Fellowship for Lindsey Mattick: Follicle Stimulating Hormone and Bone Loss in Postmenopausal Women

PROJECT SUMMARY Decreased bone density and quality is a major source of morbidity and mortality in the U.S. and globally. With an aging population, the disease burden of osteoporosis is expected to drastically increase. Conflicting evidence of an estrogen independent association between follicle stimulating hormone (FSH) levels and bone loss has been observed from both in vivo studies and observational research. While there is biological rationale and cross-sectional evidence for the proposed association, no longitudinal studies have explored the relationship between FSH and bone loss in postmenopausal women. Additionally, there has never been a study pertaining to the relationship between FSH and fracture risk in any age group. Understanding this association among postmenopausal women is critical because current treatment and prevention options for osteoporosis are limited. Therefore, identifying biologic processes related to the progression of bone loss in postmenopausal women will open the door to further epidemiological and pharmacological research into this area. The long term goal of the proposed research is to better understand the estrogen-independent role of FSH in the process of bone degradation which accompanies menopause. The purpose of this proposal is to investigate the association between serum FSH and multiple outcomes associated with the process of bone aging, including changes in bone mineral density (BMD) and incident low bone mass, osteoporosis, and fracture. We hypothesize that there will be an inverse association between serum FSH levels and BMD in postmenopausal women as well as increased risk of incident low bone mass, osteoporosis and fracture in those with higher FSH levels. We will accomplish this using data from a sample of 685 postmenopausal women within the Buffalo Osteoporosis and Periodontal Disease Study (a prospective ancillary study within the Women's Health Initiative). This cohort of postmenopausal women is uniquely suited to the evaluation of these associations as it includes measures of BMD, low bone mass, osteoporosis, FSH, taken at baseline and a five year follow up visit, in addition to diagnoses of fracture over 22 years of follow up. The analyses will be conducted within the context of the complex pituitary negative feedback mechanism between FSH and other endogenous hormones, this dataset contains measures of estradiol, sex hormone binding globulin, and testosterone. The proposed project will greatly expand my epidemiologic training by incorporating both cross- sectional and longitudinal methods. Also included is robust training and understanding of the complex endocrine feedback mechanism between endogenous hormones and osteoclastic bone formation and resorption. My proposed training plan will be two-pronged to assist me in both my epidemiologic and biologic training as a researcher, while the proposed research will fill a gap in literature on FSH and BMD in postmenopausal women.