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 #
2R01AR049747-06
Application #
8035812
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
2010-09-10
Budget End
2011-08-31
Support Year
6
Fiscal Year
2010
Total Cost
$666,161
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
Zhao, Qian; Zmuda, Joseph M; Kuipers, Allison L et al. (2017) Muscle Attenuation Is Associated With Newly Developed Hypertension in Men of African Ancestry. Hypertension 69:957-963
Kuipers, Allison L; Zmuda, Joseph M; Carr, J Jeffrey et al. (2017) Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men. Atherosclerosis 263:198-204
Kuipers, Allison L; Kammerer, Candace M; Pratt, J Howard et al. (2016) Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families. Hypertension 67:977-82
Kuipers, A L; Miljkovic, I; Evans, R et al. (2016) Optimal serum cholesterol concentrations are associated with accelerated bone loss in African ancestry men. Osteoporos Int 27:1577-1584
Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa et al. (2016) Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ Genetic Architecture of Fasting Glucose and Insulin. Am J Hum Genet 99:56-75
Miljkovic, Iva; Kuipers, Allison L; Cvejkus, Ryan et al. (2016) Myosteatosis increases with aging and is associated with incident diabetes in African ancestry men. Obesity (Silver Spring) 24:476-82
Tilves, Curtis M; Zmuda, Joseph M; Kuipers, Allison L et al. (2016) Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men. Diabetes Care 39:385-91
Kuipers, Allison L; Yu, Shibing; Kammerer, Candace M et al. (2015) Heritability and genetics of serum dickkopf 1 levels in African ancestry families. Calcif Tissue Int 96:155-9
Kuipers, Allison L; Miljkovic, Iva; Carr, J Jeffery et al. (2015) Association of circulating sclerostin with vascular calcification in Afro-Caribbean men. Atherosclerosis 239:218-23
Yu, Shibing; Yerges-Armstrong, Laura M; Chu, Yanxia et al. (2015) AP2 suppresses osteoblast differentiation and mineralization through down-regulation of Frizzled-1. Biochem J 465:395-404

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