Effect of Adrenal and Gonadal Hormones on Bone Marrow and Appendicular BMD

Summary

Principal Investigator: Catherine M Gordon
Abstract: DESCRIPTION (provided by applicant): Adolescent girls with anorexia nervosa (AN) exhibit hormonal abnormalities that predispose to alterations in bone turnover, accrual, and modeling that can ultimately lead to irreversible skeletal deficits. The current investigators have a longtime interest in how hormonal alterations in this disease lead to changes in bone marrow composition and skeletal losses. The proposed project builds on a recent double-blind, placebo- controlled trial of dehydroepiandrosterone (DHEA) and estrogen replacement therapy (ERT) in adolescents with AN. The current investigators have shown that this combined anabolic + antiresorptive regimen mitigated bone loss of the axial skeleton as evidenced by dual-energy x-ray absorptiometry (DXA) measures of the spine and whole body. There is interest in whether this therapeutic regimen also affects the appendicular skeleton, a question of high clinical importance as young adolescents fracture extremities much more commonly than the axial skeleton. Preliminary data from the current group have also shown that adolescents with AN exhibit shifts from red to yellow (fatty) marrow with progression of disease and develop increased marrow fat. These young women, who paradoxically have depleted subcutaneous fat, have increased fat within bone marrow, with potential adverse long-term consequences for bone formation, bone accretion during adolescence, and ultimately, lifetime skeletal health. Further research is needed to determine whether this conversion of red to yellow marrow in adolescents mirrors findings in adults indicating an associated decreased bone density and increased fracture risk. This proposal seeks to investigate this question through a novel clinical trial of combined therapy with DHEA+ERT on bone mineral density (BMD) and bone marrow composition, examining the role of hormonal factors in the conversion of red to yellow marrow and relation of findings to appendicular BMD. Over the one-year trial, state-of-the-art imaging techniques will be employed, including peripheral quantitative computed tomography (pQCT), visual assessments of magnetic resonance imaging (MRI) data, MR relaxometry and magnetic resonance spectroscopy to measure bone mineral density and evaluate bone marrow composition, respectively. We also seek to understand hormonal mediators of the changes observed in both bone density and bone marrow composition, including adrenal and gonadal steroids, insulin-like growth factors, growth hormone, and ghrelin, adiponectin, and leptin. The proposed project will test hypotheses raised by the pilot imaging data, in particular whether hormonal abnormalities in girls with AN influence mesenchymal stem cells to differentiate preferentially into adipocytes over osteoblasts. Enhancing understanding of the mechanisms underlying skeletal losses in this young patient population has the potential to fill critical knowledge gaps that will improve the care of adolescents with AN. Knowledge gained from this study may also have application to other diseases across the age spectrum that are associated with bone loss and involve alterations in bone marrow composition.
Funding Period: 2011-08-01 - 2015-05-31
more information: NIH RePORT

Top Publications

  1. pmc Vertebral fracture assessment in adolescents and young women with anorexia nervosa: a case series
    Amy D DiVasta
    Division of Adolescent Medicine, Boston Children s Hospital and Harvard Medical School, Boston, MA, USA Division of Gynecology, Boston Children s Hospital and Harvard Medical School, Boston, MA, USA Electronic address
    J Clin Densitom 17:207-11. 2014
  2. pmc Percentage body fat by dual-energy X-ray absorptiometry is associated with menstrual recovery in adolescents with anorexia nervosa
    Sarah Pitts
    Division of Adolescent Young Adult Medicine and Division of Endocrinology, Boston Children s Hospital, Boston, Massachusetts Electronic address
    J Adolesc Health 54:739-41. 2014

Detail Information

Publications2

  1. pmc Vertebral fracture assessment in adolescents and young women with anorexia nervosa: a case series
    Amy D DiVasta
    Division of Adolescent Medicine, Boston Children s Hospital and Harvard Medical School, Boston, MA, USA Division of Gynecology, Boston Children s Hospital and Harvard Medical School, Boston, MA, USA Electronic address
    J Clin Densitom 17:207-11. 2014
    ..In conclusion, ill young women with AN were at low risk for asymptomatic VF in our cohort. VFs were not predicted by duration of illness, severity of malnutrition, or traditional measures of areal BMD at the lumbar spine. ..
  2. pmc Percentage body fat by dual-energy X-ray absorptiometry is associated with menstrual recovery in adolescents with anorexia nervosa
    Sarah Pitts
    Division of Adolescent Young Adult Medicine and Division of Endocrinology, Boston Children s Hospital, Boston, Massachusetts Electronic address
    J Adolesc Health 54:739-41. 2014
    ..To evaluate mediators of resumption of menses (ROM) in adolescents with anorexia nervosa (AN)...

Research Grants30

  1. Biomechanical Stimulation &Skeletal Health in Adolescents with Anorexia Nervosa
    Amy D DiVasta; Fiscal Year: 2013
    ..Given the health care burden associated with the current epidemic of osteoporosis in the elderly, establishing effective measures to prevent bone loss during childhood and adolescence is paramount. ..
  2. Skeletal health in obesity and after bariatric surgery
    ELAINE WEI YIN YU; Fiscal Year: 2013
    ....
  3. Effects of Anorexia Nervosa on Peak Bone Mass
    Anne Klibanski; Fiscal Year: 2013
    ..This proposal will examine possible therapeutic strategies to increase bone density and optimize peak bone mass in adolescents with anorexia nervosa. ..
  4. Effects of Gastric Bypass Surgery on Calcium Metabolism and the Skeleton
    ANNE LOUISE SCHAFER; Fiscal Year: 2013
    ..Dr. Schafer is committed to improving the health care of veterans through clinical research, and the CDA-2 is critical for the attainment of her career objectives. ..
  5. Pharmacology of Risperidone Effects on Bone Remodeling and Energy Metabolism
    Karen L Houseknecht; Fiscal Year: 2013
    ....
  6. Obesity and bone development in young girls
    Scott B Going; Fiscal Year: 2013
    ..We expect to clarify the currently controversial relationships and provide critical information needed to develop efficacious interventions for optimal bone development. ..
  7. Genome Wide Association Study of Bone Mineral Accretion During Childhood
    Babette S Zemel; Fiscal Year: 2013
    ....
  8. IGF-1, bone turnover and response to teriparatide in premenopausal women with IOP
    Adi Cohen; Fiscal Year: 2013
    ....
  9. NEW MODALITIES FOR TREATMENT OF PAIN AND DRUG ABUSE
    Victor J Hruby; Fiscal Year: 2013
    ....
  10. Bone Metabolism and Body Composition in Young Athletes
    Madhusmita Misra; Fiscal Year: 2013
    ....
  11. Serotonin Reuptake Inhibitors and Bone Mineralization in Adolescents
    Chadi A Calarge; Fiscal Year: 2013
    ..This is consistent with the mission of the National Institute of Mental Health. ..