Speaker 1 00:05 Lange, welcome to HelixTalk, a podcast presented by the Rosalind Franklin University College of Pharmacy. Narrator - Dr. Abel 00:11 This podcast is produced by pharmacy faculty to supplement study material and provide relevant drug and professional topics. Speaker 1 00:19 We're hoping that our real life clinical pearls and discussions will help you stay up to date and improve your pharmacy knowledge. Narrator - Dr. Abel 00:27 This is an educational production copyright Rosalind Franklin University of Medicine and Science. Speaker 1 00:32 This podcast contains general information for educational purposes only. This is not professional advice and should not be used in lieu of obtaining advice from a qualified health care provider. Narrator - Dr. Abel 00:47 And now on to the show. Dr. Sean Kane 00:51 Welcome to Episode 12 of HelixTalk. I'm your co host, Dr. Kane. I'm Dr. Schuman, and I'm Dr. Patel. Today we're talking about osteoporosis, and we're going to briefly discuss kind of the go to therapies for osteoporosis, but we're really going to focus on two newer agents. The brand name is Prolia or denosumab, and then the other agent is Forteo or teriparatide. Speaker 2 01:13 And if you think about what main governing body who is responsible for publishing the practice and guideline for osteoporosis, we have the National Osteoporosis Foundation, NOF. The recent guidelines are updated in April 2014 and they are focused more towards patients who are greater than 50 years of age. As you can imagine, this condition comes with the increased age and post menopausal status. Dr. Sean Kane 01:34 It's kind of nice to see updated guidelines. You know, we talked about the HAP, VAP, and CAP guidelines, which were quite old, almost a decade old. So it's nice to see guidelines being updated as new drug therapies come out and new evidence comes out. Speaker 3 01:48 So I think one of the first places to kick off is to talk about what exactly is osteoporosis. So I know if you look at the breakdown of the word, we can think of osteo, meaning bone and process meaning porousness. So seems fairly straightforward. Do we have any kind of measurements we can use to kind of look at osteoporosis, other than just kind of opening somebody Speaker 2 02:06 up and checking the bones? So if you think about a healthy bone, it's a nicely organized matrix structure. And what happens in osteoporosis that these matrix of bone tissues basically dissolve, and so the gaps in the matrix actually increases, and that's how we lose something called bone mineral density. So we do have tests to actually assess this bone mineral density, and a pretty common one that's done for screening as well as for treatment response or efficacy measurement perspective is DEXA scan, and it stands for dual energy X ray absorptiometry. Actually, even though NOF publishes the treatment guidelines, we follow the interpretation of DEXA results, the guidelines that are published by the WHO Dr. Sean Kane 02:50 that's the World Health Organization, correct. So how do they describe osteoporosis or even osteopenia based on the bone mineral density? Speaker 2 02:59 So bone mineral density, when they do the DEXA scan, it spits out two different results, the T scores and the z scores. Our focus is more on t score, and that's the treatment and screening actually wraps around that. So if the t score of a patient's bone mineral density is less than negative 2.5 it's considered osteoporosis, the beginning of osteoporosis, or defined as low bone density, or aka osteopenia, is of t score between negative 2.5 to negative 1.0 and if your patient has bone mineral density again, DEXA scan t score of greater than negative 1.0 then it's considered to have a normal bone density. Dr. Sean Kane 03:41 Dr. Patel, I'm gonna be honest with you, I haven't had my Nexus scan this year. Is that something I need to talk to my doctor about? Speaker 2 03:47 You don't need to worry about that right now. Dr. Kane, like we mentioned, most of these guidelines or the condition itself pertains to patients who are older than 50. So again, NOF goes goes ahead and actually describes what patients we should be proactively thinking about screening for osteoporosis. Speaker 3 04:07 Yes, and I think if you look at the NOF guidelines, it appears that the main recommendations are for women 65 years and older, again, those post menopausal as well as men age 70 or older. And then if there are certain individuals who are post menopausal women as well as men 50 to 69 who are concerned with risk factor profile, for example, if they're on certain medications that we may discuss, or also men and women who have already had a fracture in those populations, I believe it's recommended we go ahead and get those scans. Dr. Sean Kane 04:34 So you mentioned medications as a potential risk factor. Are there any other methods that we can discern whether a patient is at high risk or not at high risk, and should or should not have a DEXA scan done. I believe Speaker 3 04:45 one way we can look at that as something called a FRAX score, F, R, A, X, it's a 10 year fracture risk score, and it looks at the major bone, so they're primarily looking at the hip, the spine, the forearm and the shoulder. Dr. Sean Kane 04:57 So how do I have a FRAX score done? Speaker 2 05:00 Okay, so basically, FRAX score is a simple screening tool, and it's derived off of looking at the DEXA scan as well as a screening tool called osteoporosis self assessment tool. You then take the patient’s age, race, and then basically, that's how we're not going to go into the detail how exactly that it's done, but these all factors are considered into the FRAX score. Dr. Sean Kane 05:25 So we talked about how FRAX is a way of assessing patient specific risk factors. There's other risk factors that FRAX doesn't you know, accommodate for that as healthcare providers, we should probably be familiar with in terms of whether it decreases bone mineral density and or increases fracture risk, Speaker 2 05:42 and talk about fracture risk or risk of osteoporosis itself. There are a lot of medical conditions that can fall into this category of risk factors. So we're going to focus more on medication related causes. So you know, as a pharmacist, it's really important to know drug induced conditions as well. And so if your patient has you know long term use of corticosteroids. And by definition, NOF describes long term use as more than five milligrams daily dose of steroid, and this is based off of prednisone dose. So five milligram prednisone dose more than six months at a time. It's considered a long term use of corticosteroid. So the Dr. Sean Kane 06:21 typical patient for that might be a COPD patient, maybe someone with ulcerative colitis or some other inflammatory condition, Speaker 2 06:29 correct, or patients with autoimmune conditions too, who normally are placed on steroidal agents, gotcha. Speaker 3 06:36 And I know another medication we have to be concerned with seem to be your proton pump inhibitors or your ppi. So I know I've been kind of following this issue for a couple years, as we've been looking at ppi use with other medications. So I know this is one, just another reason that we have to keep indicating whether or not these medications, you know, are still necessary for an individual, or if they were started maybe arbitrarily, in a hospital visit and maybe just hung out for a while. Dr. Sean Kane 06:58 So another drug class are many of the anti epileptics, so phenytoin, carbamazepine and barbiturates are definitely implicated in causing bone mineral density problems. And at least with phenytoin, in particular, it deals with inadequate amount of vitamin D absorption or maintenance of vitamin D levels in the body. And as we know, Vitamin D is important for calcium levels and bone health, in terms of preventing osteoporosis. So lack of vitamin D from things like phenytoin can definitely cause Speaker 2 07:26 problems, and that is, brings up other reasons, such as hormonal medication. So if the patient is receiving excess thyroid hormone supplementation, or if patients receiving hormonal contraceptives, such as medroxyprogesterone, and there is actually a max number of time patients can receive this medication because it's known to cause osteoporosis otherwise. Dr. Sean Kane 07:51 So you'd be surprised, if you look at the literature, the number of medications that are implicated either strongly or associated with osteoporosis, and we're not going to cover all of them today, but there's a pretty extensive list we've only covered, you know, kind of the more common and more implicated agents with osteoporosis. So before we even talk about pharmacotherapy, what are some non pharmacologic interventions that patients can have to minimize their risk of osteoporosis and then minimize their Speaker 3 08:17 fracture risk? I think one that I always think of root off the bat, as with many other conditions, both cardiovascular and otherwise, it can be smoking cessation Speaker 2 08:26 and going along with the, you know, substance we're going to go with alcohol too. You know, ask a patient to limit the alcohol to two to three drinks per day, because we know if patient have issues with alcoholism or continuous alcohol usage, then their nutritional status also drops, and that affects the vitamin D and calcium absorption as well. Talking about calcium and vitamin D, we also need to ask patients to actually have proper supplementation. That could be a whole nother podcast in itself to talk about, you know, what's the proper calcium and vitamin D supplementation? But on average, 1200 milligram of calcium, elemental calcium is recommended per day, again not all at once but in divided doses. And about 800 to 2,000 units of vitamin D3 is recommended per day as well. The other Dr. Sean Kane 09:12 thing we should think about is recommending weight bearing exercises, not only for bone health, but for overall health. And then finally, not even thinking about changing your bone mineral density per se, but decreasing the risk of a fall. We should be thinking about optimizing medications for a patient to prevent fall, so things like benzodiazepines, anti hypertensives, if the patient gets orthostasis from those agents, Anticholinergics, we should be thinking about either optimizing these or minimizing these to make sure that a patient is at a lower risk of fall if their baseline risk is already high. So once we've decided non pharmacologic therapy maybe isn't doing it for us, and we want to start evaluating the patient for pharmacologic therapy, who are the patients that deserve to have any of these agents that we're about to discuss? Speaker 2 09:59 So obviously. Anyone, without even looking at the age, anyone who comes in with a new hip or vertebral fracture, we should be considering increasing their bone mineral density somehow, using these agents. Speaker 3 10:10 And I believe another group of individuals that would be important is those, as we stated, based upon the T scores, those who have a score below negative 2.5 so we're at the higher risk and have a definition of osteoporosis, especially at the femur, the hip or the spine. I think Dr. Sean Kane 10:25 that's important too, that it's an OR NOT AN and so if your femur t score is normal, but your hip t score is low, then you qualify for this. It's not that you have to have osteoporosis everywhere. It's that one of these three measurements has to qualify for osteoporosis. Then the third group that we can think about pharmacologic therapy with is if you're above 50 years of age, if you have osteopenia, which again, was a DEXA score between minus one and minus 2.5 which was osteopenia. And then if your FRAX score is high. So this is essentially looking at patients at moderate risk compared to the first two groups, but probably still a group that we can consider for pharmacologic therapy. Speaker 3 11:05 And I know that one of the first options if we are looking at pharmacologic therapy is going to be a class of medications called the bisphosphonates. And these can come in both oral and IV formulations, and various brands such as Fosamax, Boniva, Actonel or Reclast. And the way these work is they inhibit the osteoclast activity, and so these osteoclasts would essentially chew up the old bone and then allow the osteoblast blast, meaning build bone, so they allow them to dominate and then come in and rebuild New bones. So your bone is always in this process of breaking down and building up. And over time, the process becomes a little more balanced. You have too much of the breakdown, maybe not enough of the build up. So we're just trying to balance that out again, Speaker 2 11:44 and just to throw it out there. You know, these are the bisphosphonates. Are the oldest class of medications we have to treat osteopenia, osteoporosis. What I do want to also mention that we have the biggest clinical evidence with this medications as well, compared to the new ones that are out there we're going to discuss today, Prolia and Forteo. Dr. Sean Kane 12:02 Are there any safety concerns that we should be worried about with our bisphosphonate therapy? Speaker 2 12:06 A whole lot of safety concerns that comes to mind when we talk about bisphosphonates. We as we know we have the oral bisphosphonates available, then we also have the IV kind, as alendronate, as well as ibandronate. It's also available IV. So if we could talk about IV and oral together, common safety concerns such as musculoskeletal pain, osteonecrosis of the jaw is also documented in clinical trials too, although this risk is less than 1% but every single patient who is placed on this medication, we need to let them know about this side effect, or at least, we need to ask them that they're following up with their dentist, you know, regularly, and when they go to their dental appointment, let their dentist know that they are starting this medication too. Speaker 3 12:51 Okay, so we have some a few concerns about both the IV and the oral medications. Dr. Kane, are there any specific side effects about the IV medications? Yeah. Dr. Sean Kane 12:59 So with the IV medication, we can see infusion related reactions. So that would be essentially flu like symptoms, fever, chills, things like that. Again, we can see some of the arthralgia, myalgia, or musculoskeletal pain, and just kind of the run of the mill, nausea, vomiting, diarrhea that we see with a lot of different medications. Again, kind of playing along the line of a flu like syndrome that can happen with the infusion itself. Speaker 3 13:23 And I don't believe that the oral medications are without some of their own unique problems either. It seems, as I've heard about dyspepsia and harboring from individuals that take these medications, even some esophagitis, some irritation, even down to abdominal pain or even diarrhea, Dr. Sean Kane 13:37 that really highlights the importance of counseling the patient that the when they take an oral bisphosphonate, they have to take it on an empty stomach first thing in the morning with a full glass of water, and they can't lie down for at least 30 minutes, depending on the agent that they are taking. Speaker 2 13:53 And actually, in the clinical practice, I do see a lot of patients for osteoporosis treatment. And the major reason for discontinuation of oral bisphosphonate is because they develop some sort of Gi discomfort. Dr. Sean Kane 14:07 What is the timeframe that we're using these agents? Speaker 2 14:10 So bisphosphonates in itself are very interesting, because there is a concept of something called drug holiday that takes place. Actually, the recommendation from NOF is to continue the treatment with bisphosphonates to increase the bone mineral density for about five years and in order to maximize the benefit. Because we do know most of these agents have a very long half life. If you look at alendronate, the half life is almost 10 years. 10 years. That is correct, and that is the reason behind the concept of drug holiday. So a lot of the physicians, a lot of the physicians who know the guidelines well enough, what they will do is put the patient on these agents for two years, give them two or three years off, and then complete it with another three year hoping that this medication is sustaining in their own. On in their system in the body. Dr. Sean Kane 15:01 So doing some quick math, patients on alendronate will likely have the drug still in their body. Speaker 2 15:06 Then right, if they were to go under autopsy, and, you know, extract out some of the bone tissues and do some chemical analysis, they will most likely find some sort of bisphosphonate residuals in there. Dr. Sean Kane 15:18 So then you have to kind of wonder, you know, what is the optimal duration? You know, what is the evidence supporting that? And I think that we really don't know, because these clinical trials don't go out for 3040, years. It's, you know, a three year study to show that they decrease fracture risk. And some of the newer data correct me, if I'm wrong, is showing with prolonged use, so more than five years, we're starting to see weird kinds of fractures. They call it atypical femur fractures, where the femur is fracturing at weird places that it normally wouldn't in patients who are not on bisphosphonates, Speaker 2 15:49 absolutely and femur is like the strongest bone in your body. And so if something goes wrong with femur, that rings a bell, that something's not right, and yes, you're absolutely correct, that over usage or longer usage of this phosphonate has shown increased risk of atypical fractures. Speaker 3 16:06 And I think one more reason that we have to be careful about figuring you know how these medications are used long term is that I believe the assessments and the way we go about it may not always be a good way of detecting it. The DEXA scan may not be sensitive to detect those small variations, either an improvement or worsening after if you've done a retesting years later. So we may say, Okay, you have a low score, will start you on the medication. And then look later on and think, Okay, what is it doing now? So it may not again at this current junction, be able to use that number to then guide whether or not we should continue the medication Dr. Sean Kane 16:36 or not. So kind of going into some of the newer agents. Clearly, bisphosphonates are the cornerstone of osteoporosis care. We're not debating that at all, but I think it's important that we discuss some of the second line newer agents that we may be seeing more of. And one of the first ones is calcitonin or myocalcin. It's been around a while, but it's still one of those second line agents that we can at least discuss or think about. Speaker 3 16:58 This is an interesting one, because, like a few other medications. Its base was derived out of an animal. So this one is a salmon based protein, and the calcitonin here is similar to the human calcitonin, and it comes either as a nasal spray or an injection. And it's kind of the counter to parathyroid hormone, or the arch nemesis, if you will. I know I was taught in school that you think calcitonin, you think bone. So it builds up the bone, inhibits the osteoclast, and so allows for just more of the osteoblastic formation of the bone. And I believe, as with the other medications, there's some unique safety concerns with it, some some general nausea, flushing, runny nose, particularly, believe with the nasal spray, hypersensitivity reactions, because we are using a salmon derived product, and maybe some hypocalcemia as we are moving some of the mobilizing the calcium into the bone, Dr. Sean Kane 17:45 I did want to mention, and this goes along with one of our pet peeves from our previous podcast, that when this drug was initially approved by the FDA, and you can actually still see it in the package insert if you go to daily Med, which is a website run by the US government to view monographs of drugs this drug, when it was approved, did not show any benefit with fracture. All it showed was an improvement in total body calcium, which, again, is one of those surrogate end points that we'd really love to see a fracture benefit, given that we have other drugs that have shown that. So in my mind, until the proof study came out in 2004 where it did show that vertebral fracture benefit. I don't understand how this could have made it to the market with an indication of osteoporosis. So are there any patients that we shouldn't give this myocalcin or calcitonin to, I Speaker 3 18:30 believe, again, owing to the fact that it is salmon based, if somebody has a fish allergy, this may not be the medication for you. And then, as we mentioned, patients with hip fracture concern doesn't really have some of the data there to guide its benefit, and then a limit, less than five years post menopausal. It's never really studied in that population. So your than that, you may want to look at a different option. Dr. Sean Kane 18:50 And then thinking about the nasal spray, it's about $100 for a 30 day supply. So it's not exactly a cheap medication either. So not cheap medication combined with kind of not that great efficacy, and we don't have the data support in it compared to the bisphosphonates. It's something that is definitely second, maybe even third line for osteoporosis, Speaker 2 19:09 and second or third tiers for the PBMs too, for the same given reason that you just mentioned, exactly. Dr. Sean Kane 19:14 So the next agent that we wanted to discuss is relaxifen, or Avista, and this is a SERM which is a selective estrogen receptor modulator, so it works completely different. The way it works is it blocks estrogen in the breast and the uterus tissue, but it acts like estrogen. So it's an estrogen agonist at the bone, and we know that premenopausal women tend to have less fracture than postmenopausal women, so that's the thought in terms of bone health with this agent, Speaker 2 19:41 some of the safety concerns when we think about raloxifen is increased risk of thromboembolic events, so a DVT or PE some people are some women will also complain of hot flashes and then black cramps. Is one of the side annoying type of side effect that's been seen too. Dr. Sean Kane 19:59 So this is. Is, again, second line it may be appropriate for a patient who is at very high risk for breast cancer. Again, we said that it blocks estrogen receptors in the breast tissue, which could be a good thing if it's an estrogen, you know, responsive tumor that could grow, and if you can't take a bisphosphonate, this seems like a good option as a second line therapy, absolutely. Speaker 2 20:19 And I do want to, you know, as we were talking about all these agents, I do want to make a different variation between prevention and treatment. So prevention of osteoporosis is considered treatment of osteopenia. So if your patient's dexterous and scan spits out the result that falls into the osteopenia category, the only medication you're going to be able to get especially I'm talking about Medicare patient is bisphosphonates or a VISTA. So you're only playing with two agents. Once they cross that t score to be in the danger zone, which is osteoporosis, then you can go ahead and consider all the other more expensive agents as well. Dr. Sean Kane 20:57 So going along, some of the adverse effects this agent would not be good for someone at high risk or with a history of venous thromboembolism or vte, which is blood clots in the lung or in the extremities, because it can potentially exacerbate the risk of VTE. So moving on to our next agent. It's called denosumab, or Prolia, and if you just look at the generic name denosumab, you could probably assume that it's a monoclonal antibody based on the MAB ending Speaker 2 21:24 that it is. So basically this monoclonal antibody acts at the Rankl gene, and basically it inhibits the Rankl gene, which is then responsible for the functions of osteoclast so if you stop the Rankl production, then you're going to stop the osteoclast activity. We're going to give some time for the osteoblast to come in the picture and bump up the BMD. Speaker 3 21:46 So at this time, I know that there are a few CHP currents we have. Once again, hypocalcemia is going to be a concern, some dermatologic reactions, dry skin plaques, pruritus, eczema and cellulitis, and then, once again, osteonecrosis of the jaw and muscle pain. So again, if you are on these medications, and if you're someone who has, you know, history of dental procedures, or maybe thinking about them in the past, this is something you want to consider, as well as make both your your dental providers and your medical providers aware of the as you're involving with one another. Dr. Sean Kane 22:19 So in thinking about the kind of patient that may be a candidate for this drug, this is going to be the patient who either can't tolerate or fail to bisphosphonate therapy or can't take it because of something like end stage renal disease. The other thing to think about is that denosumab, or Prolia, is also marketed under a different brand name called Xgeva. That is studied for bone metastases and certain types of cancers related to the bone. So there may be some benefit in patients who have cancer who also have some bone involvement. Speaker 2 22:49 So as you can imagine, this agent that's pretty new out in the market the cost of one syringe. Again, this is a subcutaneous injection taken every six months. So for a whole Europe therapy, if they're being out of pocket, it will be about four or 5000 or $5,000 per syringes. It comes to be about $2,000 good thing about this medication is that it's a first line, just like bisphosphonates, for patients who have Medicare. And you know, if they have Medicare D, they can still do it, but it's a bad luck if they have, you know, if they're in the donut hole situation. But what you can also do is use the Medicare B insurance part and do an office administration so they're only responsible for the 20% of the cost. 80% of the cost is covered. And for those lucky patients who have Medicare C, the advantage plan takes care of that 20% cost too. So this therapy comes out to be a very cost effective therapy. Dr. Sean Kane 23:43 So I'm going to claim some ignorance here with the differences in Medicare. I know Medicare Part D is outpatient prescription drug coverage, correct? Absolutely. So how is that different in terms of B and C for an inpatient provider administration versus an outpatient patient administered drug. Speaker 2 24:01 So Medicare D, if you want to have this drug covered as any prescription, you would write a prescription. Patient will go to the pharmacy obtain the drug. You can also teach the patient how to do the subcutaneous administration. If they're competent enough, they can go ahead and do so. Not really sure what tiers it falls on for the Medicare D, I'm pretty sure it's going to be a little bit higher tier compared to bisphosphonates, for sure. But Medicare B is the insurance that covers a lot of infusion. So if you're talking about Reclast, which is the zoledronic acid, that's our IV bisphosphonate, patients are covered under Medicare B for that 80/20 cost ratio, and so Prolia falls under that therapy as well. As a matter of fact, any infusion related therapy falls under Medicare B. So if you think about different A, B, C, D, different Medicares, A, think about hospital coverage. B, think about clinic coverage, and then that clinic coverage also includes the outpatient infusion. Inclusion centers too, and that's where these drugs are usually infused or given. And then C patients are not required to have it. But it's good to have Medicare C, because it kind of covers these ancillary costs that are not covered by A and B. So it's a glorified coverage, if you were to say so. And we all know Bush signed in 2000 and fine for all the patients do have Medicare D as well, which is the outpatient prescription benefit. So you can Dr. Sean Kane 25:24 probably then appreciate that there may be a good conversation in terms of cost benefit to the patient, in terms of having it under Medicare Part B as an outpatient infusion cost versus having the patient fill it at a pharmacy, there could be a huge difference in out of pocket cost to the patient, Speaker 2 25:40 absolutely and manufacturer recommends the very first dose. Even though you have trained the patient you know to do this subcutaneous injection, the manufacturer recommends that that first dose is in some sort of medical observation, just to observe the patient for about 1015 minutes, making sure there is no hypersensitivity type of reaction. Dr. Sean Kane 25:58 So moving on to our final agent. The generic is teriparatide, and the brand name is Forteo. Speaker 3 26:03 This is another medication that is somewhat unique in how it works. It's a recombinant parathyroid hormone, which allows for promotion of osteoblast activity. And it's the only agent that enhances osteoblast activity in the Osteoporosis treatment pool. Dr. Sean Kane 26:18 And if you look at things like the manufacturer marketing information, they really sell this as the only agent that works on osteoblasts, as opposed to all of the other agents that only inhibit osteoclasts. So this one builds it, as opposed to the other ones that stop the consumption of bone. Speaker 3 26:33 And I think one interesting thing to be considered of in this medication is that there is a box warning with it about the risk in animal studies of osteosarcoma, and so that may be a concern that some individuals may have. And just to clarify, it is even though it does state a warning that is based upon animal data, and up to this point, they have not found it in human studies. Dr. Sean Kane 26:54 And for our listeners, osteosarcoma is a tumor in the bone or derived from the bone itself, right? Speaker 2 26:59 Yes, and it makes sense, because we're talking about enhancing the activity of osteoblasts, which forms the bone, and there could always be a mutation that would take the things in a different direction. Speaker 3 27:10 And then with that, there are a few other safety concerns, some general nausea, dizziness, headache, leg, tramp, orthostatic hypotension, and in this case, hypercalcemia, versus some of the others, which promoted hypocalcemia. So I find that to be a little bit interesting. Dr. Sean Kane 27:24 So the type of patient that we should be thinking about for teriparatide would be those with very, very high fracture risk. Again, it's not a first line agent, and because of cost, it's typically a last line agent. It's about $15,000 per year, and we should be avoiding it in those with severe renal impairment certain types of bone disorders like pageants disease or other metabolic bone disease, right? Speaker 2 27:47 And the way the studies are done, their maximum of two years in length so far, and then we've also found osteosarcoma in rats. And so that's why FDA came down with the recommendation that this medication has a total lifetime Max she used, and that's two years. So you can only use this medication for two years of maximum time. And so what usually happens in practice is, you know, if the physicians really want to build a patient's bone mineral density, they'll give this medication for two years and then chase it with bisphosphonates that would, you know, keep down the osteoclast activity problem. About convincing a patient to be on this medication for two years is the way it's available. So it's a daily subcutaneous injection. Think about not only the cost, but the for the fact that, you know, mostly these medications are used in elderly patients, that we have to think about dexterity issues and other administration related issues too. Dr. Sean Kane 28:44 Again, this is in contrast to Prolia or denosumab, where it was every six months subcutaneous injection. This is once a day with teriparatide, Forteo, which could definitely be an issue for patients, absolutely. So now that we've treated our patient with whatever agent we've discussed what's kind of our follow up and monitoring for these patients. Speaker 2 29:04 So the monitoring, again, would be done via completing a DEXA study. So the recommendation are twofold, considering patients if they have if they have fracture, and if they don't have fracture, obviously, if they have fracture, they're already at a very high risk of recurring fractures. But if they don't have fractures, then we look at the T scores and break it down so the t score is greater than negative 1.5 we only repeat the DEXA if the number of risk factors surrounding the patient increases over the years. If it is between negative 1.5 and negative 1.9 the recommendation to repeat the DEXA is about every five years. Then we get closer to that danger. You know, the T score, bone mineral density area, so negative two to negative 2.4 the recommendation is to complete it every two years in patients who have osteoporosis, so the t score of less than 2.5 but who not receiving any treatment. Again, it's every two years. But if they are receiving treatment, and particularly we do have recommendation for bisphosphonates, to repeat the DEXA scan over every five years. And then we talked about certain medications that put patients at risk of absolute risk of developing osteoporosis. One of them I mentioned was corticosteroid. So the recommendation is to do follow up DEXA scan six months after starting the corticosteroid, and then the yearly thereafter, having all this said, I do want to mention that there is a minimum requirement, or I should say, maximum requirement, when it comes to having the DEXA test paid for by the insurance. And so most of the insurance will not repeat the DEXA scan or will not pay for the DEXA scan if it's repeated in less than two years. Dr. Sean Kane 30:47 So to kind of summarize, again, we're really focusing on the last two agents, denosumab or Prolia, teriparatide or Forteo. One of the differences is the administration. So with Prolia, where denosumab, it's every six month subcutaneous injection, whereas with teriparatide or Forteo, it's every day subcutaneous injection. Speaker 3 31:08 And then I always like to think about the mechanism of action for these medications. So with denosumab or Prolia, we're looking at it's a rankled gene inhibitor. So this is going to inhibit some of that osteoclast activity and then kind of prevent some of that reformation of the bone there, or the chewing away of it. And then that's compared to the teriparatide or Forteo, which is recombinant parathyroid hormone, and it actually directly promotes the osteoblast activity, so allowing for more of the bone to be laid down. Speaker 2 31:35 And you also want to think about the safety concerns. So if you talk about Prolia, the risks are hypocalcemia, lowering of the calcium and benefit lies where we can use this medication in patients who have end stage renal disease, even if they're on hemodialysis. Not so true for teriparatide. So it's actually flipped. You know, the benefit there is hypercalcemia, but unfortunately, we cannot use this medication in patients who whose renal function is not up to par. Talking about comparing and contrasting these two agents, I do want to throw that out there that there is no maximum time period for therapy for Prolia. There is a study that's actually evaluating 10 year use as well. However, FDA limits the use of teriparatide to two years only at this point. Dr. Sean Kane 32:21 All right, so with that, I'm going to go ahead and conclude we would really appreciate a five star review in iTunes. If you want to visit us online, we're at HelixTalk.com with that, I'm Dr. Kane, I'm Dr. Schuman, Speaker 2 32:32 and I'm Dr. Patel, and as Elvis study hard. Narrator - Dr. Abel 32:37 Thank you for listening to this episode of HelixTalk. For more information about the show, please visit us at HelixTalk.com you.