The goal of this application is to support my professional development as a clinical investigator and a mentor to junior faculty and fellows interested in patient-oriented research. My research has focused on the in depth investigation of various disease states and medications and their effects on bone mass, bone remodeling and mineral metabolism. This proposal stems from preliminary work that has begun to elucidate the pathogenesis of idiopathic osteoporosis (IOP) in pre-menopausal women. Transiliac crest bone biopsies from a small number of such women have revealed uncoupled remodeling, with increased bone resumption and markedly decreased formation. The hypothesis of this proposal is that IOP in premenopausal women is a disorder characterized by abnormal skeletal micro architecture and remodeling, in which there is uncoupling of formation from resumption, the imbalance favoring resumption. I will test this hypothesis in a cross-sectional study in which premenopausal women with IOP will be compared to normal women. Other goals are to investigate the etiology and pathogenesis and to assess various measures of bone quality in women with IOP. The five specific aims are to: 1. Describe the clinical phenotype. 2: Define the relationship between central and peripheral volumetric measurements of bone mineral density and fracture prevalence. 3: Define pathogenesis abnormalities in bone utilizing quantitative histomorphometry, micro-CT, micro-FE and FTIRI. 4: Characterize estrogen status, and 5: Elucidate biochemical characteristics that may contribute to the pathogenesis. The results should have important therapeutic implications for the diagnosis and management of IOP in premenopausal women. Importantly, the proposal will provide many opportunities to mentor beginning junior investigators. I have had excellent success as a mentor, with two recent K-23 awardees and 16 former or current trainees. There has been significant interest in my research from Endocrine Fellows and from Fellows and junior faculty in other disciplines. The Department of Medicine and the GCRC have made substantial commitments toward my development as a clinical investigator. However, it is clearly necessary for me to reduce my clinical, administrative and teaching loads in order to devote sufficient time to clinical research and to training and mentoring junior faculty and fellows. The K24 award is the ideal mechanism to ensure the support essential for my continued success as a mentor and patient-oriented investigator.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24AR052665-03
Application #
7282496
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Mcgowan, Joan A
Project Start
2005-09-05
Project End
2010-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$176,333
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Cohen, Adi; Kousteni, Stavroula; Bisikirska, Brygida et al. (2017) IGF-1 Receptor Expression on Circulating Osteoblast Progenitor Cells Predicts Tissue-Based Bone Formation Rate and Response to Teriparatide in Premenopausal Women With Idiopathic Osteoporosis. J Bone Miner Res 32:1267-1273
Young, P; Shah, J; Zhang, C et al. (2016) Frailty in Postmenopausal African American and Hispanic HIV-Infected Women. J Frailty Aging 5:242-246
Wang, Ji; Stein, Emily M; Zhou, Bin et al. (2016) Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures. Bone 88:39-46
Boutroy, Stephanie; Khosla, Sundeep; Sornay-Rendu, Elisabeth et al. (2016) Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T-Score: An International Multicenter Study. J Bone Miner Res 31:1158-66
Nishiyama, Kyle K; Pauchard, Yves; Nikkel, Lucas E et al. (2015) Longitudinal HR-pQCT and image registration detects endocortical bone loss in kidney transplantation patients. J Bone Miner Res 30:554-61
Stein, Emily M; Rogers, Halley; Leib, Alexa et al. (2015) Abnormal Skeletal Strength and Microarchitecture in Women With Celiac Disease. J Clin Endocrinol Metab 100:2347-53
Cohen, Adi; Kamanda-Kosseh, Mafo; Recker, Robert R et al. (2015) Bone Density After Teriparatide Discontinuation in Premenopausal Idiopathic Osteoporosis. J Clin Endocrinol Metab 100:4208-14
Misof, B M; Dempster, D W; Zhou, Hua et al. (2014) Relationship of bone mineralization density distribution (BMDD) in cortical and cancellous bone within the iliac crest of healthy premenopausal women. Calcif Tissue Int 95:332-9
Nishiyama, Kyle K; Cohen, Adi; Young, Polly et al. (2014) Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab 99:2418-25
Stein, Emily M; Kepley, Anna; Walker, Marcella et al. (2014) Skeletal structure in postmenopausal women with osteopenia and fractures is characterized by abnormal trabecular plates and cortical thinning. J Bone Miner Res 29:1101-9

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