Mentoring is a critical component of the career of a patient-oriented-researcher, and essential for a successful career in patient-oriented research. The PI has a successful record of mentoring a number of fellows and trainees in the complex techniques of metabolic and bone health assessment in a large population of young athletes, particularly those with associated amenorrhea. The scientific aims of the application are based on the candidate's successfully funded R01, investigating: 1) whether low fat mass and altered levels of adipokines and fat regulated hormones determine alterations in LH pulsatility patterns in amenorrheic athletes (AA), that differentiate them from eumenorrheic athletes (EA) and non-athletes, and 2) treatment strategies to optimize bone accrual and structure in AA over a 12-month period. Several new directions are proposed in the current application, and it is hypothesized (1) that bone strength [assessed using finite element analysis (FEA)] is lower in AA compared with EA and non-athletes 14-21 y at baseline and decreases prospectively over a one- year duration in AA, whereas bone strength increases in EA over the same duration, (2) that greater visceral adipose tissue (VAT) and marrow fat are associated with lower bone density, impaired microarchitecture and lower bone strength, and (3) that in young AA, compared to oral estradiol or no treatment, transdermal estradiol replacement will increase bone strength to approximate that in controls, associated with decreases in marrow fat and no changes in regional body composition. Detailed assessment of regional body composition and bone strength will be performed. Adipocytokines will be measured and related to changes in bone density, structure and strength in longitudinal studies, controlling for traditional risk factrs. The mentoring goals of this proposal include the development of a comprehensive multidisciplinary mentoring and training program, in which trainees will be selected, based on their interest in patient oriented research, work habits and ethical standards. Projects will be selected that are unique and achievable, and significant time will spent by the PI guiding trainees in protocol design, regulatory requirements, didactic coursework, and funding opportunities. Trainees will be exposed to detailed techniques of body composition and bone strength assessment. This K-24 proposal is critical to support the PI's significant time spent in mentoring. The training environment at the PI's institution is outstanding in terms of didactic resources and availability of techniques to assess complex metabolic endpoints. Importantly, the PI enjoys significant support from her Unit and Division Chiefs, who have enthusiastically endorsed her successful mentoring efforts to date and the plans in the current proposal. Taken together, the proposed K-24 application offers a strong mentoring program in patient oriented research that is based on the teaching of important principles of endocrinology and metabolism. The studies are to be carried out in a population at significant risk for impaired bone accrual, with which the PI has significant expertise. The Midcareer Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure the candidate's continued success as a mentor and clinical researcher.

Public Health Relevance

This award will provide the PI with the protected time necessary to spend a significant amount of her time mentoring fellows and trainees in patient-oriented research. Mentees will work on the various specific aims of the proposal that relate to assessment of bone metabolism and its determinants in non-menstruating athletes compared with menstruating athletes and non-athletes, and development of therapeutic strategies to optimize bone health in non-menstruating athletes.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Midcareer Investigator Award in Patient-Oriented Research (K24)
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Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Winer, Karen
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Massachusetts General Hospital
United States
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Misra, Madhusmita; Klibanski, Anne (2014) Anorexia nervosa and bone. J Endocrinol 221:R163-76
Singhal, Vibha; Lawson, Elizabeth A; Ackerman, Kathryn E et al. (2014) Irisin levels are lower in young amenorrheic athletes compared with eumenorrheic athletes and non-athletes and are associated with bone density and strength estimates. PLoS One 9:e100218
Singhal, Vibha; Misra, Madhusmita; Klibanski, Anne (2014) Endocrinology of anorexia nervosa in young people: recent insights. Curr Opin Endocrinol Diabetes Obes 21:64-70
Misra, Madhusmita; Klibanski, Anne (2014) Endocrine consequences of anorexia nervosa. Lancet Diabetes Endocrinol 2:581-92
Faje, Alexander T; Fazeli, Pouneh K; Miller, Karen K et al. (2014) Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord 47:458-66
Lawson, Elizabeth A; Ackerman, Kathryn E; Slattery, Meghan et al. (2014) Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletes. J Clin Endocrinol Metab 99:E881-5
Slattery, Meghan J; Bredella, Miriam A; Thakur, Hena et al. (2014) Insulin resistance and impaired mitochondrial function in obese adolescent girls. Metab Syndr Relat Disord 12:56-61
Misra, Madhusmita; Katzman, Debra K; Clarke, Hannah et al. (2013) Hip structural analysis in adolescent boys with anorexia nervosa and controls. J Clin Endocrinol Metab 98:2952-8
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

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