Dr. Polgreen is an Assistant Professor in the Department of Pediatrics, Division of Endocrinology, at the University of Minnesota (UM). Since starting in this position in August 2008, she has devoted 75% of her time to patient-oriented research in the field of pediatric bone disease and will continue this during this career development award period. Dr. Polgreen's long-term career goal is to become an independent academic physician researcher, with internationally recognized expertise in the area of pediatric bone and endocrine disease in children with mucopolysaccharidoses (MPS). Specific goals to be accomplished during this award period include: 1) improve knowledge in basic bone biology, bone assessment methodology, and clinical trials management;2) completion of a clinical trial and a longitudinal study of bone and endocrine disease in MPS. Although children with MPS I, II, and VI who are treated with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT) are living into adulthood with good cognitive outcomes, their quality of life is significantly impacted by their persistent skeletal abnormalities, contractures, and severe short stature. Under the guidance of Dr. Chester Whitley, the project sponsor, Dr. Polgreen will pursue the following specific aims: 1) To determine the impact of 24 months of recombinant human growth hormone therapy versus no therapy on bone development and growth in 34 children with MPS I, II, and VI and short stature with a Phase 2/3 randomized controlled trial design;2) To develop a registry of bone development (bone density, geometry, and estimated strength) and endocrine function in children with MPS I, II, and VI using a 3-year prospective study design with yearly evaluations with peripheral quantitative computer tomography (pQCT), dual energy x- ray absorptiometry (DXA), biomarkers of bone metabolism, and laboratory tests of endocrine function. These research projects and career development will be conducted under the guidance of the following mentorship team: Dr. Chester Whitley, Dr. Antoinette Moran, Dr. Moira Petit, and Dr. William Thomas. This team provides expertise in the areas of the study of rare disease (Whitley), clinical trials management (Moran), theories and methods of bone assessment in pediatrics (Petit), and biostatistics (Thomas). The extensive experience with MPS and pediatric bone disease, and the large cohort of children with MPS followed at UM, make this the ideal environment for Dr. Polgreen's research and career development into an independent investigator of pediatric metabolic bone disease.
Osteoporosis is becoming increasingly identified in children. Since peak bone mass is achieved prior to adulthood (with subsequent progressive loss during adult life), it is critical to address bone health in a pediatric population. This project will explore methodologies for assessment of pediatric bone disease and the impact of human growth hormone on bone health in a group of children with the metabolic disease Mucopolysaccharidosis. The knowledge gained from this study will support the use of these assessments and clinical trial skills in other pediatric populations with osteoporosis.
|Polgreen, Lynda E; Vehe, Richard K; Rudser, Kyle et al. (2016) Elevated TNF-? is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. Mol Genet Metab 117:427-30|
|Chahla, Saydi E; Frohnert, Brigitte I; Thomas, William et al. (2015) Higher daily physical activity is associated with higher osteocalcin levels in adolescents. Prev Med Rep 2:568-571|
|McCauley, Laura A; Thomas, William; Laguna, Theresa A et al. (2014) Vitamin D deficiency is associated with pulmonary exacerbations in children with cystic fibrosis. Ann Am Thorac Soc 11:198-204|
|Forlenza, Gregory P; Polgreen, Lynda E; Miller, Bradley S et al. (2014) Growth hormone treatment of patients with Fanconi anemia after hematopoietic cell transplantation. Pediatr Blood Cancer 61:1142-3|
|Polgreen, Lynda E; Thomas, William; Orchard, Paul J et al. (2014) Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Mol Genet Metab 111:101-6|
|Polgreen, Lynda E; Thomas, William; Fung, Ellen et al. (2014) Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. J Clin Densitom 17:200-6|
|Taylor, Natalie E; Dengel, Donald R; Lund, Troy C et al. (2014) Isokinetic muscle strength differences in patients with mucopolysaccharidosis I, II, and VI. J Pediatr Rehabil Med 7:353-60|
|Stevenson, David A; Rudser, Kyle; Kunin-Batson, Alicia et al. (2014) Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. J Pediatr Rehabil Med 7:159-65|
|Gustafson, Kimara L; Eckerle, Judith K; Howard, Cynthia R et al. (2013) Prevalence of vitamin D deficiency in international adoptees within the first 6 months after adoption. Clin Pediatr (Phila) 52:1149-53|
|Karras, Nicole A; Polgreen, Lynda E; Ogilvie, Christian et al. (2013) Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol 31:e200-2|
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