Adolescent Bone Density & Body Composition Section

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

Investigators

Linked publications, trials & patents

Abstract

Hormone Replacement Therapy in Adolescents with Premature Ovarian Insufficiency Premature Ovarian Insufficiency is a rare condition, characterized by absent or irregular menstrual cycles, which represents a significant cause of infertility in women with estrogen deficiency before the age of 40. Relatively little is known about the presentation of POI in young adolescents. The etiology for POI includes chromosomal (Turner Syndrome, Fragile-X Syndrome), iatrogenic (chemotherapy, radiation, or surgery), autoimmune, or idiopathic (unknown) causes. POI has a complicated clinical presentation with various health complications such as vasomotor or menopausal symptoms, decreased bone mineral density (BMD) leading to osteoporosis and increased risk of fractures, infertility, as well as increased risk for cardiovascular, autoimmune diseases and mood disorders. Hormone-replacement therapy (HRT), which is the physiologic replacement of premenopausal levels of estrogen and progesterone, is the most common treatment option for women with POI, that has shown a positive effect on bone and cardiovascular health. However, there is a substantial lack of controlled trials in adolescents and young women with POI. Therefore, we are conducting a clinical trial in adolescents with POI to identify the most effective dosage, regimen, and preparation of HRT for these patients and are investigating the effects of this therapy on multiple health outcomes. A primary aim of the study is to understand the bone phenotype through use of high-resolution peripheral quantitative computed tomography (HRpQCT), which represents a cutting-edge imaging research tool that provides valuable data on the bone microarchitecture and structure and will also allow us to follow skeletal changes in response to HRT. Assessment of Bone Phenotype in Individuals with Androgen Insensitivity Syndrome Androgen Insensitivity Syndrome (AIS) is a rare genetic disorder, that represents the most common cause of sexual differentiation disorders in 46,XY individuals. It is caused by mutation on X-linked androgen receptor gene which encodes the androgen receptor, leading to differing levels of hormonal resistance and its manifestation in three forms as a complete AIS (CAIS), partial (PAIS) or mild (MAIS). Gonadectomy is the standard way of treating individuals with AIS to prevent cancer development, a procedure that was previously performed before puberty. However, current clinical practice includes delaying the surgical removal of gonads until late puberty to optimize peak bone mass. Androgens play an important role in bone development and our lab is collaborating with Dr. Veronica Gomez-Lobo and her team to investigate the bone phenotype in individuals with AIS and provide further insights into the role of androgens on bone. We are also using DXA and HRpQCT as imaging tools to evaluate bone density and strength and provide information on fracture risk. Skeletal Phenotype in Ollier disease and Maffucci syndrome Enchondromas are benign tumors of cartilage that usually grow in the metaphysis of bone. Ollier disease (OD) or Maffucci syndrome (MS) are rare disorders with skeletal abnormalities which are primarily characterized by multiple enchondromas. In OD, enchondromas often develop during the first decade of life but also can appear as an individual ages. Enchondromas in MS develop in association with vascular anomalies which can be detected in the first year of age. Both disorders can cause swelling of the extremities, joints deformities and decreased joint mobility, scoliosis, limb shortening, leg-length discrepancy, gait disturbances, bone fractures and facial asymmetry. Currently, the only treatment of patients with OD and MS involves surgical removal of oversized enchondromas. In collaboration with Dr. Nara Sobreira from John Hopkins University we are conducting a natural history, observational study of children and adults with OD and MS and examining their skeletal phenotype with DXA and stand radiographic assessments, as well as investigating the genetic background and molecular mechanisms underlying tumor development. Association of Skin Tone and Muscle Grip with Bone Mineral Density Low BMD in women is a risk factor associated with both osteoporosis and fracture risk. Women with darker skin tone have been reported to have higher BMD compared to women with a lighter complexion. However, the correlation between skin tone and BMD is poorly understood, especially in adolescents. This correlation is further obscured with the reporting of skin tone in a binary fashion as Black and non-Black, as is found in standard pediatric reference DXA databases. Therefore, we are obtaining skin tone measurements using spectrophotometry in pediatric and adolescent populations with gynecologic syndromes who present to the NIH Clinical Center. In addition, we are studying the "muscle bone unit," examining the relationship between bone density and muscle strength and mass, by evaluating muscle grip strength using a hand-held dynamometer and body composition by DXA, respectively, the latter which affords a measurement of lean body mass.