Effects of Risedronate and Low-Dose Testosterone Replacement Skin Patch on Bone Density in Anorexia Nervosa

Dr. David Herzog was the first Endowed Professor of Psychiatry in the Field of Eating Disorders at Harvard Medical School.  For over 25 years, he has collaborated with the Neuroendocrine Unit at Massachusetts General Hospital to learn more about the biology of anorexia nervosa and interventions that affect the course of the illness.  Several studies test treatments for complications such as severe bone loss, which occurs in nearly half of adult women with anorexia nervosa, increasing their risk for fractures and permanent disability.

Bone loss in adults with anorexia nervosa is characterized by both increased bone resorption (breakdown) and decreased formation. Risedronate is a biphosphonate, a class of drugs that slows bone resorption and has been shown to be effective in the treatment of osteoporosis in postmenopausal women.

Although some people think of testosterone as existing only in men, small amounts of this hormone are also produced by women, mostly in the ovaries. One of testosterone’s roles is to stimulate bone formation. Testosterone levels are low in women with anorexia nervosa (as compared to normal controls) and this deficiency is associated with abnormal bone density.

Dr. Herzog and his team in the Neuroendocrine Unit conducted a one-year study to determine whether therapy with risedronate alone or in combination with a low-dose testosterone replacement skin patch would increase bone density in women with anorexia nervosa.  77 ambulatory women with anorexia nervosa were randomly assigned to receive one of four treatments: 1) risedronate 35 mg. weekly plus a placebo (inert) patch, 2) a daily low-dose testosterone replacement skin patch plus a weekly placebo pill, 3) risedronate 35 mg. weekly plus the daily testosterone patch, or 4) double placebo. All participants had dual energy x-ray absorptiometry (DXA) to measure their bone density and blood tests to determine their hormone levels.

The study demonstrated that risedronate administration increased spinal bone density, the primary site of bone loss in women with anorexia nervosa.  Low-dose testosterone did not change bone density but increased lean body mass.  This is an important finding given the lack of effectiveness of other agents, including estrogen, to prevent or reverse bone loss in adults with anorexia nervosa.  Additional studies are needed to optimize treatment for the severe bone loss experienced in this population at increased risk for fracture.

 

Oxytocin is Associated with Anxiety and Depression in Anorexia Nervosa

Dr. David Herzog is an internationally renowned eating disorders expert credited with over 280 publications and board certified in Pediatrics, Child and Adolescent Psychiatry and General Psychiatry.  Dr. Herzog was the first Endowed Professor of Psychiatry in the Field of Eating Disorders at Harvard Medical School.  For over 25 years, he has teamed with the Neuroendocrine Unit at Massachusetts General Hospital to better understand the hormonal factors that contribute to anorexia nervosa and to develop interventions that address complications, such as anxiety and depression.

Produced in the hypothalamus and secreted by the pituitary gland, the peptide hormone oxytocin helps regulate appetite and may have properties that help alleviate anxiety and depression. Prior research by Dr. Herzog and his team found that women with anorexia nervosa have abnormal post-meal levels of oxytocin, even after weight recovery. To follow up on these findings, these scientists investigated the relationship between abnormal oxytocin secretion in anorexia nervosa and psychiatric symptoms.

35 women between the ages of 18 and 28 were recruited from the community to participate in the study. 13 of these 35 had active anorexia nervosa, 9 were weight-recovered from anorexia nervosa, and 13 were healthy controls.  All the subjects were given a meal standardized for nutrient content.  The participants had serial blood tests that measured their hormone levels and completed questionnaires that assessed their symptoms of anxiety and depression.   

The study found that increased post-meal oxytocin secretion was associated with severity of anxiety and depressive symptoms in women with anorexia nervosa. These relationships remained significant after the investigators controlled for the appetite-regulating hormone cortisol, which has been implicated in anxiety and depressive symptoms in anorexia nervosa.

The findings of the study raised the question of whether abnormal post-meal oxytocin levels are, in part, a response to food-induced stress in individuals with anorexia.  Further research is needed to shed light on this question.

The Use of Psychiatric Medications in Anorexia Nervosa

Dr. David Herzog, Emeritus Professor of Psychiatry at Harvard Medical School, has collaborated with the Neuroendocrine Unit at Massachusetts General Hospital for over 25 years to better understand the hormonal factors that contribute to anorexia nervosa and the interventions that influence the course of the illness.  Many of these studies have tested effective treatments for complications such as bone loss, anxiety and depression.  Recently, Dr. Herzog and the team investigated the use of antidepressants, particularly SSRIs (selective serotonin reuptake inhibitors), and atypical antipsychotics from 1997 to 2009 in women with anorexia nervosa.

525 participants were identified through the Neuroendocrine Unit’s research database and included in the analysis. To investigate changes in medication between 1997 and 2009, the scientists divided the women into two groups based on their date of presentation. Group I consisted of the 325 subjects who were screened between 1997 and 2002, and Group II consisted of the 200 participants screened between 2003 and 2009.  All subjects had a complete medical history and physical exam.  

Overall, 53% of the participants reported current use of any psychiatric medication. 48.4% reported use of an antidepressant and 13% reported use of an antipsychotic. The use of antidepressants remained stable between 1997 and 2009 but the rate of atypical antipsychotic use doubled over this time period.  These findings are concerning because antidepressants and atypical antipsychotics have not been shown to be effective in anorexia nervosa and may have significant negative impact on the bone health of this population.  Longer-term studies are necessary to evaluate the effectiveness and benefits of these medications before their widespread use continues.

 

Bone Density and Major Depression in Adolescents

For over a decade, Dr. David Herzog, Emeritus Professor of Psychiatry at Harvard Medical School, has collaborated with the Neuroendocrine Unit at Massachusetts General Hospital (MGH) to learn more about the impact of anorexia nervosa on bone formation during adolescence.  Now the team is also examining bone mass in teenagers diagnosed with major depressive disorder.

Major depression is common in adolescents.  Among school-aged children, the prevalence is 2%-3% and increases to 4% to 8% among teenagers.  Adolescence is also a key period of bone growth.  Over 90% of a person’s bone mass has developed by age 18.

Dr. Herzog and his team of scientists in the MGH Neuroendocrine Unit recruited 65 adolescents between the ages of 12 and 18.  32 participants were boys (16 with major depressive disorder and 16 healthy controls) and 33 were girls (17 with major depressive disorder and 16 controls). Dual energy x-ray absorptiometry (DXA) was used to measure participants’ bone density of the lumbar spine and hip, and blood tests were drawn to determine levels of estradiol (the major form of estrogen), testosterone, Vitamin D, and bone turnover markers (biochemical markers of either bone formation or bone resorption).

The study found that boys with major depressive disorder had a significantly lower bone mineral density compared with healthy controls after adjusting for body mass index. This significant finding was maintained after also adjusting for lean mass and bone age.  In contrast, bone mineral density in girls with major depression did not differ from controls.  It is important for clinicians caring for adolescents, especially boys with depression to be of aware of these findings and the potential for increased risk of fracture. This was the first time the relationship between bone density and depression in adolescent boys has been studied, and further research will shed more light on the topic.

Postdoctoral Fellowship Program

Throughout his career, Dr. David Herzog – Emeritus Professor of Psychiatry at Harvard Medical School – has endeavored to improve the lives of individuals with eating disorders.  Dr. Herzog was the first Endowed Professor of Psychiatry in the Field of Eating Disorders at Harvard Medical School.  He founded and directed the Harvard Eating Disorders Center, which later became the Harris Center for Education and Advocacy in Eating Disorders at Massachusetts General Hospital (MGH). 

Dr. Herzog has been deeply committed to helping young scientists embark on careers in eating disorders.  He established the Matina S. Horner, Ph.D. Research Fellowship in 1997 for college and graduate students.  Beginning in 2007 – as part of his work for the Harris Center at MGH – he also hosted a Postdoctoral Fellowship to train professionals in the specialized treatment of individuals with eating disorders. 

The Postdoctoral Fellowship offered early-career investigators the opportunity to contribute to and learn from the expertise of the Harris Center staff, MGH, and the eating disorders field. In addition to conducting innovative research, Harris Center Postdoctoral Fellows treated individuals with eating disorders under Dr. Herzog’s supervision.

As part of their training, the fellows attended the MGH Department of Psychiatry's Weekly Grand Rounds and played an active role in the meetings of the New England Eating Disorders Research Collaborative, a group of over 25 clinicians and scientists in the greater New England area who come together to share ideas, highlight recent advances in the field, and discuss future directions in research. Postdoctoral fellows also had the opportunity to participate in MGH and Harvard Medical School training sessions, such as a weekly Psychiatric Genetics Seminar and a cognitive behavioral therapy course. 

The Harris Center's first Postdoctoral Fellow (2007-2008) was Kamryn T. Eddy, Ph.D., an exceptional researcher and clinician. As a Postdoctoral Fellow, Dr. Eddy carried a full clinical caseload and contributed significantly to the Harris Center's research, particularly through her work in the areas of the classification of eating disorders and the treatment of children and adolescents. During her Fellowship she received two awards for her eating disorders research—the Livingston Award (from Harvard Medical School) and the Clinical Research Day Psychiatry Award (from MGH).

At the completion of her Postdoctoral Fellowship, Dr. Eddy continued under Dr. Herzog’s mentorship.  She is now an Assistant Professor of Psychiatry at Harvard Medical School and a staff psychologist at MGH.



 

 

  

Matina S. Horner, Ph.D. Fellowship

Dr. David Herzog, Emeritus Professor of Psychiatry at Harvard Medical School, is an internationally recognized eating disorders expert. He is board certified in pediatrics, child and adolescent psychiatry and general psychiatry and has treated over 3,000 women with anorexia nervosa, bulimia nervosa, and associated diagnoses. Dr. David Herzog was the first Endowed Professor of Psychiatry in the Field of Eating Disorders at Harvard Medical School. He founded and directed the Harris Center for Education and Advocacy in Eating Disorders at Massachusetts General Hospital and, prior to that, the Harvard Eating Disorders Center.

One of Dr. Herzog’s priorities has been to educate new leaders in the field of eating disorders.  In 1997, as part of his work for the Harvard Eating Disorders Center, he established a summer fellowship program, which offered undergraduate and graduate students the opportunity for mentorship and supervision as they conducted independent research projects.  Dr. Herzog named the fellowship for former Radclife College President Matina S. Horner, Ph.D. in honor of her commitment to the development of women, to the advancement of science, and to the field of health care. 

The Matina Horner fellows' eating disorder research projects have covered a wide range of topics, from prevention, to cross-cultural dimensions, to personality and biological factors.  Many trainees have contined their independent projects after their fellowships have ended, resulting in published papers.  A number of fellows, including S. Bryn Austin, ScD, have achieved academic positions in universities across the nation.

The Matina Horner Fellowship -- the first of its kind -- has now enjoyed 16 years of progress and sponsored 47 young scientists.

 

 

 

New England Eating Disorders Research Collaborative

Dr. David Herzog—Emeritus Professor of Psychiatry at Harvard Medical School—founded the Harvard Eating Disorders Center in 1994, which later became the Harris Center at Massachusetts General Hospital (MGH). For over a decade, he has collaborated with Dr. Anne Klibanski in the Neuroendocrine Unit at MGH to better understand the hormonal factors that contribute to anorexia nervosa and interventions that affect the complications of that disorder.

In 2006, the Harris Center and the Neuroendocrine Unit established the New England Research Collaborative to promote interaction among researchers in the field of eating disorders. Twice a year, the Collaborative brings together scientists, clinicians, and educators to discuss advances in eating disorder research and possible applications to treatment.  Attended by at least two dozen professionals, these forums consist of presentations on particular topics followed by group discussion. Examples of recent presentations include “Experiential Skill Building,” “IGF-1 Treatment of Low Bone Mass in Anorexia Nervosa,” “Anorexia Nervosa in Female Adolescents: A Look at the Big Picture,” and “Eating Disorders on Campus: Integrated Treatment and Challenges.”

Dr. David Herzog’s Work with the Council of Fashion Designers of America

Dr. David Herzog, Emeritus Professor of Psychiatry at Harvard Medical School, is an internationally renowned expert on eating disorders.  He is board certified in pediatrics, child and adolescent psychiatry, and general psychiatry and has authored over 280 publications. Dr. Herzog founded and directed the Harris Center for Education and Advocacy in Eating Disorders at Massachusetts General Hospital in Boston and, prior to that, the Harvard Eating Disorders Center at Harvard Medical School.

For several years, Dr. Herzog has worked with the fashion industry to change female size standards from those that glorify extreme thinness to those that support health.  In February of 2010, he served as moderator for a panel discussion titled “The Beauty of Health: Resizing the Sample Size.”  Hosted in New York City by the Council of Fashion Designers of America (CFDA), this event convened nearly 150 leaders of the fashion industry to address concerns about the increasing number of unhealthy, too thin models.  The outcome of the discussion was the CFDA recommendation that models must be at least 16 years of age.

In March of 2010, Dr. David Herzog hosted 3 fashion luminaries – Anna Wintour, Michael Kors and Natalia Vodianova  – at a Harvard Business School panel discussion titled “Health Matters: Weight and Wellness in the World of Fashion.” Over 700 people – students, parents, educators and members of the press -- attended this event, which focused on the creation of the CFDA’s Health Initiative and its role in promoting realistic body images.  One of the many highlights of the evening was Mr. Kors’ pledge to follow the CFDA’s recommendation to stop hiring models under 16 years old.  He was the first leading U.S. designer to commit to this reform in front of a public audience.

Dr. Herzog continued to collaborate with the CFDA and its President, Diane von Furstenberg, to address beauty and health.  He and Ms. Furstenberg coauthored an essay titled entitled “Healthier Standards,” which called upon everyone in the fashion industry – designers, casting directors, agents, fashion-magazine editors, and show producers – to join forces in support of the Health Initiative’s efforts.  Ms. von Furstenberg reinforced this message when she spoke at the Harris Center’s March 8, 2011 Public Forum about the topics of empowerment, resilience and health. 

Early in 2011, the CFDA Health Initiative launched its Ambassador Program, which allowed very well known and respected models to serve as mentors to their younger peers.  The Program’s inaugural event – a seminar for models ages 16-20 – took place on February 7^th in New York City at DNA Model Management.  At this event, renowned model Stella Tennant shared her insights and advice based on her personal experience. Alongside Stella and CFDA Executive Director Steven Kolb was Dr. David Herzog, who offered guidance and expertise. 

The CFDA Health Initiative works year-round to make a difference on runways and in the pages of magazines.  The Initiative shared with the fashion community a document created by Dr. Herzog elucidating the warning signs of eating disorders; and every season, Ms. von Furstenberg sends out a letter to the industry reminding everyone about the importance of not hiring models under 16 and highlighting the progress of the Models Ambassadors program.