Anorexia Nervosa (AN) affects 0.5-1% of college-aged women in the US and is characterized by extreme, self- induced starvation. Of the many medical co-morbidities associated with AN, severe bone loss is the most common and often persists despite weight recovery. This bone loss is significant because women with AN also have an increased fracture risk;a prospective study demonstrated that women with AN have a 7-fold increased risk of fractures as compared to age-matched controls. Therefore, a treatment to prevent the severe bone loss associated with AN is critical. There are currently no approved treatments for AN-associated bone loss. Therapies which prevent bone loss in normal-weight, hypogonadal women, such as estrogen, do not improve bone mineral density in women with AN. This is likely because the pathogenesis of bone loss due to nutritional deprivation differs from that of post-menopausal osteoporosis. In AN, there is a dramatic decrease in bone formation. Therefore an agent which stimulates bone formation would be an important potential treatment. Currently teriparatide (PTH) is the only anabolic agent approved by the FDA for the treatment of osteoporosis. As the effects of PTH on bone are known to be mediated through IGF-I and IGF-I levels are low in states of nutritional deficiency, we propose to investigate the effects of PTH on bone mass in women with AN. We will randomize thirty women with AN to treatment with either PTH or placebo and follow them prospectively for 6 months. We will measure bone mineral density, parameters of bone microarchitecture and bone strength at baseline and at 6 months. We will also measure markers of bone formation and resorption, IGF-I and sclerostin levels at baseline and monthly during the course of the study. Dr. Fazeli is an Instructor in Medicine at Harvard Medical School and Assistant in Medicine at Massachusetts General Hospital (MGH). She is on staff in the Neuroendocrine Unit at MGH and devotes the majority of her time to clinical research. Her expertise in studying hormonal abnormalities in AN positions her to lead the proposed project. She is well-supported by MGH and has full access to the Neuroendocrine Unit, Clinical Research Center and Harvard Catalyst CTSC resources. Her co-mentors, Drs. Anne Klibanski and Mary Bouxsein, are well-funded and invested in the direction of Dr. Fazeli's research. During the award period, Dr. Fazeli will obtain critical trainig in biostatistics and research design at the Harvard School of Public Health, where she is currently a Master of Public Health student, as well as important skills in novel investigational methods of determining bone strength. If awarded, this grant will support Dr. Fazeli's training in clinical research, with the ultimate goal of becoming an independent investigator with an expertise in combining neuroendocrinology and bone biology to better understand the pathophysiology of bone loss in disorders of under-nutrition.

Public Health Relevance

Anorexia nervosa, a disorder predominantly affecting women and characterized by extreme self-imposed weight loss, is associated with many medical complications including severe bone loss and an increased fracture risk. Therapies which prevent bone loss in post-menopausal women, such as estrogen, do not improve or stabilize bone mineral density in women with anorexia nervosa and there are currently no approved therapies for bone loss associated with anorexia nervosa. The goal of this study is to investigate the effects of teriparatide on bone density, bone microarchitecture and bone strength in this group of women and to better understand the pathophysiology of bone loss in anorexia nervosa.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK094820-02
Application #
8461456
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2012-07-01
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
2
Fiscal Year
2013
Total Cost
$186,587
Indirect Cost
$13,821
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Fazeli, Pouneh K; Klibanski, Anne (2014) Anorexia nervosa and bone metabolism. Bone 66:39-45
Fazeli, Pouneh K; Klibanski, Anne (2014) Bone metabolism in anorexia nervosa. Curr Osteoporos Rep 12:82-9
Fazeli, Pouneh K; Klibanski, Anne (2014) Determinants of GH resistance in malnutrition. J Endocrinol 220:R57-65
Fazeli, Pouneh K; Wang, Irene S; Miller, Karen K et al. (2014) Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa. J Clin Endocrinol Metab 99:1322-9
Fazeli, Pouneh K; Horowitz, Mark C; MacDougald, Ormond A et al. (2013) Marrow fat and bone--new perspectives. J Clin Endocrinol Metab 98:935-45
Fazeli, P K; Ackerman, K E; Pierce, L et al. (2013) Sclerostin and Pref-1 have differential effects on bone mineral density and strength parameters in adolescent athletes compared with non-athletes. Osteoporos Int 24:2433-40
Fazeli, Pouneh K; Mendes, Nara; Russell, Melissa et al. (2013) Bone density characteristics and major depressive disorder in adolescents. Psychosom Med 75:117-23