All right. Welcome back, everybody. So we're going to go ahead and start with our third lecture of the morning. So we've got a great talk called Breaking Free from Osteoporosis. And it's my pleasure to introduce Dr. Robin Kramer. She is the wife of Mike Kramer, so we're very happy to have them here. But Dr. Kramer is a board-certified family medicine and geriatric medicine physician who earned her medical degree from the Chicago College of Osteopathic Medicine. She went on to complete her residency in family medicine at Florida Hospital, which is now Advent Health in Orlando, where she was also the chief resident. She completed her fellowship in geriatric medicine at Winter Park Memorial Hospital, now known as Advent Health Winter Park. And she is a presenter and lecturer on many important topics affecting the elderly with a special interest in osteoporosis. She's also an active community volunteer and serves as a committee member for several local organizations. Please join me in welcoming her. Good morning. And is that a little loud? OK. Well, thank you so much, Jenny and the Academy, for inviting me. And thank you for coming this morning to listen. I really appreciate that. You know, neurologic and muscular diseases are a very common cause of osteoporosis. And really, physiatrists see this in your office every day. When you think about it, the patients who've had a stroke, who have difficulty weight bearing on that side, patients with Parkinson's, MS, muscular dystrophy, all with the lack of weight bearing on an extremity, really predisposes people to osteoporosis. And say the spinal cord patients. It's known that a year after a spinal cord injury, that proximal femur can lose up to 20% of the density. About 50% of the patients are diagnosed with a densimetric diagnosis of osteoporosis a year after a spinal cord injury. But also in secondary fracture prevention, you see people after hip fractures, vertebral fractures, and pelvic fractures. And we need to connect that fracture equals check for osteoporosis. In fact, any fracture after the age of 50, we want to get a DEXA scan and evaluate for osteoporosis. But it's usually up to us to start that conversation. Generally, our patients don't ask. But once we do bring up the topic, I find most patients are very interested in really optimizing their bone health. But yet, they're reluctant to take the medication. So I hope in this talk that I'll give you some tools, some ideas to help with that. So I don't have anything to disclose. We're going to discuss the risk factors, apply screening criteria for osteoporosis, and talk about the importance of treating. This slide shows some websites, mainly, to help with the treatment of osteoporosis. The lecture is going to be taken from the American College of Endocrinology guideline, as well as the ACP guideline in 2017. The National Osteoporosis Foundation this year has changed its name. It is now the National Bone Health and Osteoporosis Foundation. The last guideline was actually in 2014. But next week, next Thursday, at their annual meeting, they're going to release the 2022 guideline. I don't expect a lot of change there. But I was not able to get a hold of it before today, or I would have. It's going to be a live presentation. The FRAX, the Fracture Risk Assessment website, is listed here. This is a fracture assessment tool. It's been validated in 26 countries, over a million patients. And this tool can help you both identify patients who are at risk of having osteoporosis and who to get a DEXA scan for, as well as the treatment criteria, especially for osteopenic patients. There is a tele-mentoring, basically a virtual osteoporosis educational panel that meets weekly out of the University of New Mexico. It's excellent. It's called Bone Health Echo. And last is a website for the Mayo Clinic, the Shared Decision Aid tool, which I find helps patients in the exam room to show them this nice Mayo tool. It gives them more confidence about taking medications. So we know that osteoporosis is a bone disease that really weakens the bones and predisposes people to fracture. It's really all about fracture prevention. But we know that that bone strength is not just the density that we see on the DEXA scan, but it's also the design or the microarchitecture that's harder to really tell. It can be seen on MRI and CRT, but that's not commonly done. The FRAX questions actually help us have some insight into what the patient's bone quality or microarchitecture is. So it's really the combination of the bone mass and the architecture. So what is an osteoporotic fracture? How do we know if it's a fragility fracture? How do we define that for a patient? Well, generally, we think that's a fracture that happens from a fall from standing height or less, or more simply, a fracture that probably wouldn't have happened when we were younger. So we know that osteoporosis is way too common. For women over the age of 50, one half will experience a fracture and a quarter of the men will experience an osteoporotic fracture. Each year, there are 300,000 hip fractures, of which a year following, a quarter will die. A quarter of the patients end up in a nursing home and half will need ambulatory aid. Osteoporotic fractures are very expensive, expecting to cost 25 billion by the year of 2025. Honestly, we're not doing a very good job at treating it. As primary physicians, as any physician's physiatrist, there's an 80% care gap. After a fracture, only one in five women over the age of 67 are either treated or even tested for osteoporosis. So it's not all about hip fractures. Retieval fractures are actually the most common, with anterior wedge fracture being the most common fracture. Thus, fracture begets fracture, and you can picture that kyphotic hump that can develop with those anterior compression fractures. So patients who have a spine fracture have a five-fold increased risk of having another fracture and double the risk of having a hip fracture. But 75% of these are not clinically found at that time. People think they just have a back strain. Sometimes we'll pick them up on a chest X-ray. But I think that y'all as physiatrists, especially those who do the vertebral augmentation procedures, you do see the 25% who are symptomatic and who have that pain. And for those whose pain we're not able to control through other means, have a vertebroplasty. One study showed that just one vertebral fracture can decrease the pulmonary vital capacity by 9%. Other consequences of osteoporosis from the vertebral compression fractures, the GI can lead to constipation, early satiety, that smaller GI cavity. And after a fracture, patients are afraid of falling there. Their world kind of shrinks. They tend to stay at home, and depression is common. So we know that strong bones really begin in childhood. We build up to that peak bone mass around the age of 30, which is why it's so important that children and adolescents have a great diet, a well-rounded diet with adequate calcium and vitamin D, and that they get enough exercise, that they're getting that impact exercise on their bones. Especially racket sports have been shown to help increase the bone density, the weight-bearing exercises. Whereas swimming and biking, not so much. So if you have athletes who are really just into swimming, you want to make sure that they're also getting enough weight-bearing. In fact, one study that they did in baseball players, they studied the forearm density, and they found that the pitching arm was definitely denser by that peak bone period, and that the baseball players maintained that higher peak density in the pitching arm throughout a lifetime. So even though osteoporosis is a systemic disease, certainly the exercise is site-specific. So we want people getting a lot of good exercise to really build up that peak bone mass. Now, around the age of 50, when women go through menopause and lose estrogen, they can lose 5 percent a year. So up to 20 percent of their bone mass can be lost at the time over the years of menopause. And then it slows down to a loss of about 1 percent a year. For men around the age of 70, they lose approximately 1 percent per year of bone mass. So since we can't always prevent osteoporosis, there are guidelines to help us screen for it. We screen with a bone mineral density test called a DEXA scan. And the USPSTF, that's the United States Preventative Services Task Force, our most recent guidelines were in 2018 that advised to get a DEXA scan in every woman age 65 and older and younger women who are at increased risk. They did not find sufficient evidence to check for osteoporosis in men who do not have other risk factors. But certainly the National Bone Health and Osteoporosis Foundation does recommend that men age 70 and older have a DEXA scan, as well as younger men who have had a fracture. And really, any patient over 50 who's had a non-traumatic fracture, you want to get a DEXA scan in. So let's talk a little bit about the FRAX. The FRAX helps us identify those women less than the age of 65 who might have osteoporosis and how we can objectively quantify that. So this slide shows a screenshot of a typical US Caucasian woman at the age of 65 with no other risk factors. And this is the standard that is used to determine in the United States which other women who are younger should get a DEXA scan. So we see here, let's see, does this have a pointer? Anyway, okay. So there are 11 questions in the FRAX. And the most important questions we put in the age, the sex, the weight, the average woman in the United States, the BMI is 28.8. And that is able to be calculated when you go to the website, just using the height and the weight. And then the other fractures, factors, the patient had a previous fracture. Did the patient's either parent have a hip fracture? Do they currently smoke? Have they used steroids? The steroids is an average of three months of five milligrams a day. It's what quantifies as corticosteroid use. Do they have rheumatoid arthritis or other secondary causes of osteoporosis? This would be like hyperthyroidism, hyperparathyroidism, early menopause before the age of 45, insulin-dependent diabetes, COPD. I would certainly think we know that a spinal cord injured patient would certainly fall there. And alcohol, that's three glasses or more a day. And so for the purpose of this slide, the reason I put this up there is it shows that average 65-year-old female. So when you push the calculate button, this is what you see, that in the next 10 years, the risk of having a major osteoporotic fracture, and that's a fracture of the spine or hip as well as the wrist, is 8.4. So that's really the magic number that you want to use in your FRACs to know what other women or other men as well who are younger, that you can use this to have insurance pay for the DEXA scan if they have a fracture risk in the next 10 years of a major of 8.4 or higher. Okay. So there are four other risk assessment tools that were listed in the guideline. There are four simple tools. I think the first one is the most simple, and you can use this instead of using the FRACs if you have someone in your office. It's just simply the patient's weight in kilograms minus their age in years, and if that's less than 10, boom, you get a DEXA scan. These other four tests simply add in one other factor. The next one adds in whether the patient's on estrogen. The next adds in if they've had a prior fracture. The next adds in if they're of non-Black race or have rheumatoid arthritis. But to me, the first one is the easiest to use. So as far as if you get a DEXA scan, say on a primary, we get them on those women at the age of 65, you get a DEXA scan on any patient, and you're wondering, when do I need to repeat it? Well, certainly if they're osteoporotic, you're going to want to repeat that DEXA scan in two years. But what about if they're osteopenic? Well, this study that was just put out in JAMA in 21 uses both the T-score but also the FRAC score to help determine that next repeat interval for the DEXA scan. So in here, you can see T-score in the osteopenic range from minus 1.5 to minus 1.9. And here's that major osteoporotic risk from the FRACs. If that's 15 to 19, or the initial hip fracture risk is 1.5 to 2, then you're going to repeat in three to five years. Basically, as the osteopenia worsens, or as the density worsens, as the FRACs score goes up, you're going to get a DEXA scan more frequently. But what if it's a normal DEXA? What if somebody gets a DEXA scan, it's totally normal, their FRACs risk is low, you really don't have to get another DEXA scan for 10 years or more, okay? So the diagnosis of osteoporosis is certainly made if a patient has a fracture of the hip or spine from a fall from standing height or less, but also through the DEXA scan. The DEXA scan chart is here. A normal T-score on the DEXA is 1 or better. An osteopenic or low bone mass T-score is between minus one down to minus 2.5, and osteoporotic T-score is minus 2.5 or less. Well, the Endocrinology Society realized that those guidelines did not include osteopenic patients who were at very high risk as having osteoporosis. And we know, actually, most fractures happen in women with osteopenic bones, and that's just because there are more women with osteopenia than osteoporosis. And we want to be able to justify to the pharmaceutical companies as well the insurance companies about treating patients. So it's important to be able to identify and diagnose osteopenic patients who are at high risk of fracturing. So the new Endocrine Guideline includes here patients who are osteopenic with a T-score between minus one and minus 2.5 who have had a fracture of the proximal humerus, distal forearm, or of the pelvis, as well as patients who are osteopenic with an elevated FRAX score. And in the United States, we use the cutoffs of a major, the risk in the next 10 years of having a major fracture of 20% or a hip fracture of three. So those are kind of magic numbers in the United States of FRAX scores. We have three FRAX numbers, right? Back, who to get a DEXA scan on if that major is 8.4 or higher, and then if you have an osteopenic patient that you're gonna treat, you put them into the FRAX, and if the FRAX score is 20 or higher for a risk of the major, remember back on that red box, right, whoop, right there, if this number is 20 or higher for the major, or if the hip fracture is three or higher, then that is defined as osteoporosis, even with an osteopenic T-score, okay? So because, again, we know that our bone strength's not just that density, that's why we see these fractures in the osteopenic range. It's that microarchitecture quality. There is a software package that's available on DEXA scans that looks at that microarchitecture. It's called a trabecular bone score, and the DEXAs in your community may have that. I know our DEXA scans have had them, but the radiologists haven't read it. It doesn't give you the diagnosis of osteoporosis, but it does give you some insight to improve the fracture risk assessment. So it's called a TBS, or fracture, trabecular bone score. So I really like this slide. It shows the importance of identifying osteopenic patients who are at risk of fracturing. You see here the y-axis include both the fracture rate and the incidence of fracture. The fracture rate, the incidence of fracture, are the black columns going up. So you see here that actually most of the fractures happen with T-scores on the x-axis. It's going across, this is T-scores from one down to minus 3.5. So here in that osteopenic range of T-scores, you see is where most fractures happen. So that's why it's important to identify those osteopenic patients. Now the gray bars simply show the rate of fracture. So we know that the fracture rate increases as that T-score goes down. So it's important to diagnose osteoporosis, right? And since we know that 75% of the vertebral fractures are actually silent, that's a big area of patients we may be missing. So doing x-rays on everybody is pretty high radiation. I don't think we want to do that. So a software package that's now available on the DEXA scan as well, is called a vertebral fracture assessment. And this is actually just a low dose x-ray that looks at the morphology of the vertebrae to identify compression fractures. So when would you get a VFA with your DEXA? When would you get a vertebral fracture? So you could get an x-ray, right? To find a compression fracture. And actually if I see a compression fracture on a VFA, I usually always get an x-ray to confirm it. But generally I use this when it's gonna make a difference in your treatment recommendation. If you have a patient who's osteopenic, say a patient who's lost height, it's normal to lose up to an inch and a half of height, but anything more than that, you're gonna be concerned about vertebral compression fractures. You might get this with the DEXA scan. At the same time, it doesn't cost much. Insurance cover it. The hospitals don't get reimbursed well for it, or the offices, but it is a helpful tool to look for vertebral fractures. So it helps us identify those subclinical unidentified vertebral fractures. Also we want to get a VFA at the time of a drug holiday, which we're going to talk about to make sure the patient hasn't had an interval fracture while on treatment. So, who do we treat? Well, the guidelines for treatment look a lot like the guidelines for diagnosing, which really they are. We know we want to treat patients with osteoporosis. That's somebody who's had a hip or spine fracture from a fall from standing height or less. For patients we know with that osteoporotic T-score of minus 2.5 and lower, as well as those osteopenic patients who have that high FRAX risk. So, this is what we're talking about. The 10-year probability on the FRAX of having a major fracture of 20 percent or the hip fracture of three. So, those are the patients we want to treat, and you saw that category included now in the endocrine guidelines as a diagnosis of osteoporosis, and that's part of the reason. Okay, when we find one of our patients has osteopenia or osteoporosis, we want to make sure there isn't an underlying cause that we can treat and possibly help reverse. This lists the most common undiagnosed disorders of bone and mineral metabolism, hypercalciuria, malabsorption of calcium. That can be after bariatric surgery. It can be with celiac disease is a common one, hyperparathyroidism, vitamin D deficiency, hyperthyroidism, and Cushing's disease. So, these are labs to consider to order to, at the initial diagnosis of osteopenia or osteoporosis, as well as we order some labs every year when patients are on medication, some of these. But we want to order a chem panel, including the calcium, liver function tests, CBC, thyroid, parathyroid, vitamin D, testosterone in younger men, and a 24-hour urine. That's kind of a difficult test for patients to do. They have to take the urine jug home and keep it cold while they're collecting the urine, collect the urine the morning before they take it back in. But the importance of that, I explain to patients, is that when they see their serum calcium, a lot of times they think, oh, good, I'm getting enough calcium. And I have to remind them, no, you know, really our serum calcium is going to be normal if we don't have any calcium in our diet. And that's because the parathyroid hormone is going to borrow or really steal the calcium from the bone to keep that serum calcium normal. So, the only way that we can really tell that patients are both consuming enough calcium and that their gut is absorbing it is to check a 24-hour urinary calcium. So, on the right-hand column, these are more specialized tests that you might want to consider in certain cases. Your serum protein electrophoresis, celiac disease markers, iron and ferritin, homocysteine. I've never ordered some of these in patients. Mainly a CMP, CBC, TSH, PTH, and a vitamin D is what I order most of the time. So, all right, so we really know that osteoporosis takes a lot of time to teaching, but it is so much patient education and those universal bone health recommendations are so important and they don't change depending on a patient's bone health. We really want to recommend that all of our patients, whether they have healthy bones or whether or not they have osteoporosis, it stays the same, they need to take adequate dietary calcium and supplement if the diet is insufficient. They want to get adequate vitamin D. We know that that's really a hormone that our skin makes from the sun. It's hard to get in the diet. Most people need to supplement vitamin D to not smoke, limit alcohol and caffeine, and certainly recommend exercise. As the last lecture said, exercise is just so important. Strength, posture, balance, and fall prevention. So, discussion question, which is true? Do we want to advise patients with osteoporosis to consume more calcium than patients with normal density? Do we want to advise patients with osteoporosis to consume more vitamin D than patients with normal density? Do we want to advise patients with osteoporosis to avoid spinal forward flexion exercises? Or do we want to advise patients with osteoporosis to avoid spinal extension exercises? Which is true? It's C, right. So, let's go through them. Really, patients, whether they have healthy bones or not, need the same amount of calcium and vitamin D. It's something that many people are insufficient in, but enough is what is needed. More is not necessarily better. As far as the exercise, we'll review this a little bit. That forward flexion increases the pressure on the anterior vertebrae, so we want to avoid that. But we do want to advise those spinal extension strength exercises. So, the Institute of Medicine guidelines for calcium and vitamin D really haven't changed in over 10 years. And that's basically, for most adults, 1,200 milligrams of calcium. Remember, that needs to be in divided dose, and it does include the diet. In fact, the diet is the best way to get the calcium. So, I hand out a lot of information on dietary calcium from the NOF, now the NBHOF. And then explain to patients that, really, they only need to supplement what they're not getting in their diet. And if I'm gonna do a 24-hour urine, I tell them to find a diet that they're comfortable with, that they can be consistent with, and then get the 24-hour urine collection. As far as vitamin D, 800 IUs a day should be sufficient. But we know, a lot of our patients are insufficient or deficient in vitamin D. So, what do we do when that happens? By the way, one way that you can get a vitamin D covered, the test, lab test, vitamin D is covered with osteopenia, or osteoporotic diagnosis. One that I use a lot is long-term drug therapy. So, the ICD code for long-term therapy covers vitamin D. So, if our patient's insufficient or deficient, we used to recommend the 50,000 units, 50,000 IUs weekly for eight to 12 weeks. Now, we break that down into the smaller daily, 5,000 units a day for eight to 12 weeks. The really high doses, the 250,000 doses, they've actually found have increased fall risk. And there was a study out in the Annals of Internal Medicine last year, in 2021, that it looked at the effects of four different doses of vitamin D supplements on fall risk, and found that in community-dwelling adults, age 70 and older, that patients were given 200, 1,000, 2,000, and 4,000 IUs of vitamin D a day. And really, they found there was no benefit at the higher doses. We know that 4,000 IUs of vitamin D a day is the maximum recommended daily allowance. For most patients, honestly, I recommend 1,000 a day. It's not too much, it's not too little. I don't think there's any harm in recommending 1,000 a day. And that's a very common over-the-counter dosage. So, exercise. We know that exercise probably helps every single disease out there, right? But also for our bone health. There's a consensus statement through exercise physiologists and physical therapists called the Too Fit to Fracture Recommendations from Canada. And it recommends strength training for those major muscle groups. This is the same for everyone, right? Two or more times a week. Balance challenges, Tai Chi, 15 to 20 minutes a day. Moderate to vigorous aerobic activity, over 150 minutes a week, or again, 20 to 30 minutes a day. But for osteoporosis, what we want to add in is for patients to protect their spine. And that's avoiding those spinal flexion exercises. This slide shows yoga poses that are recommended on the left and discouraged on the right. So basically, you see the straight spine or the extended spine is recommended and you want to avoid that forward flexion. Luckily, Medicare does pay for physical therapy with a diagnosis of osteopenia or osteoporosis. And my patients really appreciate being able to go see a physical therapist. In our area, I have several physical therapists who have taken an extra course on osteoporosis. And the patients, even with osteopenia, will go in, they'll go through their exercise routine, make sure that they're getting enough strength training, make sure that their posture during the strength training is good, that they're not starting to bend over, that they're getting enough impact on their bones. And we certainly know that physical therapy does decrease the risk of subsequent vertebral fractures after a compression fracture. So the ACP had guidelines published in 2017. These are a little older now. I want to go through them, though. The first one is that we want to treat patients with osteoporosis with abyssophosphonate or denosamide. Since this time, we've realized that denosamide has discontinuation fractures, or delay in treatment fractures. So I would not put denosamide in my top line. We'll go through that. We do want to treat women with osteoporosis for five years. This is a somewhat arbitrary number. There weren't any really randomized control study that said that five years, but it makes sense because abyssophosphonates build up bone to three years and possibly two more years to have it cemented in. It is three years for the IV. We'll go over that in a minute. We want to treat with abyssophosphonates to reduce the risk of vertebral fractures in men. The ACP did not recommend getting a DEXA scan within that five-year treatment period because even if the bone density had gone down, we know that the fracture risk decreases for patients on abyssophosphonates. So they said, start your patient, don't even get a DEXA scan for five years. But honestly, I usually always get it at two years. My patients want to know, I want to know that I'm not missing a secondary cause. Also helps look at compliance, maybe need to switch from an oral to an IV. Insurance does pay for it at that two-year mark. It advises against using hormone replacement therapy just for osteoporosis, and it advises us to treat those osteopenic women who are at high risk of fracturing. So let's look at the pharmacology. Remember those osteoblastic cells primarily build up our bone, and the osteoclastic cells primarily take it away, and it's really a balance between the osteoblastic and the osteoclastic activity. So our anabolic medications, which are all injections, our anabolic medicines, they primarily build up that osteoblastic cells, right? And the anteresorptive cells, their anteresorptive medications are slowing down that osteoclastic activity. They're slowing down the taking away of the old bone. Well, we have many more anteresorptive medications than we do for the anabolic. The main category of anteresorptives are the bisphosphonates. The oral, this includes the list of the orals. Alendronate, which is Fosamex, bandronate, residronate, and zoledronic acid, which is the IV bisphosphonate, includes denosamide, or Prolea, as well as riloxifen, estrogen, and calcitonin. The anabolic drugs are the two parathyroid hormone derivatives, which is teriparatide and abaloparatide. These are daily injections for two years. And our newest medication, romazosamide, which is a monoclonal antibody anti-sclerosin inhibitor, or called Avenity, and that is an injection, it's actually two injections, once a month for a year. These next two slides show the fracture data for the medications. We know that for the bisphosphonates, they all decrease the risk of fracturing at the hip, spine, or nonvertebral area, except for one, and that's a bandronate. So I really don't prescribe a bandronate, because it doesn't have the hip fracture data. That's Beneva. But all of the others have the data behind them. Here we see that all the spine, the hip, and nonvertebral fractures are decreased with denosamide, as well as estrogen, as well as the new medication, Avenity. So let's talk a bit about the bisphosphonates. This is really our first go-to medication, is the oral bisphosphonate for postmenopausal women, men, and steroid-induced osteoporosis. We have randomized controlled trials that show we can decrease the risk of fracturing in the spine by 50% and of the hip in 40% with all the medications except for a bandronate or Beneva. We know that the short-term benefits far outseed. The short-term, first three to five years, the benefits exceed the risk, but after five years, the benefits are smaller and the risks are higher. We know with bisphosphonates that there are incremental gains in the spine and hip for the first three years, and that fracture protection starts early, really within 12 months. So if you have a 90- and 92-year-old patient, 95-year-old patient who's very active and fit, yes, you would still want to check for osteoporosis and consider a medication because it's only one year to decrease that patient's fracture risk. There is a specific dosing regimen. You're probably familiar with the oral bisphosphonates where the patients have to take it first thing in the morning, eight ounces of water, stay upright, don't eat or drink anything else for 30 minutes. Oral lalendronate's really our first go-to, Fosamax. We use the IV zoledronic acid for patients who are not able to follow that dosing regime or for patients who have GI contraindications, esophagitis, or a history of ulcer disease. We do want to use caution if the creatinine clearance is less than 35, and we want to monitor calcium, magnesium, and phosphorus annually. So as you probably know, our patients aren't excited about taking these medications, and it's primarily because of these rare but serious adverse effects, right? And there are two of them. There are the atypical femur fractures as well as osteonecrosis of the jaw. So they're both very rare, a risk of about 1 in 10,000. The atypical femur fractures, those are really spiral fractures of mid-shaft. These primarily happened in osteopenic women. In fact, we've never had one in men, but it was primarily back in the day, osteopenic women who were treated with the bisphosphonate for over five, over 10 years. But we do want to ask patients when they come in for their appointments if they have any thigh or groin pain. If they have any pain, we want to get a bilateral femur X-ray to evaluate for any stress fracture or early findings of stress fracture. Now, O and J is also very rare, but our dentists are definitely concerned about it if any of you prescribe these medications. But I do advise my patients to see their dentist, get any dental work done before they start on a bisphosphonate and then to keep up good oral hygiene. For the bisphosphonates, generally what we do if they need dental procedures done, we stop the medication three months ahead of the procedure and then restart it once their extraction occurs. Osteonecrosis of the jaw, it's really, it's where the bone just doesn't heal. It's generally after an extraction. It's generally in patients with cancer, on the cancer doses of zologenic acid. It can be treated when it happens. We actually treat it with the antibiotics, with a teriparatide or a valoparatide to help heal the osteonecrosis of the jaw. Osteonecrosis of the jaw does happen in patients who are not on bisphosphonates as well, but the dentists are quite concerned. I've never had a patient with O and J, but I probably get a letter from a dentist once a month to ask me to clear the patient. It's a conversation. Certainly if patients need to have their dental surgery done, we don't ever want to delay that. And I will with the bisphosphonates, stop it three months ahead. Prolea's a little different. We'll get to that. Prolea, I just advise them to have the dental surgery right at the time of that next dose at six months. And this is that Mayo Clinic shared, Mayo Clinic shared decision aid tool that you can use right at the bedside. I like it because it shows how the fracture risk is reduced, relative risk is reduced by 50%, and it lists for the patient the side effects right there as far as GI side effects and how rare one in 10,000, both the O and J and the atypical femur fractures are. This is my favorite side. This is my favorite side about communicating risk for patients. It really helps them get it. I compare, this was made by Dr. Lewicki out at University of New Mexico, but it compares the risk of having a serious side effect from an osteoporosis medication to the risk of having an injury from a seatbelt. And it also compares the benefit of wearing a seatbelt to the benefit of using an osteoporosis medicine to prevent a fracture. So patients get it. I said, you know that seatbelts help. Yes, well so do the osteoporotic medicines. And you know that you actually could get an injury from a seatbelt, but you wear it anyway. And that really helps them get that perspective of risk. So I find this is kind of an aha moment with some patients. So another question for discussion. Which scenario is it appropriate to consider a drug holiday? Patients who've been on oral bisphosphonate for five years and IV bisphosphonate for three years after treatment with denosamide, that's Prolea for five years, or after treatment with teriparatide for two years? Yes, it's either actually A or B. A and B are both correct. Really drug holidays are only after bisphosphonates. Okay, the other osteoporosis medications we really don't want to just stop. So the recommendation for a drug holiday after five years is for the oral bisphosphonates, and the three year is for the IV bisphosphonate. After treatment with denosamide or Prolea, we want to transition to oral bisphosphonates. We want to transition over, preferably, to an oral bisphosphonate. And after you've used an anabolic, such as the teriparatide, you want to also treat with an antiresorptive. So when is it time to take a drug holiday? You know, that's one thing that I really like when I explain to patients about taking alendronate. You know, we're gonna stay on this medicine. We'll get a DEXA scan at two years, see how you're doing, but we're gonna, if you're doing well, we're gonna keep you on it for five years. If at five years your numbers have reversed, your bones look stable, you get to take a drug holiday. Everybody loves that. And that drug holiday can be for two years, get another DEXA scan, maybe another two years, get another DEXA scan before restarting. So drug holidays are only after bisphosphonates, okay? The reason that we do this is because it allows the bones to kind of breathe again, right? Because remember that the bisphosphonates shut down that osteoclastic activity. They stopped taking away the old bone. They stopped the resorption. So we notice that the risk of the atypical femoral, well, we know that the risk of the atypical femoral fractures, they increase after five years. Osteocorrhizal jaw really stays the same. The risk of ONJ doesn't go up in time, but the atypical fracture does. So I explain to patients we do things differently than back when the big black box came out in 2012 about the atypical femoral fractures. We've learned we do things differently. We sequence the bisphosphonates. And I tell patients any dose of a bisphosphonate that you take is great. It's going to stay in your bones. It'll slowly go away. But the benefit is going to help you. And I explain that we do things differently. We treat, and then we take a holiday, and then we sequence. You can treat again, take another holiday, because the treatment of osteoporosis is really a lifelong disease. And patients like that idea. They like knowing if I take a medication and I don't like it and I stopped it, I've only helped myself in general. So let's see. I think we've gone over all of that. At the time of the drug holiday, you want to get a DEXA scan and assess for vertebral fractures. You can get an x-ray or that vertebral fracture assessment that we mentioned. For patients who are at a high risk, we're going to want to continue them on for the oral bisphosphonate up to 10 years and the IV up to six years. So after you've had your patient on the oral bisphosphonate for five years, you do your evaluation. If that DEXA scan, the T-score is still less than minus 2.5 or they've had a fracture, you're going to continue them, if everything else is normal, you're going to continue them on the oral up to 10 years. If they're getting the IV zoledronic acid, which we dose annually, it actually can be stretched out to every 18 months. And they've gotten three doses of that, you're going to give them three more doses of zoledronic acid before a holiday. So it's a drug holiday, not a drug retirement. It's just a holiday. So during the holiday, we do want to assess the need to restart treatment with a DEXA scan every two to four years. The fracture risk protection starts to wane about two years after stopping the bisphosphonate. But the good news is the risk of the atypical fracture, it quickly stops after the bisphosphonate has only been stopped for a year. And then we also want to make sure that we have the right medication after the bisphosphonate has only been stopped for a year. And then we'll go back on to the therapy with a patient has a fracture or if they meet their initial treatment criteria. If during therapy we notice that the patient has a fracture, that their T-score is decreasing, we want to evaluate, I would evaluate for other secondary factors as well as non-compliance, especially if the patient's on an oral bisphosphonate, we know that the compliance is only 50% at the greatest and we might want to consider changing over to an IV. So bisphosphonates have several different roles. They can be used as the initial treatment of osteoporosis, as the last treatment for anabolic, like after you've used an anabolic medication to help cement in, kind of hold that wonderful bone, that bone density increase of the anabolic, then you use a bisphosphonate for a couple of years to hold it and then consider a drug holiday. And denosamide. Denosamide is a great medication. That's Prolia. It continues to build up the bone density and continues to decrease fractures over 10 years. But if a patient is late for a dose, it's usually dosed every six months. If they're just as little as two months late in getting their dose or if they stop Prolia, there's a withdrawal, discontinuation, spontaneous vertebral fractures. So I call it withdrawal fractures of the spine. It's a 14% risk of having that. And the patient's bone density, when Prolia stops, the bone density goes back to where it was before the treatment in about a year. So Prolia is a great medication, but patients kind of go through withdrawal if they're taken off of it or if they're late. So the way that we prevent those fractures is by using alendronate. Okay, the oral bisphosphonate does help protect that. In fact, in the study, they found that patients who had taken oral alendronate before and then stopped Prolia, they didn't even have the fracture. So alendronate can be used at that time. And alendronate, the oral bisphosphonate, it's really nice to use sequencing on and off throughout a lifetime. All right, this is a really busy slide. I'll just try to talk a little bit about Prolia. Prolia is denosumide. It's a monoclonal antibody, rank L inhibitor. It's given every six months in the office. It costs about $1,000 in injection. In the FREEDOM trial, it does decrease the risk of all the different types of fractures. The FREEDOM trial went out to 10 years. I know that there are people on it longer than that. One niche to use denosumide right now is in patients who you're never going to plan to take off of it, right? Patients with maybe less than a 10-year life expectancy. So for my patients in their 80s and 90s, sometimes I'll start Prolia, as long as they're able to get into the office. So Prolia is a little bit of a responsibility, I feel, prescribing it, because now we know of that delay in treatment, discontinuation fracture, and it's often hard for people to get in right on time. But that is a niche for it. So the benefit of Prolia is that it continues to build up the density and decrease the fracture risk over 10 years. So, and I know next week at the osteoporosis conference, there's going to be another talk on getting basically discontinuing Prolia, what we can use besides alendronate, because I know a lot of my patients who are on Prolia, the twice-a-year dose, they're on it because they didn't tolerate alendronate, right? So that's why we went to Prolia. So how do you get off? Well, some people will use the IV bisphosphonate, the zoledronic acid, but that hasn't consistently shown to decrease the fractures. They think that's partly because of the timing of making sure that the bone turnover has started when the zoledronic acid is given. So one study out now is the zoledronic acid is given right at that six-month mark when the next Prolia would be given, and then another zoledronic acid infusion six months after that, whereas usually zoledronic acid is just given annually. But look for more answers to Prolia discontinuation fractures. So I think we've pretty much covered this. If you're starting alendronate after somebody's been on Prolia, you want to continue that alendronate for one to two years, and then you can consider the drug holiday. We know that the ACP guidelines and other guidelines really did not recommend hormone replacement therapy for the treatment of osteoporosis. If you have a woman who's on estrogen because of chymacteric symptoms, it is fantastic for her bones, but we can't start estrogen or other hormones. They're not recommended just for the treatment of osteoporosis. Calcitonin is especially useful in our patients after vertebral fractures. It does decrease the pain of the vertebral fractures as well as it decreases like 30% the risk of having subsequent fractures. Usually we limit using that at about two years though because it has been associated with the risk of some malignancies. But I have patients in their 90s, I just keep them on calcitonin after vertebral fractures. So the Endocrinology Society also added in an extra category of very high risk patients, very high risk of fracturing patients, and this is to help identify patients who can be treated with the anabolic therapies initially, which is really the gold standard because we know that starting that anabolic therapy right away, that's going to be a daily shot of your teriparatide or abaloparatide generally. We know that that helps build that bone density up and then use the antiresorptive medication to kind of hold it there, your bisphosphonate, right? We know that if we use, I'll go in sequence, if we use the bisphosphonates first and then use the anabolic, there's a little bit of a blunted effect. So that's why it's really nice to be able to identify these patients right away. So patients that fall into the very high fracture risk are those with advanced age, frailty, increased fall risk, a fracture within the last 12 months, they found that fractures actually cluster together. So patients who've had a fracture in the last year, they're especially high, kind of like an MI, of having another fracture in that year. Or patients with multiple fractures, patients on steroids, T-score of less than minus three, and a high FRAX risk. So there are two, with the anabolics, we have our two parathyroid hormone medications, I call them, they're PTH1 receptor ligands, teriparatide and abalaparatide. Teriparatide is FORTEO, abalaparatide is TIMLAS. These are daily injections for two years. There was a black box warning that they needed to be stopped at two years because of an increased risk of osteosarcoma in mice. That was actually never found in people. And so the brand name FORTEO has now been able to have that black box warning removed. So FORTEO could be used longer, or probably even more importantly, could be used in that sequencing again in a lifetime. But the other, the generic teriparatide and TIMLAS did not have the black box warning removed yet. So we do want to use caution in patients who might be at risk of osteosarcoma though. That would be patients with a history of Paget's disease, prior radiation therapy, bone metastases, hypercalcemia, hysteroskeletal malignancy, anything like that. You would not want to use one of the parathyroid hormone receptor ligands. So teriparatide, that's FORTEO, is also indicated for men and for steroid-induced osteoporosis. The advantage of TIMLAS is that it doesn't have to be refrigerated. So for my patients who travel, they're outdoors women, and they don't want to have to keep their medication refrigerated, who travel a lot, TIMLAS has that advantage. So the newest medication is an antibiotic called remazosamide or Avena-T. It is a monoclonal antibody to sclerostin. It was just approved by the FDA in 2019. It's two shots a month for a year. Remember, you're going to want to follow that with an antiresortive, follow it with a bisphosphonate. But I was really slow in starting to prescribe this. I think I still only have one or two patients on remazosamide. And that's because of the increased risk of heart attack, stroke, and death. So it should not be used in a patient who's had a heart attack or a stroke in the last year. So I've not been the first one to jump out in prescribing this. It has been out for, you know, what, three years now? But I think we may see ROMO being used more and more. But actually, it didn't go through the FDA the first time, and they redid the data and got it through because of the vascular risk. So just another, I already touched on this, but as far as sequencing the medicines, as far as using a medication, and then what medication do I go to next? In an ideal world, we'd love to start everybody with an antibiotic, but they're really expensive. So we need the high-risk patients in order to justify that. So in general, we're going to start with an oral bisphosphonate, usually oral alendronate. But we know if we use the antibiotics right after the bisphosphonates, there is that wanted effect because the bisphosphonates stay in the bone so long. So they've actually found traces of alendronate 10 years after the last dose, just traces. Not that it's still really working. So ideally, it would be nice to start with the antibiotics. After we do antibiotic therapy, generally for a year or two years for the parathyroid hormones, then you're going to want to use that antiresorptive, the bisphosphonate, for one to two years to hold the bone. When patients are on the medication, we want to see them in the office once a year, do the basic lab tests, check their kidney function, vitamin D, make sure they're getting enough calcium, go over them with them again, how they need their daily calcium, that the diet is best, only supplement what they're not getting in their diet, make sure they're on their vitamin D, talk to them about exercise, make sure they haven't lost 0.8 of an inch or more. If so, you might want to check for a spinal fracture. Again, that DEXA while the patient's being treated, I still do it at two years and then at the three-year mark if they're on the five-year schedule. So there's some hospital programs and initiatives that are trying to catch people who have fractured to address their bone health. One is called the American Orthopedics Association Own the Bone Program. Some of your hospitals may have that where patients who are hospitalized then see a nurse or somebody to address their bone health and we try to capture them and coordinate their care. Kaiser probably has the, was really the initial Own the Bone Program and is probably the most successful at this. I know that my hospital, Advent, now has this program. The International Osteoporosis Foundation has a program called Capture the Fracture. So it wouldn't be good to talk about osteoporosis without at least mentioning fall prevention because over 95% of the fractures happen from a fall. Now, I know for the patients you all care for, such as your spinal cord patients, they even fracture just simply transitioning. But for community-dwelling adults, what helps them prevent fractures and falling? Well, the fall prevention studies the USPSTF looked at showed, guess again what helps? Exercise, exercise, exercise. The multifactorial intervention programs such as the CDC's STEADI program that's Stopping Traumatic Accidental Death in the Elderly, we know that that makes good sense, right? We want to review our patients' medications. It had a C recommendation. And vitamin D supplement is not recommended. I tell our residents, that's just really for your board questions. And our fellows, I say, vitamin D, you do want to check vitamin D. But because of this caveat, it says, these apply to community-dwelling adults not known to have osteoporosis or vitamin D insufficiency. And so many people do have that insufficiency. But that was the recommendation. So we want to remember that education is key. We need to talk to our patients and have other people talk to them, like physical therapists, talk to them about exercise, dieticians to help talk about their diet. We can use the chronic care management coordination codes in our office for education and consider starting a National Osteoporosis Foundation support group in your community. We have one of those that haven't met in the last couple of years because of COVID, but it was a monthly group. We're different people from the community. We had a physiatrist come in and talk about rehab after a fracture, orthopedic surgeon who came in and talked about fracture, you know, hip fractures. Endocrinologist or radiologist came and described the DEXA scan process and meaning to patients, dieticians, Tai Chi experts, physical therapists. It was a great program. And the National Osteoporosis Foundation, now the National Bone Health and Osteoporosis Foundation, will help you start a group in your community. If anybody is interested in it, I find that patients really want this information. And so much of it is education. So we want to counsel our patients on prevention, use a formal risk assessment tool. That would be the FRAX or one of those other easier questions to diagnose and screen for osteoporosis. We want to individualize the treatment. Each patient's treatment, as you could tell with all of these medications, it's really individualized. It's individualized on their other medications, on what their preferences are, on what their other medical conditions are. Really, the oral bisphosphonates are our first go-to. We want to evaluate for that drug holiday at five years with a DEXA antevertebral fracture assessment. That could be either the VFA or a spine x-ray. Counsel patients on prolea or denosumide not to be late for that shot. Those fractures happen as soon as eight months, okay? And if they're going to stop their prolea for whatever reason, if their bones have, you know, the bone density is now normal, remember to transition over to antiresorptive, preferably oral alendronate. And encourage patients to exercise to decrease their risk of falls. Okay, any questions? Yes? I have a few, just three really quick questions. One, it's a great point. You have a dental stopping it three months before your dental work for Fosamax and right at the end of the prolea. When do you restart it? When they've healed. Once the surgery, once the dentist says that they're well-healed. It's usually six weeks, two months after. Okay, second thing is, if they're doing well on prolea, I've called the company. They don't list an end point. They don't list 10 years when I call the company. Oh, yeah. Why do you hold it at 10 years if they're doing well? They stop the freedom extension study at 10 years. But you can continue past that. Right. Absolutely. And the third question, because I don't want to monopolize your question time, is, so in terms of Forteo and Tymlos, as long as you avoid those red flags, my understanding was there was never a case of cancer except in rats. That's right. Okay. That's right. But being able to pull that data back out now, Forteo's been able to do that, the brand name Terapuritide, the generics don't have the data to pull the black box off yet as well as Tymlos does. But I'm sure that Tymlos will get the black box removed in time. But you're absolutely right. We really haven't been able to determine that there have been any osteosarcoma in patients on Terapuritide or Valipuritide. Yeah. It's more about telling the patients. It's in the rats. There's more rats. Yeah. Great. That was a great talk. Thank you. Matt, can you say, do we have any questions on the chat at all? And I just have to say that that lecture was outstanding. So I've been to several national conferences where I've been trying to find a talk like this. I had so many questions that I wanted to ask, and you just kept hitting every single one that I had. So really thorough, really helpful. I think going over the recommendations for the calcium and the vitamin D in the different age groups and talking about the transitioning with the different therapies. And especially, we always get questions about the risks with the osteonecrosis of the jaw and the atypical femur fractures. So being able to show what those statistics are. And then, of course, the black box warning on the Forteo. So being able to, I didn't know that that had actually come off, that's a big deal. So just wonderful. Thank you so much. Well, thank you. I enjoyed being here. Great. Well, thank you so much, Dr. Kramer.

osteoporosis

women over 50

early detection

bone density testing

FRAX tool

oral bisphosphonates

lifestyle changes

neurologic diseases

patient education