So after screening and diagnosing, let us move on to the guideline-based osteoporosis management strategies. So firstly, let us see what are the universal recommendations. Council on the risk of fractures, eat a diet rich in fruits and vegetables, supplemented if necessary to a total calcium intake of 1000mg per day for men aged between 50-70 years, 1200mg per day for women aged more than 51 years, 1200mg per day for men aged more than 71 years, vitamin D intake should be 800-1000 IU per day if age is more than 50 years, regular weight-bearing and muscle-strengthening exercises should be encouraged, fault prevention evaluation and training should be given, cessation of tobacco use and avoidance of excessive alcohol intake should be encouraged. In terms of laboratory evaluation, comprehensive metabolic panel should be assessed along with parathyroid hormone assessment, phosphate and vitamin D levels, testosterone evaluation in men aged between 50-69 years, thyroid-stimulating hormone should be assessed, 24-hour urine for calcium, creatinine and sodium in patients with a history of kidney stones or someone with a decline in bone density or on treatment, bone turnover markers in special cases, vertebral fracture assessment should be assessed in patients with height loss. Hello everyone, welcome to this next section on osteoporosis management. By now you have heard from Dr. Srivastava about who to screen for osteoporosis, who needs to be tested and basic lab and imaging studies that need to be completed. The next section is going to talk about treatment strategies for osteoporosis, how to choose a therapy which is best suited for your patient and we will go over various anti-resorptive drug therapies that are needed. So let's start with a case. This is a 75 year old woman, she presents to your clinic after she fell and broke her wrist. This was a fall from a standing height. A bone density test was done several years ago and it showed low bone mass and she has been taking calcium and vitamin D since then. You check basic labs on her and everything is unremarkable. She has a follow-up bone density testing that you order and it shows a decline at the hip and spine. T-score of the total hip, femoral neck and lumbar spine are minus 2.3, minus 2.6 and minus 1.8 respectively. So what should we do next? There is an emerging concept in osteoporosis treatment which talks about goal-directed therapy. Just as we have targets for treatment for patients with diabetes and hypertension, similarly osteoporosis therapies should be chosen in order to actively increase bone density and the overarching goal of osteoporosis management as we know is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment sequence is selected for individual patients. In patients who have diabetes or hypertension, the goals are very well validated. You have an A1c goal or a blood pressure goal that you target and similarly what we are trying to do in osteoporosis is to find similar goals that we can use on our patients so that we always choose the best possible osteoporosis therapy first to give them the most benefit for the treatment. If you have a patient who is at high risk or imminent risk for a fracture, we should choose the first treatment which will give them the maximum benefit in terms of not only improving their bone density but also to reduce their risk of having a fracture. And treatment targets have to be tailored to each patient just as we talk about A1c goals in patients based on their age and their comorbidities, in similar terms we should be targeting treatment based on each patient risk factors. Treatment selection should also take into account if the bone density target can be reached in a reasonable amount of time. Treatment targets should be individualized. They should be based on the specific indication for beginning treatment. Did you start therapy on a patient because they had a recent fracture which increases their risk of a future fracture? The number and site of prior fractures also makes a big difference. Did they have a vertebral fracture or did they have multiple vertebral fractures and what was the bone density at the total hip femoral neck or lumbar spine? Age by itself is also a major factor because we know that advancing age increases your risk of having a fracture. Does the patient have other strong risk factors for a fracture like taking high-risk medications which cause bone loss? The categories for treatment targets are patients at imminent risk of fracture or in other words patients who have a very high risk of fracture, patients with a baseline t-score of less than or equal to minus 2.5 and the third category would be patients with a baseline t-score over minus 2.5. The endocrine society in addition talks about very high risk groups and these are patients who have a t-score less than minus 2.5 and a fragility fracture, someone who has a t-score less than minus 3 or a fracture within the last 12 months, fractures which occur while taking an approved osteoporosis medication, multiple vertebral fractures and patients who have a frag score over 30% for major osteoporotic fracture or above 4.5% for the hip. All of these patients would fall in the high risk fracture category. So what are the treatment targets for these three broad categories of risk? The first one are patients with imminent risk of fracture or patients who are at very high risk of fracture. Patients with a recent fracture are at very high risk of future fractures over the next two years. Now, this is independent of baseline T-score. The baseline T-score may be in the low bone mass range, but they're at high risk because of the fact that they had a recent fracture. Patients who have had multiple prior fractures, even if they were not sustained within the last two years, are also at imminent risk. Now, for these patients, the treatment goal is to rapidly and maximally reduce fracture risk. These patients require sustained treatment in order to reduce their risk of future fracture. The second category is patients with baseline T-score less than or equal to minus 2.5 at the total hip, femoral neck, and or lumbar spine. The treatment target here is a T-score level of at least over minus 2.5 at the respective sites. So you're aiming for a T-score above the treatment threshold. So wherever you started the treatment, that T-score should at least go above minus 2.5 to reduce their fracture risk. Improving T-scores to levels over minus 2.5 at the total hip is associated with a lower risk for nonvertebral and vertebral fractures, which is why we tend to follow total hip T-scores with repeated bone density. Improving T-scores to levels over minus 2.5 at the lumbar spine is associated with lower risk for vertebral fractures. The third category is patients with a baseline T-score which is above minus 2.5, so they're not in the osteoporosis T-score range. So these people are recommended to have treatment because their FRAX score might be high. For these people, what you want is an improvement in bone density, which is associated with reduced fracture risk. However, we cannot define a T-score target for such patients because they really did not have a very low T-score to begin with, but improvement in their T-score is consistent with reduced fracture risk in future. Once we have decided that our patient now needs a therapy for osteoporosis, the next step is to choose the correct drug for them. In the current armamentarium of osteoporosis therapies, we have medications that fall in one of the three major categories. The first one is anabolic therapy, and in this category, we have teriparatide and anabaloparatide. The anabolic therapy results in stimulation of bone formation by stimulating osteoblast activity. These medications improve bone density and also reduce risk of fractures. The second category is the antiresorptive therapy. In this category, medications decrease osteoclast action, thereby reducing bone turnover, which improves bone density and reduces bone loss. The medications that fall in this category are the bisphosphonates, the SERMs, which is riloxifene, denosumab, hormone replacement therapy, and calcitonin. In this presentation, we will not be talking about hormone replacement therapy and calcitonin in the interest of time. And the third category is the newest kid on the block, the dual-action agent, romososumab. This medication stimulates initial anabolic action for the first few months of therapy followed by antiresorptive action. And this is something which you'll be discussing in detail in the next few slides. So let's talk about bisphosphonates first. These are the most commonly used osteoporosis medications all over the world. We have four approved agents, alendronate, resedronate, ebandronate, and the IV formulation zoledronic acid. There's no head-to-head fracture studies comparing these medications to each other, but we know from network meta-analysis that they have similar efficacy in fracture reduction. New vertebral fractures are reduced about 40 to 50%, non-spine fractures are reduced by 20%, and hip fractures are reduced by 50% if they have existing vertebral fracture or they have a low hip bone mineral density with a T-score less than minus 2.5. So if you're in the high-risk category, the hip fracture reduction is more. We also have to know that ebandronate does not have fracture prevention data at the hip and non-vertebral sites. So if you have patients who are at high risk for hip fracture, this is not the agent of choice. In spite of the fact that they have relatively similar efficacy, we have to remember that not all oral bisphosphonates are the same. For instance, alendronate is more potent compared to resedronate because of its longer half-life in the bone and it's considered a longer-acting bisphosphonate. Zoledronic acid is the most potent bisphosphonate out of all of these and tends to be in the bone for a longer period of time and has more improvement in bone density and fracture efficacy. So going back to the patient that I had presented in the very beginning, this 75-year-old lady who had a fall from a standing height and has low bone density and fractured her wrist. Now, this is a woman who has high risk of fracture. For that person, you would probably use either alendronate if she was going to start an oral medication or preferably the IV form, which is zoledronic acid. So this is how you sort of pick a medication based on the patient's fracture risk. We know that bisphosphonates are very good agents to decrease risk of future fractures. Sometimes it helps to frame the data in the number needed to treat. So for instance, in this slide, if we treat 35 patients, the number of events prevented per 1,000 patient treated is about 29 for nonvertebral fractures. For the hip, you need to treat a few more patients to prevent events. It sometimes helps to give the analogy to a patient about statin use, for instance. We'll tell them that the risk reduction of fractures with bisphosphonates is similar to potent statin use in patients to prevent cardiovascular events. And it does give the patient a better sense of the risk reduction that can be seen with these medications. In addition to talking about the efficacy of these medications, it's important to know what the major or common side effects are when we are treating these medications. For the oral bisphosphonates, the most common side effects are upper GI discomfort. There are some patients who do have bone pain that they experience, but the vast majority of patients will come to you with symptoms of reflux or even peptic ulcer kind of symptoms. With the oral bisphosphonates, you have to be very meticulous on how you take the medication. Most of the oral bisphosphonates tend to be either weekly or monthly. The patient has to take the medication on an empty stomach with water. They have to make sure that they don't take their other medications along with the bisphosphonate. They have to make sure that they're sitting upright and they don't eat food. These medications tend to be very poorly absorbed to begin with, and if you're taking them meticulously, the absorption rates are better. For IV reclassed, there tends to be this acute phase reaction that patients may experience after you give them the first infusion. It consists of patients complaining of myalgias, arthralgias, low-grade fever, which happens after the first day of the infusion. Most of the time, these medications, you can use over-the-counter, either non-steroidals or Tylenol to help with the symptoms. Sometimes, very, very rarely, it is that the patients have severe bone pain to the point that we may have to prescribe them a short course of steroids to help with the symptomatology. But for the vast majority of patients who take these medications, they're very well tolerated. The other caveat with the bisphosphonates is that these medications cannot be given to patients who have severe chronic kidney disease because these medications do leave the body, they're renally excreted. So patients who are very low GFR, bisphosphonate therapy is relatively contraindicated. The next drug in the antiresorptive category is riloxephine. This is a selective estrogen receptor modulator that partially mimics the effects of estrogens in bone and the cardiovascular system while functioning as an anti-estrogen in endometrial and breast tissue. So it has two actions which are both beneficial to the person using the medication. Lumbar spine bone density increases by 1.6 to 3.4% and it decreases spine fractures by about 36%. Femoral neck and total hip bone densities increase between 2.3 to 1.6%. However, the important caveat is that there is no benefit in fractures of the hip despite improvement in bone density. So you would not choose this in a patient who has a high risk of hip fracture, for instance. There's reduction in the risk of fractures and there's reduction in the risk of invasive breast cancer by about 76% during a median of 40 months follow-up in post-menopausal patients with osteoporosis and no history of breast cancer. This is huge for patients who are at high risk for breast cancer. Venous thromboembolism is a serious adverse event and is three times more common compared to placebo. And there's worsening of vasomotor symptoms in some patients. So this would not be a good choice in a patient who is recently post-menopausal and is experiencing hot flushes and night sweats, for instance. I would see this being used in a relatively younger woman who has low bone mass and you're trying to prevent ongoing bone loss. And this woman may also have a higher than normal risk factor for breast cancer, for instance, a family history of breast cancer. That would be one of the ideal candidates for this medication. So going back to our patient that we presented in the beginning, the 75-year-old who recently had a fracture, this is not the best choice of agent in that patient because her future risk of fracture is quite high. And this medication may not be the best choice because it will not give her as much fracture risk reduction as you would want. Next in the category of antiresorptive medications is dinosumab. Dinosumab is a human monoclonal antibody against rank ligand, which is a cytokine that is essential for the formation, function, and survival of osteoclasts. So since osteoclast activity goes down, bone turnover is reduced and the patient has improvement in bone density. Dinosumab results in a rapid and marked reduction in bone resorption. There's increases in bone density in the trabecular and cortical compartments and significant reductions in fracture risk. It's administered twice a year in the office and is very well tolerated for the most part. And it can be given in patients with chronic kidney disease. So patients who cannot take bisphosphonates because they have reduction in GFR can be safely given dinosumab. The caveat is that you should not be giving dinosumab to patients who have end-stage renal disease or impending end-stage renal disease because those patients tend to be at very high risk of developing hypocalcemia. It's approved as a primary agent or secondary agent to treat patients in the high to very high risk category. In the FREEDOM trial, which is the initial trial that came out for dinosumab, there was a reduced risk of new vertebral, hip, and non-vertebral fractures by 68%, 40%, and 20% respectively. So very excellent data in terms of fracture risk efficacy. This is the graphical summary of the FREEDOM trial. This study was the pivotal trial which led to the approval of dinosumab. It was a three-year study where they took 7,868 post-menopausal women with osteoporosis and they were randomized either to placebo or to dinosumab therapy. The primary endpoint was the rate of new vertebral fractures after three years of treatment. And what they found was that new vertebral fractures were reduced by 68%, non-vertebral fractures by 20%, and hip fractures by about 40%. The increase in lumbar spine bone density was about 9.2% and total hip increased by about 6%. After the initial FREEDOM study ended in three years, participants were then enrolled in the FREEDOM Extension Study for another seven years. All subjects in the original FREEDOM study who had completed that trial without discontinuing treatment or missing more than one dose of either dinosumab or placebo were eligible to enroll in the open-label seven-year FREEDOM Extension Study in which all participants received dinosumab. Patients who were in the placebo group in the original FREEDOM study were then assigned to the crossover group and started on dinosumab. Patients who were in the dinosumab category continued dinosumab and they were forming the long-term treatment group. After seven years of treatment, it was found that in the crossover group which received placebo before, the lumbar spine bone density improved by about 16% and the total hip, the gain was about 7.4%. In the group that received dinosumab all along, lumbar spine bone density improved by 21% and total hip by about 9.2%, so impressive gains at both sides. Since this was a safety and tolerability study, which was the primary endpoint for this study. They looked at the risks of atypical femoral fractures and osteonecrosis of the jaw. The numbers were quite low, and so this drug is considered quite safe even after long duration of therapy. So going back to our patient, who I presented at the beginning of the session, the 75-year-old who had a low trauma fracture and has low bone density, and consequently a higher risk of fracture, dinosumab would be probably a very good option for therapeutic intervention in this patient because not only would her bone density improve, but more importantly, her risk of future fractures would be quite low. This concludes the section on antiresorptives, and I'm very happy to introduce my colleague, Dr. Jennifer Kelly, who is going to now talk about anabolic therapy next. We will now focus on anabolic agents that are available to treat osteoporosis, particularly for people at very high risk for fracture. In the category of purely anabolic agents, we have teriparatide and abaloparatide. Teriparatide is a synthetic form of PTH, parathyroid hormone. It consists of the first 34 amino acids. It is given as a daily subcutaneous injection by the patient. Abaloparatide is a synthetic form of PTHRP, parathyroid hormone-related peptide. It also consists of the first 34 amino acids and also is given daily by the patient as a subcutaneous injection. When either of these hormones are elevated in the body in a continuous fashion, PTH or PTHRP, it is catabolic to bone. However, when they are administered as daily injections and therefore just stimulating the bone at the time it is administered, it produces an anabolic or bone-forming effect. Looking at the fracture efficacy of teriparatide, in the Phase III Pivotal Fracture Trial published in New England Journal by Nir et al. in 2001, this study involved a high-risk fracture cohort of over 1,600 postmenopausal women with previous vertebral fractures. The dose of 20 micrograms of teriparatide a day yielded a remarkable 65% reduction of new vertebral fractures, 35% reduction of nonvertebral fractures, and 53% reduction of nonvertebral fragility fractures. This study was not powered to capture data for hip fracture reduction. There was a meta-analysis performed by Perez et al. published in Bone in 2018, which was based on over 8,600 subjects enrolled in 23 randomized controlled clinical trials, which demonstrated a 56% reduction in hip fractures with teriparatide. Here are some of the data available on abaloparatide. On this slide shows information from the ACTIV trial, which was published by Miller et al. in JAMA in 2016. This trial was a Phase III double-blinded randomized control trial, which consisted of postmenopausal women with low bone density T-scores along with a history of vertebral fractures. These women were randomized to receive either placebo, abaloparatide, or teriparatide. There were approximately over 800 subjects in each group. Here you can see that there were impressive bone density gains seen at the different timeframes of six months, 12 months, and 18 months with abaloparatide and teriparatide compared to placebo. The improvements with abaloparatide were significantly greater than those with teriparatide at the total hip and femoral neck at all time points and at the lumbar spine at six and 12 months. Regarding fracture data in the ACTIV trial, looking at the primary endpoint of reduction in vertebral fractures, both abaloparatide and teriparatide significantly reduced the risk of vertebral fractures compared to placebo with reductions of 86% and 80% respectively. Although abaloparatide demonstrated a lower instance of major osteoporotic fractures compared to teriparatide, 1.5 versus 3.1%, no statistical significant difference was found in the rates of nonvertebral fractures with abaloparatide and teriparatide showing reductions of 43 and 28% compared to placebo respectively. Shown here are Kaplan-Meier curves indicating the time to the first nonvertebral fracture, which was a pre-specified secondary endpoint. Nonvertebral fractures were defined as fractures excluding those of the spine, sternum, patella, toes, fingers, skull and face and those with high trauma. For abaloparatide versus placebo, the hazard ratio was 0.57 and for teriparatide versus placebo, the hazard ratio was 0.72. For major osteoporotic fractures, looking at time to event, for abaloparatide versus placebo, the hazard ratio was 0.30 and for teriparatide versus placebo, the hazard ratio was 0.67. Looking at the potential adverse effects of both abaloparatide and teriparatide, they are quite similar. They both work to simulate bone formation by binding to the PTH type 1 receptor. Potential adverse effects include hypercalciuria and hypercalcemia, which makes sense considering that they are both PTH analogs or types thereof. It is important to perform the correct type of laboratory screening prior to starting these medications, which one would do anyways looking to properly evaluate a person who has a high risk for a fracture, particularly ordering a 24-hour urine calcium collection prior to starting this medication would be helpful as if a person had a predisposition to hypercalciuria prior to starting this medication, either one, this could be exacerbated. Other potential adverse effects include dizziness, palpitations, headaches. There was previously a black box warning of osteosarcoma in rats on both of these medications. The black box has been removed from each of these medications. Teriparatide was initially FDA approved over 20 years ago. Abaloparatide was FDA approved in 2017. We can give teriparatide for longer than two years if deemed appropriate. The two year warning time limit for abaloparatide persists. However, because of this history of a concern for osteosarcoma in rats, it is not recommended to use either of these agents in a patient with Paget disease, idiopathic increased alkaline phosphatase levels, open epiphyseal plates, bone malignancies, or previous radiation therapy. Some of the data from the active trial showed that the incidence of hypercalcemia was lower with abaloparatide than with teriparatide treatment. This is consistent with the proportional less amount of bone resorption that can occur with abaloparatide. Another anabolic agent that is available to treat postmenopausal women with osteoporosis at a high risk for fracture is romazosumab. Romazosumab is a monoclonal antibody directed against sclerostin. Sclerostin binds with the Wnt receptor and inhibits the differentiation of precursor cells into mature bone forming osteoblasts. By blocking sclerostin, both bone formation is stimulated and bone resorption is inhibited. Because of this unique mechanism of action, this is the only medication that has a dual effect where there is an uncoupling of formation and resorption. And with this, we see rapid gains in bone mass occur. This also provides for a very robust fracture protection. The data is quite impressive in terms of increasing bone density, mostly at the spine, but also at the hip. Looking at the two main trials available on romazosumab, first was the FRAME trial published in the New England Journal by Kosman et al in 2016. This trial enrolled 7,100 postmenopausal women with low T-scores and they were randomized to receive either subcutaneous romazosumab for one year or placebo. In that study, vertebral fracture reduction at one year was 73%, which is quite impressive. Non-vertebral fracture reduction was 25%. Another study called the ARCH trial, which was published in the New England Journal by Sag et al in 2017, enrolled almost 4,100 postmenopausal women with osteoporosis and fragility fractures who were randomly assigned in a one-to-one ratio to receive either monthly subcutaneous romazosumab or weekly oral alendronate for 12 months. After that time, they were followed by an open-label alendronate prescription for one year. In that trial, vertebral fracture reduction was lowered by 48% in the romazosumab group, non-vertebral fractures by 19% and hip fractures by 38%. Romazosumab is currently FDA approved and indicated for the treatment of postmenopausal women at high risk for fracture. The dose is 210 milligrams given subcutaneously monthly for 12 months, so it is just a one-year course. The anabolic effects of romazosumab will start to wane after these 12 months of therapy and it is important for this medication to be followed up with an antiresorptive therapy afterwards to maintain gains and fracture efficacy. In terms of adverse effects, most people tolerate this medication well. Occasionally, patients may complain of nauseas or headaches. There have been reports of osteoporosis of the jaw and an atypical femur fracture with the use of romazosumab as it does contain an antiresorptive component to the medication. These reports are very rare. Here is some of the data from the FRAME trial where romazosumab was given for one year versus placebo given for one year in postmenopausal women with osteoporosis. At first year, both groups received anosumab subcutaneously 60 milligrams every six months for one year. As shown here in box A, incidence of new vertebral fractures, the risk ratio was 0.27 for 12 months and at 24 months, 0.25. Both of these reductions in the treatment groups were considered statistically significant. In the lower boxes labeled B and C, it is shown in terms of time to event analysis, time to first clinical fracture and to first non-vertebral fracture at 12 months and 24 months. There's an enlarged Y-axis shown in the lower graphs. Shown here are the remarkable improvements in bone density displayed during the FRAME trial with the use of romazosumab. In box A, change in bone marrow density at the lumbar spine over the full 24-month trial and for romazosumab at the six and 12-month timeframes, as you can see, the lumbar spine density improvements are quite impressive, 9.7% at six months, 13% at 12 months. And then by giving denosumab afterwards, the improvement continued, whereas with placebo, there was very minimal, hardly any change in lumbar spine density in the first year and improvement was seen afterwards with the use of denosumab. Similar types of efficacy were seen at the total hip and femoral neck. These numbers that we see in this trial for gains in bone density at one year for romazosumab are quite larger than we see in other studies looking at other agents. In the lower boxes, bone turnover marker data is shown. Changes in P1NP levels in box D, P1NP being a marker of bone formation. So for the first 12 months when the person was on romazosumab, it makes sense that the P1NP level would be higher, but as we know with this medication, the anabolic effects will start to wane over time, which is demonstrated in this graph. The CTX levels are on the lower end, which we would expect with an antiresorptive in both the placebo and in the romazosumab group, lower with romazosumab. And then once the patients are transitioned to denosumab at 12 months, both P1NP and CTX levels go low. Here is some data from the STRUCTURE trial. This was published in Lancet in 2017, which showed a comparison of romazosumab versus another anabolic agent, teriparatide. The STRUCTURE trial stands for the study to evaluate the effect of treatment with romazosumab compared with teriparatide in post-menopausal women at high risk for fracture, previously treated with a bisphosphonate. In this study, there were over 430 subjects who were randomly assigned to romazosumab or teriparatide for one year. These subjects were all previously treated with at least three years of an oral bisphosphonate prior to screening. As shown here based on the bone mineral density data, romazosumab led to greater BMD increases at the lumbar spine and total hip then teriparatide after 12 months. There is a concern about a potential increased cardiovascular incidents with romazosumab. This was based on data from the ARCH trial, which in the first 12 months, patients were randomized to either romazosumab versus alendronate. In that trial, there was an increase in cardiovascular events seen in the romazosumab group, 12.5% versus 1.9% in the alendronate arm. This was not seen in the larger trial that took place called FRAME. Because of this data, this led to a black box warning being placed on romazosumab by the FDA to not use this medication if a person has had an MI or a cardiovascular event within the past year. This is very specific wording. It remains unclear at this time whether this observation that was seen in the ARCH trial is due to the use of sclerosin inhibition in older population that is causing a higher cardiovascular risk, or could there have been a protective effect from the alendronate arm that has been postulated, or perhaps this occurred by chance alone. More data is needed in this area. Let's look now at a case. We have a 75-year-old woman who presents to the office after she fell and broke her wrist. A bone density test was performed several years ago, which showed low bone mass or osteopenia, and she has been taking calcium vitamin D since that time. She had updated labs performed, which are unremarkable. She also had a follow-up bone density test performed, which showed a decline at the hip and spine. What should we do at this point? Well, we know that this person is at high risk for future fracture, particularly as she just had a recent fracture. We could consider treatment with a bisphosphonate or possibly denosumab, or it may be ideal to consider an anabolic agent first. We know that anabolic agents work better when given first. If an anabolic agent is used later in sequencing of medications, its effects can be blunted by previous use of antiresorptives. Also, the argument can be made that now that this person has had a recent fracture, she is in a high-risk category for future fracture, and a more potent medication, such as an anabolic agent, should be considered. After the use of an anabolic agent, an antiresorptive would need to be used to maintain the gains and provide further fracture protection. Now at this time, I would like to toss it over to Dr. Ban to talk about osteoporosis management strategy.

osteoporosis management

fracture prevention

bone density

antiresorptive therapies

anabolic therapies

calcium and vitamin D

treatment strategies