Commentary

DR. LEFFLER: My name is Dr. Daniel Leffler. I’m in the Division of Gastroenterology at Beth Israel Deaconess Medical Center, and I direct the clinical research at our Celiac Center.

MS. DENNIS: My name is Melinda Dennis and I’m the nutrition coordinator of the Celiac Center at Beth Israel Deaconess Medical Center. I work with Dr. Leffler, Dr. Kelly, and the other Celiac Center gastroenterologists.

DR. MUSHLIN: Great. So, as the moderator of this conversation, I’d like to start us off with a case. This case presented to me in my primary care practice.

I saw a Harvard Medical student who came to see me regarding a stress fracture in her right foot. She was a runner and had run in 3marathons over the last 4 years. She was quite slender and had a BMI of only 19, but she quite adamantly denied being anorectic or bulimic.

She had been treated for anemia in her senior year of college with iron. She had no idea whether her anemia had improved. She had always had irregular menses since menarche, but for the past year as her running increased, she was completely amenorrheic.

After physical examination, x-ray examination revealed that she did indeed have a fracture of a metatarsal. I then obtained a bone density examination that showed osteoporosis—not just osteopenia but osteoporosis. She also had an anemia with a hematocrit of 33%, and she had microcytic hypochromic indices. I then, because of her osteoporosis, got a vitamin D level, which was definitely low. It was under 20, and that’s the lower limit of normal in our institution. She also had slightly elevated parathyroid hormone levels.

I obtained an IgA tissue transglutaminase (tTG) antibody test, and it was highly positive. I then placed her on a gluten-free diet with calcium, vitamin D, and oral iron supplementation, and that’s the case.

Dr. Leffler, would you say that this would be a pretty typical presentation of celiac disease?

DR. LEFFLER: Yes. I think all of us working with celiac disease have seen patients just like this, but it also highlights the fact that there really is no typical patient with celiac disease. A picture of what was previously considered typical involved severe malabsorptive symptoms, but that was really just scratching the tip of the iceberg for what is out there. While iron-deficiency anemia, osteoporosis, and vitamin D deficiency are very common in celiac disease, you can have all or none of these symptoms. Like this patient, you can have no gastrointestinal symptoms. Alternatively, you can have predominantly gastrointestinal symptoms.

Certainly, this patient had a number of red flags that would make you worry about celiac disease such as the early onset fracture, the osteoporosis, and the iron-deficiency anemia. Although the latter is not an uncommon thing to see in a young woman, it’s the combination of all these factors that, in my mind, would alert a clinician to the fact that these are not normal findings for a young healthy woman.

DR. MUSHLIN: If you looked at all the patients who were ultimately diagnosed with celiac disease who presented to the family practitioner or the primary care internist, what would you say would be the most common red flags? I know this case, which is a true case, had a lot of red flags, but what would be the most common symptoms that might raise your consciousness that you might be dealing with celiac disease?

DR. LEFFLER: Approximately 40% of patients with celiac disease will have chronic gastrointestinal symptoms. These can vary and can be very similar to those of irritable bowel syndrome, but gastrointestinal symptoms in the presence of a significant nutritional deficiency like iron deficiency or vitamin D deficiency, as in this case, would be very typical of celiac disease and raise a lot of red flags. A lot of these patients will also have either a personal history or a family history of other autoimmune diseases, type 1 diabetes, thyroid disease, and other similar conditions.

So, very common presentations and red flag conditions would include a patient who says, “my mother has thyroid disease” or “I have thyroid disease and now I’m iron deficient,” or “now I’m experiencing significant fatigue.” Overall, the most common presentations of celiac disease these days are gastrointestinal symptoms, iron-deficiency anemia, vitamin D deficiency, and fatigue.

DR. MUSHLIN: Certainly, all of those things are seen in an internist’s or a family practitioner’s office. I guess the real key here is that when you start to see this constellation, you should raise your consciousness that there may be one unifying diagnosis rather than multiple diagnoses.

DR. LEFFLER: Exactly. I think that the response to therapy can also be a good hint that there might be something else going on. Most young women with iron-deficiency anemia simply due to menses will do pretty well on oral iron supplementation alone. If they have severe and significant anemia and it’s just not responding to iron supplementation for instance, or if their vitamin D level is low and it does not improve with a regular dose of vitamin D, then you really have to wonder whether there is something that’s preventing absorption of this nutrient in the intestinal tract. Once you get to that level, then celiac disease is by far the most common diagnosis in these situations.

DR. MUSHLIN: We are having this colloquium here in Boston and there are a lot of people in the greater Boston area who are of Northern European extraction. Are there certain ethnic groups that have a predominance of celiac disease, or can it be found in virtually any ethnic group?

DR. LEFFLER: Earlier, we used to say this was essentially an Irish/Italian or western European disease, but now we can more easily pick out the populations that celiac disease doesn’t occur in. Celiac disease has a strong genetic predisposition with human leukocyte antigen (HLA) types, but really the populations that are at risk for celiac disease cover most of the globe: all of North and South America, Europe, the Middle East, North Africa, India, and northern China. Southeast Asians and Sub-Saharan Africans have a very low risk, but the majority of people have a significant risk of celiac disease, and I think that like all other autoimmune and inflammatory disorders, whether it’s type 1 diabetes or asthma or inflammatory bowel disease, the prevalence of celiac disease just continues to rise over time. We’re seeing it in populations that never had this disorder before.

DR. MUSHLIN: Why do you think the prevalence is increasing? Is it that our diagnostic ability is better, or do you think it’s truly increasing?

DR. LEFFLER: Well, we’ve certainly gotten a lot better at diagnosing celiac disease. You mentioned the celiac tTG antibody test earlier, which has really revolutionized the way that we diagnose celiac disease because it’s so accurate, affordable, and widespread. That being said, even in prevalence studies,^1,2 there really is a dramatic increase—something in the range of a doubling—and true prevalence every 30 years or so. This is right alongside these other autoimmune and inflammatory diseases.

Clearly, nothing in our genetic heritability is changing that quickly. It’s something in the environment that is leading to an increase in the incidence of celiac disease and autoimmune diseases in general. Lots of people have theories about what that might be, and the most common theory is that we live in such a clean environment now that our immune system doesn’t have the normal feedback it needs to develop in a healthy way, and so, our immune function may start to become abnormal.

DR. MUSHLIN: This is similar to the asthma hypothesis.

DR. LEFFLER: Exactly. All of this can in some way be explained by the hygiene hypothesis.

DR. MUSHLIN: Right. When you live in Germany and the cows are housed in the same house that you live in, there’s less asthma.

DR. LEFFLER: Exactly. The same phenomenon has been seen in celiac disease in some populations, especially in northern Europe where you cross a national border and you encounter very different socioeconomic conditions. Even though you have virtually the same genetic lineage, you can have very different rates of celiac disease. I think this is very much the case.

DR. MUSHLIN: Ms. Dennis, I have a large number of patients who come into my office and say to me, “I went on a gluten-free diet and I feel so much better.” Can you address the question of gluten sensitivity versus true celiac disease? Do you feel comfortable doing that?

MS. DENNIS: Sure. We know that celiac disease is a genetic autoimmune disease, and we know that non-celiac gluten sensitivity is not considered an autoimmune disease. Dr. Leffler would be in a better position to address the issue of whether there is an inflammatory response, but there are plenty of people who come into the office confused about the 2. In order to obtain a diagnosis of non-celiac gluten sensitivity, celiac disease and wheat allergy would both need to be ruled out.

There is no positive gene testing for non-celiac gluten sensitivity, but what makes it difficult for patients is that the symptoms can mimic one another almost exactly. All the gastrointestinal symptoms, as well as some of the other extraintestinal manifestations like headaches, poor concentration, memory loss, and other similar conditions, can occur in both conditions. It’s complicated, and there is much more research that needs to be done in this area.

DR. LEFFLER: I’ll just corroborate all of that. We’ve known about celiac disease for a long time. Gluten intolerance, or non-celiac gluten sensitivity as it’s becoming more commonly known, is a very new entity that we’ve really only starting believing in, clinically at least, over the last couple of years. We’re learning about it quickly, but we still don’t have a very good sense of its prevalence.

It does appear to be a non-inflammatory disorder, which separates it from celiac disease. It doesn’t appear to have any autoimmune component and likely does not have a lot of the long-term risks associated with celiac disease such as osteoporosis or even cancer and infection risk, but at the same time, it can be associated with significant quality of life impairment, and the symptoms can mimic celiac disease. So, it is something that everyone needs to be aware of; however, while the diet-related treatment is similar, it seems that a lot of the peripheral things that we should do for our celiac patients such as getting them vaccinated and performing a bone mineral density study are not required for patients who have non-celiac gluten intolerance or gluten sensitivity. We do recommend that people work with their physicians to make a clear distinction between these 2 disorders.

DR. MUSHLIN: Just to expand on that point, would a negative tTG antibody test basically exclude celiac disease with a high degree of certainty and leave you with a diagnosis of gluten sensitivity without celiac disease (assuming the symptoms were consistent)?

DR. LEFFLER: Yes. For a typical patient who is on a regular gluten-containing diet and doesn’t have a strong family history of celiac disease or other factors that would increase risk, a negative tTG would certainly be sufficient and would imply that the chances that the patient has true celiac disease are quite low. We can then proceed with a non-celiac gluten sensitivity diagnosis and see how the patient does clinically.

DR. MUSHLIN: It seems that everywhere I go, there are more and more gluten-free choices. In fact, the wife of my closest friend here in town just started a gluten-free bakery and she’s so busy that he’s making deliveries for her now every day instead of 3 times a week. Are there any dangers to adhering to a gluten-free diet?

MS. DENNIS: There are inherent nutritional deficiencies in a gluten-free diet. So, if the diet is not proper, yes, you can lack certain vitamins and minerals. For example, wheat is a major source of protein and B vitamins as well as iron, trace minerals, and fiber.

When you switch to the gluten-free diet, you need to be able to replace those nutrients. Many people don’t focus immediately on the alternative whole and healthier gluten-free grains like amaranth, buckwheat, millet, quinoa, sorghum, and teff. They tend to move toward rice, corn, and potatoes, which tend to be lower in fiber, nutrient poor, and can cause or exacerbate constipation and weight gain when eaten in large quantities. So, that’s one of the main issues.

Additionally, we find that many people are concurrently lactose intolerant when they’re first diagnosed with celiac disease. So, we need to consider the possibility that their calcium and vitamin D intakes may be inadequate. Then, of course, we need to consider the B vitamins, which are present throughout the food chain but are present in large quantities in grains.

DR. MUSHLIN: Ms. Dennis, a lot of my patients are curious about purchasing gluten-free materials either from stores or online. Do you feel comfortable recommending any websites that you feel are legitimate for our patients to access?

DR. LEFFLER: My name is Dr. Daniel Leffler. I’m in the Division of Gastroenterology at Beth Israel Deaconess Medical Center, and I direct the clinical research at our Celiac Center.

MS. DENNIS: My name is Melinda Dennis and I’m the nutrition coordinator of the Celiac Center at Beth Israel Deaconess Medical Center. I work with Dr. Leffler, Dr. Kelly, and the other Celiac Center gastroenterologists.

DR. MUSHLIN: Great. So, as the moderator of this conversation, I’d like to start us off with a case. This case presented to me in my primary care practice.

I saw a Harvard Medical student who came to see me regarding a stress fracture in her right foot. She was a runner and had run in 3marathons over the last 4 years. She was quite slender and had a BMI of only 19, but she quite adamantly denied being anorectic or bulimic.

She had been treated for anemia in her senior year of college with iron. She had no idea whether her anemia had improved. She had always had irregular menses since menarche, but for the past year as her running increased, she was completely amenorrheic.

After physical examination, x-ray examination revealed that she did indeed have a fracture of a metatarsal. I then obtained a bone density examination that showed osteoporosis—not just osteopenia but osteoporosis. She also had an anemia with a hematocrit of 33%, and she had microcytic hypochromic indices. I then, because of her osteoporosis, got a vitamin D level, which was definitely low. It was under 20, and that’s the lower limit of normal in our institution. She also had slightly elevated parathyroid hormone levels.

I obtained an IgA tissue transglutaminase (tTG) antibody test, and it was highly positive. I then placed her on a gluten-free diet with calcium, vitamin D, and oral iron supplementation, and that’s the case.

Dr. Leffler, would you say that this would be a pretty typical presentation of celiac disease?

DR. LEFFLER: Yes. I think all of us working with celiac disease have seen patients just like this, but it also highlights the fact that there really is no typical patient with celiac disease. A picture of what was previously considered typical involved severe malabsorptive symptoms, but that was really just scratching the tip of the iceberg for what is out there. While iron-deficiency anemia, osteoporosis, and vitamin D deficiency are very common in celiac disease, you can have all or none of these symptoms. Like this patient, you can have no gastrointestinal symptoms. Alternatively, you can have predominantly gastrointestinal symptoms.

Certainly, this patient had a number of red flags that would make you worry about celiac disease such as the early onset fracture, the osteoporosis, and the iron-deficiency anemia. Although the latter is not an uncommon thing to see in a young woman, it’s the combination of all these factors that, in my mind, would alert a clinician to the fact that these are not normal findings for a young healthy woman.

DR. MUSHLIN: If you looked at all the patients who were ultimately diagnosed with celiac disease who presented to the family practitioner or the primary care internist, what would you say would be the most common red flags? I know this case, which is a true case, had a lot of red flags, but what would be the most common symptoms that might raise your consciousness that you might be dealing with celiac disease?

DR. LEFFLER: Approximately 40% of patients with celiac disease will have chronic gastrointestinal symptoms. These can vary and can be very similar to those of irritable bowel syndrome, but gastrointestinal symptoms in the presence of a significant nutritional deficiency like iron deficiency or vitamin D deficiency, as in this case, would be very typical of celiac disease and raise a lot of red flags. A lot of these patients will also have either a personal history or a family history of other autoimmune diseases, type 1 diabetes, thyroid disease, and other similar conditions.

So, very common presentations and red flag conditions would include a patient who says, “my mother has thyroid disease” or “I have thyroid disease and now I’m iron deficient,” or “now I’m experiencing significant fatigue.” Overall, the most common presentations of celiac disease these days are gastrointestinal symptoms, iron-deficiency anemia, vitamin D deficiency, and fatigue.

DR. MUSHLIN: Certainly, all of those things are seen in an internist’s or a family practitioner’s office. I guess the real key here is that when you start to see this constellation, you should raise your consciousness that there may be one unifying diagnosis rather than multiple diagnoses.

DR. LEFFLER: Exactly. I think that the response to therapy can also be a good hint that there might be something else going on. Most young women with iron-deficiency anemia simply due to menses will do pretty well on oral iron supplementation alone. If they have severe and significant anemia and it’s just not responding to iron supplementation for instance, or if their vitamin D level is low and it does not improve with a regular dose of vitamin D, then you really have to wonder whether there is something that’s preventing absorption of this nutrient in the intestinal tract. Once you get to that level, then celiac disease is by far the most common diagnosis in these situations.

DR. MUSHLIN: We are having this colloquium here in Boston and there are a lot of people in the greater Boston area who are of Northern European extraction. Are there certain ethnic groups that have a predominance of celiac disease, or can it be found in virtually any ethnic group?

DR. LEFFLER: Earlier, we used to say this was essentially an Irish/Italian or western European disease, but now we can more easily pick out the populations that celiac disease doesn’t occur in. Celiac disease has a strong genetic predisposition with human leukocyte antigen (HLA) types, but really the populations that are at risk for celiac disease cover most of the globe: all of North and South America, Europe, the Middle East, North Africa, India, and northern China. Southeast Asians and Sub-Saharan Africans have a very low risk, but the majority of people have a significant risk of celiac disease, and I think that like all other autoimmune and inflammatory disorders, whether it’s type 1 diabetes or asthma or inflammatory bowel disease, the prevalence of celiac disease just continues to rise over time. We’re seeing it in populations that never had this disorder before.

DR. MUSHLIN: Why do you think the prevalence is increasing? Is it that our diagnostic ability is better, or do you think it’s truly increasing?

DR. LEFFLER: Well, we’ve certainly gotten a lot better at diagnosing celiac disease. You mentioned the celiac tTG antibody test earlier, which has really revolutionized the way that we diagnose celiac disease because it’s so accurate, affordable, and widespread. That being said, even in prevalence studies,^1,2 there really is a dramatic increase—something in the range of a doubling—and true prevalence every 30 years or so. This is right alongside these other autoimmune and inflammatory diseases.

Clearly, nothing in our genetic heritability is changing that quickly. It’s something in the environment that is leading to an increase in the incidence of celiac disease and autoimmune diseases in general. Lots of people have theories about what that might be, and the most common theory is that we live in such a clean environment now that our immune system doesn’t have the normal feedback it needs to develop in a healthy way, and so, our immune function may start to become abnormal.

DR. MUSHLIN: This is similar to the asthma hypothesis.

DR. LEFFLER: Exactly. All of this can in some way be explained by the hygiene hypothesis.

DR. MUSHLIN: Right. When you live in Germany and the cows are housed in the same house that you live in, there’s less asthma.

DR. LEFFLER: Exactly. The same phenomenon has been seen in celiac disease in some populations, especially in northern Europe where you cross a national border and you encounter very different socioeconomic conditions. Even though you have virtually the same genetic lineage, you can have very different rates of celiac disease. I think this is very much the case.

DR. MUSHLIN: Ms. Dennis, I have a large number of patients who come into my office and say to me, “I went on a gluten-free diet and I feel so much better.” Can you address the question of gluten sensitivity versus true celiac disease? Do you feel comfortable doing that?

MS. DENNIS: Sure. We know that celiac disease is a genetic autoimmune disease, and we know that non-celiac gluten sensitivity is not considered an autoimmune disease. Dr. Leffler would be in a better position to address the issue of whether there is an inflammatory response, but there are plenty of people who come into the office confused about the 2. In order to obtain a diagnosis of non-celiac gluten sensitivity, celiac disease and wheat allergy would both need to be ruled out.

There is no positive gene testing for non-celiac gluten sensitivity, but what makes it difficult for patients is that the symptoms can mimic one another almost exactly. All the gastrointestinal symptoms, as well as some of the other extraintestinal manifestations like headaches, poor concentration, memory loss, and other similar conditions, can occur in both conditions. It’s complicated, and there is much more research that needs to be done in this area.

DR. LEFFLER: I’ll just corroborate all of that. We’ve known about celiac disease for a long time. Gluten intolerance, or non-celiac gluten sensitivity as it’s becoming more commonly known, is a very new entity that we’ve really only starting believing in, clinically at least, over the last couple of years. We’re learning about it quickly, but we still don’t have a very good sense of its prevalence.

It does appear to be a non-inflammatory disorder, which separates it from celiac disease. It doesn’t appear to have any autoimmune component and likely does not have a lot of the long-term risks associated with celiac disease such as osteoporosis or even cancer and infection risk, but at the same time, it can be associated with significant quality of life impairment, and the symptoms can mimic celiac disease. So, it is something that everyone needs to be aware of; however, while the diet-related treatment is similar, it seems that a lot of the peripheral things that we should do for our celiac patients such as getting them vaccinated and performing a bone mineral density study are not required for patients who have non-celiac gluten intolerance or gluten sensitivity. We do recommend that people work with their physicians to make a clear distinction between these 2 disorders.

DR. MUSHLIN: Just to expand on that point, would a negative tTG antibody test basically exclude celiac disease with a high degree of certainty and leave you with a diagnosis of gluten sensitivity without celiac disease (assuming the symptoms were consistent)?

DR. LEFFLER: Yes. For a typical patient who is on a regular gluten-containing diet and doesn’t have a strong family history of celiac disease or other factors that would increase risk, a negative tTG would certainly be sufficient and would imply that the chances that the patient has true celiac disease are quite low. We can then proceed with a non-celiac gluten sensitivity diagnosis and see how the patient does clinically.

DR. MUSHLIN: It seems that everywhere I go, there are more and more gluten-free choices. In fact, the wife of my closest friend here in town just started a gluten-free bakery and she’s so busy that he’s making deliveries for her now every day instead of 3 times a week. Are there any dangers to adhering to a gluten-free diet?

MS. DENNIS: There are inherent nutritional deficiencies in a gluten-free diet. So, if the diet is not proper, yes, you can lack certain vitamins and minerals. For example, wheat is a major source of protein and B vitamins as well as iron, trace minerals, and fiber.

When you switch to the gluten-free diet, you need to be able to replace those nutrients. Many people don’t focus immediately on the alternative whole and healthier gluten-free grains like amaranth, buckwheat, millet, quinoa, sorghum, and teff. They tend to move toward rice, corn, and potatoes, which tend to be lower in fiber, nutrient poor, and can cause or exacerbate constipation and weight gain when eaten in large quantities. So, that’s one of the main issues.

Additionally, we find that many people are concurrently lactose intolerant when they’re first diagnosed with celiac disease. So, we need to consider the possibility that their calcium and vitamin D intakes may be inadequate. Then, of course, we need to consider the B vitamins, which are present throughout the food chain but are present in large quantities in grains.

DR. MUSHLIN: Ms. Dennis, a lot of my patients are curious about purchasing gluten-free materials either from stores or online. Do you feel comfortable recommending any websites that you feel are legitimate for our patients to access?

DR. LEFFLER: My name is Dr. Daniel Leffler. I’m in the Division of Gastroenterology at Beth Israel Deaconess Medical Center, and I direct the clinical research at our Celiac Center.

MS. DENNIS: My name is Melinda Dennis and I’m the nutrition coordinator of the Celiac Center at Beth Israel Deaconess Medical Center. I work with Dr. Leffler, Dr. Kelly, and the other Celiac Center gastroenterologists.

DR. MUSHLIN: Great. So, as the moderator of this conversation, I’d like to start us off with a case. This case presented to me in my primary care practice.

I saw a Harvard Medical student who came to see me regarding a stress fracture in her right foot. She was a runner and had run in 3marathons over the last 4 years. She was quite slender and had a BMI of only 19, but she quite adamantly denied being anorectic or bulimic.

She had been treated for anemia in her senior year of college with iron. She had no idea whether her anemia had improved. She had always had irregular menses since menarche, but for the past year as her running increased, she was completely amenorrheic.

After physical examination, x-ray examination revealed that she did indeed have a fracture of a metatarsal. I then obtained a bone density examination that showed osteoporosis—not just osteopenia but osteoporosis. She also had an anemia with a hematocrit of 33%, and she had microcytic hypochromic indices. I then, because of her osteoporosis, got a vitamin D level, which was definitely low. It was under 20, and that’s the lower limit of normal in our institution. She also had slightly elevated parathyroid hormone levels.

I obtained an IgA tissue transglutaminase (tTG) antibody test, and it was highly positive. I then placed her on a gluten-free diet with calcium, vitamin D, and oral iron supplementation, and that’s the case.

Dr. Leffler, would you say that this would be a pretty typical presentation of celiac disease?

DR. LEFFLER: Yes. I think all of us working with celiac disease have seen patients just like this, but it also highlights the fact that there really is no typical patient with celiac disease. A picture of what was previously considered typical involved severe malabsorptive symptoms, but that was really just scratching the tip of the iceberg for what is out there. While iron-deficiency anemia, osteoporosis, and vitamin D deficiency are very common in celiac disease, you can have all or none of these symptoms. Like this patient, you can have no gastrointestinal symptoms. Alternatively, you can have predominantly gastrointestinal symptoms.

Certainly, this patient had a number of red flags that would make you worry about celiac disease such as the early onset fracture, the osteoporosis, and the iron-deficiency anemia. Although the latter is not an uncommon thing to see in a young woman, it’s the combination of all these factors that, in my mind, would alert a clinician to the fact that these are not normal findings for a young healthy woman.

DR. MUSHLIN: If you looked at all the patients who were ultimately diagnosed with celiac disease who presented to the family practitioner or the primary care internist, what would you say would be the most common red flags? I know this case, which is a true case, had a lot of red flags, but what would be the most common symptoms that might raise your consciousness that you might be dealing with celiac disease?

DR. LEFFLER: Approximately 40% of patients with celiac disease will have chronic gastrointestinal symptoms. These can vary and can be very similar to those of irritable bowel syndrome, but gastrointestinal symptoms in the presence of a significant nutritional deficiency like iron deficiency or vitamin D deficiency, as in this case, would be very typical of celiac disease and raise a lot of red flags. A lot of these patients will also have either a personal history or a family history of other autoimmune diseases, type 1 diabetes, thyroid disease, and other similar conditions.

So, very common presentations and red flag conditions would include a patient who says, “my mother has thyroid disease” or “I have thyroid disease and now I’m iron deficient,” or “now I’m experiencing significant fatigue.” Overall, the most common presentations of celiac disease these days are gastrointestinal symptoms, iron-deficiency anemia, vitamin D deficiency, and fatigue.

DR. MUSHLIN: Certainly, all of those things are seen in an internist’s or a family practitioner’s office. I guess the real key here is that when you start to see this constellation, you should raise your consciousness that there may be one unifying diagnosis rather than multiple diagnoses.

DR. LEFFLER: Exactly. I think that the response to therapy can also be a good hint that there might be something else going on. Most young women with iron-deficiency anemia simply due to menses will do pretty well on oral iron supplementation alone. If they have severe and significant anemia and it’s just not responding to iron supplementation for instance, or if their vitamin D level is low and it does not improve with a regular dose of vitamin D, then you really have to wonder whether there is something that’s preventing absorption of this nutrient in the intestinal tract. Once you get to that level, then celiac disease is by far the most common diagnosis in these situations.

DR. MUSHLIN: We are having this colloquium here in Boston and there are a lot of people in the greater Boston area who are of Northern European extraction. Are there certain ethnic groups that have a predominance of celiac disease, or can it be found in virtually any ethnic group?

DR. LEFFLER: Earlier, we used to say this was essentially an Irish/Italian or western European disease, but now we can more easily pick out the populations that celiac disease doesn’t occur in. Celiac disease has a strong genetic predisposition with human leukocyte antigen (HLA) types, but really the populations that are at risk for celiac disease cover most of the globe: all of North and South America, Europe, the Middle East, North Africa, India, and northern China. Southeast Asians and Sub-Saharan Africans have a very low risk, but the majority of people have a significant risk of celiac disease, and I think that like all other autoimmune and inflammatory disorders, whether it’s type 1 diabetes or asthma or inflammatory bowel disease, the prevalence of celiac disease just continues to rise over time. We’re seeing it in populations that never had this disorder before.

DR. MUSHLIN: Why do you think the prevalence is increasing? Is it that our diagnostic ability is better, or do you think it’s truly increasing?

DR. LEFFLER: Well, we’ve certainly gotten a lot better at diagnosing celiac disease. You mentioned the celiac tTG antibody test earlier, which has really revolutionized the way that we diagnose celiac disease because it’s so accurate, affordable, and widespread. That being said, even in prevalence studies,^1,2 there really is a dramatic increase—something in the range of a doubling—and true prevalence every 30 years or so. This is right alongside these other autoimmune and inflammatory diseases.

Clearly, nothing in our genetic heritability is changing that quickly. It’s something in the environment that is leading to an increase in the incidence of celiac disease and autoimmune diseases in general. Lots of people have theories about what that might be, and the most common theory is that we live in such a clean environment now that our immune system doesn’t have the normal feedback it needs to develop in a healthy way, and so, our immune function may start to become abnormal.

DR. MUSHLIN: This is similar to the asthma hypothesis.

DR. LEFFLER: Exactly. All of this can in some way be explained by the hygiene hypothesis.

DR. MUSHLIN: Right. When you live in Germany and the cows are housed in the same house that you live in, there’s less asthma.

DR. LEFFLER: Exactly. The same phenomenon has been seen in celiac disease in some populations, especially in northern Europe where you cross a national border and you encounter very different socioeconomic conditions. Even though you have virtually the same genetic lineage, you can have very different rates of celiac disease. I think this is very much the case.

DR. MUSHLIN: Ms. Dennis, I have a large number of patients who come into my office and say to me, “I went on a gluten-free diet and I feel so much better.” Can you address the question of gluten sensitivity versus true celiac disease? Do you feel comfortable doing that?

MS. DENNIS: Sure. We know that celiac disease is a genetic autoimmune disease, and we know that non-celiac gluten sensitivity is not considered an autoimmune disease. Dr. Leffler would be in a better position to address the issue of whether there is an inflammatory response, but there are plenty of people who come into the office confused about the 2. In order to obtain a diagnosis of non-celiac gluten sensitivity, celiac disease and wheat allergy would both need to be ruled out.

There is no positive gene testing for non-celiac gluten sensitivity, but what makes it difficult for patients is that the symptoms can mimic one another almost exactly. All the gastrointestinal symptoms, as well as some of the other extraintestinal manifestations like headaches, poor concentration, memory loss, and other similar conditions, can occur in both conditions. It’s complicated, and there is much more research that needs to be done in this area.

DR. LEFFLER: I’ll just corroborate all of that. We’ve known about celiac disease for a long time. Gluten intolerance, or non-celiac gluten sensitivity as it’s becoming more commonly known, is a very new entity that we’ve really only starting believing in, clinically at least, over the last couple of years. We’re learning about it quickly, but we still don’t have a very good sense of its prevalence.

It does appear to be a non-inflammatory disorder, which separates it from celiac disease. It doesn’t appear to have any autoimmune component and likely does not have a lot of the long-term risks associated with celiac disease such as osteoporosis or even cancer and infection risk, but at the same time, it can be associated with significant quality of life impairment, and the symptoms can mimic celiac disease. So, it is something that everyone needs to be aware of; however, while the diet-related treatment is similar, it seems that a lot of the peripheral things that we should do for our celiac patients such as getting them vaccinated and performing a bone mineral density study are not required for patients who have non-celiac gluten intolerance or gluten sensitivity. We do recommend that people work with their physicians to make a clear distinction between these 2 disorders.

DR. MUSHLIN: Just to expand on that point, would a negative tTG antibody test basically exclude celiac disease with a high degree of certainty and leave you with a diagnosis of gluten sensitivity without celiac disease (assuming the symptoms were consistent)?

DR. LEFFLER: Yes. For a typical patient who is on a regular gluten-containing diet and doesn’t have a strong family history of celiac disease or other factors that would increase risk, a negative tTG would certainly be sufficient and would imply that the chances that the patient has true celiac disease are quite low. We can then proceed with a non-celiac gluten sensitivity diagnosis and see how the patient does clinically.

DR. MUSHLIN: It seems that everywhere I go, there are more and more gluten-free choices. In fact, the wife of my closest friend here in town just started a gluten-free bakery and she’s so busy that he’s making deliveries for her now every day instead of 3 times a week. Are there any dangers to adhering to a gluten-free diet?

MS. DENNIS: There are inherent nutritional deficiencies in a gluten-free diet. So, if the diet is not proper, yes, you can lack certain vitamins and minerals. For example, wheat is a major source of protein and B vitamins as well as iron, trace minerals, and fiber.

When you switch to the gluten-free diet, you need to be able to replace those nutrients. Many people don’t focus immediately on the alternative whole and healthier gluten-free grains like amaranth, buckwheat, millet, quinoa, sorghum, and teff. They tend to move toward rice, corn, and potatoes, which tend to be lower in fiber, nutrient poor, and can cause or exacerbate constipation and weight gain when eaten in large quantities. So, that’s one of the main issues.

Additionally, we find that many people are concurrently lactose intolerant when they’re first diagnosed with celiac disease. So, we need to consider the possibility that their calcium and vitamin D intakes may be inadequate. Then, of course, we need to consider the B vitamins, which are present throughout the food chain but are present in large quantities in grains.

DR. MUSHLIN: Ms. Dennis, a lot of my patients are curious about purchasing gluten-free materials either from stores or online. Do you feel comfortable recommending any websites that you feel are legitimate for our patients to access?

Dr. Maricic, what are the different types of osteopenia that primary care clinicians encounter in their practice?

DR. MARICIC: Osteopenia has several connotations, depending on the setting in which it is diagnosed. Radiologists will describe a patient as being osteopenic based on the subjective assessment that the patient has low bone density on radiography. With particular reference to osteoporosis or bone densitometry, osteopenia refers to a dual-energy X-ray absorptiometry (DEXA) T-score, which is a comparison of the bone mass of a patient to that of a young, ideal patient of the same sex and ethnicity.

DR. GALL: Is osteoporosis the only disease or are there other diseases that we may see associated with osteopenia?

DR. MARICIC: Neither osteopenia nor osteoporosis diagnosed by the DEXA score is necessarily caused by estrogen deficiency. The DEXA report tells you whether a patient has low bone density but not about the etiology. Although estrogen deficiency is a common cause of osteopenia or osteoporosis, other conditions such as primary hyperparathyroidism, multiple myeloma, vitamin D deficiency, osteomalacia and the conditions associated with it, chronic renal failure with osteitis, fibrosis cystica, and hyperparathyroidism should be considered by the primary care physician.

It’s typically recommended that all patients with low bone density diagnosed by their DEXA score have a chemistry screening done to determine the calcium and alkaline phosphatase levels, as well as 25-hydroxy-vitamin D level, in order to ensure that the patient is not vitamin D deficient. A 24-hour urine test is also recommended to ensure that the vitamin D level is not low, suggesting malabsorption, such as what we see in vitamin D deficiency or celiac disease, or that it’s not high, suggesting idiopathic hypercalciuria.

Those are the main, most common disorders that we’d like to exclude in patients with osteopenia or especially osteoporosis. We would also want to exclude secondary hyperparathyroidism; vitamin D deficiency; and, when suspected, celiac disease, idiopathic hypercalciuria, and multiple myeloma. Those are some of the conditions to be considered, especially when the T-score does not accord with the clinical history.

DR. GALL: Dr. McClung, can you please discuss the use of X-ray and DEXA scan as diagnostic tools?

DR. MCCLUNG: These 2 tools have completely different roles. We use the DEXA scan to measure bone density, primarily in the hip and the spine, in postmenopausal women and older men to obtain a T-score that is, a value comparing the patient’s bone density to the average bone density value of young adults of the same sex. A T-score of −2.5 is thought to be consistent with osteoporosis in postmenopausal women and older men, but, as Dr. Maricic pointed out, a T-score of −2.5 only tells us that the patient has low bone density. Before we conclude that the patient has osteoporosis, all of the other causes of low bone density, including osteomalacia, osteogenesis imperfecta, and any of the secondary causes that were outlined, need to be excluded.

I believe that osteopenia, which is defined as a T-score value between −1 and −2.5, is not a very useful diagnostic term for clinical purposes. We know that low bone density is one of several risk factors for fracture. Within the group of patients with osteopenia are those who are at very high risk for fracture, including older people and those who have had fractures, as well as many patients who are not at high risk for fracture. In response to this problem, the World Health Organization developed the Fracture Risk Assessment Tool (FRAX), a fracture risk assessment tool used to help distinguish patients with high or low fracture risk.¹

DR. GALL: Clinicians often find the terms used in the DEXA report confusing. Could you define absolute bone mineral density (BMD) and Z-score for the clinician?

DR. MCCLUNG: The BMD test measures the bone mineral content of a specific anatomic region and the area of that region and divides those 2 numbers to get an estimate of the BMD. It is not a true bone density test, but rather a measurement of calcium content within a region of bone.

The BMD value is translated into a T-score by comparing it to the average value for healthy young adults of the same sex and is then used for diagnosis in postmenopausal women. The Z-score is obtained by comparing the patient’s BMD value with the expected average value for healthy adults of the same age and sex and is used to determine whether a low BMD value for that patient is unexpected. A low T-score for a 55-year-old woman may be surprising, whereas a low T-score for a 90-year-old woman would be expected. A Z-score lets us know how concerned we should be.

DR. GALL: Dr. Lisse, you read a lot of DEXA scans. What can give a false value? Can you tell us about that and discuss the FRAX?

DR. LISSE: Dr. McClung wrote a very nice treatise on the FRAX,² a tool that assesses the risk of fracture in bisphosphonate-naïve patients based on the consideration of risk factors, in addition to the BMD value. The DEXA measures bone quantity, but does not assess the risk factors for osteoporosis, of which I think prior fracture and patient age are the most important.

By considering the risk factors of smoking history, advanced age, prior fracture, and family history of fracture, and by adjusting for the country and racial origin of the patient, the FRAX provides a better measure of fracture risk for the osteopenic patient compared to BMD alone. It also provides a value, the 10-year fracture risk, that’s easier for the primary doctor to interpret compared to T-scores and Z-scores, which require comparison in terms of standard deviations.

DR. GALL: How can we use the FRAX if we are interested in doing so?

DR. LISSE: The tool is available online and very easy to use. Usually, you complete the assay using the BMD value. You can actually perform the assay without a BMD value, but I think that including the BMD value improves the precision and predictive value of the results. You just plug in the information online and are given a reading. Recent literature suggests that you can use it for patients who are taking bisphosphonates, but I think that’s a little bit further down the line in our discussion.

DR. GALL: A FRAX result states that a patient has a 10-year risk of major fracture of 8%. How do I use that result? Should I start treating the patient?

DR. LISSE: Several studies that examined local socioeconomic factors concluded that using a 20% risk of major osteoporotic fracture and a 3% risk of hip fracture are cost-effective thresholds for the diagnosis of patients in the United States. Although they should not be considered absolute, they are the current thresholds, and I think physicians can use them as criteria to make treatment decisions.

DR. MCCLUNG: That description is correct. FRAX has a scientific base and is a very highly validated tool that accurately predicts fracture probability in healthy middle-aged and older adults.¹ Using the tool is a good first step while considering whether osteoporosis treatment is justified. The threshold values of a 10-year probability of hip fracture of 3% and a 10-year probability of major osteoporotic fracture of 20% are specific to the United States, which is based on the United States healthcare policy and where osteoporosis fits into the United States medical priorities. Other countries have their own thresholds that are very different.

DR. GALL: Dr. Maricic, we’ve talked about the DEXA and the FRAX. What other imaging tools are available and what are their roles?

Dr. Maricic, what are the different types of osteopenia that primary care clinicians encounter in their practice?

DR. MARICIC: Osteopenia has several connotations, depending on the setting in which it is diagnosed. Radiologists will describe a patient as being osteopenic based on the subjective assessment that the patient has low bone density on radiography. With particular reference to osteoporosis or bone densitometry, osteopenia refers to a dual-energy X-ray absorptiometry (DEXA) T-score, which is a comparison of the bone mass of a patient to that of a young, ideal patient of the same sex and ethnicity.

DR. GALL: Is osteoporosis the only disease or are there other diseases that we may see associated with osteopenia?

DR. MARICIC: Neither osteopenia nor osteoporosis diagnosed by the DEXA score is necessarily caused by estrogen deficiency. The DEXA report tells you whether a patient has low bone density but not about the etiology. Although estrogen deficiency is a common cause of osteopenia or osteoporosis, other conditions such as primary hyperparathyroidism, multiple myeloma, vitamin D deficiency, osteomalacia and the conditions associated with it, chronic renal failure with osteitis, fibrosis cystica, and hyperparathyroidism should be considered by the primary care physician.

It’s typically recommended that all patients with low bone density diagnosed by their DEXA score have a chemistry screening done to determine the calcium and alkaline phosphatase levels, as well as 25-hydroxy-vitamin D level, in order to ensure that the patient is not vitamin D deficient. A 24-hour urine test is also recommended to ensure that the vitamin D level is not low, suggesting malabsorption, such as what we see in vitamin D deficiency or celiac disease, or that it’s not high, suggesting idiopathic hypercalciuria.

Those are the main, most common disorders that we’d like to exclude in patients with osteopenia or especially osteoporosis. We would also want to exclude secondary hyperparathyroidism; vitamin D deficiency; and, when suspected, celiac disease, idiopathic hypercalciuria, and multiple myeloma. Those are some of the conditions to be considered, especially when the T-score does not accord with the clinical history.

DR. GALL: Dr. McClung, can you please discuss the use of X-ray and DEXA scan as diagnostic tools?

DR. MCCLUNG: These 2 tools have completely different roles. We use the DEXA scan to measure bone density, primarily in the hip and the spine, in postmenopausal women and older men to obtain a T-score that is, a value comparing the patient’s bone density to the average bone density value of young adults of the same sex. A T-score of −2.5 is thought to be consistent with osteoporosis in postmenopausal women and older men, but, as Dr. Maricic pointed out, a T-score of −2.5 only tells us that the patient has low bone density. Before we conclude that the patient has osteoporosis, all of the other causes of low bone density, including osteomalacia, osteogenesis imperfecta, and any of the secondary causes that were outlined, need to be excluded.

I believe that osteopenia, which is defined as a T-score value between −1 and −2.5, is not a very useful diagnostic term for clinical purposes. We know that low bone density is one of several risk factors for fracture. Within the group of patients with osteopenia are those who are at very high risk for fracture, including older people and those who have had fractures, as well as many patients who are not at high risk for fracture. In response to this problem, the World Health Organization developed the Fracture Risk Assessment Tool (FRAX), a fracture risk assessment tool used to help distinguish patients with high or low fracture risk.¹

DR. GALL: Clinicians often find the terms used in the DEXA report confusing. Could you define absolute bone mineral density (BMD) and Z-score for the clinician?

DR. MCCLUNG: The BMD test measures the bone mineral content of a specific anatomic region and the area of that region and divides those 2 numbers to get an estimate of the BMD. It is not a true bone density test, but rather a measurement of calcium content within a region of bone.

The BMD value is translated into a T-score by comparing it to the average value for healthy young adults of the same sex and is then used for diagnosis in postmenopausal women. The Z-score is obtained by comparing the patient’s BMD value with the expected average value for healthy adults of the same age and sex and is used to determine whether a low BMD value for that patient is unexpected. A low T-score for a 55-year-old woman may be surprising, whereas a low T-score for a 90-year-old woman would be expected. A Z-score lets us know how concerned we should be.

DR. GALL: Dr. Lisse, you read a lot of DEXA scans. What can give a false value? Can you tell us about that and discuss the FRAX?

DR. LISSE: Dr. McClung wrote a very nice treatise on the FRAX,² a tool that assesses the risk of fracture in bisphosphonate-naïve patients based on the consideration of risk factors, in addition to the BMD value. The DEXA measures bone quantity, but does not assess the risk factors for osteoporosis, of which I think prior fracture and patient age are the most important.

By considering the risk factors of smoking history, advanced age, prior fracture, and family history of fracture, and by adjusting for the country and racial origin of the patient, the FRAX provides a better measure of fracture risk for the osteopenic patient compared to BMD alone. It also provides a value, the 10-year fracture risk, that’s easier for the primary doctor to interpret compared to T-scores and Z-scores, which require comparison in terms of standard deviations.

DR. GALL: How can we use the FRAX if we are interested in doing so?

DR. LISSE: The tool is available online and very easy to use. Usually, you complete the assay using the BMD value. You can actually perform the assay without a BMD value, but I think that including the BMD value improves the precision and predictive value of the results. You just plug in the information online and are given a reading. Recent literature suggests that you can use it for patients who are taking bisphosphonates, but I think that’s a little bit further down the line in our discussion.

DR. GALL: A FRAX result states that a patient has a 10-year risk of major fracture of 8%. How do I use that result? Should I start treating the patient?

DR. LISSE: Several studies that examined local socioeconomic factors concluded that using a 20% risk of major osteoporotic fracture and a 3% risk of hip fracture are cost-effective thresholds for the diagnosis of patients in the United States. Although they should not be considered absolute, they are the current thresholds, and I think physicians can use them as criteria to make treatment decisions.

DR. MCCLUNG: That description is correct. FRAX has a scientific base and is a very highly validated tool that accurately predicts fracture probability in healthy middle-aged and older adults.¹ Using the tool is a good first step while considering whether osteoporosis treatment is justified. The threshold values of a 10-year probability of hip fracture of 3% and a 10-year probability of major osteoporotic fracture of 20% are specific to the United States, which is based on the United States healthcare policy and where osteoporosis fits into the United States medical priorities. Other countries have their own thresholds that are very different.

DR. GALL: Dr. Maricic, we’ve talked about the DEXA and the FRAX. What other imaging tools are available and what are their roles?

Dr. Maricic, what are the different types of osteopenia that primary care clinicians encounter in their practice?

DR. MARICIC: Osteopenia has several connotations, depending on the setting in which it is diagnosed. Radiologists will describe a patient as being osteopenic based on the subjective assessment that the patient has low bone density on radiography. With particular reference to osteoporosis or bone densitometry, osteopenia refers to a dual-energy X-ray absorptiometry (DEXA) T-score, which is a comparison of the bone mass of a patient to that of a young, ideal patient of the same sex and ethnicity.

DR. GALL: Is osteoporosis the only disease or are there other diseases that we may see associated with osteopenia?

DR. MARICIC: Neither osteopenia nor osteoporosis diagnosed by the DEXA score is necessarily caused by estrogen deficiency. The DEXA report tells you whether a patient has low bone density but not about the etiology. Although estrogen deficiency is a common cause of osteopenia or osteoporosis, other conditions such as primary hyperparathyroidism, multiple myeloma, vitamin D deficiency, osteomalacia and the conditions associated with it, chronic renal failure with osteitis, fibrosis cystica, and hyperparathyroidism should be considered by the primary care physician.

It’s typically recommended that all patients with low bone density diagnosed by their DEXA score have a chemistry screening done to determine the calcium and alkaline phosphatase levels, as well as 25-hydroxy-vitamin D level, in order to ensure that the patient is not vitamin D deficient. A 24-hour urine test is also recommended to ensure that the vitamin D level is not low, suggesting malabsorption, such as what we see in vitamin D deficiency or celiac disease, or that it’s not high, suggesting idiopathic hypercalciuria.

Those are the main, most common disorders that we’d like to exclude in patients with osteopenia or especially osteoporosis. We would also want to exclude secondary hyperparathyroidism; vitamin D deficiency; and, when suspected, celiac disease, idiopathic hypercalciuria, and multiple myeloma. Those are some of the conditions to be considered, especially when the T-score does not accord with the clinical history.

DR. GALL: Dr. McClung, can you please discuss the use of X-ray and DEXA scan as diagnostic tools?

DR. MCCLUNG: These 2 tools have completely different roles. We use the DEXA scan to measure bone density, primarily in the hip and the spine, in postmenopausal women and older men to obtain a T-score that is, a value comparing the patient’s bone density to the average bone density value of young adults of the same sex. A T-score of −2.5 is thought to be consistent with osteoporosis in postmenopausal women and older men, but, as Dr. Maricic pointed out, a T-score of −2.5 only tells us that the patient has low bone density. Before we conclude that the patient has osteoporosis, all of the other causes of low bone density, including osteomalacia, osteogenesis imperfecta, and any of the secondary causes that were outlined, need to be excluded.

I believe that osteopenia, which is defined as a T-score value between −1 and −2.5, is not a very useful diagnostic term for clinical purposes. We know that low bone density is one of several risk factors for fracture. Within the group of patients with osteopenia are those who are at very high risk for fracture, including older people and those who have had fractures, as well as many patients who are not at high risk for fracture. In response to this problem, the World Health Organization developed the Fracture Risk Assessment Tool (FRAX), a fracture risk assessment tool used to help distinguish patients with high or low fracture risk.¹

DR. GALL: Clinicians often find the terms used in the DEXA report confusing. Could you define absolute bone mineral density (BMD) and Z-score for the clinician?

DR. MCCLUNG: The BMD test measures the bone mineral content of a specific anatomic region and the area of that region and divides those 2 numbers to get an estimate of the BMD. It is not a true bone density test, but rather a measurement of calcium content within a region of bone.

The BMD value is translated into a T-score by comparing it to the average value for healthy young adults of the same sex and is then used for diagnosis in postmenopausal women. The Z-score is obtained by comparing the patient’s BMD value with the expected average value for healthy adults of the same age and sex and is used to determine whether a low BMD value for that patient is unexpected. A low T-score for a 55-year-old woman may be surprising, whereas a low T-score for a 90-year-old woman would be expected. A Z-score lets us know how concerned we should be.

DR. GALL: Dr. Lisse, you read a lot of DEXA scans. What can give a false value? Can you tell us about that and discuss the FRAX?

DR. LISSE: Dr. McClung wrote a very nice treatise on the FRAX,² a tool that assesses the risk of fracture in bisphosphonate-naïve patients based on the consideration of risk factors, in addition to the BMD value. The DEXA measures bone quantity, but does not assess the risk factors for osteoporosis, of which I think prior fracture and patient age are the most important.

By considering the risk factors of smoking history, advanced age, prior fracture, and family history of fracture, and by adjusting for the country and racial origin of the patient, the FRAX provides a better measure of fracture risk for the osteopenic patient compared to BMD alone. It also provides a value, the 10-year fracture risk, that’s easier for the primary doctor to interpret compared to T-scores and Z-scores, which require comparison in terms of standard deviations.

DR. GALL: How can we use the FRAX if we are interested in doing so?

DR. LISSE: The tool is available online and very easy to use. Usually, you complete the assay using the BMD value. You can actually perform the assay without a BMD value, but I think that including the BMD value improves the precision and predictive value of the results. You just plug in the information online and are given a reading. Recent literature suggests that you can use it for patients who are taking bisphosphonates, but I think that’s a little bit further down the line in our discussion.

DR. GALL: A FRAX result states that a patient has a 10-year risk of major fracture of 8%. How do I use that result? Should I start treating the patient?

DR. LISSE: Several studies that examined local socioeconomic factors concluded that using a 20% risk of major osteoporotic fracture and a 3% risk of hip fracture are cost-effective thresholds for the diagnosis of patients in the United States. Although they should not be considered absolute, they are the current thresholds, and I think physicians can use them as criteria to make treatment decisions.

DR. MCCLUNG: That description is correct. FRAX has a scientific base and is a very highly validated tool that accurately predicts fracture probability in healthy middle-aged and older adults.¹ Using the tool is a good first step while considering whether osteoporosis treatment is justified. The threshold values of a 10-year probability of hip fracture of 3% and a 10-year probability of major osteoporotic fracture of 20% are specific to the United States, which is based on the United States healthcare policy and where osteoporosis fits into the United States medical priorities. Other countries have their own thresholds that are very different.

DR. GALL: Dr. Maricic, we’ve talked about the DEXA and the FRAX. What other imaging tools are available and what are their roles?

DR. BLOCK: Throughout the 20th century, we always considered OA to be primarily a degenerative disease of cartilage, but during the past decade or more, 2 things have become apparent: First, from a clinical perspective, OA is not just a structural degenerative process, it is primarily a very painful disease with pain being its most prominent feature. Second, the degenerative process involves not only the cartilage but the entire joint and all the involved structures within it.

A reasonable working definition of OA right now would be a painful degenerative process involving all the joint structures and is not primarily inflammatory but involves progressive deterioration of joint structures including articular cartilage. It’s important to keep in mind that pain itself is critical because as individuals age, everybody has some degenerative processes in their joints, and if we look hard enough, we can find the pathological features of OA in all elderly people. However, not all elderly people actually have the clinical disease.

DR. GALL: In a moment, we’ll talk about the causes of this, but, Dr. Moskowitz, would you tell us what the burden of this disease is here in the United States and worldwide?

DR. MOSKOWITZ: Well, it’s the most common form of arthritis and affects nearly 27 million or more Americans.¹ It’s the most common disabling disease of the rheumatologic group, and it’s very disabling among all diseases.

DR. GALL: In the United States, you say that there’s about—

DR. MOSKOWITZ: About 27 million people with OA. And, in a decade, it is anticipated that the number will significantly increase.

DR. GALL: How many of those people are affected to the point that they’re unable to do their normal activities of daily living (ADLs)?

DR. MOSKOWITZ: Well, in terms of disability, about 80% of patients with OA have some degree of movement limitation, 25% cannot perform major ADLs, 11% of adults with knee OA need help with personal care, and 14% require help with routine needs.²

DR. GALL: Dr. Block, you talked about pain as a major manifestation of this disease. Does everybody who has OA present with pain?

DR. BLOCK: Again, it’s a definitional question; there is a distinction between clinically evident OA and asymptomatic structural degeneration of the joint. The population that Dr. Moskowitz was just describing, which comprises 20 to 30 million people, has doctor-diagnosed symptomatic OA, which is a painful disease. A much higher number of people who have structural degenerative disease would be diagnosed by radiography and said to fulfill a radiographic definition of OA, but all of the people who Dr. Moskowitz refer to have pain.

DR. MOSKOWITZ: Pain is what brings a patient to the doctor. I’ll often ask my patients, “How are you doing and what can I do for you?” They have limited motion and can’t get around. They say, “Dr. Moskowitz, I just want to get rid of the pain. I’ll worry about the swelling and getting around later.” And, that’s what really motivates them to get medical attention.

DR. GALL: Often, we will get consultations from primary care physicians for a patient who has OA that’s been picked up by radiography, and the patients will come and really not complain of pain in that area or possibly might have another underlying disease that’s causing the pain that’s not related to the OA. Dr. Block, do you want to say a word about that?

DR. BLOCK: Sure. By the age of 80 years, essentially, 100% of the population will have evidence of radiographic OA in at least one of their large joints. If you start with that number and you’re then referred an elderly patient merely for the radiographic appearance of OA, that doesn’t tell you very much about what’s going on clinically, and so, most of us would not even describe that as a clinical disease.

They may have a degenerative process in their knee, hip, etc, but of that group, say at the age of 80 years where almost 100% of people will have radiographic evidence of OA, only about 15% to 20% have symptomatic disease.³ That’s the culprit that I think we’re talking about clinically—people who not only have degenerative structural disease but also have symptoms that are interfering with their quality of life or their daily activities.

DR. MOSKOWITZ: I think that’s an important point, Dr. Block. For example, we all see patients who come in complaining of hip pain and you examine their knees as well and they have terrible genu varum (bowleg) and you say, “Do your knees bother you?” and they say, “Doctor, my knees are fine.” You think, my goodness, how can you walk? It isn’t necessarily true that if you have a deformity or involvement of a joint that you’re going to have pain, but if you have painful joints, that brings you to the doctor.

DR. GALL: Dr. Block, once again, I would like you to summarize the etiology of OA. Obviously, there has been much research and much information that has come to light in recent years regarding the causes of this disease.

DR. BLOCK: As I said, throughout the 20th century, people interested in the pathophysiology of OA were quite convinced that it was a degenerative process of the articular cartilage. As people age, the articular cartilage starts degenerating, and when there is absence of intact cartilage that ought to be providing essentially frictionless articulation of the bones during motion, there is deterioration, and that’s what we always considered to be OA.

Of course, the missing link in that paradigm is that cartilage itself has no nerve or blood supply and is therefore painless, and yet, people have horrible pain with this disease. So, our understanding over the past 10 or 15 years has really dramatically progressed, and we have begun to appreciate both degenerative and reactive processes in the subchondral bone, the ligaments, and the muscle.

The way we look at the pathophysiology of the onset and progression of the disease today is that there is primarily a degenerative process that stimulates reactive processes throughout the joint and even in the immune and inflammatory pathways. So, the reaction to that degenerative process sometimes causes stimulation of nociceptors and a lot of pain because of either local inflammation or mechanical alterations.

The degeneration itself, as I said, is painless. Often, people can have very degenerative joints, as Dr. Moskowitz just mentioned, and have no pain and therefore no clinical symptoms, so the disease is a combination of the degeneration and the secondary stimulated pain.

DR. GALL: So, is this primarily a biochemical or a cellular disease? Is it a genetic disease?

DR. BLOCK: Yes to all.

DR. MOSKOWITZ: There are a number of factors, Dr. Gall, involved in this condition. First, for example, is aging. We see that the frequency of OA increases logarithmically as we age, and there are pathologic changes with age that appear to lead to OA. For example, pigmented collections in the joint, comprising advanced glycation end products, occur that may predispose a patient to OA. You’re going to find more OA in an aging population.

The second factor is trauma. Professional football and basketball players, for example, who have chronic trauma, meniscal injuries, or cruciate ligament injuries are predisposed to OA. Third—the big risk factor, of course—is being overweight or obese. Patients who are overweight have a much higher frequency of OA, particularly in the knees. Last, there are genetic factors. For example, OA in the hands, which is more often seen in women, is genetically oriented so that if your mother had it or your aunt had it, you’re more likely to get it. Accordingly, there are multifactorial etiological factors that we have to try to address.

DR. GALL: Can you say a word about the different areas of the body that are associated with OA and talk a little bit about the difference between OA of the hands that we see frequently in women in relation to OA of the knee, hips, and spine, which can be devastating for individuals?

DR. MOSKOWITZ: Any joint can have it. It can be in the ankle, for example, if there has been trauma, but we’re looking particularly at the knees, the hips, the hands, and the spine. It’s interesting—certain joints in the hands are predisposed to OA including the distal and proximal interphalangeal joints. It tends not to involve the metacarpophalangeal joints, although it can in severe cases. Of course, the first carpometacarpal joint is frequently involved, and OA in this joint can be very disabling.

I have patients, for example, who are pianists or people who use their hands in their daily occupation. Their problem is often unfortunately minimized, with the doctor saying, “Oh, you’ve got a touch of OA, you can live okay with it.” However, this is hard to do because of pain and decreased function—OA can be a very disabling disease. In a number of women, the joints of the hands can be very inflamed. There’s a form of hand OA called erosive inflammatory OA, which can be especially troublesome because it’s very destructive. It’s almost like a low-grade rheumatoid arthritis where you actually get a lot of joint breakdown and deformity—it can be very disabling. OA of the knees or hips obviously can be a problem because of difficulties with ambulation.

DR. BLOCK: Throughout the 20th century, we always considered OA to be primarily a degenerative disease of cartilage, but during the past decade or more, 2 things have become apparent: First, from a clinical perspective, OA is not just a structural degenerative process, it is primarily a very painful disease with pain being its most prominent feature. Second, the degenerative process involves not only the cartilage but the entire joint and all the involved structures within it.

A reasonable working definition of OA right now would be a painful degenerative process involving all the joint structures and is not primarily inflammatory but involves progressive deterioration of joint structures including articular cartilage. It’s important to keep in mind that pain itself is critical because as individuals age, everybody has some degenerative processes in their joints, and if we look hard enough, we can find the pathological features of OA in all elderly people. However, not all elderly people actually have the clinical disease.

DR. GALL: In a moment, we’ll talk about the causes of this, but, Dr. Moskowitz, would you tell us what the burden of this disease is here in the United States and worldwide?

DR. MOSKOWITZ: Well, it’s the most common form of arthritis and affects nearly 27 million or more Americans.¹ It’s the most common disabling disease of the rheumatologic group, and it’s very disabling among all diseases.

DR. GALL: In the United States, you say that there’s about—

DR. MOSKOWITZ: About 27 million people with OA. And, in a decade, it is anticipated that the number will significantly increase.

DR. GALL: How many of those people are affected to the point that they’re unable to do their normal activities of daily living (ADLs)?

DR. MOSKOWITZ: Well, in terms of disability, about 80% of patients with OA have some degree of movement limitation, 25% cannot perform major ADLs, 11% of adults with knee OA need help with personal care, and 14% require help with routine needs.²

DR. GALL: Dr. Block, you talked about pain as a major manifestation of this disease. Does everybody who has OA present with pain?

DR. BLOCK: Again, it’s a definitional question; there is a distinction between clinically evident OA and asymptomatic structural degeneration of the joint. The population that Dr. Moskowitz was just describing, which comprises 20 to 30 million people, has doctor-diagnosed symptomatic OA, which is a painful disease. A much higher number of people who have structural degenerative disease would be diagnosed by radiography and said to fulfill a radiographic definition of OA, but all of the people who Dr. Moskowitz refer to have pain.

DR. MOSKOWITZ: Pain is what brings a patient to the doctor. I’ll often ask my patients, “How are you doing and what can I do for you?” They have limited motion and can’t get around. They say, “Dr. Moskowitz, I just want to get rid of the pain. I’ll worry about the swelling and getting around later.” And, that’s what really motivates them to get medical attention.

DR. GALL: Often, we will get consultations from primary care physicians for a patient who has OA that’s been picked up by radiography, and the patients will come and really not complain of pain in that area or possibly might have another underlying disease that’s causing the pain that’s not related to the OA. Dr. Block, do you want to say a word about that?

DR. BLOCK: Sure. By the age of 80 years, essentially, 100% of the population will have evidence of radiographic OA in at least one of their large joints. If you start with that number and you’re then referred an elderly patient merely for the radiographic appearance of OA, that doesn’t tell you very much about what’s going on clinically, and so, most of us would not even describe that as a clinical disease.

They may have a degenerative process in their knee, hip, etc, but of that group, say at the age of 80 years where almost 100% of people will have radiographic evidence of OA, only about 15% to 20% have symptomatic disease.³ That’s the culprit that I think we’re talking about clinically—people who not only have degenerative structural disease but also have symptoms that are interfering with their quality of life or their daily activities.

DR. MOSKOWITZ: I think that’s an important point, Dr. Block. For example, we all see patients who come in complaining of hip pain and you examine their knees as well and they have terrible genu varum (bowleg) and you say, “Do your knees bother you?” and they say, “Doctor, my knees are fine.” You think, my goodness, how can you walk? It isn’t necessarily true that if you have a deformity or involvement of a joint that you’re going to have pain, but if you have painful joints, that brings you to the doctor.

DR. GALL: Dr. Block, once again, I would like you to summarize the etiology of OA. Obviously, there has been much research and much information that has come to light in recent years regarding the causes of this disease.

DR. BLOCK: As I said, throughout the 20th century, people interested in the pathophysiology of OA were quite convinced that it was a degenerative process of the articular cartilage. As people age, the articular cartilage starts degenerating, and when there is absence of intact cartilage that ought to be providing essentially frictionless articulation of the bones during motion, there is deterioration, and that’s what we always considered to be OA.

Of course, the missing link in that paradigm is that cartilage itself has no nerve or blood supply and is therefore painless, and yet, people have horrible pain with this disease. So, our understanding over the past 10 or 15 years has really dramatically progressed, and we have begun to appreciate both degenerative and reactive processes in the subchondral bone, the ligaments, and the muscle.

The way we look at the pathophysiology of the onset and progression of the disease today is that there is primarily a degenerative process that stimulates reactive processes throughout the joint and even in the immune and inflammatory pathways. So, the reaction to that degenerative process sometimes causes stimulation of nociceptors and a lot of pain because of either local inflammation or mechanical alterations.

The degeneration itself, as I said, is painless. Often, people can have very degenerative joints, as Dr. Moskowitz just mentioned, and have no pain and therefore no clinical symptoms, so the disease is a combination of the degeneration and the secondary stimulated pain.

DR. GALL: So, is this primarily a biochemical or a cellular disease? Is it a genetic disease?

DR. BLOCK: Yes to all.

DR. MOSKOWITZ: There are a number of factors, Dr. Gall, involved in this condition. First, for example, is aging. We see that the frequency of OA increases logarithmically as we age, and there are pathologic changes with age that appear to lead to OA. For example, pigmented collections in the joint, comprising advanced glycation end products, occur that may predispose a patient to OA. You’re going to find more OA in an aging population.

The second factor is trauma. Professional football and basketball players, for example, who have chronic trauma, meniscal injuries, or cruciate ligament injuries are predisposed to OA. Third—the big risk factor, of course—is being overweight or obese. Patients who are overweight have a much higher frequency of OA, particularly in the knees. Last, there are genetic factors. For example, OA in the hands, which is more often seen in women, is genetically oriented so that if your mother had it or your aunt had it, you’re more likely to get it. Accordingly, there are multifactorial etiological factors that we have to try to address.

DR. GALL: Can you say a word about the different areas of the body that are associated with OA and talk a little bit about the difference between OA of the hands that we see frequently in women in relation to OA of the knee, hips, and spine, which can be devastating for individuals?

DR. MOSKOWITZ: Any joint can have it. It can be in the ankle, for example, if there has been trauma, but we’re looking particularly at the knees, the hips, the hands, and the spine. It’s interesting—certain joints in the hands are predisposed to OA including the distal and proximal interphalangeal joints. It tends not to involve the metacarpophalangeal joints, although it can in severe cases. Of course, the first carpometacarpal joint is frequently involved, and OA in this joint can be very disabling.

I have patients, for example, who are pianists or people who use their hands in their daily occupation. Their problem is often unfortunately minimized, with the doctor saying, “Oh, you’ve got a touch of OA, you can live okay with it.” However, this is hard to do because of pain and decreased function—OA can be a very disabling disease. In a number of women, the joints of the hands can be very inflamed. There’s a form of hand OA called erosive inflammatory OA, which can be especially troublesome because it’s very destructive. It’s almost like a low-grade rheumatoid arthritis where you actually get a lot of joint breakdown and deformity—it can be very disabling. OA of the knees or hips obviously can be a problem because of difficulties with ambulation.

DR. BLOCK: Throughout the 20th century, we always considered OA to be primarily a degenerative disease of cartilage, but during the past decade or more, 2 things have become apparent: First, from a clinical perspective, OA is not just a structural degenerative process, it is primarily a very painful disease with pain being its most prominent feature. Second, the degenerative process involves not only the cartilage but the entire joint and all the involved structures within it.

A reasonable working definition of OA right now would be a painful degenerative process involving all the joint structures and is not primarily inflammatory but involves progressive deterioration of joint structures including articular cartilage. It’s important to keep in mind that pain itself is critical because as individuals age, everybody has some degenerative processes in their joints, and if we look hard enough, we can find the pathological features of OA in all elderly people. However, not all elderly people actually have the clinical disease.

DR. GALL: In a moment, we’ll talk about the causes of this, but, Dr. Moskowitz, would you tell us what the burden of this disease is here in the United States and worldwide?

DR. MOSKOWITZ: Well, it’s the most common form of arthritis and affects nearly 27 million or more Americans.¹ It’s the most common disabling disease of the rheumatologic group, and it’s very disabling among all diseases.

DR. GALL: In the United States, you say that there’s about—

DR. MOSKOWITZ: About 27 million people with OA. And, in a decade, it is anticipated that the number will significantly increase.

DR. GALL: How many of those people are affected to the point that they’re unable to do their normal activities of daily living (ADLs)?

DR. MOSKOWITZ: Well, in terms of disability, about 80% of patients with OA have some degree of movement limitation, 25% cannot perform major ADLs, 11% of adults with knee OA need help with personal care, and 14% require help with routine needs.²

DR. GALL: Dr. Block, you talked about pain as a major manifestation of this disease. Does everybody who has OA present with pain?

DR. BLOCK: Again, it’s a definitional question; there is a distinction between clinically evident OA and asymptomatic structural degeneration of the joint. The population that Dr. Moskowitz was just describing, which comprises 20 to 30 million people, has doctor-diagnosed symptomatic OA, which is a painful disease. A much higher number of people who have structural degenerative disease would be diagnosed by radiography and said to fulfill a radiographic definition of OA, but all of the people who Dr. Moskowitz refer to have pain.

DR. MOSKOWITZ: Pain is what brings a patient to the doctor. I’ll often ask my patients, “How are you doing and what can I do for you?” They have limited motion and can’t get around. They say, “Dr. Moskowitz, I just want to get rid of the pain. I’ll worry about the swelling and getting around later.” And, that’s what really motivates them to get medical attention.

DR. GALL: Often, we will get consultations from primary care physicians for a patient who has OA that’s been picked up by radiography, and the patients will come and really not complain of pain in that area or possibly might have another underlying disease that’s causing the pain that’s not related to the OA. Dr. Block, do you want to say a word about that?

DR. BLOCK: Sure. By the age of 80 years, essentially, 100% of the population will have evidence of radiographic OA in at least one of their large joints. If you start with that number and you’re then referred an elderly patient merely for the radiographic appearance of OA, that doesn’t tell you very much about what’s going on clinically, and so, most of us would not even describe that as a clinical disease.

They may have a degenerative process in their knee, hip, etc, but of that group, say at the age of 80 years where almost 100% of people will have radiographic evidence of OA, only about 15% to 20% have symptomatic disease.³ That’s the culprit that I think we’re talking about clinically—people who not only have degenerative structural disease but also have symptoms that are interfering with their quality of life or their daily activities.

DR. MOSKOWITZ: I think that’s an important point, Dr. Block. For example, we all see patients who come in complaining of hip pain and you examine their knees as well and they have terrible genu varum (bowleg) and you say, “Do your knees bother you?” and they say, “Doctor, my knees are fine.” You think, my goodness, how can you walk? It isn’t necessarily true that if you have a deformity or involvement of a joint that you’re going to have pain, but if you have painful joints, that brings you to the doctor.

DR. GALL: Dr. Block, once again, I would like you to summarize the etiology of OA. Obviously, there has been much research and much information that has come to light in recent years regarding the causes of this disease.

DR. BLOCK: As I said, throughout the 20th century, people interested in the pathophysiology of OA were quite convinced that it was a degenerative process of the articular cartilage. As people age, the articular cartilage starts degenerating, and when there is absence of intact cartilage that ought to be providing essentially frictionless articulation of the bones during motion, there is deterioration, and that’s what we always considered to be OA.

Of course, the missing link in that paradigm is that cartilage itself has no nerve or blood supply and is therefore painless, and yet, people have horrible pain with this disease. So, our understanding over the past 10 or 15 years has really dramatically progressed, and we have begun to appreciate both degenerative and reactive processes in the subchondral bone, the ligaments, and the muscle.

The way we look at the pathophysiology of the onset and progression of the disease today is that there is primarily a degenerative process that stimulates reactive processes throughout the joint and even in the immune and inflammatory pathways. So, the reaction to that degenerative process sometimes causes stimulation of nociceptors and a lot of pain because of either local inflammation or mechanical alterations.

The degeneration itself, as I said, is painless. Often, people can have very degenerative joints, as Dr. Moskowitz just mentioned, and have no pain and therefore no clinical symptoms, so the disease is a combination of the degeneration and the secondary stimulated pain.

DR. GALL: So, is this primarily a biochemical or a cellular disease? Is it a genetic disease?

DR. BLOCK: Yes to all.

DR. MOSKOWITZ: There are a number of factors, Dr. Gall, involved in this condition. First, for example, is aging. We see that the frequency of OA increases logarithmically as we age, and there are pathologic changes with age that appear to lead to OA. For example, pigmented collections in the joint, comprising advanced glycation end products, occur that may predispose a patient to OA. You’re going to find more OA in an aging population.

The second factor is trauma. Professional football and basketball players, for example, who have chronic trauma, meniscal injuries, or cruciate ligament injuries are predisposed to OA. Third—the big risk factor, of course—is being overweight or obese. Patients who are overweight have a much higher frequency of OA, particularly in the knees. Last, there are genetic factors. For example, OA in the hands, which is more often seen in women, is genetically oriented so that if your mother had it or your aunt had it, you’re more likely to get it. Accordingly, there are multifactorial etiological factors that we have to try to address.

DR. GALL: Can you say a word about the different areas of the body that are associated with OA and talk a little bit about the difference between OA of the hands that we see frequently in women in relation to OA of the knee, hips, and spine, which can be devastating for individuals?

DR. MOSKOWITZ: Any joint can have it. It can be in the ankle, for example, if there has been trauma, but we’re looking particularly at the knees, the hips, the hands, and the spine. It’s interesting—certain joints in the hands are predisposed to OA including the distal and proximal interphalangeal joints. It tends not to involve the metacarpophalangeal joints, although it can in severe cases. Of course, the first carpometacarpal joint is frequently involved, and OA in this joint can be very disabling.

I have patients, for example, who are pianists or people who use their hands in their daily occupation. Their problem is often unfortunately minimized, with the doctor saying, “Oh, you’ve got a touch of OA, you can live okay with it.” However, this is hard to do because of pain and decreased function—OA can be a very disabling disease. In a number of women, the joints of the hands can be very inflamed. There’s a form of hand OA called erosive inflammatory OA, which can be especially troublesome because it’s very destructive. It’s almost like a low-grade rheumatoid arthritis where you actually get a lot of joint breakdown and deformity—it can be very disabling. OA of the knees or hips obviously can be a problem because of difficulties with ambulation.

Michael Kurisu is at the University of California San Diego Health System where he’s a faculty member in the Department of Family Medicine. He also teaches at a number of osteopathic medical schools across the country, has a particular interest in osteopathic manual therapy as well as prevention of musculoskeletal injury, and works closely with our colleagues in physical therapy. Hollis King, DO and PhD, is a fellow of the American Academy of Osteopathy, Program Director of Osteopathic Residency Education, and Professor in the Department of Family Medicine at the University of Wisconsin School of Medicine and Public Health. Howard Schubiner is the Director of the Mind-Body Medicine Center in the Department of Internal Medicine at Providence Hospital in Southfield, Michigan, and is a Clinical Professor at Wayne State University.

Chronic back pain is among the most common patient complaints. Its prevalence and impact have spawned a rapidly expanding range of tests and treatments. Some of these have become widely used for indications that are not well validated, leading to uncertainty about efficacy and safety, increasing complication rates, and marketing abuses. Recent studies document a 629% increase in Medicare expenditures for epidural steroid injections, a 423% increase in expenditures for opioids for back pain, a 307% increase in the number of lumbar magnetic resonance images among Medicare beneficiaries, and a 220% increase in spinal fusion surgery rates. The limited studies available suggest that these increases have not been accompanied by population-level improvements in patient outcomes or disability rates. We suggest a need for a better understanding of the basic science of pain mechanisms, more rigorous and independent trials of many treatments, a stronger regulatory stance toward approval and postmarketing surveillance of new drugs and devices for chronic pain, and a chronic disease model for managing chronic back pain.¹

Despite this increase in investment, we have not seen a significant reduction in morbidity of low back pain.¹

When we refer to integrative medicine, what we’re actually talking about is combining the therapies that work best to understand how humans heal within complex systems. Low back pain is a perfect example of how complexity based on biopsychosocial-spiritual influences can influence the severity of pain as well as suffering.

The Centers for Disease Control and Prevention National Health statistics report² showed that low back pain was, by far, the most common condition for which patients seek complementary and alternative medicine care. We hope to eliminate these terms and refer to them instead as just good medicine, where the research guides us toward what works best. With this goal in mind, the National Institute of Clinical Excellence in England released their guidelines for low back pain that were published in the British Medical Journal.³ They summarized those therapies that had the best evidence for yielding beneficial effects.

The therapies that had the most benefit with the least potential for harm were physical therapy but not traction, exercise, mind/body influences including psychology, acupuncture, and surgery when indicated, particularly for severe radicular pain. That’s almost a different diagnosis when you have severe radicular pain. We will focus more on low back pain and chronic low back pain, without significant radicular symptoms. The guidelines also supported nonsteroidal anti-inflammatory drugs.

Two things that the guidelines did not support in this evidence-based review were epidural steroids and opioids. We use opioids a lot, but the research shows that maybe we shouldn’t do so. The Danish health and morbidity study⁴ of more than 10 000 patients who were treated with opioids for noncancer pain showed that the patients did not meet any of the 3 outcome measures associated with pain management. Surprisingly, opioids did not result in improved function, improved quality of life, or a reduction in pain.

When we talk about how to deal with these different aspects of pain, we’d like to use the expertise of our panel to focus on 3 main therapeutic areas. We will use a 3-legged stool model to highlight each of these 3 therapeutic areas. The first leg is the external or physical parts of low back pain, including structure and mechanics. The second leg is the internal or emotional aspect, ie, the importance of stress and emotions on why that pain might be persisting. The third leg of the stool is reconditioning. How can we get the body to be strong and supportive? How can we work with our colleagues to create these interdisciplinary teams to yield better outcomes, particularly as accountable care organizations become more popular with regard to improving outcome measures for low back pain? What professionals would we want to work with for the best outcome?

Dr. King, I’d like to start with you. You could talk about exploring the external and the physical piece. You have particular expertise in osteopathic manual therapy as well as research in this area. Would you mind sharing some of your insights with regard to manual therapy and the treatment of this condition?

DR. KING: In the present medical research context of needing to have your work be well justified by evidence-based medicine research, all the professions who use their hands in health care have been striving to generate acceptable research. At present, the chiropractic profession is probably the one that has produced the most practical research on spinal manipulation. The osteopathic profession has followed suit pretty well too. That’s where I have personally been involved in the research.

For instance, with chronic low back pain, this is one of the subjects where we actually have state-of-the-art evidence-based research. A systematic review and meta-analysis that was conducted by Licciardone et al and published in 2005,⁵ which is a Cochrane review level of evidence, describes all the necessary meta-analysis aspects indicating that osteopathic manipulative treatment (OMT) significantly reduces low back pain. From the osteopathic perspective, OMT is delivered to patients with the diagnoses of somatic dysfunction or malalignment of the vertebral column, as well as malalignment of the appendicular skeleton for upper and lower extremities. In this case, we’re talking about the low back.

We now have state-of-the-art evidence of the benefit of OMT for low back pain. This evidence has been established in practice guidelines published by the Agency for Healthcare Research and Quality.⁶ These guidelines indicate where OMT should be utilized in the treatment of chronic low back pain. This is in the context of conventional medical treatment of chronic low back pain, where essentially the guidelines say that OMT should be used. The administration of OMT typically occurs as a part of an outpatient visit, for either musculoskeletal pain or even for a sore throat, or the physician may have a day in his clinic schedule when all that is done is OMT—an OMT clinic if you will; this is my style of doing OMT. For a sore throat, OMT can quickly be done to enhance lymphatic drainage and augment the healing process and even help any prescribed medication get to the infected area through improved circulation.

We have reached this level of medical research. The outcome is that, in my experience at least, there is very little resistance on the part of third-party carriers including Medicare to reimburse people for the delivery of OMT wherein the diagnosis is low back pain and particularly, chronic low back pain. This has been very helpful because the reimbursement element is critical in order to provide this service.

There are several other research initiatives, one of which was undertaken by Licciardone et al,⁷ in which OMT for 488 subjects was compared for chronic low back pain by using ultrasound. I was a treatment provider in that study, the results of which support the meta-analysis discussed above. The first publication derived from this study reports a subgroup analysis that assesses cytokine production after OMT. The results were that the cytokine interleukin 6 was correlated with back pain severity.⁸

From the research side, we are gradually—certainly between the osteopathic and the chiropractic professions—generating the evidence that spinal manipulation, the hands-on work, is of definite benefit in the care of patients who have been diagnosed with chronic low back pain.

DR. RAKEL: You mentioned about reimbursement, which can be a significant barrier. There’s a study I just reviewed in the journal Spine that looked at what the patients perceived as most helpful for their low back pain. The number one response was massage. Number two was chiropractic therapy and OMT, and the last was conventional medicine. Unfortunately, massage isn’t covered by most reimbursement plans and acupuncture, included in the National Institute for Health and Care Excellence (NICE) guidelines,³ is also not covered. When you look at the cost-benefit of acupuncture versus epidural steroids, there’s a tremendous difference favoring acupuncture.^7–10

So what you’re saying, Dr. King, is that this research is going to support the reimbursement for manual therapy whether that be OMT or chiropractic therapy?

DR. KING: Yes.

DR. RAKEL: Is that happening now? Isn’t OMT covered by most insurances?

DR. KING: It is. In the osteopathic professional societies that I belong to, these issues come up; for example, a certain third-party carrier would deny reimbursement for OMT services. We have been increasingly successful in educating the third-party carriers that there is a scientifically demonstrated benefit for manual medicine and manual therapy. This reimbursement advocacy based on evidenced-based research is an important element in making sure that it is readily available. If the third-party carriers accept the benefits of OMT, it will help research go forward. I’m just amazed that the interested companies don’t read the scientific literature; they seem to make us prove points. When the professional organizations have the opportunity to show them the evidence, the insurance companies say, “Well, yes, I guess we’ll have to reimburse it.”

The other element that I observed when I was in practice in San Diego and now in Madison, Wisconsin, is that if the patients who have benefited request that their coverage for OMT be increased, the insurance companies, especially the health maintenance organizations, respond and increase coverage, as the trend is for patient improvement and overall less insurance company payments for certain musculoskeletal conditions. Therefore, patient advocacy has helped, in my experience, in receiving sufficient reimbursement for the delivery of hands-on applications in health care.

DR. RAKEL: As we transition into our next topic with Dr. Schubiner, Dr. King, I know you have, as they say in the business, good hands. In your care of patients, it’s much more than just manipulation. Would you mind just touching quickly on that? You do more than just manipulation. In your delivery of care with your hands on the patient, what do you think makes the biggest difference in your ability to influence their outcomes?

DR. KING: I talk to the patient while I’m doing a 20- to 25-minute OMT service, about their life. Often, to a patient complaining of low back pain, I’ll ask, “Who’s the pain in your back?” Sometimes I refer to anatomy below the low back, but it gets the patient to think about their pain and talk about it, thus establishing a more direct mind-body connection.

My experience from body-mind-spirit integrative medicine is that if I’m able to address where the somatic dysfunction, that is, the malalignment, is, I associate it with the mental, emotional, and psychosocial components that the patient almost cannot resist. It’s what comes to their mind when I say, “Okay, who’s the pain in your rear?” They then start talking about some event or some situation, and you can feel the tissues of the low back respond even better when their mind is engaged in the full component of the true causes of the pain.

Sometimes, the key element in the benefit of the OMT is just re-living the incident itself—the injury, the fall, and the strain—and they go back to that moment of impact. You may be able to remind the person of the injury time that they may have forgotten about, sometimes on purpose. Just by undergoing the mental process of remembering the fear and the anger of falling or straining, they can remember the “injury,” “Oh darn, that hurts now.” If you take them back to the time of the initiation of the injury in the treatment of musculoskeletal malalignment, you do get a more effective, successful treatment, if you’re able to combine the mental and emotional as well as the physical aspects at the same time during the treatment.

So, yes, I go out of my way to do that. I think it really establishes a strong doctor-patient relationship when you have that kind of time, that 20- to 25-minute dialogue. The patients appreciate that you’re taking the time to do it, that you’re not only talking to them but you are touching them.

DR. RAKEL: That is a beautiful segue way to iterate the importance of the complexity of human beings with conditions such as low back pain. Dr. Schubiner has conducted research in this area and has developed patient resources.¹¹ So, Dr. Schubiner, would you mind sharing some of your insights about how you might encourage us to explore this mind-body connection in our everyday practice of this common condition?

DR. SCHUBINER: There are 3 areas that I thought I could talk about. First, there is some cutting-edge neuroscience on the relationship between emotions and pain. Second, there’s some data on mind/body approaches to chronic pain, musculoskeletal pain, and fibromyalgia. And finally, I will briefly discuss how I approach this problem.

First, there’s been some cutting-edge research on the relationship between emotions and pain. At the University of California at Los Angeles, they’ve showed that social exclusion causes activation of the anterior cingulate cortex and decreases the pain threshold.¹²

Ethan Kross at the University of Michigan has shown that creating physical pain causes activation of the same pathways in the brain, ie, the so-called pain pathways, that are activated by causing someone to have emotional pain.¹³ John Burns, in Chicago, has shown that asking people with low back pain to recall a time when they were particularly angry causes spasm of the muscles of the low back, and that holding in emotion or asking people to suppress emotion decreases pains threshold.^14,15 Finally, Apkarian and colleagues have shown that activation of emotional pathways in the brain (the nucleus accumbens in the limbic system) predicts which patients with subacute back pain are more likely to develop chronic back pain.¹⁶

The data on mind/body approaches to chronic musculoskeletal pain, primarily back pain, show that mindfulness mediation, cognitive behavioral therapies, acceptance and commitment therapy, loving/kindness meditative therapies, and expressive writing therapies are effective for this condition. However, the effect sizes are relatively small, in the range of 0.3 to 0.5.¹⁷

When these approaches are used, they generally do not challenge the traditional biomedical model that assumed that all people with back pain have a musculoskeletal condition or some kind of ongoing tissue damage process. However, if you follow the back pain research closely, you realize that 85% of back pain cannot be diagnosed accurately, according to Richard Deyo, on the basis of current testing that we have available.¹⁸

In my practice, I try to help determine if each patient has primarily a tissue-damage problem or, what I would call, a nerve-pathway problem. A nerve pathway consists of the connection of millions of neurons in the brain that have been trained to create some reaction in the body, such as pathways of how to talk, walk, sign one’s name, ride a bicycle, or swing a golf club. A recent realization is that nerve pathways can be causes of pain. If one has a nerve pathway problem, the pain, of course, is very real and often is as severe, or even more severe, as a tissue-damage–related pain. We have discovered that nerve pathway pain, whether it’s diagnosed as fibromyalgia, neck or back pain, headache, or any other painful condition in the body, can be dramatically reduced or even eliminated. The bottom line is that the majority of people with these painful conditions do not have ongoing tissue injury but have nerve pathway-related pain.

In brief, let me describe the approach that I have taken to reversing pain from nerve pathway-related conditions.¹¹ First, I rule out a structural process such as a tumor, fracture, infection, or condition that causes clear evidence of nerve compression (ie, an abnormal neurologic examination). The program involves the following: (1) educate patients that they do not have tissue damage and that they can get better; (2) teach them to take control of the pain by removing the fear of pain and literally “telling the pain to go away” along with meditative and visualization techniques; (3) process past and current life stressors emotionally (using a therapy known as intensive short-term dynamic psychotherapy¹⁸); and (4) help them make positive changes in their life. We have conducted research to evaluate this model in patients with fibromyalgia¹⁹ and those with back and neck pain.²⁰ The data are encouraging and show large effect sizes of approximately 1.1 to 1.4.

After a relatively brief 4-week intervention, approximately 50% of patients have more than a 50% reduction in pain at a 6-month follow-up assessment, which is obviously a very dramatic reduction in pain. The key to these results is in helping patients understand that they have a nerve-pathway problem as opposed to a tissue-damage problem and empower them to believe that they can actually overcome the pain. We offer them behavioral strategies to help them eliminate the pain and, most importantly, work on the emotions, as Dr. King was discussing. I’ve been using very specific techniques, such as intensive short-term dynamic psychotherapy, for dealing with emotions such as anger, guilt, fear, and sadness or grief to help people express and release the emotions that, from my point of view, comprise the underlying cause of the origin and perpetuation of nerve pathway pain.

Michael Kurisu is at the University of California San Diego Health System where he’s a faculty member in the Department of Family Medicine. He also teaches at a number of osteopathic medical schools across the country, has a particular interest in osteopathic manual therapy as well as prevention of musculoskeletal injury, and works closely with our colleagues in physical therapy. Hollis King, DO and PhD, is a fellow of the American Academy of Osteopathy, Program Director of Osteopathic Residency Education, and Professor in the Department of Family Medicine at the University of Wisconsin School of Medicine and Public Health. Howard Schubiner is the Director of the Mind-Body Medicine Center in the Department of Internal Medicine at Providence Hospital in Southfield, Michigan, and is a Clinical Professor at Wayne State University.

Chronic back pain is among the most common patient complaints. Its prevalence and impact have spawned a rapidly expanding range of tests and treatments. Some of these have become widely used for indications that are not well validated, leading to uncertainty about efficacy and safety, increasing complication rates, and marketing abuses. Recent studies document a 629% increase in Medicare expenditures for epidural steroid injections, a 423% increase in expenditures for opioids for back pain, a 307% increase in the number of lumbar magnetic resonance images among Medicare beneficiaries, and a 220% increase in spinal fusion surgery rates. The limited studies available suggest that these increases have not been accompanied by population-level improvements in patient outcomes or disability rates. We suggest a need for a better understanding of the basic science of pain mechanisms, more rigorous and independent trials of many treatments, a stronger regulatory stance toward approval and postmarketing surveillance of new drugs and devices for chronic pain, and a chronic disease model for managing chronic back pain.¹

Despite this increase in investment, we have not seen a significant reduction in morbidity of low back pain.¹

When we refer to integrative medicine, what we’re actually talking about is combining the therapies that work best to understand how humans heal within complex systems. Low back pain is a perfect example of how complexity based on biopsychosocial-spiritual influences can influence the severity of pain as well as suffering.

The Centers for Disease Control and Prevention National Health statistics report² showed that low back pain was, by far, the most common condition for which patients seek complementary and alternative medicine care. We hope to eliminate these terms and refer to them instead as just good medicine, where the research guides us toward what works best. With this goal in mind, the National Institute of Clinical Excellence in England released their guidelines for low back pain that were published in the British Medical Journal.³ They summarized those therapies that had the best evidence for yielding beneficial effects.

The therapies that had the most benefit with the least potential for harm were physical therapy but not traction, exercise, mind/body influences including psychology, acupuncture, and surgery when indicated, particularly for severe radicular pain. That’s almost a different diagnosis when you have severe radicular pain. We will focus more on low back pain and chronic low back pain, without significant radicular symptoms. The guidelines also supported nonsteroidal anti-inflammatory drugs.

Two things that the guidelines did not support in this evidence-based review were epidural steroids and opioids. We use opioids a lot, but the research shows that maybe we shouldn’t do so. The Danish health and morbidity study⁴ of more than 10 000 patients who were treated with opioids for noncancer pain showed that the patients did not meet any of the 3 outcome measures associated with pain management. Surprisingly, opioids did not result in improved function, improved quality of life, or a reduction in pain.

When we talk about how to deal with these different aspects of pain, we’d like to use the expertise of our panel to focus on 3 main therapeutic areas. We will use a 3-legged stool model to highlight each of these 3 therapeutic areas. The first leg is the external or physical parts of low back pain, including structure and mechanics. The second leg is the internal or emotional aspect, ie, the importance of stress and emotions on why that pain might be persisting. The third leg of the stool is reconditioning. How can we get the body to be strong and supportive? How can we work with our colleagues to create these interdisciplinary teams to yield better outcomes, particularly as accountable care organizations become more popular with regard to improving outcome measures for low back pain? What professionals would we want to work with for the best outcome?

Dr. King, I’d like to start with you. You could talk about exploring the external and the physical piece. You have particular expertise in osteopathic manual therapy as well as research in this area. Would you mind sharing some of your insights with regard to manual therapy and the treatment of this condition?

DR. KING: In the present medical research context of needing to have your work be well justified by evidence-based medicine research, all the professions who use their hands in health care have been striving to generate acceptable research. At present, the chiropractic profession is probably the one that has produced the most practical research on spinal manipulation. The osteopathic profession has followed suit pretty well too. That’s where I have personally been involved in the research.

For instance, with chronic low back pain, this is one of the subjects where we actually have state-of-the-art evidence-based research. A systematic review and meta-analysis that was conducted by Licciardone et al and published in 2005,⁵ which is a Cochrane review level of evidence, describes all the necessary meta-analysis aspects indicating that osteopathic manipulative treatment (OMT) significantly reduces low back pain. From the osteopathic perspective, OMT is delivered to patients with the diagnoses of somatic dysfunction or malalignment of the vertebral column, as well as malalignment of the appendicular skeleton for upper and lower extremities. In this case, we’re talking about the low back.

We now have state-of-the-art evidence of the benefit of OMT for low back pain. This evidence has been established in practice guidelines published by the Agency for Healthcare Research and Quality.⁶ These guidelines indicate where OMT should be utilized in the treatment of chronic low back pain. This is in the context of conventional medical treatment of chronic low back pain, where essentially the guidelines say that OMT should be used. The administration of OMT typically occurs as a part of an outpatient visit, for either musculoskeletal pain or even for a sore throat, or the physician may have a day in his clinic schedule when all that is done is OMT—an OMT clinic if you will; this is my style of doing OMT. For a sore throat, OMT can quickly be done to enhance lymphatic drainage and augment the healing process and even help any prescribed medication get to the infected area through improved circulation.

We have reached this level of medical research. The outcome is that, in my experience at least, there is very little resistance on the part of third-party carriers including Medicare to reimburse people for the delivery of OMT wherein the diagnosis is low back pain and particularly, chronic low back pain. This has been very helpful because the reimbursement element is critical in order to provide this service.

There are several other research initiatives, one of which was undertaken by Licciardone et al,⁷ in which OMT for 488 subjects was compared for chronic low back pain by using ultrasound. I was a treatment provider in that study, the results of which support the meta-analysis discussed above. The first publication derived from this study reports a subgroup analysis that assesses cytokine production after OMT. The results were that the cytokine interleukin 6 was correlated with back pain severity.⁸

From the research side, we are gradually—certainly between the osteopathic and the chiropractic professions—generating the evidence that spinal manipulation, the hands-on work, is of definite benefit in the care of patients who have been diagnosed with chronic low back pain.

DR. RAKEL: You mentioned about reimbursement, which can be a significant barrier. There’s a study I just reviewed in the journal Spine that looked at what the patients perceived as most helpful for their low back pain. The number one response was massage. Number two was chiropractic therapy and OMT, and the last was conventional medicine. Unfortunately, massage isn’t covered by most reimbursement plans and acupuncture, included in the National Institute for Health and Care Excellence (NICE) guidelines,³ is also not covered. When you look at the cost-benefit of acupuncture versus epidural steroids, there’s a tremendous difference favoring acupuncture.^7–10

So what you’re saying, Dr. King, is that this research is going to support the reimbursement for manual therapy whether that be OMT or chiropractic therapy?

DR. KING: Yes.

DR. RAKEL: Is that happening now? Isn’t OMT covered by most insurances?

DR. KING: It is. In the osteopathic professional societies that I belong to, these issues come up; for example, a certain third-party carrier would deny reimbursement for OMT services. We have been increasingly successful in educating the third-party carriers that there is a scientifically demonstrated benefit for manual medicine and manual therapy. This reimbursement advocacy based on evidenced-based research is an important element in making sure that it is readily available. If the third-party carriers accept the benefits of OMT, it will help research go forward. I’m just amazed that the interested companies don’t read the scientific literature; they seem to make us prove points. When the professional organizations have the opportunity to show them the evidence, the insurance companies say, “Well, yes, I guess we’ll have to reimburse it.”

The other element that I observed when I was in practice in San Diego and now in Madison, Wisconsin, is that if the patients who have benefited request that their coverage for OMT be increased, the insurance companies, especially the health maintenance organizations, respond and increase coverage, as the trend is for patient improvement and overall less insurance company payments for certain musculoskeletal conditions. Therefore, patient advocacy has helped, in my experience, in receiving sufficient reimbursement for the delivery of hands-on applications in health care.

DR. RAKEL: As we transition into our next topic with Dr. Schubiner, Dr. King, I know you have, as they say in the business, good hands. In your care of patients, it’s much more than just manipulation. Would you mind just touching quickly on that? You do more than just manipulation. In your delivery of care with your hands on the patient, what do you think makes the biggest difference in your ability to influence their outcomes?

DR. KING: I talk to the patient while I’m doing a 20- to 25-minute OMT service, about their life. Often, to a patient complaining of low back pain, I’ll ask, “Who’s the pain in your back?” Sometimes I refer to anatomy below the low back, but it gets the patient to think about their pain and talk about it, thus establishing a more direct mind-body connection.

My experience from body-mind-spirit integrative medicine is that if I’m able to address where the somatic dysfunction, that is, the malalignment, is, I associate it with the mental, emotional, and psychosocial components that the patient almost cannot resist. It’s what comes to their mind when I say, “Okay, who’s the pain in your rear?” They then start talking about some event or some situation, and you can feel the tissues of the low back respond even better when their mind is engaged in the full component of the true causes of the pain.

Sometimes, the key element in the benefit of the OMT is just re-living the incident itself—the injury, the fall, and the strain—and they go back to that moment of impact. You may be able to remind the person of the injury time that they may have forgotten about, sometimes on purpose. Just by undergoing the mental process of remembering the fear and the anger of falling or straining, they can remember the “injury,” “Oh darn, that hurts now.” If you take them back to the time of the initiation of the injury in the treatment of musculoskeletal malalignment, you do get a more effective, successful treatment, if you’re able to combine the mental and emotional as well as the physical aspects at the same time during the treatment.

So, yes, I go out of my way to do that. I think it really establishes a strong doctor-patient relationship when you have that kind of time, that 20- to 25-minute dialogue. The patients appreciate that you’re taking the time to do it, that you’re not only talking to them but you are touching them.

DR. RAKEL: That is a beautiful segue way to iterate the importance of the complexity of human beings with conditions such as low back pain. Dr. Schubiner has conducted research in this area and has developed patient resources.¹¹ So, Dr. Schubiner, would you mind sharing some of your insights about how you might encourage us to explore this mind-body connection in our everyday practice of this common condition?

DR. SCHUBINER: There are 3 areas that I thought I could talk about. First, there is some cutting-edge neuroscience on the relationship between emotions and pain. Second, there’s some data on mind/body approaches to chronic pain, musculoskeletal pain, and fibromyalgia. And finally, I will briefly discuss how I approach this problem.

First, there’s been some cutting-edge research on the relationship between emotions and pain. At the University of California at Los Angeles, they’ve showed that social exclusion causes activation of the anterior cingulate cortex and decreases the pain threshold.¹²

Ethan Kross at the University of Michigan has shown that creating physical pain causes activation of the same pathways in the brain, ie, the so-called pain pathways, that are activated by causing someone to have emotional pain.¹³ John Burns, in Chicago, has shown that asking people with low back pain to recall a time when they were particularly angry causes spasm of the muscles of the low back, and that holding in emotion or asking people to suppress emotion decreases pains threshold.^14,15 Finally, Apkarian and colleagues have shown that activation of emotional pathways in the brain (the nucleus accumbens in the limbic system) predicts which patients with subacute back pain are more likely to develop chronic back pain.¹⁶

The data on mind/body approaches to chronic musculoskeletal pain, primarily back pain, show that mindfulness mediation, cognitive behavioral therapies, acceptance and commitment therapy, loving/kindness meditative therapies, and expressive writing therapies are effective for this condition. However, the effect sizes are relatively small, in the range of 0.3 to 0.5.¹⁷

When these approaches are used, they generally do not challenge the traditional biomedical model that assumed that all people with back pain have a musculoskeletal condition or some kind of ongoing tissue damage process. However, if you follow the back pain research closely, you realize that 85% of back pain cannot be diagnosed accurately, according to Richard Deyo, on the basis of current testing that we have available.¹⁸

In my practice, I try to help determine if each patient has primarily a tissue-damage problem or, what I would call, a nerve-pathway problem. A nerve pathway consists of the connection of millions of neurons in the brain that have been trained to create some reaction in the body, such as pathways of how to talk, walk, sign one’s name, ride a bicycle, or swing a golf club. A recent realization is that nerve pathways can be causes of pain. If one has a nerve pathway problem, the pain, of course, is very real and often is as severe, or even more severe, as a tissue-damage–related pain. We have discovered that nerve pathway pain, whether it’s diagnosed as fibromyalgia, neck or back pain, headache, or any other painful condition in the body, can be dramatically reduced or even eliminated. The bottom line is that the majority of people with these painful conditions do not have ongoing tissue injury but have nerve pathway-related pain.

In brief, let me describe the approach that I have taken to reversing pain from nerve pathway-related conditions.¹¹ First, I rule out a structural process such as a tumor, fracture, infection, or condition that causes clear evidence of nerve compression (ie, an abnormal neurologic examination). The program involves the following: (1) educate patients that they do not have tissue damage and that they can get better; (2) teach them to take control of the pain by removing the fear of pain and literally “telling the pain to go away” along with meditative and visualization techniques; (3) process past and current life stressors emotionally (using a therapy known as intensive short-term dynamic psychotherapy¹⁸); and (4) help them make positive changes in their life. We have conducted research to evaluate this model in patients with fibromyalgia¹⁹ and those with back and neck pain.²⁰ The data are encouraging and show large effect sizes of approximately 1.1 to 1.4.

After a relatively brief 4-week intervention, approximately 50% of patients have more than a 50% reduction in pain at a 6-month follow-up assessment, which is obviously a very dramatic reduction in pain. The key to these results is in helping patients understand that they have a nerve-pathway problem as opposed to a tissue-damage problem and empower them to believe that they can actually overcome the pain. We offer them behavioral strategies to help them eliminate the pain and, most importantly, work on the emotions, as Dr. King was discussing. I’ve been using very specific techniques, such as intensive short-term dynamic psychotherapy, for dealing with emotions such as anger, guilt, fear, and sadness or grief to help people express and release the emotions that, from my point of view, comprise the underlying cause of the origin and perpetuation of nerve pathway pain.

Michael Kurisu is at the University of California San Diego Health System where he’s a faculty member in the Department of Family Medicine. He also teaches at a number of osteopathic medical schools across the country, has a particular interest in osteopathic manual therapy as well as prevention of musculoskeletal injury, and works closely with our colleagues in physical therapy. Hollis King, DO and PhD, is a fellow of the American Academy of Osteopathy, Program Director of Osteopathic Residency Education, and Professor in the Department of Family Medicine at the University of Wisconsin School of Medicine and Public Health. Howard Schubiner is the Director of the Mind-Body Medicine Center in the Department of Internal Medicine at Providence Hospital in Southfield, Michigan, and is a Clinical Professor at Wayne State University.

Chronic back pain is among the most common patient complaints. Its prevalence and impact have spawned a rapidly expanding range of tests and treatments. Some of these have become widely used for indications that are not well validated, leading to uncertainty about efficacy and safety, increasing complication rates, and marketing abuses. Recent studies document a 629% increase in Medicare expenditures for epidural steroid injections, a 423% increase in expenditures for opioids for back pain, a 307% increase in the number of lumbar magnetic resonance images among Medicare beneficiaries, and a 220% increase in spinal fusion surgery rates. The limited studies available suggest that these increases have not been accompanied by population-level improvements in patient outcomes or disability rates. We suggest a need for a better understanding of the basic science of pain mechanisms, more rigorous and independent trials of many treatments, a stronger regulatory stance toward approval and postmarketing surveillance of new drugs and devices for chronic pain, and a chronic disease model for managing chronic back pain.¹

Despite this increase in investment, we have not seen a significant reduction in morbidity of low back pain.¹

When we refer to integrative medicine, what we’re actually talking about is combining the therapies that work best to understand how humans heal within complex systems. Low back pain is a perfect example of how complexity based on biopsychosocial-spiritual influences can influence the severity of pain as well as suffering.

The Centers for Disease Control and Prevention National Health statistics report² showed that low back pain was, by far, the most common condition for which patients seek complementary and alternative medicine care. We hope to eliminate these terms and refer to them instead as just good medicine, where the research guides us toward what works best. With this goal in mind, the National Institute of Clinical Excellence in England released their guidelines for low back pain that were published in the British Medical Journal.³ They summarized those therapies that had the best evidence for yielding beneficial effects.

The therapies that had the most benefit with the least potential for harm were physical therapy but not traction, exercise, mind/body influences including psychology, acupuncture, and surgery when indicated, particularly for severe radicular pain. That’s almost a different diagnosis when you have severe radicular pain. We will focus more on low back pain and chronic low back pain, without significant radicular symptoms. The guidelines also supported nonsteroidal anti-inflammatory drugs.

Two things that the guidelines did not support in this evidence-based review were epidural steroids and opioids. We use opioids a lot, but the research shows that maybe we shouldn’t do so. The Danish health and morbidity study⁴ of more than 10 000 patients who were treated with opioids for noncancer pain showed that the patients did not meet any of the 3 outcome measures associated with pain management. Surprisingly, opioids did not result in improved function, improved quality of life, or a reduction in pain.

When we talk about how to deal with these different aspects of pain, we’d like to use the expertise of our panel to focus on 3 main therapeutic areas. We will use a 3-legged stool model to highlight each of these 3 therapeutic areas. The first leg is the external or physical parts of low back pain, including structure and mechanics. The second leg is the internal or emotional aspect, ie, the importance of stress and emotions on why that pain might be persisting. The third leg of the stool is reconditioning. How can we get the body to be strong and supportive? How can we work with our colleagues to create these interdisciplinary teams to yield better outcomes, particularly as accountable care organizations become more popular with regard to improving outcome measures for low back pain? What professionals would we want to work with for the best outcome?

Dr. King, I’d like to start with you. You could talk about exploring the external and the physical piece. You have particular expertise in osteopathic manual therapy as well as research in this area. Would you mind sharing some of your insights with regard to manual therapy and the treatment of this condition?

DR. KING: In the present medical research context of needing to have your work be well justified by evidence-based medicine research, all the professions who use their hands in health care have been striving to generate acceptable research. At present, the chiropractic profession is probably the one that has produced the most practical research on spinal manipulation. The osteopathic profession has followed suit pretty well too. That’s where I have personally been involved in the research.

For instance, with chronic low back pain, this is one of the subjects where we actually have state-of-the-art evidence-based research. A systematic review and meta-analysis that was conducted by Licciardone et al and published in 2005,⁵ which is a Cochrane review level of evidence, describes all the necessary meta-analysis aspects indicating that osteopathic manipulative treatment (OMT) significantly reduces low back pain. From the osteopathic perspective, OMT is delivered to patients with the diagnoses of somatic dysfunction or malalignment of the vertebral column, as well as malalignment of the appendicular skeleton for upper and lower extremities. In this case, we’re talking about the low back.

We now have state-of-the-art evidence of the benefit of OMT for low back pain. This evidence has been established in practice guidelines published by the Agency for Healthcare Research and Quality.⁶ These guidelines indicate where OMT should be utilized in the treatment of chronic low back pain. This is in the context of conventional medical treatment of chronic low back pain, where essentially the guidelines say that OMT should be used. The administration of OMT typically occurs as a part of an outpatient visit, for either musculoskeletal pain or even for a sore throat, or the physician may have a day in his clinic schedule when all that is done is OMT—an OMT clinic if you will; this is my style of doing OMT. For a sore throat, OMT can quickly be done to enhance lymphatic drainage and augment the healing process and even help any prescribed medication get to the infected area through improved circulation.

We have reached this level of medical research. The outcome is that, in my experience at least, there is very little resistance on the part of third-party carriers including Medicare to reimburse people for the delivery of OMT wherein the diagnosis is low back pain and particularly, chronic low back pain. This has been very helpful because the reimbursement element is critical in order to provide this service.

There are several other research initiatives, one of which was undertaken by Licciardone et al,⁷ in which OMT for 488 subjects was compared for chronic low back pain by using ultrasound. I was a treatment provider in that study, the results of which support the meta-analysis discussed above. The first publication derived from this study reports a subgroup analysis that assesses cytokine production after OMT. The results were that the cytokine interleukin 6 was correlated with back pain severity.⁸

From the research side, we are gradually—certainly between the osteopathic and the chiropractic professions—generating the evidence that spinal manipulation, the hands-on work, is of definite benefit in the care of patients who have been diagnosed with chronic low back pain.

DR. RAKEL: You mentioned about reimbursement, which can be a significant barrier. There’s a study I just reviewed in the journal Spine that looked at what the patients perceived as most helpful for their low back pain. The number one response was massage. Number two was chiropractic therapy and OMT, and the last was conventional medicine. Unfortunately, massage isn’t covered by most reimbursement plans and acupuncture, included in the National Institute for Health and Care Excellence (NICE) guidelines,³ is also not covered. When you look at the cost-benefit of acupuncture versus epidural steroids, there’s a tremendous difference favoring acupuncture.^7–10

So what you’re saying, Dr. King, is that this research is going to support the reimbursement for manual therapy whether that be OMT or chiropractic therapy?

DR. KING: Yes.

DR. RAKEL: Is that happening now? Isn’t OMT covered by most insurances?

DR. KING: It is. In the osteopathic professional societies that I belong to, these issues come up; for example, a certain third-party carrier would deny reimbursement for OMT services. We have been increasingly successful in educating the third-party carriers that there is a scientifically demonstrated benefit for manual medicine and manual therapy. This reimbursement advocacy based on evidenced-based research is an important element in making sure that it is readily available. If the third-party carriers accept the benefits of OMT, it will help research go forward. I’m just amazed that the interested companies don’t read the scientific literature; they seem to make us prove points. When the professional organizations have the opportunity to show them the evidence, the insurance companies say, “Well, yes, I guess we’ll have to reimburse it.”

The other element that I observed when I was in practice in San Diego and now in Madison, Wisconsin, is that if the patients who have benefited request that their coverage for OMT be increased, the insurance companies, especially the health maintenance organizations, respond and increase coverage, as the trend is for patient improvement and overall less insurance company payments for certain musculoskeletal conditions. Therefore, patient advocacy has helped, in my experience, in receiving sufficient reimbursement for the delivery of hands-on applications in health care.

DR. RAKEL: As we transition into our next topic with Dr. Schubiner, Dr. King, I know you have, as they say in the business, good hands. In your care of patients, it’s much more than just manipulation. Would you mind just touching quickly on that? You do more than just manipulation. In your delivery of care with your hands on the patient, what do you think makes the biggest difference in your ability to influence their outcomes?

DR. KING: I talk to the patient while I’m doing a 20- to 25-minute OMT service, about their life. Often, to a patient complaining of low back pain, I’ll ask, “Who’s the pain in your back?” Sometimes I refer to anatomy below the low back, but it gets the patient to think about their pain and talk about it, thus establishing a more direct mind-body connection.

My experience from body-mind-spirit integrative medicine is that if I’m able to address where the somatic dysfunction, that is, the malalignment, is, I associate it with the mental, emotional, and psychosocial components that the patient almost cannot resist. It’s what comes to their mind when I say, “Okay, who’s the pain in your rear?” They then start talking about some event or some situation, and you can feel the tissues of the low back respond even better when their mind is engaged in the full component of the true causes of the pain.

Sometimes, the key element in the benefit of the OMT is just re-living the incident itself—the injury, the fall, and the strain—and they go back to that moment of impact. You may be able to remind the person of the injury time that they may have forgotten about, sometimes on purpose. Just by undergoing the mental process of remembering the fear and the anger of falling or straining, they can remember the “injury,” “Oh darn, that hurts now.” If you take them back to the time of the initiation of the injury in the treatment of musculoskeletal malalignment, you do get a more effective, successful treatment, if you’re able to combine the mental and emotional as well as the physical aspects at the same time during the treatment.

So, yes, I go out of my way to do that. I think it really establishes a strong doctor-patient relationship when you have that kind of time, that 20- to 25-minute dialogue. The patients appreciate that you’re taking the time to do it, that you’re not only talking to them but you are touching them.

DR. RAKEL: That is a beautiful segue way to iterate the importance of the complexity of human beings with conditions such as low back pain. Dr. Schubiner has conducted research in this area and has developed patient resources.¹¹ So, Dr. Schubiner, would you mind sharing some of your insights about how you might encourage us to explore this mind-body connection in our everyday practice of this common condition?

DR. SCHUBINER: There are 3 areas that I thought I could talk about. First, there is some cutting-edge neuroscience on the relationship between emotions and pain. Second, there’s some data on mind/body approaches to chronic pain, musculoskeletal pain, and fibromyalgia. And finally, I will briefly discuss how I approach this problem.

First, there’s been some cutting-edge research on the relationship between emotions and pain. At the University of California at Los Angeles, they’ve showed that social exclusion causes activation of the anterior cingulate cortex and decreases the pain threshold.¹²

Ethan Kross at the University of Michigan has shown that creating physical pain causes activation of the same pathways in the brain, ie, the so-called pain pathways, that are activated by causing someone to have emotional pain.¹³ John Burns, in Chicago, has shown that asking people with low back pain to recall a time when they were particularly angry causes spasm of the muscles of the low back, and that holding in emotion or asking people to suppress emotion decreases pains threshold.^14,15 Finally, Apkarian and colleagues have shown that activation of emotional pathways in the brain (the nucleus accumbens in the limbic system) predicts which patients with subacute back pain are more likely to develop chronic back pain.¹⁶

The data on mind/body approaches to chronic musculoskeletal pain, primarily back pain, show that mindfulness mediation, cognitive behavioral therapies, acceptance and commitment therapy, loving/kindness meditative therapies, and expressive writing therapies are effective for this condition. However, the effect sizes are relatively small, in the range of 0.3 to 0.5.¹⁷

When these approaches are used, they generally do not challenge the traditional biomedical model that assumed that all people with back pain have a musculoskeletal condition or some kind of ongoing tissue damage process. However, if you follow the back pain research closely, you realize that 85% of back pain cannot be diagnosed accurately, according to Richard Deyo, on the basis of current testing that we have available.¹⁸

In my practice, I try to help determine if each patient has primarily a tissue-damage problem or, what I would call, a nerve-pathway problem. A nerve pathway consists of the connection of millions of neurons in the brain that have been trained to create some reaction in the body, such as pathways of how to talk, walk, sign one’s name, ride a bicycle, or swing a golf club. A recent realization is that nerve pathways can be causes of pain. If one has a nerve pathway problem, the pain, of course, is very real and often is as severe, or even more severe, as a tissue-damage–related pain. We have discovered that nerve pathway pain, whether it’s diagnosed as fibromyalgia, neck or back pain, headache, or any other painful condition in the body, can be dramatically reduced or even eliminated. The bottom line is that the majority of people with these painful conditions do not have ongoing tissue injury but have nerve pathway-related pain.

In brief, let me describe the approach that I have taken to reversing pain from nerve pathway-related conditions.¹¹ First, I rule out a structural process such as a tumor, fracture, infection, or condition that causes clear evidence of nerve compression (ie, an abnormal neurologic examination). The program involves the following: (1) educate patients that they do not have tissue damage and that they can get better; (2) teach them to take control of the pain by removing the fear of pain and literally “telling the pain to go away” along with meditative and visualization techniques; (3) process past and current life stressors emotionally (using a therapy known as intensive short-term dynamic psychotherapy¹⁸); and (4) help them make positive changes in their life. We have conducted research to evaluate this model in patients with fibromyalgia¹⁹ and those with back and neck pain.²⁰ The data are encouraging and show large effect sizes of approximately 1.1 to 1.4.

After a relatively brief 4-week intervention, approximately 50% of patients have more than a 50% reduction in pain at a 6-month follow-up assessment, which is obviously a very dramatic reduction in pain. The key to these results is in helping patients understand that they have a nerve-pathway problem as opposed to a tissue-damage problem and empower them to believe that they can actually overcome the pain. We offer them behavioral strategies to help them eliminate the pain and, most importantly, work on the emotions, as Dr. King was discussing. I’ve been using very specific techniques, such as intensive short-term dynamic psychotherapy, for dealing with emotions such as anger, guilt, fear, and sadness or grief to help people express and release the emotions that, from my point of view, comprise the underlying cause of the origin and perpetuation of nerve pathway pain.