The main focus of my research is pediatric osteoporosis. I am particularly interested in the effect of chronic illness on bone acquisition in pediatrics. Bone metabolism is a tightly regulated process involving the coupling between bone formation and bone resorption. An imbalance between bone formation and resorption can result in low bone density and subsequent fractures. A variety of hormonal and paracrine-autocrine factors regulate this process. Childhood and adolescence are critical periods for skeletal growth. Peak bone mass is achieved in early adult life. Patients who do not reach optimal peak bone mass are at risk for osteoporosis in adult life and frequent fractures. Determining the factors that may affect of bone accrual is particularly relevant to our understanding of low bone mass. Abnormalities of bone metabolism in childhood and adolescence may adversely effect the achievement of optimal peak bone mass.
At the moment, I am involved with the following clinical and basic science projects:
Study of the mechanisms by which chronic anemia affects bone remodeling. Using thalassemia as a disease model of chronic anemia and mouse models of the disease, the project examines the role of hematopoietic stem cells, various hematopoietic progenitors and erythropoietin (EPO) on the function of osteoblasts and bone formation.
Study of the mechanisms by which iron overload leads to bone loss and osteoporosis. Transfusional iron overload is a frequent complication in diseases that require regular transfusions. Using a mouse model of iron overload, we have shown that bone loss in this case is caused by increased oxidative stress and increased resorption. The project wants to identify the inflammatory response that is induced by iron and how if leads to osteoporosis.
Study of vitamin D supplementation in thalassemia. Various doses of vitamin D are administered. Changes in serum vitamin D concentrations and in urine calcium excretion are determined. Our preliminary results suggest that raising 25 hydroxyvitamin D concentrations above 30ng/ml results in hypercalciuria in a significant number of thalassemia patients. The study is supported by a grant from Cooley's anemia foundation.
In addition, I collaborate with other faculty in the development and execution of additional projects. These include
- The development of a protocol that determines outcome of bariatric surgery in obese adolescents with metabolic syndrome;
- Behavioral interventions to increase compliance and improve glycemic control among children and adolescents with type 1 diabetes;
- Dance in the school system as an intervention to improve metabolic syndrome among obese elementary school children;
- Development of a comprehensive care center for congenital adrenal hyperplasia (CAH).
ADDITIONAL RESEARCH AREAS
- Bone mass accrual in children with chronic illness
- Management of frequent fractures in children
- Studies of growth in children with hyperandrogenemia, such as Congenital Adrenal Hyperplasia (CAH). Our group has tested the effect of growth hormone therapy and suppression of puberty on growth in children with CAH, advanced bone age and poot height prediction. Our results indicate that this therapy improves final height compared to children who did not receive the therapy.