Training In The Epidemiology Of Aging
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5T32AG000181-18 from National Institute On Aging IRG: ZAG1
Abstract: This is a proposal for the competing continuation of a Training Program in Aging Epidemiology, funded by NIA since 1989. At no point in history have laboratory and clinical sciences advanced at such a rapid pace. It is imperative that epidemiology integrate and keep pace with these other disciplines. The University of Pittsburgh provides access to individuals and facilities representing the broadest range of research endeavors in aging. For future research in aging to be meaningful, knowledge and skills from multiple areas must be integrated. Therefore, there is a pressing need for a cadre of epidemiological investigators who can function effectively in this rapidly evolving research environment. The overall objective of the Training Program is to enroll individuals who are well-trained in a relevant scientific discipline and to provide them with theoretical instruction and practical field experience in epidemiological aging research. Our philosophy has been to customize the training experience to the background and interests of the individual trainee, and to capitalize on the rich and diverse research training opportunities available at the University of Pittsburgh. Specifically, we will 1) train individuals in the field of epidemiology with particular emphasis on the application of epidemiologic methods to important research questions related to older adults. Emphasis is placed on the teaching of traditional epidemiologic methods, as well as methodological considerations unique to older adults; 2) gain a better understanding of the pathophysiology and determinants of important diseases of older adults, emphasizing the spectrum of "normal" age-related changes, pre-clinical disease states, and clinical onset of disease; 3) emphasize domains of health status and function (physical, cognitive, psychological, sensory and social); and 4) evaluate potential mechanisms of disease and disability prevention.
Project start date: 1989-09-04
Project end date: 2010-04-30
5T32AG000181-18 (2007): $347166
Sponsored Links Excellgen http://Excellgen.com
Training In The Epidemiology Of Aging
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5T32AG000181-17 from National Institute On Aging IRG: ZAG1
Abstract: This is a proposal for the competing continuation of a Training Program in Aging Epidemiology, funded by NIA since 1989. At no point in history have laboratory and clinical sciences advanced at such a rapid pace. It is imperative that epidemiology integrate and keep pace with these other disciplines. The University of Pittsburgh provides access to individuals and facilities representing the broadest range of research endeavors in aging. For future research in aging to be meaningful, knowledge and skills from multiple areas must be integrated. Therefore, there is a pressing need for a cadre of epidemiological investigators who can function effectively in this rapidly evolving research environment. The overall objective of the Training Program is to enroll individuals who are well-trained in a relevant scientific discipline and to provide them with theoretical instruction and practical field experience in epidemiological aging research. Our philosophy has been to customize the training experience to the background and interests of the individual trainee, and to capitalize on the rich and diverse research training opportunities available at the University of Pittsburgh. Specifically, we will 1) train individuals in the field of epidemiology with particular emphasis on the application of epidemiologic methods to important research questions related to older adults. Emphasis is placed on the teaching of traditional epidemiologic methods, as well as methodological considerations unique to older adults; 2) gain a better understanding of the pathophysiology and determinants of important diseases of older adults, emphasizing the spectrum of "normal" age-related changes, pre-clinical disease states, and clinical onset of disease; 3) emphasize domains of health status and function (physical, cognitive, psychological, sensory and social); and 4) evaluate potential mechanisms of disease and disability prevention.
Project start date: 1989-09-04
Project end date: 2010-04-30
5T32AG000181-17 (2006): $347166
5T32AG000181-15 (2004): $274762
5T32AG000181-14 (2003): $11431
5T32AG000181-13 (2002): $301176
5T32AG000181-12 (2001): $280278
5T32AG000181-10 (1999): $128905
5T32AG000181-09 (1998): $201954
5T32AG000181-08 (1997): $205051
5T32AG000181-07 (1996): $198826
Grants awarded to Jane A Cauley
Training In The Epidemiology Of Aging
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2T32AG000181-16 from National Institute On Aging IRG: ZAG1
Abstract: This is a proposal for the competing continuation of a Training Program in Aging Epidemiology, funded by NIA since 1989. At no point in history have laboratory and clinical sciences advanced at such a rapid pace. It is imperative that epidemiology integrate and keep pace with these other disciplines. The University of Pittsburgh provides access to individuals and facilities representing the broadest range of research endeavors in aging. For future research in aging to be meaningful, knowledge and skills from multiple areas must be integrated. Therefore, there is a pressing need for a cadre of epidemiological investigators who can function effectively in this rapidly evolving research environment. The overall objective of the Training Program is to enroll individuals who are well-trained in a relevant scientific discipline and to provide them with theoretical instruction and practical field experience in epidemiological aging research. Our philosophy has been to customize the training experience to the background and interests of the individual trainee, and to capitalize on the rich and diverse research training opportunities available at the University of Pittsburgh. Specifically, we will 1) train individuals in the field of epidemiology with particular emphasis on the application of epidemiologic methods to important research questions related to older adults. Emphasis is placed on the teaching of traditional epidemiologic methods, as well as methodological considerations unique to older adults; 2) gain a better understanding of the pathophysiology and determinants of important diseases of older adults, emphasizing the spectrum of "normal" age-related changes, pre-clinical disease states, and clinical onset of disease; 3) emphasize domains of health status and function (physical, cognitive, psychological, sensory and social); and 4) evaluate potential mechanisms of disease and disability prevention.
Project start date: 1989-09-04
Project end date: 2010-04-30
2T32AG000181-16 (2005): $347166
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5U01AR045654-07 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZAR1
Abstract: There has long been an appreciation of the importance of osteoporosis in women, and decades of research have yielded a strong foundation of mechanistic and practical knowledge that underlies clinical decision- making. On the other hand, very little information is available to direct the management of osteoporosis in men. The primary goal of this study (MR.OS) is to determine the extent to which fracture risk in order men is related to bone mass, bone geometry, lifestyle factors, biochemical measures, fall propensity, and other variables. This information is essential for understanding the genesis of fractures, and for the formulation of clinical algorithms for detection and treatment of osteoporosis in men. A second goal is to determine the relationships between osteoporotic fracture and two common chronic conditions in older men prostate cancer and osteoarthritis (OA). This will be a multicenter, prospective study of risk factors for vertebral and all non- vertebral fractures in older men (> 65 years). A total of 5,700 men will be recruited in six diverse geographical areas (Portland, OR; Pittsburgh; Minneapolis; San Diego; Palo Alto; and Birmingham), and will be followed for an average of three years. Baseline assessments will include BMD and bone geometry, vertebral morphometry, OA, neuromuscular and visual function, anthropometrics, nutrition, medical history, medication use, serum/urine/DNA collections, and functional status. Repeat measures of BMD and health/functional status will be obtained at two follow-up visits. The final exam will include repeat radiographs of the spine, hips and knees to determine incident vertebral fracture rate, and incidence and progression of OA. Participants will be followed every 4 months by postcard to determine the rates of non-vertebral fracture, falls, and prostate cancer. Data analysis will utilize proportional hazards and logistic regression models, depending on the type of outcome being analyzed. The study will have 90% power to detect RR of 1.35 for vertebral fractures and OR of 1.22 for non-spine fractures. MR.OS will provide unique information concerning osteoporosis and other common disorders, and will provide a basis for the construction of crucial preventative and treatment strategies.
Keywords: bone fracture, epidemiology, human old age (65+), male, osteoporosis, accidental fall, body physical characteristic, bone density, comorbidity, cooperative study, disease /disorder proneness /risk, functional ability, lifestyle, longitudinal human study, osteoarthritis, prostate neoplasm, clinical research, human subject, musculoskeletal imaging /visualization /scanning
Project start date: 1999-09-30
Project end date: 2006-06-30
5U01AR045654-07 (2005): $490972
5U01AR045654-06 (2004): $112957
5U01AR045654-03 (2001): $525455
5U01AR045654-02 (2000): $864673
1U01AR045654-01 (1999): $542328
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01AR035582-10 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: EDC
Abstract: The Study of Osteoporotic Fractures (SOF) is a multicenter prospective study of this important source disability in a cohort of 9,704 women over age 65. Three examinations have yielded a comprehensive set of measurements that include bone mineral density (BMD), neuromuscular function, functional status, and other factors for fractures; follow-up over 2.7 years has been 99% complete. Among the many findings of SOF are the demonstration that appendicular BMD predicts hip and other types of fractures; the of the risk factors for wrist and humerus fractures; the observation that the two types of hip fractures (cervical and intertrochanteric) have different relationships to bone density; and the discovery that women with low bone density have an increased risk of death from stroke. We propose to continue SOF to answer additional questions about fractures in women. A Year 5 examination and continued follow-up will allow us to test the ability of ultrasound to predict fractures and determine whether it adds information on fracture risk to that provided by densitometry. At the Year 5 examination, we will also measure calcium absorption to test the hypothesis that it is associated with more rapid bone loss and more fractures. Updated measures of bone density, functional status, and neuromuscular function will provide values proximate to subsequent fractures and allow us to examine rate of change as a predictor of hip and other fractures. Continued follow-up will also allow a test of the hypothesis that intertrochanteric and cervical fractures of the hip have different risk factors. To study biochemical antecedents of fracture, we will use serum stored at -190 degrees Celsius since the baseline examination; we have demonstrated that hormone levels have remained stable in these samples over 3.5 years. We will examine the levels of hormones, growth factors, and markers of bone turnover as predictors of subsequent hip, wrist, and vertebral fractures. Using an efficient nested case-cohort approach, we will test, for example, whether women with low levels of 25(OH) Vitamin D have an increased risk of hip fracture. The strengths of SOF include its large sample of well-characterized older women, its prospective design with excellent rates of follow-up, its comprehensive measurements of bone mass and neuromuscular function, and its stable bank of frozen sera. Continued study of this unique cohort is likely to produce important advances in understanding and preventing fractures in older women.
Keywords: aging, disease proneness /risk, female, handicapped, hip fracture, injury prevention, limb fracture, osteoporosis, wrist, accidental fall, biomarker, bone density, calcium metabolism, caucasian American, densitometry, dietary constituent, growth factor, hormone regulation /control mechanism, human old age (65+), life style, longitudinal human study, neuromuscular function, skeletal disorder diagnosis, ultrasonography, vitamin D deficiency, clinical chemistry, human subject, nutrition related tag, photon absorptiometry, radiography, skeletal visualization
Project start date: 1986-02-01
Project end date: 1997-01-31
5R01AR035582-10 (1995): $200514
5R01AR035582-09 (1994): $256965
5R01AR035582-08 (1993): $486672
2R01AR035582-07 (1992): $484269
Sponsored Links Excellgen http://Excellgen.com
Study Of Osteoporotic Fractures
Jane A Cauley, Professor
Epidemiologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 2R01AR035582-17 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZAR1
Abstract: The Study of Osteoporotic Fractures (SOF) is a multi-center longitudinal study in a cohort of 9,704 older women. SOF has comprehensive data about risk factors for osteoporosis and other diseases, along with an archive of serum, buffy coat and urine specimens. Data from SOF have served for (1) developing osteoporosis guidelines, (2) estimating the cost-effectiveness of screening for osteoporosis, and (3) planning trials of osteoporosis therapies. They propose to renew SOF to sustain this unique resource and to pursue several new hypotheses. Osteoporosis is a chronic disease and prevention of fractures must be considered over the very long-term, not just the 3-5 year duration of most studies in the field. As the study of osteoporosis and aging with the longest (nearly 15 years) follow-up, SOF will provide the foundation for describing ways to identify people at greatest risk of osteoporosis and fractures decades in advance. They envision a new generation of clinical guidelines based on long-term prediction of risk of fractures and disability. Because they have enriched the cohort with African-American women, SOF will also provide unique information on risk factors for osteoporosis and non-spine fractures in older African American women. SOF was the first study to show a link between low BMD and risk of stroke and this has helped to fuel the interest and new investigations about the links between arterial calcification and osteoporosis. If they demonstrate, and can begin to explain, the link between these two diseases, this may lead to screening tools and treatments that simultaneously decrease the risk of both of these disabling conditions. Preliminary results from SOF suggest that impaired sleep may be a major cause of fractures, disability and decline in cognition in older women. If the next phase of SOF confirms these relationships using more objective measures of insomnia and other sleep disorders, then this might change current clinical policies and practices toward more aggressive screening and better coverage for treatment of sleep disorders. Finally, the value of SOF could be magnified by recruiting other scientists to work on SOF data and samples. They propose to make the database easily accessible to investigators outside of SOF and assist them in making productive use of a database that represents one of the most comprehensive prospective sources of information about the health of older women
Keywords: bone fracture, disease /disorder proneness /risk, human old age (65+), longitudinal human study, osteoporosis, women`s health African American, bone density, breast neoplasm, caucasian American, estrogen receptor, human very old age (85+), information dissemination, muscle strength, sleep disorder clinical chemistry, clinical research, densitometry, female, human subject, photon absorptiometry, polysomnography, questionnaire
Project start date: 1986-02-01
Project end date: 2006-07-31
2R01AR035582-17 (2001): $585702
Jane A Cauley, Professor
Epidemiologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 2R01AR035582-12 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: AMS
Abstract: The Study of Osteoporotic Fractures (SOF) is a community-based prospective study in a cohort of 9,704 older women. SOF has comprehensive data about osteoporosis risk factors, along with an archive of serum, bully coat and urine specimens. Data from SOF have served for (1) developing osteoporosis guidelines, (2) estimating the cost-effectiveness of screening for osteoporosis, and (3) planning trials of osteoporosis therapies. We propose to renew SOF to sustain this unique resource and to pursue several new hypotheses. Our preliminary findings suggest that BMD may lose predictive value for hip fractures after 4-5 years. We will study the long-term predictive value of BMD, and other risk factors, after 10-15 years; substantial declines would strongly effect guidelines concerning the frequency and cost-effectiveness of screening. We recently discovered that women with osteoporosis have a decreased risk of breast cancer, suggesting that these conditions share common etiologies. We will begin the search for these links by investigating whether endogenous sex steroids are associated with breast cancer, and whether other indices of osteoporosis, such as height loss, low ultrasound values, or incident fractures, indicate a lower risk of breast cancer. We have found that, contrary to previous beliefs, the rate of bone loss increases with age in Caucasian and African-American women. Elderly women also lose muscle mass as they age. We have also shown that mild chronic metabolic acidosis of dietary origin affects bone and causes negative nitrogen balance. We propose to test whether diet-induced metabolic acidosis, amplified by the normal age-related decline in renal function, is an important cause of loss of bone and muscle mass in elderly women, and is a risk factor for hip fracture. Declines in visual functions, such as contrast sensitivity, increase the risk of hip, wrist and humerus fractures and falls. Uncorrected refractive error and specific eye diseases, such as cataracts, glaucoma, and age-related macular degeneration, are common in elderly women. We will test the hypothesis that these common and potentially treatable eye diseases increase fall and fracture risk. Besides their scientific value, these findings may influence clinical guidelines and Medicare coverage for preventive eye care. Finally, there are contradictory findings about the relationship between estrogen receptor (ER) genotypes and bone mass and breast cancer, or even if ER variations have any biological effects. We propose using our archived DNA specimens and existing data about hip and vertebral fractures, breast cancer, bone mass, serum sex hormones and lipoproteins to determine whether these ER variations have biological importance
Keywords: bone fracture, disease /disorder proneness /risk, female, human old age (65+), longitudinal human study, osteoporosis African American, acidosis, bone density, breast neoplasm, caucasian American, estrogen receptor, muscle strength, sex hormone, vision disorder clinical chemistry, clinical research, densitometry, eye disorder diagnosis, human genetic material tag, human subject, interview, photon absorptiometry, questionnaire, ultrasonography
Project start date: 1986-02-01
Project end date: 2001-12-31
2R01AR035582-12 (1997): $774489
5R01AR035582-16 (2001): $193538
5R01AR035582-15 (2000): $207850
5R01AR035582-14 (1999): $340438
5R01AR035582-13 (1998): $568467
Study Of Osteoporotic Fractures
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2R01AG027576-22A1 from National Institute On Aging IRG: ZRG1
Abstract: The Study of Osteoporotic Fractures (SOF) is a cohort of 10,366 women who were greater to or equal to 65 years old at enrollment in 1986-7. During 18 years and 8 examinations, SOF has developed a comprehensive array of phenotypic data, along with archives of 53,000 biological specimens and 67,500 radiographs. Findings from SOF, reported in 235 papers, have shaped clinical practice and guidelines for fracture prevention, and advanced the understanding of cognitive function, breast cancer, osteoarthritis, and other age-related conditions. SOF continues to be very productive, with 93 publications since our last renewal in 2000, including 60 articles from 45 external, and mostly junior, investigators. All SOF data are now available publicly via SOF Online. We propose to sustain, build, and produce important discoveries from these unique SOF resources. The SOF cohort has become one of the largest, longest, and best characterized cohorts of women in the 9th and 10th decades of life, the fastest growing segment of the US population. In addition to data about risk factors, bone mass, and fractures, we have nearly two decades of serial assessments of lower extremity function, cognitive function, and falls. In a Year 20 Exam, we will examine surviving SOF participants in clinic or home to expand our assessment of cognitive function with new dimensions and assess lower extremity function using the standardized and validated Short Physical Performance Battery. These examinations will allow us to analyze why some women have excellent cognitive function and lower extremity function so late in life. We will use blood stored from our Year 10 Exam to test the hypotheses that excellent renal function, low levels of inflammation, and normal levels of 25(OH) Vitamin D are associated with maintaining and achieving excellent lower extremity function, high cognitive function, a low risk of falls, and a low risk of hip fracture into the 9th and 10th decades of life. Potential public health impacts While the oldest old women are the fastest growing segment of the US population, little is known about how to maintain their independence. Renal function, inflammation, and vitamin D levels are modifiable. If our hypotheses are born out, this may lead to trials and recommendations about lifestyle, Vitamin D supplementation, or medication, to promote high levels of function late in life.
Keywords: accidental fall, biomedical registry /referral center, cognition disorder, disease /disorder proneness /risk, functional ability, hip fracture, osteoporosis, women s health, African American, Internet, aging, archive, inflammation, interleukin 6, kidney function, limb movement, longitudinal human study, tumor necrosis factor alpha, vitamin D, behavioral /social science research tag, blood test, clinical research, female, human old age (65+), human subject
Project start date: 1986-02-01
Project end date: 2009-07-31
2R01AG027576-22A1 (2006): $403842
5R01AR035582-21 (2005): $266587
5R01AR035582-20 (2004): $260093
5R01AR035582-19 (2003): $253563
Sponsored Links Excellgen http://Excellgen.com
5R01AR035582-18 (2002): $644818
Osteoporotic Fractures In Men - MrOS Renewal - Pittsburgh
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 2U01AR045654-08A1 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZAR1
Abstract: The Osteoporotic Fractures in Men (MrOS) study was formed primarily to quantify the determinants of fracture in men. Importantly, the MrOS cohort also provides a seminal opportunity to study men as they progress through a critical period of life in which problems of aging remain poorly understood. In 2000-2002, 5995 community-dwelling men ages 65 years and older (mean age 72 years at baseline) were enrolled from 6 diverse US communities. After 5 years of follow-up, participant retention is excellent (99% of those alive remain active). We propose a new clinic visit and continued follow-up of the cohort to expand our understanding of risk factors for falls, fractures (particularly hip fracture) and other consequences of aging. At baseline, both areal (from DXA) and volumetric (from QCT) skeletal assessments were obtained. We propose to repeat the same assessments in the planned visit to identify the densitometric and biomechanical risk factors for hip fracture, as well as to characterize bone geometry changes that underlie skeletal fragility. Further, we will use the QCT scans to quantify femoral strength by finite element modeling (FEM), and assess the usefulness of FEM for fracture prediction. Additional follow-up of the cohort and repeat measures of muscle strength (grip strength, leg power), physical performance (gait speed, chair stands, and narrow walk), and self-reported physical activity will enable us to establish the extent and nature of change in activity and physical performance, identify biological predictors of these changes, and clarify the possibly joint effects of physical activity and physical performance on fracture risk. To objectively quantify physical activity we propose to obtain accelerometry measures at the new clinic visit. Using serum archived at baseline, we will test the hypothesis that renal function, vitamin D, parathyroid hormone have important effects on skeletal health, physical function and fracture risk, and will determine if lower sex steroid levels increase men s risk of skeletal deterioration and fracture, decline in physical function, and deterioration in quality of life. Combined with the considerable data and biologic specimens already collected, additional measures and extended follow-up in the MrOS cohort allows us to expand the understanding of hip fractures, the most devastating type of fracture in men, as well as address other health issues of compelling public health and clinical importance to older US men.
Keywords: bone fracture, epidemiology, human old age (65+), male, osteoporosis, accidental fall, body physical characteristic, bone density, comorbidity, cooperative study, disease /disorder proneness /risk, functional ability, lifestyle, longitudinal human study, osteoarthritis, prostate neoplasm, clinical research, human subject, musculoskeletal imaging /visualization /scanning
Project start date: 1999-09-30
Project end date: 2012-07-31
2U01AR045654-08A1 (2006): $383027
Estradiol, Cytokines & Bone Turnover-Effects On Fracture
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01AR052105-02 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZRG1
Abstract: The inflammation hypothesis of aging centers on the assertion that aging is the accumulation of damage, which results from chronic activity of immune response systems. Overproduction of pro-inflammatory cytokines has been linked to a number of chronic conditions common in older adults including cardiovascular disease, frailty, cognitive decline, dementia, and overall mortality. Evidence that pro-inflammatory cytokines contribute to hip fracture, however, does not exist despite animal and in-vitro data supporting such an association. Hip fractures are the most devastating consequence of osteoporosis. Preliminary analyses suggest that higher soluble cytokine receptor levels are associated with faster rates of bone loss and an increased risk of fracture. In the current application, we plan to test the inflammation of aging hypothesis as it relates to hip fracture in two distinct cohorts, the observational arm of The Women s Health Initiative (WHIOS) and the Study of Osteoporotic Fractures (SOF). The proposed study will consist of two prospective studies of biochemical predictors of hip fracture in the WHI-OS and SOF. In addition, we will measure cytokines, bone turnover markers and serum estradiol and vitamin D in 410 African American women enrolled in SOF and compare these levels to 700 Caucasian control women to identify the factors that contribute to ethnic differences in rates of bone loss. We hypothesize that increases in pro-inflammatory cytokines results in increased rates of bone turnover, loss of bone strength, faster rate of bone loss and an increased risk of hip fracture. Furthermore, estrogen deficiency leads to increases in pro-inflammatory cytokines and thus leads to hip fracture. Vitamin D insufficiency increases the risk of fracture by either increasing fall rates, reducing bone strength, or both. Our goal is to substantially improve our understanding of the paracrine and hormonal mediators that contribute to hip fracture in older women. Improved understanding of the biological mechanisms for these associations could lead to the development and testing of preventive intervention.
Keywords: aging, bone metabolism, cytokine, estradiol, hip fracture, hormone regulation /control mechanism, osteoporosis, vitamin D, African American, biomarker, caucasian American, collagen, cytokine receptor, interleukin 6, longitudinal human study, osteoprotegerin, pathologic bone resorption, racial /ethnic difference, tumor necrosis factor alpha, clinical research, female, human subject
Project start date: 2005-09-22
Project end date: 2008-06-30
5R01AR052105-02 (2006): $535800
Estradiol, Cytokines & Bone Turnover Effects On Fracture
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 1R01AR052105-01A1 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZRG1
Abstract: The inflammation hypothesis of aging centers on the assertion that aging is the accumulation of damage, which results from chronic activity of immune response systems. Overproduction of pro-inflammatory cytokines has been linked to a number of chronic conditions common in older adults including cardiovascular disease, frailty, cognitive decline, dementia, and overall mortality. Evidence that pro-inflammatory cytokines contribute to hip fracture, however, does not exist despite animal and in-vitro data supporting such an association. Hip fractures are the most devastating consequence of osteoporosis. Preliminary analyses suggest that higher soluble cytokine receptor levels are associated with faster rates of bone loss and an increased risk of fracture. In the current application, we plan to test the inflammation of aging hypothesis as it relates to hip fracture in two distinct cohorts, the observational arm of The Women s Health Initiative (WHIOS) and the Study of Osteoporotic Fractures (SOF). The proposed study will consist of two prospective studies of biochemical predictors of hip fracture in the WHI-OS and SOF. In addition, we will measure cytokines, bone turnover markers and serum estradiol and vitamin D in 410 African American women enrolled in SOF and compare these levels to 700 Caucasian control women to identify the factors that contribute to ethnic differences in rates of bone loss. We hypothesize that increases in pro-inflammatory cytokines results in increased rates of bone turnover, loss of bone strength, faster rate of bone loss and an increased risk of hip fracture. Furthermore, estrogen deficiency leads to increases in pro-inflammatory cytokines and thus leads to hip fracture. Vitamin D insufficiency increases the risk of fracture by either increasing fall rates, reducing bone strength, or both. Our goal is to substantially improve our understanding of the paracrine and hormonal mediators that contribute to hip fracture in older women. Improved understanding of the biological mechanisms for these associations could lead to the development and testing of preventive intervention.
Keywords: aging, bone metabolism, cytokine, estradiol, hip fracture, hormone regulation /control mechanism, osteoporosis, vitamin D, African American, biomarker, caucasian American, collagen, cytokine receptor, interleukin 6, longitudinal human study, osteoprotegerin, pathologic bone resorption, racial /ethnic difference, tumor necrosis factor alpha, clinical research, female, human subject
Project start date: 2005-09-22
Project end date: 2008-06-30
1R01AR052105-01A1 (2005): $529197
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5P30AG024827-039002 from National Institute On Aging IRG: ZAG1
Abstract: The goal of the Participant Core is to ensure and optimize the recruitment and retention of participants for studies of balance and aging. Successful recruitment of older persons for study participation is an essential, core function for our research. Investigators at the University of Pittsburgh have established successful methods for recruitment older adults into a full range of ongoing and completed studies of older persons, including large epidemiological cohorts, clinical trials and mechanistic investigations. This collective expertise has developed in an environment of extensive cross-departmental collaboration. The Core will provide centralized access to this expertise, through a series of recruitment training seminars as well as individual consultation. The Core will provide information regarding 11 participating studies with measures of mobility and balance that are available for add-on supplements. New participating studies can be added in the future. The Core provides access to four main resources for new recruitment, a health care based system (CRPRS), a primary care network (PRONET), volunteer resources and the geriatric services programs. Each specific has strengths for specific types of studies. The Participant Core will provide consultative direction and efficient access to these resources for new pilot and externally funded studies.
Keywords: aging, balance, biomedical facility, geriatrics, health science research support, medical outreach /case finding, clinical research, human old age (65+), human subject
BONE LOSS IN VERTEBRAL FRACTURE IN OLDER MEN
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 1P60AR044811-010005 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases
Abstract: Osteoporosis and its associated fractures represent an increasingly important health problem among older men. It is estimated that approximately one-third of all hip fractures occur in men. The lifetime risk of hip fracture in white men age > is about 6%, less than the lifetime risk of 18% in 50 year old white women. Recent data suggest that vertebral fractures are as common in men as in women. Osteoporosis is also an important contributor to disability in older men. Mortality after a hip fracture may actually be higher among men than women. In contrast to the vast amount of data that has accumulated on the etiology and prevention of osteoporosis in women, considerably less I s known about osteoporosis in older men. We propose to continue our Study of Osteoporotic Risk in Men (STORM), an observational study of the determinants of bone mineral density (BMD) in 523 men, ages 50-88. Men originally studied between 1991-1992 will be reconnected for a follow-up examination to be completed as part of this application in 1998- 1999 (after approximately 75 years of follow-up). Based on follow- u rates in our other studies, we expect that at least 75% of the cohort will return for a clinic visit. BMD at the proximal femur and lumbar spine will l be remeasured using dual-energy x-ray absorptiometry, and the annualized rate of change in BMD at these skeletal sites determined. 1.) Examine the pattern and determinants of one loss in older men to test several hypotheses 2). To test the hypothesis that allelic variation at the apolipoprotein E gene locus predicts BMD bone turnover and the rate of bone loss. 3). Describe the prevalence and risk factors for vertebral fractures in older men to test several hypotheses The long-term objective of this project is to improve our understanding of the causes of age- related bone loss and the risk factors for vertebral fractures in men.
Keywords: apolipoprotein E, bone density, bone fracture, disease /disorder proneness /risk, epidemiology, human old age (65+), male, osteoporosis, spine injury, genetic polymorphism, clinical research, human subject
Outcomes Of Sleep Disorders In Older Men - Pittsburgh
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01HL070842-04 from National Heart, Lung, And Blood Institute IRG: CLTR
Abstract: It is estimated that over 50% of adults aged 65 and older report some sleep disruption, while about 20% suffer from chronic insomnia. Obstructive sleep apnea, a major cause of daytime drowsiness, occurs in an estimated 20-60% of older people, depending on the definition used and the specific population being studied. Despite the high prevalence of sleep disorders in the elderly, there have been relatively few studies focused on the consequences. Most studies have been limited by cross-sectional design, small sample size, or lack of comprehensive and objective assessment of sleep. The proposed study, Outcomes of Sleep Disorders in Older Men, will take advantage of the established cohort that has been recruited for the Osteoporotic Fractures in Men (MrOS) study (5U01AR045647-Dr. Eric Orwoll, PI). MrOS, a 7-year study that began in July 1999, is a multi-center prospective study of approximately 6000 men aged 65 and older. During the MrOS baseline visit, a broad variety of measurements were collected, including body composition and body fat distribution (by DEXA and quantitative computed tomography), bone density, anthropometry, performance-based tests of strength and balance, medical history, medication use, smoking and alcohol use, and other parameters. Blood, urine, and DNA specimens have been archived for use in future studies of importance to the health of older men. In a subcohort of 3000 MrOS participants, we propose to add comprehensive and accurate assessments of sleep using in-home polysomnography, wrist actigraphy, questionnaires and other measures; and prospective adjudication of CVD events, to the extensive measures that have already been performed or planned in the MrOS cohort study. These new measures will enable us to test several important hypotheses 1) to characterize the associations between sleep disruption and subsequent CVD events during 3.5 years of follow-up, 2) to determine if sleep disturbances are associated with an increased risk of total and cause-specific mortality in older men, 3) to test whether sleep disturbances are associated with increased risk of falls and decreased physical function, 4) to test whether sleep disturbances are associated with impaired cognitive function in older men, and 5) to test whether sleep disorders are associated with bone density and fracture risk in older men. We will also supplement the bank of MrOS specimens to allow for testing of future hypotheses concerning the role of sleep in the development of age-related diseases and conditions.
Keywords: cardiovascular disorder risk, geriatrics, human old age (65+), sleep disorder, accidental fall, bone density, bone fracture, cognition, functional ability, human mortality, longitudinal human study, outcomes research, sleep apnea, actigraphy, clinical research, human subject, neuropsychological test, patient oriented research, polysomnography, questionnaire
Project start date: 2003-09-15
Project end date: 2008-06-30
5R01HL070842-04 (2006): $108271
5R01HL070842-03 (2005): $91611
Sponsored Links Excellgen http://Excellgen.com
5R01HL070842-02 (2004): $472875
1R01HL070842-01A1 (2003): $480319
RISK FACTORS FOR HIP AND COLLES FRACTURES
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R01AR035582-06 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: EDC
Abstract: Fractures of the hip and wrist are a costly and preventable threat to the health and survival of the elderly. A better understanding of the risk factors for hip and Colles fractures will add to our knowledge about the etiology of this condition and help focus research and preventive efforts on those who are at greatest risk. We propose to characterize risk factors for hip and Colles fractures in a multicenter prospective study of 9,600 elderly women followed quarterly for an average of 3.5 years. Our cohort will be a population-based sample of non-black women aged 65 or greater who are screened from 1985 thru 1988 at clinical centers in Pittsburgh, Portland, Maryland and Minneapolis. In Pittsburgh we will recruit 2400 individuals from population listings resulting in as close as possible to a representative sample. At the baseline exam, we will measure a large set of potential historical and clinical predictors of fractures. We will use single-photon absorptiometry of the radius and also x-ray the hand, spine and hips to determine whether simple radiographic measurements can identify those with the greatest risk of fracture. We will also freeze serum from all participants at the outset and test the stability of hormone measurements on a subsample after storage at -196 degrees C for several years; measurements that are shown to be stable will be the subject of a future study of the hormonal differences between women who suffer fractures and those who do not. We conservatively estimate that 165 hip and 150 Colles fractures will occur, yielding a power of .90 to detect risk ratios of less than 2.0 for common risk factors. Our prospective design will yield more information with fewer biases that the previous (retrospective) studies on this topic, and our nested-case control analyses will minimize the costs of the expensive endocrinologic and radiologic measurements. The study cohort, and its bank of sera, x-rays and clinical data is an excellent resource for future studies of osteoporosis, fractures and other diseases of the elderly. The results of our study will guide future research and rationalize clinical and public health efforts to prevent these fractures.
Keywords: aging, disease proneness /risk, female, hip fracture, injury prevention, limb fracture, wrist, bone density, caucasian American, dietary constituent, hormone regulation /control mechanism, human old age (65-84), life style, medical record, osteoporosis, skeletal disorder diagnosis, skeletal visualization, clinical chemistry, human clinical subject, photon absorptiometry, radiography
Project start date: 1986-02-01
Project end date: 1992-01-31
EPIDEMIOLOGY OF APO- & LIPO-PROTEINS IN ELDERLY WOMEN
Jane A Cauley, Professor
University Of Pittsburgh At Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
Grant 5R29HL040489-05 from National Heart, Lung, And Blood Institute IRG: EDC
Abstract: Coronary Heart Disease (CHD) is the leading cause of death in older women and accounts for a large proportion of illness and disability in women 65 years of age and older. However, the potential risk factors associated with the development and progression of CHD in elderly women remain poorly understood. The proposed research will examine the complex interactions between the traditional cardiovascular risk factors, in particular lipoprotein and apoprotein levels, and certain genetic and host characteristics and lifestyle habits. Specifically, this investigation will 1. described the distribution and interrelationships of lipoproteins and apoproteins in a large cohort of elderly women recruited for a prospective study of hip and wrist fractures; 2. examine the relationship of important host and lifestyle factors to the lipoprotein and apoprotein levels; 3. examine the population frequencies of phenotypes of the polymorphisms of apoprotein A-IV and E and to determine whether these polymorphisms are associated with specific patterns of lipo and apoproteins; and 4. test the hypothesis that the degree to which lifestyle and host characteristics explain the variability in lipoproteins and apoproteins depends on the genetic make up of the individual. This study is ancillary to the multicenter Study of Osteoporotic Fractures (SOF) and will involve 1000 of the 2400 women over the age of 65 recruited for SOF. It is believed that this study has the potential to advance our understanding of the risk factors for CHD in elderly women. The proposed study represents a new direction for epidemiologic studies by incorporating genetic markers and analyzing the degree to which these genetic markers can explain the variability in lipoprotein and apoprotein levels.
Keywords: apolipoprotein, biological polymorphism, cardiovascular disorder epidemiology, coronary disorder, disease proneness /risk, gene expression, genetic marker, hormone regulation /control mechanism, human old age (65+), life style, nonblood lipoprotein, alcoholic beverage consumption, body physical activity, cardiovascular disorder diagnosis, caucasian American, estrogen, female, heart disorder diagnosis, menopause, obesity, postmenopause, progestin, tobacco abuse, computer processing of clinical data, human clinical subject
Project start date: 1988-04-01
Project end date: 1994-03-31
5R29HL040489-05 (1992): $86266
TRAINING IN THE EPIDEMIOLOGY OF AGING
Jane A Cauley, Professor
Epidemiologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 2T32AG000181-11 from National Institute On Aging IRG: ZAG1
Project start date: 1989-09-04
Project end date: 2005-04-30
2T32AG000181-11 (2000): $265827
Jane A Cauley, Professor
Epidemiologyuniversity Of Pittsburgh At Pittsburgh
350 Thackeray Hall
pittsburgh, Pa 15260
Grant 5R01AR035582-11 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: EDC
Project start date: 1986-02-01
Project end date: 1996-12-31
5R01AR035582-11 (1996): $388896
3R01AR035582-11S1 (1996): $51755
3R01AR035582-10S2 (1995): $49687
3R01AR035582-10S1 (1995): $422795
3R01AR035582-07S1 (1992): $33350
Sponsored Links Excellgen http://Excellgen.com