The proposed competitive renewal of our grant, Bone Strength Through the Menopausal Transition: Trabecular Bone Score, builds upon the Study of Women's Health Across the Nation (SWAN) Bone Project. SWAN is a multi-site, multi-racial/ethnic longitudinal study designed to characterize the physiological and psychosocial changes that occur during the menopausal transition (MT). One of the key physiological consequences of ovarian aging that was specifically targeted in SWAN was loss in skeletal mass. In SWAN, areal bone mineral density (aBMD) loss begins 2 years before the final menstrual period (FMP) at both the lumbar spine (LS) and femoral neck (FN) sites. Cumulative rates of bone loss are greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Bone loss 2-5 years after the FMP slows. Germane to this application, transmenopausal BMD loss is greater at the LS than at FN, concordant with the higher proportion of trabecular bone in the LS. We also found that LS, but not FN, aBMD was associated with incident fractures across the MT, again emphasizing the potential dominant role of trabecular bone. However, in SWAN we are currently limited to dual-energy x-ray absorptiometry (DXA) measures of aBMD which cannot distinguish trabecular and cortical bone. The trabecular bone score (TBS) is a new index of trabecular bone structure that can be obtained from LS DXA scans. Microarchitecture of trabecular bone is a key determinant of bone strength. Both thinning of trabeculae and loss of trabecular connectivity substantially undermines structural integrity and weakens bone. TBS is associated with other measures of trabecular bone structure and predicts fracture in postmenopausal women. Our proposal offers an unprecedented cost-efficient opportunity to investigate trabecular bone structure longitudinally in the SWAN cohort. No other study has LS aBMD serially for a 20- year time span that includes the entire MT in a large multiracial sample. By reanalyzing SWAN spine DXA scans to obtain TBS we have the unique opportunity to isolate trabecular microarchitecture and test several novel hypotheses.
The specific aims of our study are to: (1)Determine the direction and magnitude of ethnic difference in TBS at baseline when all participants were either premenopausal or early perimenopausal and so at or near their peak BMD. (2)Examine the rate of longitudinal change in TBS with aging and with the MT (3) Examine the association between baseline TBS and incident fractures in midlife women. (4)Examine the effect of diabetes and insulin resistance on TBS at baseline and longitudinally as women traverse the MT. The central tenet of our work is beyond aBMD. This proposal builds on our initial grant where we made sub- stantial contributions showing that hip structural, biomechanical and geometric elements improves risk class- ification. We now propose to focus on LS trabecular microarchitecture and test whether the rapid trans- menopausal loss preferentially effects trabecular bone which could lead to irreparable structure damage. Our long term objective is to substantially improve our understanding of aging, menopause and skeletal strength.

Public Health Relevance

Our proposal offers an unprecedented cost-efficient opportunity to investigate trabecular bone structure across the menopausal transition (MT). No other existing study has longitudinal information on spine BMD across the MT in a large cohort of multiethnic women. With the development of the TBS, we have the unique opportunity to specifically target trabecular microarchitecture and test novel hypotheses about race/ethnic differences in trabecular microarchitecture and changes across the MT.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG026463-08
Application #
9249445
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Joseph, Lyndon
Project Start
2007-06-01
Project End
2019-04-30
Budget Start
2017-07-15
Budget End
2018-04-30
Support Year
8
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Jepsen, Karl J; Kozminski, Andrew; Bigelow, Erin Mr et al. (2017) Femoral Neck External Size but not aBMD Predicts Structural and Mass Changes for Women Transitioning Through Menopause. J Bone Miner Res 32:1218-1228
Chang, Po-Yin; Gold, Ellen B; Cauley, Jane A et al. (2016) Triglyceride Levels and Fracture Risk in Midlife Women: Study of Women's Health Across the Nation (SWAN). J Clin Endocrinol Metab 101:3297-305
Greendale, Gail A; Wilhalme, Holly; Huang, Mei-Hua et al. (2016) Prevalent and Incident Vertebral Deformities in Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN). PLoS One 11:e0162664
Mori, Takahiro; Ishii, Shinya; Greendale, Gail A et al. (2015) Parity, lactation, bone strength, and 16-year fracture risk in adult women: findings from the Study of Women's Health Across the Nation (SWAN). Bone 73:160-6
Mori, T; Ishii, S; Greendale, G A et al. (2014) Physical activity as determinant of femoral neck strength relative to load in adult women: findings from the hip strength across the menopause transition study. Osteoporos Int 25:265-72
Ishii, Shinya; Cauley, Jane A; Greendale, Gail A et al. (2014) Pleiotropic effects of obesity on fracture risk: the Study of Women's Health Across the Nation. J Bone Miner Res 29:2561-70
Danielson, Michelle E; Beck, Thomas J; Lian, Yinjuan et al. (2013) Ethnic variability in bone geometry as assessed by hip structure analysis: findings from the hip strength across the menopausal transition study. J Bone Miner Res 28:771-9
Danielson, M E; Beck, T J; Karlamangla, A S et al. (2013) A comparison of DXA and CT based methods for estimating the strength of the femoral neck in post-menopausal women. Osteoporos Int 24:1379-88
Ishii, Shinya; Cauley, Jane A; Greendale, Gail A et al. (2013) C-reactive protein, bone strength, and nine-year fracture risk: data from the Study of Women's Health Across the Nation (SWAN). J Bone Miner Res 28:1688-98
Ishii, S; Cauley, J A; Greendale, G A et al. (2013) Trajectories of femoral neck strength in relation to the final menstrual period in a multi-ethnic cohort. Osteoporos Int 24:2471-81

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