This career development grant will prepare the candidate to pursue her goal of becoming an independently funded academician devoted to investigating pre- menopausal determinants of bone health and the preventive efforts that will maintain healthy bone remodeling in young women. The novel research proposed in this application benefits from mentoring by a strong, multidisciplinary team of senior investigators and uses lactation as a physiological model of bone loss during estrogen deficiency and subsequent recovery of bone density after weaning. By studying lactation, there is the opportunity to identify optimal conditions for bone mass remodeling and formation. The overall hypotheses of this proposal are that 1) the skeletal response to lactation is mediated through the elaboration of one or more anabolic hormones in conjunction with the return of adequate estradiol production; and 2) these events lead to both quantitative (BMD) and qualitative (bone geometry) changes in the skeleton that may confer a structural advantage for women later in life.
In aim 1, a prospective cohort study will be conducted in postpartum women to assess hormonal determinants of bone density losses and recovery and an assessment of bone structural parameters usingdual-energy x-ray absorptiometry (DXA).
Aim 1 will utilize a large, well-established clinical cohort enrolling pregnant women at UNC-CH (PIN Study).
In aim 2, the association of lactation duration and bone mineral density later in life will be examined using a cohort originally assembled in 1978 (NIEHS - Timing of Menopause Study). This cohort has the advantage of having lactation history well documented in the past. In addition to the mentored research, the candidate will undertake formal advanced training in epidemiology, biostatistics and outcomes research that will allow her to solidify her foundation in clinical research and epidemiological principles. The application benefits from the robust, research-intensive environment and resources provided by the Division of Endocrinology, the General Clinical Research Center, and the School of Public Health at UNC as well as assured access to the clinical populations of the two large, well-established cohorts. The combination of protected time for mentored research and didactics are ideal and will allow her to develop the experience, skills and preliminary data to develop as an independent clinician-scientist.
Bornstein, Sheila; Brown, Sue A; Le, Phuong T et al. (2014) FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice. Endocrinology 155:3516-26 |
Brown, Sue A; Guise, Theresa A (2009) Cancer treatment-related bone disease. Crit Rev Eukaryot Gene Expr 19:47-60 |
Brown, Sue A; Guise, Theresa A (2007) Cancer-associated bone disease. Curr Osteoporos Rep 5:120-7 |
Brown, Sue A; Clines, Gregory A; Guise, Theresa A (2007) Local effects of malignancy on bone. Curr Opin Endocrinol Diabetes Obes 14:436-41 |