Predictors of Bone Health in Adolescents and Young Adults
- Catherine Gordon, MD, Head, Adolescent Bone & Body Composition Laboratory
- Devora Stein, FNP, Nurse Practitioner
- Milena Jovanovic, PhD, Staff Scientist
The major aim of our lab is to understand adolescence factors that impact bone density and skeletal strength during the adult years. We are examining how modifiable factors such as nutrition and physical activity influence the development of peak bone mass, as well as variables such as skin pigmentation and an individual’s genotype that are determined at birth. In both healthy youth and those with chronic disease, we are exploring the interrelationship between body composition, circulating hormones, and bone marrow adiposity and its effect on bone turnover and skeletal accrual.
A focus of our research is how physical and emotional health are compromised in adolescents and young women with premature ovarian insufficiency (POI). POI presents along a broad clinical spectrum. We are interested in both the presentation and causes of POI, including those seen in childhood cancer survivors, and ovarian dysfunction resulting from to autoimmune, metabolic, genetic/syndromic, and idiopathic (unknown) causes. We are conducting a natural history study to characterize numerous health outcomes and are launching a clinical trial to identify the optimal estrogen replacement regimen for adolescents and young women with this diagnosis. We are also employing novel tools to provide state-of-the-art assessments of bone density, body composition, and skeletal strength.
We are also interested in the skeletal phenotype associated with rare genetic diagnoses, some of which resemble or meet criteria for a skeletal dysplasia. Examples include progeria (Hutchinson-Gilford progeria syndrome), Ollier disease, and Maffucci syndrome.
High-resolution peripheral computed tomography
High-resolution peripheral computed tomography (HRpQCT) is a bone assessment modality that affords measurements of the appendicular (peripheral) skeleton, as well as evaluation of bone microarchitecture and skeletal strength. As a non-invasive tool, it is ideal for obtaining measurements in the pediatric and adolescent population. Our lab is one of a relatively small number of centers that has an HRpQCT scanner. In a number of chronic disease models, we are examining the relation between failure load and other HRpQCT–derived outcomes and fracture risk.
Figure 1. HRpQCT image
Click image to view.
HRpQCT assessments (after trabecular segmentation) of the tibia in a 28 year-old woman with cystic fibrosis (a) and 28-year-old healthy female control participant (b).
Evaluations of bone marrow composition
Our team is using magnetic resonance (MR) imaging and spectroscopy to evaluate bone marrow fat, an outcome that is directly influenced by hormonal signals. We have studied bone marrow composition in adolescents with anorexia nervosa, and are employing this technique to examine the correlation between marrow fat and bone accrual in adolescents with inflammatory bowel disease and other pediatric clinical models. T1 maps and MR spectroscopy evaluations afford non-invasive means to evaluate bone marrow composition in children and adolescents.
Figure 2. Magnetic resonance (MR) spectroscopy assessment of bone marrow composition
Click image to view.
MR spectroscopy images from the left knee (distal femur) of an adolescent girl with anorexia nervosa
Additional Funding
- U01HD107957-01 (Sobreira/Gordon), Delineation of the natural history of Ollier disease and Maffucci syndrome and investigation of their genetic bases
Publications
- Wasserman HM, Kalkwarf HJ, Altaye M, Yolton K, Kanj RV, Gordon CM. Characterizing the adolescent premature ovarian insufficiency phenotype: a case control study. J Pediatr Adolesc Gynecol 2022 36:122–127.
- Kanj RV, Ofei-Tenkorang NA, Altaye M, Gordon CM. Evaluation and management of primary ovarian insufficiency in adolescents and young adults. J Pediatr Adolesc Gynecol 2018 31:13–18.
- Gordon CM, Cleveland RH, Baltrusaitis K, Massaro J, D'Agostino RB Sr, Liang MG, Snyder B, Walters M, Li X, Braddock DT, Kleinman ME, Kieran MW, Gordon LB. Extraskeletal calcifications in Hutchinson-Gilford progeria syndrome. Bone 2019 125:103–111.
- Gordon RJ, Pappa HM, Vajapeyam S, Mulkern R, Ecklund K, Snapper SB, Gordon CM. Bone marrow adiposity in pediatric Crohn's disease. Bone 2022 162:116453.
- Pitts S, DiVasta AD, Gordon CM. Evaluation and management of amenorrhea. JAMA 2021 326:1962–1963.
Collaborators
- Amy DiVasta, MD, MMSc, Boston Children's Hospital, Boston, MA
- Veronica Gomez-Lobo, MD, Pediatric and Adolescent Gynecology, NICHD, Bethesda, MD
- Heidi Kalkwarf, PhD, RD, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
- Jacqueline Maher, MD, FACOG, Pediatric and Adolescent Gynecology, NICHD, Bethesda, MD
- Nara Sobreira, MD, PhD, Johns Hopkins School of Medicine, Baltimore, MD
Contact
For more information, email catherine.gordon@nih.gov.
