Osteoporotic fractures are a major source of morbidity and mortality in older women. The incidence of hip fractures in women doubles every five to sex years after age 40; 25-30% of women with hip fracture lose their independence as a result of fracture. Vertebral crush fractures also increase with age and may result in substantial pain and functional decline. Although women over 70 years are at the highest risk for osteoporotic hip and spine fractures, most research has focused on prevention of fractures in more recently menopausal women. We propose a three- part intervention development study (IDS) to closely examine the effect of estrogen on local factors in bone, bone turnover, and bone loss at the hip. Part A of IDS#1 will examine skeletal dose response, as measured by biochemical markers of bone turnover, to randomized, sequential 6-week courses of micronized 17beta-estradiol (0.25mg, 0.5 mg, 1.0 mg.). Sixty women, stratified by age (55-69 years or 70-85 years), will then be randomized to a treatment regimen (order of estrogen does). Serum and urine will be collected for measurement of biochemical markers at baseline, 6 weeks on treatment and 6 weeks post-treatment for each dose of estrogen. There will be a 6-week wash-out period between each dose; all woman will receive each dose of estrogen. We will also determine the lowest dose of estrogen to decrease bone turnover in the older age group; this dose will be used in Part b of IDS#1. Part B is a 2-year study to compare the effect of estrogen, calcium, the combination of estrogen and calcium and a control group on bone density at the hip in women over 70-85 years. One-hundred and sixty women will be randomized to the above treatment groups for 2 years. Part C of IDS#1 is a pilot study to quantitate gene expression of local regulatory factors and constitutive proteins in of women who undergo estrogen withdrawal or estrogen replacement. We will recruit 12 women over 70 years -6 who have not received estrogen in the past 10 years (group 1) and 6 who have been on estrogen for at least 2 years (group 2). Group 1 will be placed on 1.0 mg/d 17beta-estradiol and Group 2 will be withdrawn from estrogen. cDNA will be prepared by reverse transcribing mRNA from small needle iliac crest biopsy obtained at baseline and 3 months after estrogen withdrawal or replacement. If bone in older women is more sensitive to ERT than younger women, then a lower dose might reduce bone turnover and prevent bone loss at the hip without producing adverse effects, such as breast tenderness and fluid retention, two very common complaints of women taking ERT. Thus, older women may be more willing to accept ERT. Further, if these studies demonstrate substantial differences in local regulators associated with estrogen deficiency and replacement, the results could lead to new approaches to the prevention and therapy of bone loss in older adults.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Comprehensive Center (P60)
Project #
5P60AG013631-04
Application #
6395463
Study Section
Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
DUNS #
City
Farmington
State
CT
Country
United States
Zip Code
06030
Fragala, Maren S; Dam, Thuy-Tien L; Barber, Vanessa et al. (2015) Strength and function response to clinical interventions of older women categorized by weakness and low lean mass using classifications from the Foundation for the National Institute of Health sarcopenia project. J Gerontol A Biol Sci Med Sci 70:202-9
Fragala, Maren S; Clark, M H; Walsh, Stephen J et al. (2012) Gender differences in anthropometric predictors of physical performance in older adults. Gend Med 9:445-56
Kenny, Anne M; Kleppinger, Alison; Annis, Kristen et al. (2010) Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc 58:1134-43
Estrada, Marcos; Kleppinger, Alison; Judge, James O et al. (2007) Functional impact of relative versus absolute sarcopenia in healthy older women. J Am Geriatr Soc 55:1712-9
Pefanco, Mary Ann; Kenny, Anne M; Kaplan, Richard F et al. (2007) The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women. J Am Geriatr Soc 55:426-31
Kenny, Anne M; Waynik, Ilana Y; Smith, JoAnne et al. (2006) Association between level of frailty and bone mineral density in community-dwelling men. J Clin Densitom 9:309-14
Unson, Christine G; Fortinsky, Richard; Prestwood, Karen et al. (2005) Osteoporosis medications used by older African-American women: effects of socioeconomic status and psychosocial factors. J Community Health 30:281-97
Boxer, R S; Kenny, A M; Dowsett, R et al. (2005) The effect of 6 months of androgen deprivation therapy on muscle and fat mass in older men with localized prostate cancer. Aging Male 8:207-12
Judge, James Oat; Kleppinger, Alison; Kenny, Anne et al. (2005) Home-based resistance training improves femoral bone mineral density in women on hormone therapy. Osteoporos Int 16:1096-108
Kenny, Anne M; Kleppinger, Alison; Wang, Yahzen et al. (2005) Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women. J Am Geriatr Soc 53:1973-7

Showing the most recent 10 out of 50 publications