AS90 - WHI sex hormone and genetic risk factors for hip fracture
Investigator Names and Contact Information
Steve Cummings (scummings@sfcc-cpmc.net)
Introduction/Intent
Hip fractures are the most serious and life-threatening outcome of osteoporosis and one the most disabling consequences of aging in women. Hip fractures are also one of the primary outcomes (along with cardiovascular disease and breast cancer) of the Women's Health Initiative (WHI). Thus, studies of hip fracture have priority within WHI; this permits us to propose to use some of the limited amount of serum and DNA to study hormonal and genetic determinants of hip fracture in this unique cohort.
Specific Aims
This proposal takes advantage of data and specimens collected as part of the racially diverse Women's Health Initiative Observational Study (WHI-OS) to test several promising hypotheses about the hormonal and genetic precursors of hip fracture in women. We will use previously collected baseline data and stored specimens to conduct a prospective nested case-control study with the following objectives:
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To test the hypothesis that postmenopausal women with very low baseline concentrations of total and bioavailable estradiol have an increased risk of subsequent hip fracture.
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To test the hypothesis that women with high levels of sex hormone binding globulin (SHBG) have an increased risk of subsequent hip fracture.
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To test the hypothesis that women with low levels of insulin like growth factor 1 (IGF-1) have an increased risk of subsequent hip fracture.
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To examine whether polymorphisms of several promising candidate genes are associated with an increased risk of hip fracture. Specifically:
4a. To test the hypothesis that the presence of at least one APOE*4 allele in the APOE gene increases the risk of hip fracture.
4b. To test the hypothesis that women with at least one Sp1 "T" allele in the collagen type I alpha 1 gene have an increased risk of hip fracture.
4c. To test the hypothesis that women with at least one VDR FokI "f" allele have an increased risk of hip fracture.
4d. To test the hypothesis that women with the transforming growth factor-beta 1 (TGFB1) Leu10 allele have an increased risk of hip fracture.
Results/Findings
Some of the publications related to this ancillary study are: 479, 481, 563.
Ms479 - LeBoff MS, Narweker R, LaCroix A, Wu L, Jackson R, Lee J, Bauer DC, Cauley J, Kooperberg C, Lewis C, Thomas AM, Cummings S. Homocysteine levels and risk of hip fracture in postmenopausal women. J Clin Endocrinol Metab. 2009 Apr;94(4):1207-13. Epub 2009 Jan 27
Ms481 - Lee JS, Lacroix AZ, Wu L, Cauley JA, Jackson RD, Kooperberg C, Leboff MS, Robbins J, Lewis CE, Bauer DC, Cummings SR. Associations of serum sex hormone-binding globulin and sex hormone concentrations with hip fracture risk in postmenopausal women. J Clin Endocrinol Metab. 2008 May;93(5):1796-803. Epub 2008 Mar 11
Ms563 - Lacroix AZ, Lee JS, Wu L, Cauley JA, Shlipak MG, Ott SM, Robbins J, Curb JD, Leboff M, Bauer DC, Jackson RD, Kooperberg CL, Cummings SR. Cystatin-C, renal function, and incidence of hip fracture in postmenopausal women. J Am Geriatr Soc. 2008 Aug;56(8):1434-41. Epub 2008 Jul 24
For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Bibliography section of this website. To search for papers by study number, access the Simple Search, and enter the study number in the “Related Studies” field.
