Osteoporosis is a disfiguring disease of older women that causes significant loss of independence and substantial morbidity and mortality. Excessive thyroid hormone, either endogenous or exogenous, may be associated with reduced bone mass and an increased risk of fracture. However, the magnitude and clinical significance of these associations are unknown and studies examining fracture risk using an objective measure of thyroid function have not been done. Thyroid dysfunction may alter the risk of fractures through mechanisms other than reduced bone mass, such as altered neuromuscular function or abnormal bone architecture. We propose a comprehensive study of the association of thyroid function, as assessed by serum TSH, and fractures, bone mass, and bone loss. We will use data already collected from the NIH-sponsored Study of Osteoporotic Fractures (SOF), the largest and most comprehensive prospective study of risk factors for osteoporotic fractures yet performed. In 1986, 9, 704 women were recruited for SOF from population-based listings in four US cities. Extensive data on multiple variables were collected at baseline, including historical information on hyperthyroidism and thyroid hormone use, and a serum sample was archived at -190 degree C. We will use an efficient nested case-cohort design: 450 women who have suffered fractures (150 vertebral fractures) since the initial exam will be compared to a random sample of 450 women from the cohort. We will measure ultra- sensitive third generation serum TSH levels on sera that was collected from subjects at baseline. We plan to test the hypotheses that low TSH levels, indicating abnormally high thyroid hormone levels, are associated with osteoporotic fractures, reduced bone mass, increased bone loss, and altered neuromuscular function. We will also examine the relationship between TSH and a newly developed technique which may assess bone quality, quantitative ultrasound (QUS). The proposed study will be the first large prospective study to examine the effects of thyroid function on bone mass, bone loss, and fractures in the same cohort. The cost of the proposed study is relatively small since it uses data and samples that have already been collected. The results of this study will help define the risks associated with excessive thyroid hormone, and contribute to our understanding of the mechanisms involved.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG000629-02
Application #
2048446
Study Section
Biological and Clinical Aging Review Committee (BCA)
Project Start
1994-05-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bauer, Douglas C; Rodondi, Nicolas; Stone, Katie L et al. (2007) Thyroid hormone use, hyperthyroidism and mortality in older women. Am J Med 120:343-9
Bauer, D C; Ettinger, B; Nevitt, M C et al. (2001) Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med 134:561-8
Stone, K; Bauer, D C; Black, D M et al. (1998) Hormonal predictors of bone loss in elderly women: a prospective study. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 13:1167-74
Bauer, D C; Ettinger, B; Browner, W S (1998) Thyroid functions and serum lipids in older women: a population-based study. Am J Med 104:546-51
Bauer, D C; Nevitt, M C; Ettinger, B et al. (1997) Low thyrotropin levels are not associated with bone loss in older women: a prospective study. J Clin Endocrinol Metab 82:2931-6
Bauer, D C; Brown, A N (1996) Sensitive thyrotropin and free thyroxine testing in outpatients. Are both necessary? Arch Intern Med 156:2333-7