Bone Health after Transplant

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Bone Health after Transplant

Wednesday, May 4, 2022

Presenter: Huifang Lu MD, PhD, Co-founder of the Multidisciplinary Bone Health Clinic for Cancer Patients at MD Anderson Cancer Center, Houston, Texas.

Presentation is 33 minutes long with 24 minutes of Q & A.

Summary: Bone loss is common after transplant and can lead to fractures with severe consequences for transplant recipients. This presentation describes the causes of bone loss and the diagnostic procedures and treatments that can minimize damage and maintain patient quality of life.

Highlights:

• Risk factors for osteoporosis include older age, female gender, and previous low impact fractures. Steroids are also a significant cause of bone loss and fractures.
• Within two years of a transplant using donor cells, transplant recipients may have 10% to 20% bone loss, due to the underlying disease and its treatment. Bone density tests should therefore be done no later than three months after transplant, if not done pre-transplant, and repeated annually to monitor bone loss.
• Bisphosphonates can treat osteoporosis by increasing bone formation, but kidney function should be monitored while on these medications. When stopping these medications, rebound bone loss may occur so prolonged treatment is often recommended.

Key Points:

(02:51): Osteoporosis is a silent disease that can progress without symptoms until fracture occurs.

(03:47): Fractures are most common in the spine, hip, and wrists.

(08:56): The DEXA scan is the gold standard for measuring bone health.

(13:45): Radiation and vitamin D deficiency can contribute to bone loss.

(15:27): Fractures are most likely to occur about two and half years posttransplant on average.

(19:02): Calcium, vitamin D, weight-bearing and resistance exercises can improve bone health.

(22:07): Proper dosing of calcium is important to realize the benefits

(24:35): Medications for osteoporosis are indicated after a fracture or a DEXA scan diagnosis

(30:49): Long term treatment with bisphosphonates can have side effects but the benefit of preventing fracture usually outweighs the risks.

(32:11): Lifestyle changes and medications can treat osteoporosis and prevent fractures.

Transcript of Presentation:

(00:00): [Marsha Seligman]     Introduction. Hello, everyone. Welcome to the workshop Bone Health after Transplant. It is my pleasure to introduce today's speaker, Dr. Huifang Lu. Dr. Lu is a rheumatologist at the University of Texas MD Anderson Cancer Center and the co-founder of the Multidisciplinary Bone Health Clinic for Cancer Patients. Her clinical practice focuses on optimizing bone health in cancer patients and survivors. She has done extensive clinical research in the field of bone health and patients who are hematopoietic stem cell transplant survivors. Please join me in welcoming Dr. Lu.

(00:42): [ Dr. Huifang Lu]    Overview of Talk. Good afternoon. Thank you to the organizers for inviting me to speak on one of my favorite topics in the rheumatology clinical practice. At MD Anderson, we formed a multidisciplinary clinic with rheumatologists, endocrinologists, radiologists, and orthopedic physicians to work side by side to help our patients in their survivorship, to improve their bone health.

(01:13): Bone loss is quite common after transplant and can lead to fractures. Without further ado, I'm going to start with our learning objectives and we're going to work together over the next hour to address this important issue. So I want to make sure that everybody understands that bone loss is quite common after transplant. Clinically, bone loss can lead to fractures in both men and women, and there are many risk factors that can contribute to bone loss and fracture. Lifestyle changes are a cornerstone of bone health. I want everybody to know there are medications to treat osteoporosis and prevent fractures safely and effectively.

(02:03): We want to start with why is bone health important. If you could focus your attention on this normal bone, you can see there are some holes. That's our bone, but all these structures look quite sturdy. Bone loss causes healthy bone to be more porous. The pores become bigger and larger, and we call it osteoporotic. What happens is that you can visibly see that the osteoporotic bone is not as sturdy as a healthy bone. The osteoporotic bone is more fragile with an increased risk of fracture.

(02:51): Osteoporosis is a silent disease that can progress without symptoms until fracture occurs. Osteoporosis has long to be known as a silent disease. It can progress undetected for many years, without symptoms, until the fracture occurs. The fractures can cause quite a few problems. For instance, spine fracture can cause severe back pain, loss of height, loss of lung volume, and a change in one's body posture. As you can see in this picture, this normal vertebral body crashed, and you can see with time, this person's body posture will become quite...we call it a kyphosis, and the upper body will bend over.

(03:47): Fractures are most common in the spine, hip, and wrists. Fracture at the other sites can cause inability for self-care or prolonged disability. Osteoporosis can affect the entire skeleton and is responsible for nearly 2 million vertebral and nonvertebral body fractures every year worldwide. Spine, usually, is the most common site of fracture followed by hip and wrists, and then the other sites.

(04:15): Fractures can have severe consequences for up to 80% of patients. Why is it important to prevent fractures? This study demonstrated that a year after a hip fracture occurs, about 20% of patients may die from complications from the fracture such as blood clots, other issues from surgery or being bedridden for a long period. About 30% percent of patients may suffer from permanent disability, and about 40% of patients may not be able to walk independently. Up to 80% of patients will not be able to carry out at least one activity of daily living independently.

(05:05): Osteoporosis is common for older women and men at an older age. Osteoporosis is actually quite prevalent, and it usually happens to people of older age. It affects about 200 million women worldwide. One in three women between age 60 to 70 has been diagnosed with osteoporosis. And two-thirds of women will be diagnosed with osteoporosis when they're age 80 and above. About 30% of women over the age of 50 will have one or more vertebral fractures.

(05:42): And this also happens to men, but at an older age. Approximately one out of five men over the age of 50 will have an osteoporosis-related fracture in the remainder of their lifetime.

(06:00): So how does bone loss happen? We have bones resorption and bone formation coupled as one mechanism to help us to build bones, repair bones, and to feed our weight-bearing needs throughout our life. But with changes of metabolism in our body, because of aging, because of loss of estrogen, and in our cancer patients because of cancer treatment, the bone resorption becomes too heavy and the bone formation cannot catch up. Therefore, you can see, as a net result, bone loss can happen.

(06:43): Risk factors for osteoporosis include older age, female gender, and previous low impact fractures. Some of the general risks for osteoporosis and fractures are listed here. For instance, older age, female gender, previous low impact fractures.

(06:54): What defines a low impact fracture? Basically, it's not a hard hit, like being hit by a car or an accident. Usually, if a person falls from standing or while walking, and sustains the fracture, we consider it a low impact fracture. That's probably because the bone is osteoporotic, fragile, not sturdy enough.

(07:22): Steroids are a significant cause of bone loss and fractures. Other factors, include a family history of hip fractures, your mom and dad. Medication can contribute to it, most notoriously glucocorticoids - we call them steroids. Prolonged steroid therapy can cause significant bone loss and fractures. And then, some other factors like ongoing cigarette smoking, alcoholism, defined as consuming at least three units of alcohol every day, low body weight, and some other secondary causes of osteoporosis.

(08:02): How do we measure the risk of fractures before a fracture happens? We have the bone mineral density study, and this has been tested in clinical settings. The numbers presented here of bone mineral density are in standard deviations, a statistical measurement. The majority of people stay around zero, meaning right in the middle. But if you were comparing the population of your gender and your race, and if your standard deviation is negative, going down more, the risk of fracture goes up high. So you can see the bone mineral density is a good surrogate for us to measure how fragile or how sturdy our bones are.

(08:56): The DEXA scan is the gold standard for measuring bone health. So DEXA scan is the gold standard for us to measure our bone health. It provides a 2-D measurement of bone mineral density. It's oftentimes office based, and we focus on the spine, hip, femur neck area, or there's measurement of total body BMD. But oftentimes, we focus on the central bone mineral density.

(09:26): There are peripheral bone density studies. You might have been tested for bone density in your wrist, heel or finger, but most of those are carried out at a health fair, and they don't represent your overall bone health as well as the central bone density measured by the DEXA scan. And therefore, if you had one of these measured, I suggest you take the result to your physician and ask for a standard DEXA test to confirm if you have osteoporosis.

(10:10): A bone density study may be done for older patients or people with low body weight, high risk medications, prior fractures or cancer patients and stem cell recipients. Who should get a bone density study? Remember we said that osteoporosis and bone loss are mostly related to aging. So the International Society of Clinical Densitometry and National Osteoporosis Foundation have been giving out recommendations for women age 65 and older, men age 70 and older and also for postmenopausal woman younger than 65 and men age between 50 to 69 in the presence of clinical factors. For instance, some of the risks include very low body weight, high risk medication - we talked about glucocorticoid steroids- and if they already have had a low impact fracture or have a disease or treatment associated with bone loss. That would include our patients who received cancer treatment and stem cell transplant.

(11:19): Patients who receive a stem cell transplant are usually younger than 65 or 70, so do we lose bone? In studies conducted in late 1990s and early 2000, scientists showed that bone loss occurs rather rapidly. For instance, this study showed - this is a spine that we measure can decrease maybe by 3% after three months. And the bone loss in the hip area, femur neck, which is the thinnest part at your hip area, and total hip decreases much more significantly, compared to the spine.

(12:06): After donor transplants, recipients may have 10% to 20% bone loss after two years due to the underlying disease and its treatment. This is the bone loss after a self-transplant [an autologous transplant], and you can see that the spine actually recovered decently after two years, whereas the hip area did not improve. This is a collection of patients' bone densities, bone loss after a donor-transplant [allogeneic transplant] at the hip area. You can see that one of the patients, after about a year, had near 30% bone loss, but the average is about 10% to 20% bone loss after two years.

(12:42): Why does bone loss happen in people who received a transplant? This is probably because of the underlying disease and its treatment. For instance, leukemia and lymphoma treatment includes steroids, chemotherapies, and some of the lymphoma treatments includes radiation. In the case of multiple myeloma, myeloma itself can make holes in the bone and the treatment can cause further bone loss.

(13:15): Secondly, chemotherapies sometimes can have an off-target effect. The ovaries can be suppressed so that a female patient develops premature menopause. Therefore, the bone will be devoid of the protection from estrogen, and high-dose steroids can cause men to have low testosterone, although some of them can recover later on.

(13:45): Radiation and vitamin D deficiency can contribute to bone loss. We talk about chemotherapy effects and radiation. A radiated bone will lose its capacity to rebuild itself. It depends on the dosage and the time period of radiation. In graft-versus-host disease treatment, oftentimes the predominant medication will be glucocorticoids, and many transplant patients have severe vitamin D deficiency.

(14:12): In our study, we have shown that in up to 79% of patients, their vitamin D was low at the time of transplant. Again, with all the treatment, patients may have malabsorption.

(14:28): The overall fracture rate for transplanted patients was 8% in one study. Several years ago, we did a study addressing the question, do our patient fracture after transplant? So, we collected a database of patients with a total of over 7,000 that we had complete data on at MD Anderson Cancer Center. In terms of self-transplant [autologous transplant] and a donor-transplant [allogeneic transplant], the numbers were about 50-50. We found out those patients fractured. About 11% of the self-transplant patients fractured, and about 5% of the donor-transplant patients fractured. The overall fracture rate is about 8%. Again, the location is predominantly in the spine, and there's hip and femur neck fractures and some other locations.

(15:27): The mean time for fractures after transplant is about two and half years. Taking a more extensive look at our 631 patients who fractured during those 14 years, we found out our patients' mean age at the time of fracture was actually quite young. The patients were about 50 years old. The male patients were 55%, and for liquid tumors - multiple myeloma, lymphoma, leukemia - were near 90%. Mean time to fracture from the transplant is somewhere around two and a half years. Again, we emphasize both men and women fractured at a similar rate, and vertebral body fractures is the predominant site and very similar in men and women. And you can see with longer time, age plays a bigger role. If we waited, the fracture rate can go up rather high.

 (16:26): Measures of risk factors can predict bone loss quite accurately. Other than bone density, there's another tool that we can use to assess the risk for fracture. This has been established and used by WHO to predict fracture risk in the future. You can see that age, gender, since we talk about the general risk factors for bone loss, are included here. And treatment recommendation is the major osteoporotic risk, higher than 20% over 10 years and hip fracture risk more than 3% in 10 years for the general population. Our group also used our database and validated that this tool can predict fracture risk rather nicely in our patient population. So if you didn't have a bone density study, but are using this tool, filling in all the information it can predict if your risk factor is high, and when treatment should also be initiated.

(17:30): When to check a bone density after transplant? At every encounter with your physician, risk factor screening should happen. For instance, lifestyle issues: tobacco smoking should be stopped, alcohol drinking should be counseled, and if a patient has a sedentary lifestyle, that should be discussed. Again, even if none of this is an issue for you, fragility, falling risk and fracture should be discussed because cancer treatment can be brutal. After several years, a patient can become frail, and tend to fall. Also, medications that patients are taking can cause bone loss.

(18:20): Bone density tests should be done no later than three months after transplant and repeated annually. A bone density should be performed three months after the transplant if it's not done around the time of transplant. However, if a patient is on prolonged high-dose steroids, then at three months a bone density should be performed regardless. And a bone density test in our transplant patients should be repeated in follow-up visits every 12 months, if they're on treatment to test the efficacy of the treatment, and every one to two years thereafter.

(19:02): Calcium, vitamin D, weight-bearing and resistance exercises can improve bone health. So how do we improve bone health after transplant? So basically, there are some cornerstones which are lifestyle changes. Take calcium either from supplement or from food on a daily basis. Get enough vitamin D to help you to absorb the calcium that you took. Start weight-bearing exercises that help to stimulate the bone, to say, we need strong bones.

(19:32): And also, remove clutter around your house to reduce your fall risk. Keep a healthy weight, because the studies show that muscles attached to your bones can have synergistic effects on your bones and nurture the bones to be stronger. If we lose a lot of muscle - we call it sarcopenia - it can be associated with more falls and more fractures. Again, do not drink alcohol, limit alcohol intake, and do not smoke.

(20:12): So basically calcium. We recommend 1,000 to 1,200 mg a day in two to three divided doses, either from food or supplement. Vitamin D. If you look at the recommendations from different societies, they talk about anywhere between 500 to 1,000 international units (IU) at least [inaudible 00:20:34] per day. It's more important to take an adequate amount to keep the serum 25-hydroxy vitamin D level, which can be measured by a blood test, between 30 to 50. And vitamin D can be taken once a day or once a week. Because it's fat soluble, it stores near fat tissue and it can be used when the body needs it.

(20:59): You need to have weight-bearing exercises. Basically, you should start a personalized exercise program of at least 30 minutes a day and weight-bearing impact exercise, meaning, you're standing on your feet, walking, jumping, skipping, and bench stepping - all of them will be very helpful. So when you walk, each step carries about 80% of your body weight. So that's the easiest, safest start-up for a weight-bearing exercise regimen.

(21:33): Resistance exercises are also important: weightlifting, resistance band exercises, pushups. Do not aim high. Probably, repetition will be safer and more important. Resistance exercise can help a patient improve strength, posture and balance, and may reduce the risk of fall and moderately increase your bone mineral density.

(22:07): Proper dosing of calcium is important to realize the benefits. I want to add a little more on calcium. We still take calcium 1,000 mg to 1,200 mg a day in two to three divided doses because you can't absorb too much at one time. Basically, one person can absorb 500 to 600 within two hours effectively, so we usually ask our patients to take calcium 500 to 600 mg at least two hours apart. We call it twice a day. You can take it from food, at least milk or other dairy products first, because in this country [the USA] the milk products you purchase from the store are enforced with calcium or vitamin D. So a cup of milk, which is 8 oz, has about 300 mg calcium.

(23:01): I had a patient who started high-dose steroid [inaudible 00:23:06] I started counseling about the health, then he told me [inaudible 00:23:06] milk a day [inaudible 00:23:06] and I said, "Okay, continue it." And you can see that yogurt 6 oz has 310 mg; cheese, 1 oz of part-skim mozzarella has about 210 mg. And some other foods like sardines canned with bones, they also have 325 mg. And salmon canned with bones has about 125 mg. Some produce, including collard greens, cooked, one cup of collard green has about 266 mg. Again, you can look at kale, bok choy, broccoli. So they average about 60 to 200 mg, not as high as dairy products, but definitely helpful and good sources of calcium that's easily absorbed.

(24:35): Medications for osteoporosis are indicated after a fracture or a DEXA scan diagnosis. When do we need medications to treat osteoporosis? One of the serious indications is that the patient had a fracture, especially a fragility fracture - we talked about low impact - that is definitely a definition of osteoporosis when the bone is frail and fractured at very low impact., Or if the person is diagnosed with osteoporosis by a DEXA scan in post-menopausal women, or men over age 50. And we talk about that the FRAX score calculation estimated 10-year fracture risk of any major osteoporotic fractures above 20% over 10 years or a hip fracture risk over 3%.

5:30): What about patients with an additional risk for osteoporosis? When a patient gets prolonged treatment with glucocorticoids, defined by 5 mg and above for more than three months, in our situation, used for the treatment of graft- versus-host disease. So for patients age 40 and above, if the person already had a fragility fracture, was diagnosed with osteoporosis by DEXA scan, had a FRAX score above 10% and hip fracture risk above 1%, the lower number comes with additional risk factors.

(26:20): At age 40, we have less data. However, we know that at any age, if a patient had a fragility fracture, their bone is frail so the next fracture can happen. So any osteoporotic fractures occurring at age less than 40, or if they have severe osteoporosis on measurement, a rapid bone loss on the DEXA scan.

(26:50): Bisphosphonates can treat osteoporosis by increasing bone formation. What are the medications we can use to treat osteoporosis? Here, I'm bringing back this balance again. We know osteoporosis happens because a patient has increased bone absorption and decreased bone formation. So we have medications to prevent bone absorption and promote bone formation. The majority of medications tested in transplant patients are called bisphosphonates. We have orals pills and injections. Denosumab is a biologic, it also binds to the bone eating cell, the osteoclast, and functions similarly to the bisphosphonate. I'm going to show you the summary of what has been tested in transplant patients.

(27:41): Kidney function should be monitored while on these medications. All three oral bisphosphonates have been tested: Fosamax, Actonel and Boniva. They can be taken once every week or once every month. Efficacy is moderate. If the pill gets stuck in the esophagus and the person feels heartburn, this should be changed to a different form of medication. And we need to be careful about the drug being secreted through the kidney. If the patient's kidney function is not good, then we have to consider alternatives. We must remember that the last medication, we actually did a clinical trial at MD Anderson, did not have efficacy data in the hip or femur neck.

(28:24): IV infusion of zoledronic acid, another bisphosphonate, has been tested in several clinical trials. It is given once a year and is stronger than many other medications. A person may suffer from a body ache and flu-like symptoms for a day or two, but it's usually self-limited and can be treated with oral Tylenol or Aleve. Again, because it's a bisphosphonate, we need to check the patient's kidney function.

(28:24): Prolia or denosumab is an anti-RANK ligand monoclonal antibody; therefore, it doesn't hurt the kidney. It should be given by injection under the skin every six months. So far, there is a clinical trial ongoing, sponsored by the company, in transplant patients and there's a case report reporting the safety and efficacy in our transplant patients. If someone takes Prolia, it is a biologic. It is probably out of your body in five to six months. Therefore, the drug regimen is every six months.

(29:52): When stopping these medications, rebound bone loss may occur so prolonged treatment is often recommended. We need to be aware that there's a clinical phenomenon called rebound bone loss or rebound fractures. So when this medication is out of your body after five to six months, without further treatment, the patient may lose all the efficacy and lose all the bone you have gained. Therefore, as long as the patient has good kidney function, we follow six months after the last dose with a dose of Reclast, zoledronic acid infusion, to lock in all the good effects made by the Prolia injection. But when we treat bone, we usually treat the patient anywhere between four to five years, and then when the patient's bone density is stable, we might consider drug holidays and follow the patient annually.

(30:49): Long term treatment can have side effects but the benefit of preventing fracture usually outweighs the risks. So with such a long term treatment, side effects should be considered. And many patients thought, "I've heard bad things about these medications. I have friends or my sister took this medication and had very bad effect." So how do we decide? Like with anything, the benefit of fracture prevention in many patients who have all the risk factors actually outweighs the small risk. There are severe side effects, such as osteonecrosis of the jaw. That is very rare and often preventable. So basically, it is not the joint where you open your mouth, you seem to be cracking. It's actually the bone underneath the tooth. If you have a rotten tooth pulled by the doctor, it should heal within a week or two. But if you are on this medication for a prolonged period of time, this healing might be delayed. Therefore, we encourage you to have very good dental hygiene, such as a regular dental cleaning, at least every six months, brush and floss every day, and check with your dentist before starting the medication. And then, we provide drug holidays once your bone density is stabilized after a few years.

(32:11): Lifestyle changes and medications can treat osteoporosis and prevent fractures. So to summarize, what we have talked about, bone health is very important after transplant because bone loss can cause fractures in both men and women leading to disability. There are many risk factors that contribute to bone loss and fracture, many of them are preventable. Lifestyle changes are a cornerstone for our bone health, and there are medications that your doctors can use to treat osteoporosis and prevent fractures safely and effectively. So I'm going to leave it here for questions you may have. Thank you. Thank you for your patience and time.

Question and Answer Session

(32:58): [Marsha Seligman]  Thank you, Dr. Lu, for your excellent presentation. We will now take questions. Dr. Lu, the first question asks, "I have osteoporosis and osteoarthritis. I am on Prolia injections every six months and haven't been able to find help for osteoarthritis. Is this due to transplant?"

(33:27): [Dr. Huifang Lu] Oh, that is a very good question. You mentioned that there are two concerns. One is osteoporosis, one is osteoarthritis. Those two are two separate disease processes. Osteoporosis is the contents within the bone that can be seen and can fracture. Whereas osteoarthritis is a different disease process. It's regarding the joint. It's on the surface of the bone. They're unrelated. So osteoarthritis can happen with age, can happen from wear and tear, and it's also genetically predisposed. So treating osteoporosis does not affect your osteoarthritis. It doesn't make it better or doesn't make it worse. So I suggest you see an arthritis doctor. You can see a local rheumatologist. If it's bone on bone, quite advanced, you probably should see an orthopedic physician. So I have to say osteoporosis and osteoarthritis are unrelated.

(34:44): [Marsha Seligman] The next question, someone would like to know about the relationship of bone mineral density and fracture risk. They would like to know if it is the same for premenopausal women, and is the relationship the same or has it not yet been studied?

(35:00): [Dr. Huifang Lu] The studies of fracture risk mainly studied postmenopausal women. Premenopausal women have the protection of estrogen. They still have a chance to repair bone to improve the bone density, so the risk is considered less. So we don't have a clear estimate of it. But overall, people with lower bone density have higher risk of fracture.

(35:44): [Marsha Seligman]  The next question is, what value is a full body scan after transplant, and should it be done on a suggested schedule?

(35:59): [Dr. Huifang Lu]  If you are talking about... There are two types of body scans. One is the body scan to look for cancer, we call it bone scan for cancer diagnosis. The other, I assume you're talking about is full body bone mineral density, and that's not routinely performed because the correlation of the bone density centrally - the spine, lumbar spine, total hip and femur neck - correlates with the whole body mineral density and fracture risk nicely. So, that is what we use as the gold standard. So we don't routinely do whole body scans.

(36:43): [Marsha Seligman] The next question is, I have GVHD and am eight years since my allotransplant. I had a hip replacement in 2020 due to avascular necrosis. I will probably have to have the left hip replaced also. Is this due to GVHD? I also have osteoporosis.

(37:04): [Dr. Huifang Lu] Well, this is an excellent question. We do see avascular necrosis happen after transplant. It's hard to separate the effect of GVHD and its treatment, because if you already know from your experience, that the first line treatment for GVHD is steroids. So steroids are one of the most important causes for avascular necrosis. So we see correlations. We see association. Patients after transplant wit GVHD, on high-dose steroids and with low bone density such as osteoporosis, have a higher risk of avascular necrosis, but the avascular necrosis process is similar to any other avascular necrosis. So it's hard to tell whether it's from GVHD alone or GVHD treatment. But it can be very disabling and you can have pain and it can be difficult to ambulate. So following an orthopedic physician, when the joint progressed to need a hip replacement, that's probably the right thing to do. And your osteoporosis should be treated aggressively to prevent fall fractures.

(38:37): [Marsha Seligman] The next question is, I had an allogeneic transplant in 2018. I have osteopenia and I am taking alendronate. My primary care doctor and hematologist/oncologist say that I can ride my horse as long as I wear a helmet, which I always do. What is your opinion on the safety of riding a horse when one has osteopenia? And they also mentioned they are a 69-year-old female, they don't smoke or drink alcohol.

(39:09): [Dr. Huifang Lu] Okay. Very good question. I applaud to you, though, for starting a very active lifestyle after transplant. When your bone density osteopenia range, you pretty much can do whatever activity you want to do as long as you do it safely. Basically, we want you to be cautious, not to have a hard fall, not have any accident, therefore minimize your chance of fracture because fracture can happen at any age, any bone density, if there's a very hard traumatic accident. So I do agree with your doctors, ride your horses, be active, walk and do it safely.

(40:02): [Marsha Seligman] Okay. The next question says, I am four years past transplant and currently have mild chronic GVHD for which I take Jakafi and tacrolimus. I had osteopenia before I was diagnosed with AML. After I was on prednisone for nine months, my bone density declined. I had three Reclast infusions after which my bone density declined even more. My endocrinologist suggest I start taking Prolia. Are there any GVHD-related reasons I should not take these injections?

(40:38): [Dr. Huifang Lu] Oh, very good question. The short answer is no. I think it's a very good alternative. You should try Prolia because it acts on the same cells as the Reclast, but probably more effectively, and make sure you take your calcium, vitamin D every day and optimize those and add the walking exercise, at least 30 minutes a day.

(41:06): [Marsha Seligman] The next question is, what about the use of Zometa for bone health?

(41:16): [Dr. Huifang Lu] Zometa is another commercial name for zoledronic acid. So the company patented it as Reclast 5 mg once a year for osteoporosis and 5 mg once every other year for osteopenia. So it is very effective, as far as a person has normal kidney function. And when a person mentions Zometa, that is usually mentioned in the context of cancer treatment. For instance, breast cancer, prostate cancer, multiple myeloma that migrate to the bone, they use Zometa in a much more frequent dose once every month for maybe two years. But the chemical inside, zoledronic acid have been used to treat osteoporosis once a year.

(42:14): [Marsha Seligman] Okay. What is considered long term steroid use?

(42:21): [Dr. Huifang Lu] Yes, the definition has been changing and we actually lowered the criteria. It's 5 mg prednisone or equivalent for more than three months.

(42:32): [Marsha Seligman] Is an inversion table good for your bones?

(42:38): [Dr. Huifang Lu] Inversion table, right? I don't think it has beneficial effect on bone health because it's not weight bearing.

(42:51): [Marsha Seligman] Okay. The next question is, what percent does osteoporosis happen after bone marrow transplant? I had my transplant at 26.

(43:05): [Dr. Huifang Lu] I don't have that number... The specific number. We have the fracture data, but it happens very often. And I'm glad to hear that you're 26. Young people, men and women, even if they develop osteoporosis after transplant, they recover much better than the older people. So I suggest you continue with a very healthy lifestyle: calcium, vitamin D, and daily weight-bearing exercises. You have a good chance to regain good healthy bone, even without treatment, but you need to be monitored.

(43:46): [Marsha Seligman] Dr. Lu, someone would like to know your thoughts on vibration plate therapy for bone regrowth.

(43:54): [Dr. Huifang Lu] It is a good idea. Vibration platforms are developed by physicists working on the mechanics of bone health. I've seen efficacy studies in elderly people, I've seen, efficacy studies done on breast cancer survivors. So basically you're standing on this platform that stimulates your bone. That sends a signal to say, this person needs strong bones. So it's not as strong as therapeutic medications, but it's definitely a positive form, especially if you're not able to walk effectively and use the vibration platform and make sure you do not fall, it's a positive thing to do.

(44:49): [Marsha Seligman] Someone would like to know which type of calcium supplement is best for osteoporosis? Which type has better absorption?

(45:00): [Dr. Huifang Lu] Most of the calcium sold over the counter can be absorbed easily. I would say, calcium in food is better absorbed. So I have that long list about medications, cheese, yogurt, and milk. If you can't take it [from food], it's not a problem. You can certainly take a pill from over the counter. So most over the counter calcium are calcium carbonate or calcium citrate, and both can be absorbed easily. If you're a person who has acid problems, take Tums, that's calcium carbonate, so you can try different things to see if it fits you better, but they overall are all okay to take.

(45:53): [Marsha Seligman] You mentioned taking a drug holiday. How long would you recommend a holiday be?

(46:01): [Dr. Huifang Lu] There are studies in the general treatment of osteoporosis. So we usually treat patients for five years. And I must say, FDA had a panel discussion, there's not enough data to support or be against the five-year recommendation, but we still consider five years a mark. We seriously consider a drug holiday. This is because clinically we see that most patients, their bone density improvement plateaus after three or four years of treatment. So if by measurement, you're not continuing to improve, you have no fractures, we want to give a patient a drug holiday and minimize the side effects. But we still measure your bone density every year or every other year to see if you drop. So there's a study showing that most people can hold the bone density four to eight years after stopping the treatment. But if you stop, if you start to decrease your bone density, we'll just retreat because osteoporosis and bone loss is part of aging. The mechanism's still there. We have the right medication. We just treat again. So after several years of drug holiday, for most patients, the potential side effects are much more reduced. That's why we do it.

(47:24): [Marsha Seligman] Someone would like to know how many years do you need to get Reclast? How often should you have DEXA scans in between treatments?

(47:36): [Dr. Huifang Lu] The first part of the question is what I previously answered. On average, we treat about five years. Most patient can maximize a response by three or four years, so we seriously consider a five year mark and consider drug holiday. And once a person starts treatment, we measure them every one to two years to test efficacy and look for potential side effects.

(48:09): [Marsha Seligman] Okay. The next question is, I had a transplant as a kid over 10 years ago. I'm recently in my twenties, had my first DEXA, which revealed osteoporosis. Is it possible transplant caused it all those years ago? Doctor ran tests but could not identify a cause. Would osteoporosis caused by a transplant improve over time? Once diagnosed with osteoporosis? How often should one get DEXA? Thank you.

(48:36): [Dr. Huifang Lu] Very good question. Transplant was one of the treatment modalities you received for your underlying disease, but I assume that prior to that, you also received chemotherapy or radiation or different things that might have affected your bones. So in your situation, you said at age 10, you received the transplant? So you received transplant at very young age. You have been receiving treatments through the years and you might not have reached your peak bone density. So I would call it multifactorial, unless you're... If GVHD or transplant is one of the major reasons that it really depends on after transplant, did you develop GVHD? Did you have to take extensive steroids or tacrolimus? But otherwise I would think it's multifactorial from the fact that the cancer treatment, young age, probably lack of vigorous exercises may have all played a role of your current low bone density. But because of your young age, you could continue to improve, you have a better chance to improve than older people, with the right lifestyle changes and the help of your doctor. I'm sorry. The last part you say, how often... Once you've been diagnosed with osteoporosis, you should be followed every one to two years to test efficacy of everything you're doing for the bone.

(50:30): [Marsha Seligman] Can blood work identify early bone loss?

(50:36): [Dr. Huifang Lu] Bone loss is defined by bone mineral density, so that's the end result of bone loss. There is blood work that can show you the work of the osteoclasts, the bone absorbing cells, and osteoblasts, the bone forming cells, but those are transient and it might not represent the long term outcome. So once in a while to determine therapy, efficacy of the therapy, we do check the fasting early morning bone turnover markers. But as a result of bone loss, we have to use a bone mineral density to identify clinical relevance.

(51:22): [Marsha Seligman] Dr. Lu, someone would like to know what is your general recommendation about dental implants for post auto transplant multiple myeloma patients?

(51:36): [Dr. Huifang Lu] Our teeth are very important to help us how we look, how we eat effectively. So if you need dental implants, then you need to have dental implants. But if you're also on osteoporosis treatment, I would like you to have your bone doctor and your dental surgeon communicate to find the optimal time. For instance, if you're on Prolia treatment, then do it at the end of the efficacy of the Prolia injection. Do it five months after the last injection. And then once you completely heal, then resume your Prolia. So you need to have a comprehensive plan, but you need to... Life needs to go back to normal. If you need dental implants, you need to have dental implants. I think that helps you to have better nutrition, better health in general, but make sure your doctors communicate with each other and do it with the best timing.

(52:41): [Marsha Seligman] Do you recommend Prolia over Reclast?

(52:46): [Dr. Huifang Lu] They're both very good drugs and both very effective, so we cannot predict which one is slightly better for which person. So if taking Reclast didn't work well for a patient, we switch to Prolia and it works wonderfully, and vice versa. So it depends on convenience, your kidney function, because one is every six months, one is every 12 months, and also your insurance status. So I do not have a preference. To me, both are very effective medications.

(53:32): [Marsha Seligman] The next question asked, is hydrocortisone for adrenal replacement at 25 mg per day considered heavy steroid use that affects bones?

(53:43): [Dr. Huifang Lu] Theoretically, if you have adrenal insufficiency, you supplement it with hydrocortisone. That maintains good function. That should be considered physiological. We all have our internal cortisols and that is not considered damaging to your bone, only if you're over supplemented for prolonged period of time. So work with your endocrinologist and keeping yourself at the lowest effective dose of hydrocortisone would be the right thing to do.

(54:18): [Marsha Seligman] The next question I ask, you mentioned a few medications that can promote bone growth; however, I've not seen them offered typically. Are they available, still in study, or have lots of side effects?

(54:31): [Dr. Huifang Lu] Oh, this is also a very good question. So in general, for osteoporosis, there are two drugs, we called anabolic. It is self-injection every day for up to two years. It actually promotes bone growth. Everything we talked about were about preventing bone loss. So you can see that it's more efficacious. But those medication have not been run in clinical trials, so safety and efficacy has not been well studied in stem cell transplant patients. So if all things failed, you should discuss with your doctor to see if it's worthwhile to take any of the potential risk factors to treat your bones. And hopefully in the future, there are more clinical trials coming up that will be well tested in our population.

(55:33): Marsha Seligman] [Someone would like to know, is estrogen supplementation beneficial for slowing down the worsening of osteoporosis?

(55:44): [Dr. Huifang Lu] In general, yes. Estrogen protects our bones., Even a small dose is helpful, but there are two concerns. Number one, you need to talk to your gynecologist. Is there any blood clot risk factor or any other things that would impact whether you should or should not take estrogen? And second thing is that if estrogen protection after menopause is actually mild to moderate, if you already have fracture with severe osteoporosis readings on your bone densities, then it's beyond estrogen alone.

(56:23): [Marsha Seligman] Okay. So we are running out of time. So this is going to have to be our last question. Someone would like to know, they are 12 years post transplant and they had to have a bone graft around a tooth implant just last week. Is this type of bone loss related to the transplant?

(56:48): [Dr. Huifang Lu] Transplants alone usually have not been reported to directly affect a piece of local bone. But again, we are talking about possibly the underlying disease, aging and treatment of transplant consequences might be affecting. So I don't think we can know for sure at this time.

(57:17): [Marsha Seligman] Closing. Thank you, Dr. Lu, on behalf of BMT InfoNet and our partners, I'd like to thank you, Dr. Lu, for your very helpful remarks, and thank you the audience for your excellent questions. Please contact BMT InfoNet if we can help you in any way. Enjoy the rest of the symposium.