Osteoporosis is a growing clinical and public health problem among older men. The greater prevalence of osteoporosis in women and white men has long over-shadowed the importance of this condition in black men. Unfortunately, there remains a widely held misconception that blacks are "protected" from bone loss and osteoporosis such that osteoporosis is underdiagnosed, undertreated and underreported in black men. As the population ages, considerably more black men will develop osteoporosis. Thus, there remains an urgent need to better understand bone loss and osteoporosis in black men so that high-risk men can be better identified for prevention and treatment. The proposed research seeks to better define the natural history and mechanisms underlying age-related bone loss in black men. To address this goal, we are proposing to continue our Tobago Bone Health Study (R01-AR049747), a unique population-based study of bone mineral density (BMD) in 2,424 black men aged e40 years. Men who completed a baseline quantitative computed tomography scan will be invited to complete a second scan, with an average follow-up of 6.6 years. Cortical and trabecular volumetric BMD and bone geometry will be remeasured to characterize the rates and determinants of bone loss. Detailed protocols, extensive training of staff, and well-established quality control procedures will continue to ensure high quality data collection. An extensive database of clinical and epidemiologic factors including anthropometry and body composition, medical conditions, lifestyle characteristics, dietary intake, and use of medications, archived specimens, and state-of-the-art biochemical assays will be used to: 1) describe the natural history of trabecular and cortical bone loss with age;2) identify the lifestyle, medical and anthropometric related risk factors for accelerated trabecular and cortical bone loss with aging;3) test the hypotheses that lower 1,25 dihydroxyvitamin D and 25-hydroxyvitamin D and higher bioactive parathyroid hormone concentrations are each associated with increased rates of trabecular and cortical bone loss with age;4) determine if higher concentrations of pro-inflammatory biomarkers, interleukin-6, tumor necrosis factor alpha and c-reactive protein, are each associated with accelerated loss of trabecular and cortical bone;and 5) evaluate if men with poorer renal function experience greater trabecular and cortical bone loss with aging. The proposed research will have a substantial impact on the field by providing deeper insight into the physiologic and clinical basis for age-related bone loss among black men, a population that has heretofore been significantly under-represented in osteoporosis research.

Public Health Relevance

Osteoporosis is a growing clinical and public health problem among older men of all race and ethnic groups. A greater prevalence of osteoporosis among Caucasians has long over-shadowed the importance of this disease in blacks, particularly among men. Indeed, osteoporosis and its associated fractures are substantially underdiagnosed, undertreated and underreported in black men. Our project is the largest and most comprehensive evaluation of skeletal health in black men and will substantially improve our understanding of bone health and skeletal aging in black men. Our proposal seeks to define the natural history, tempo and patterns of bone loss with aging among black men and to identify physiological and clinical risk factors for accelerated loss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR049747-08
Application #
8314111
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Chen, Faye H
Project Start
2003-04-01
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
8
Fiscal Year
2012
Total Cost
$636,926
Indirect Cost
$214,911
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
Sheu, Yahtyng; Bunker, Clareann H; Jonnalagadda, Pallavi et al. (2015) Rates of and risk factors for trabecular and cortical BMD loss in middle-aged and elderly African-ancestry men. J Bone Miner Res 30:543-53
Sheu, Yahtyng; Cauley, Jane A; Patrick, Alan L et al. (2014) Risk factors for fracture in middle-age and older-age men of African descent. J Bone Miner Res 29:234-41
Kuipers, A L; Zmuda, J M; Carr, J J et al. (2014) Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men. Osteoporos Int 25:1063-9
Shin, M-H; Zmuda, J M; Barrett-Connor, E et al. (2014) Race/ethnic differences in associations between bone mineral density and fracture history in older men. Osteoporos Int 25:837-45
Kuipers, A L; Zhang, Y; Yu, S et al. (2014) Relative influence of heritability, environment and genetics on serum sclerostin. Osteoporos Int 25:905-12
Miljkovic, I; Kuipers, A L; Kuller, L H et al. (2013) Skeletal muscle adiposity is associated with serum lipid and lipoprotein levels in Afro-Caribbean men. Obesity (Silver Spring) 21:1900-7
Yu, Shibing; Yerges-Armstrong, Laura M; Chu, Yanxia et al. (2013) E2F1 effects on osteoblast differentiation and mineralization are mediated through up-regulation of frizzled-1. Bone 56:234-41
Kuipers, A L; Gundberg, C; Kammerer, C M et al. (2012) Genetic analysis of serum osteocalcin and bone mineral in multigenerational Afro-Caribbean families. Osteoporos Int 23:1521-31
Forrest, Kimberly Y Z; Bunker, Clareann H; Sheu, Yahtyng et al. (2012) Patterns and correlates of grip strength change with age in Afro-Caribbean men. Age Ageing 41:326-32
Miljkovic, Iva; Cauley, Jane A; Dressen, Amy S et al. (2011) Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men. Metabolism 60:1178-85

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