Tuesday, August 4, 2009

Pediatric Endocrinology: Madhusmita Misra, MD, MPH

Madhusmita Misra, MD, MPH

Madhusmita Misra, MD, MPH

Primarily a clinical researcher, my investigations have focused on the neuroendocrine regulation of the hypothalamo-pituitary-gonadal (H-P-G) axis, particularly as it relates to bone metabolism. My most recent work indicates that adipokines and appetite regulating peptides are possible mediators of the association between low fat mass and suppression of the H-P-G axis in teenage amenorrheic athletes, and may contribute to low bone density in these athletes. My data indicate that adolescent athletes who are amenorrheic have significantly lower bone density than eumenorrheic athletes despite similar levels of physical activity, and predictors of low bone density are BMI, lean body mass, IGF-1 levels and the state of amenorrhea. These data were collected with the help of a pilot grant funded by the Harvard Clinical Nutrition Research Center, and my R0-1 grant expands on this work to define effects of hormones secreted or regulated by fat mass on the functioning of the H-P-G axis, and to develop therapeutic strategies to optimize bone health in the critical teenage years, when disruption of bone mass accrual may lead to permanent deficits in peak bone mass, an important determinant of long-term bone health.
My other research has focused on clarifying neuroendocrine, body composition and bone alterations in conditions spanning the nutritional spectrum from nutritional deprivation (anorexia nervosa) to excess (obesity). My research has contributed greatly to the understanding of low bone mass accrual rates and low bone density in teenagers with anorexia nervosa, and I am working with Anne Klibanski on therapeutic strategies to optimize bone mass accrual rates in this population. Low bone mass in seen in  more than 50% of adolescents with anorexia nervosa, and causes of low bone mass include decreased lean mass, hypogonadism, a state of acquired growth hormone resistance with low IGF-1 levels, high levels of cortisol, and alterations in adipokines such as adiponectin, and appetite regulating peptides such as ghrelin, leptin and peptide YY. Our ongoing therapeutic trials in this population include a randomized double blind controlled trial examining effects of physiological estrogen replacement on bone mass in anorexia nervosa, and a pilot study examining the effect of IGF-1 replacement on bone density and bone microarchitecture.

I have also worked on identifying neuroendocrine predictors of site specific fat depots in obese adolescents, an important determinant of the metabolic syndrome, determining associations between site specific fat depots and markers of cardiovascular risk, and understanding the implication of specific macronutrients on hunger and food intake.


FIGURE 1: Bone density measures in athletes with amenorrhea (AA) (black), eumenorrheic athletes (EA) (gray) and controls (white) (mean ± SEM). Bone density Z-scores for the lumbar spine and whole body BMC/height were lower in AA than in EA and controls. Hip bone density was lower in AA than in EA. a p<0.05 compared with controls; b p < 0.05 compared with eumenorrheic athletes; c p<0.1 compared with controls

Selected Published Reviews:

  • Collett-Solberg P, Misra M on behalf of the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. The role of rhIGF-I in treating children with short stature. J Clin Endocrinol Metab. 2008;93(1):10-8.
  • Stanley T, Misra M. Polycystic Ovarian Syndrome in Obese Adolescents. Curr Opin Endocrinol Diabetes Obes. 2008;15(1):30-6.
  • Misra M. Bone Density in the Adolescent Athlete. Rev Endocr Metab Disord 2008;9(2):139-44.
  • Misra M. Long-term Skeletal Effects of Eating Disorders with Onset in Adolescence. Annals NY Acad Sci 2008;1135(1):212-8
  • Misra M, Pacaud D, Petryk A, Collett-Solberg P, Kappy M, on behalf of the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society. Vitamin D Deficiency in Children and its Management: Review of Current Knowledge and Recommendations. Pediatrics 2008; 122: 398-417.
  • Levitsky LL, Misra M, Boepple PA, Hoppin A. Adolescent Obesity and Bariatric Surgery. Curr Opin Endocrinol Diabetes Obes. 2009;16(1):37-44.

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