This is a competitive renewal application for P01 AG004875, """"""""Physiology of Bone Metabolism in an Aging Population."""""""" Osteoporosis is an enormous public health problem, and our overall goal is to better understand the mechanisms and consequences of bone loss with aging. As in the past, the major strength of our group is to bring together diverse disciplines into synergistic interactions, and the present application includes population-based epidemiology studies, intensive studies in the Clinical Research Unit (formerly the General Clinical Research Center), animal studies using novel mouse models, and basic cellular and molecular studies. Using this integrated approach, we propose to focus on three major areas: (1) Defining the mechanisms by which estrogen (E) regulates bone metabolism;(2) With increases in bone resorption, as in the setting of E deficiency, identifying the mechanisms by which osteoclasts regulate osteoblasts;and (3) Assessing the risk factors for and consequences of fractures that increase with E deficiency and with aging. Each of the Projects are aligned with one or more of these major themes: Project 1 (""""""""Pathophysiology of Osteoporosis"""""""") uses the human as the experimental model to address key, unresolved issues regarding E action on bone, including definitively establishing whether follicle-stimulating hormone modulates bone resorption in the setting of E deficiency and defining mechanisms for the age-related decrease in bone formation;Project 2 (""""""""Risk Factors for Fractures Among the Elderly"""""""") provides a population perspective on risk factors for fractures (""""""""secondary"""""""" osteoporosis) that exacerbate bone loss with E deficiency and with aging;Project 3 (""""""""Osteoclast Regulation of Bone Formation"""""""") pursues the basic biology and functional relevance of factors made by osteoclasts that regulate bone formation;and Project 4 (""""""""Estrogen Receptor Signaling Pathways in Bone"""""""") uses in vitro and novel mouse models to dissect E signaling pathways in bone. A single Core (""""""""Administrative and Biostatistics Core"""""""") provides the necessary infrastructure to support these Projects. Collectively, these studies strive to provide a comprehensive assesment of the pathogenesis and clinical impact of one of the most important disorders facing our aging population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG004875-30
Application #
8494467
Study Section
Special Emphasis Panel (ZAG1-ZIJ-8 (J2))
Program Officer
Joseph, Lyndon
Project Start
1997-07-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
30
Fiscal Year
2013
Total Cost
$1,500,799
Indirect Cost
$507,361
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Farr, Joshua N; Xu, Ming; Weivoda, Megan M et al. (2017) Targeting cellular senescence prevents age-related bone loss in mice. Nat Med 23:1072-1079
Rocca, Walter A (2017) Time, Sex, Gender, History, and Dementia. Alzheimer Dis Assoc Disord 31:76-79
Khosla, Sundeep; Shane, Elizabeth (2017) Response to Stoecker et al. J Bone Miner Res 32:1388
Rocca, Walter A; Savica, Rodolfo; Grossardt, Brandon R (2017) Response to Letter by Friedman on ""Incidence and time trends of drug-induced parkinsonism: A 30-year population-based study"". Mov Disord 32:1111-1112
Drake, Matthew T; Khosla, Sundeep (2017) Hormonal and systemic regulation of sclerostin. Bone 96:8-17
Gazzuola Rocca, Liliana; Smith, Carin Y; Grossardt, Brandon R et al. (2017) Adverse childhood or adult experiences and risk of bilateral oophorectomy: a population-based case-control study. BMJ Open 7:e016045
Farr, Joshua N; Melton 3rd, L Joseph; Achenbach, Sara J et al. (2017) Fracture Incidence and Characteristics in Young Adults Aged 18 to 49 Years: A Population-Based Study. J Bone Miner Res 32:2347-2354
Ni Mhuircheartaigh, Orla; Crowson, Cynthia S; Gabriel, Sherine E et al. (2017) Fragility Fractures Are Associated with an Increased Risk for Cardiovascular Events in Women and Men with Rheumatoid Arthritis: A Population-based Study. J Rheumatol 44:558-564
Drake, Matthew T; Clarke, Bart L; Oursler, Merry Jo et al. (2017) Cathepsin K Inhibitors for Osteoporosis: Biology, Potential Clinical Utility, and Lessons Learned. Endocr Rev 38:325-350
Farr, Joshua N; Fraser, Daniel G; Wang, Haitao et al. (2016) Identification of Senescent Cells in the Bone Microenvironment. J Bone Miner Res 31:1920-1929

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