single fracture while on therapy is not necessarily evidence of treatment failure, but two or more fragility fractures are evidence of treatment failure. And in patients who are taking medication appropriately and there's no response, look for secondary causes. When a treatment target has not been achieved or is unlikely to be achieved, consider changing to a more potent therapy or continuing the highest potency treatment sequence. And I'll talk about treatment sequence in a couple of slides. When a treatment target has been reached, now the focus should be to maintain bone density. For this purpose, you may want to continue the medication that you currently have the patient on. You may give them a short holiday if it's a bisphosphonate, or you may administer intermittent bisphosphonate therapy for those patients to continue the bone density gains that you have made. Let's talk about sequential therapy in osteoporosis. The treatment sequence is important for attaining T-score targets, particularly in patients with baseline T-scores far below the treatment target. So selecting of initial therapy is very, very important. Patients who have very low bone density need to be on osteoanabolic therapy first to improve bone density gains, and this should be then followed by antiresorptive therapy. This treatment sequence, which involves the use of osteoanabolic therapy first and antiresorptive therapy next, gives the most increment in bone density and thereby most fracture reduction. So if a patient is at very high risk of fractures, giving them teriparatide, abelaparatide, romasosumab followed by bisphosphonate or denosumab would be the best treatment sequence. So if you have somebody who has taken a bisphosphonate or denosumab first, and then you'd switch them over to say teriparatide or abelaparatide, the bone density response will be blunted. So a naive bone treated with osteoanabolic therapy followed by antiresorptive therapy would give you the best bone density increment. If you have somebody who's on a bisphosphonate and you switch them over to denosumab, you'll see an increase in bone density. So as you can see that in the Freedom Extension Study, patients who were in the long-term treatment group continued to have increase in bone density with denosumab even after several years. With bisphosphonates, even with the potent bisphosphonates, there is an increment in bone density, but after a period of time, there's a plateau that is achieved after which there's no further increase in bone density, but with denosumab, the improvement in bone densities is ongoing for a longer period of time. If you have somebody who's taken a PTH analog and then you switch them over to denosumab, it increases their bone density, very good treatment sequence. If you have somebody who's taken denosumab first and then you try to give them an anabolic, this will cause bone loss, especially at the femoral neck. So this is something which I would not recommend doing. Denosumab to bisphosphonate. We talked about it first that you cannot stop this denosumab therapy abruptly, so this medication has to be transitioned over to a bisphosphonate, however, the data here is conflicting. If you have patients who have taken denosumab therapy for a short period of time and then you're transitioning them over to a bisphosphonate, for the most part, you may have preservation of bone density and there will be no rebound bone loss. But after long-term therapy with denosumab, when you switch them over to a bisphosphonate, even though you may use a potent bisphosphonate, there is data that it still has ongoing bone loss. So then there are some regimens where they give patients two doses of zoledronic acid after bisphosphonate. I mean, denosumab therapy is stopped, but even despite that, there might be ongoing bone loss. This area is quite a work in progress right now. On the other hand, if you have somebody who has taken romosuzumab and then you transition them over to a bisphosphonate, it improves or stabilizes bone density. So these are the sequences that we would recommend in patients where osteoanabolic therapy is used first, followed by antiresorptive therapy. And the only caveat here is that most insurance companies like to deny osteoanabolic therapy in these patients and they would like you to have the patient try bisphosphonates or denosumab first and then fail that therapy and then go to osteoanabolic therapy, unfortunately. No discussion on osteoporosis therapies is complete without addressing lifestyle modifications, as we know that they help to reduce the likelihood of developing osteoporosis and prevention in fractures. So what should we tell our patients? Avoid smoking as it can increase the rate of bone loss. We know that alcohol is a direct toxin for osteoblasts, so we tell patients to consume alcohol with moderation. Excessive consumption, which is defined as more than two drinks per day, should be avoided. Fall prevention strategies are very important because there are patients who may never go on to have a fracture unless they had a fall. So balance training exercises, strength training exercises should be incorporated in their daily regimen to decrease their risk of having falls. In addition to that, dietary calcium, vitamin D supplements are very important as they also help with bone formation and muscle strength.

osteoporosis management

drug selection

bone density monitoring

anabolic therapies

lifestyle modifications