Osteoporosis is a widespread condition associated with over 250,000 hip fractures each year. Although more than 90% of these fractures occur in individuals over 70, little information is available on the effectiveness, benefits and side effects of therapy for osteoporosis of the hip in elderly women. We postulate that in women age 65 and over: (1) a) bisphosphonate therapy will maintain femoral bone mass, b) estrogen replacement therapy will independently aid in maintaining hip bone mineral density, and c) the combination of bisphosphonate and estrogen replacement therapy will have an additional positive effect in maintaining femoral bone mass; and (2) bisphosphonate will have the unique complementary benefit of increasing femoral and radial bone strength estimates. To investigate these hypotheses, we will conduct a four-arm, double-blind, placebo-controlled study in community-dwelling elderly women age 65 years and over. Initially, all participants will complete a two month """"""""run in"""""""" phase of daily oral combined continuous estrogen-progesterone therapy to optimize compliance and reduce drop-out following subsequent randomization. Following this """"""""run in"""""""" period, 368 women will be randomized to receive daily oral therapy with (1) bisphosphonate therapy (Alendronate 10 mg), (2) standard combined continuous estrogen-progesterone replacement therapy (Premarin 0.625 g and Provera 2.5 mg), (3) standard combined continuous estrogen-progesterone replacement therapy (Premarin .625 mg and Provera 2.5 mg) and bisphosphonate (Alendronate 10 mg), or (4) placebo. The major outcome variable ill be hip bone mineral density as assessed by Dual Energy X-Ray Absorptiometry. We will follow bone density of the femoral neck, total hip, trochanter, intertrochanter, and Ward's triangle in addition to vertebral, radial and total bone density and indices of bone metabolism at six month intervals for two years. We will estimate femoral and radial bone strength as predicted by integrated measures of density and cross- sectional moments of inertia. We will investigate whether such therapy (1) will prevent or reverse femoral bone loss, (2) will maintain or increase bone strength estimates, (3) has differential effects on hip, vertebral, or radial bone mass, (4) has differential effects on cortical and trabecular bone density, and (5) alters indices of bone mineral metabolism. Furthermore, we will determine if the response to therapy can be predicted by indices of bone mineral metabolism or vitamin D receptor alleles. Data derived from this study should provide the basic for an effective intervention to stabilize or increase femoral bone mass and reserve architectural integrity in elderly women.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG013069-03
Application #
2413351
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Project Start
1995-08-20
Project End
2000-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02215
Greenspan, Susan L; Perera, Subashan; Nace, David et al. (2012) FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities. J Am Geriatr Soc 60:684-90
Levy, Matthew E; Parker, Robert A; Ferrell, Robert E et al. (2007) Farnesyl diphosphate synthase: a novel genotype association with bone mineral density in elderly women. Maturitas 57:247-52
Greenspan, Susan L; Resnick, Neil M; Parker, Robert A (2005) Vitamin D supplementation in older women. J Gerontol A Biol Sci Med Sci 60:754-9
Greenspan, Susan L; Resnick, Neil M; Parker, Robert A (2005) Early changes in biochemical markers of bone turnover are associated with long-term changes in bone mineral density in elderly women on alendronate, hormone replacement therapy, or combination therapy: a three-year, double-blind, placebo-controlled, rando J Clin Endocrinol Metab 90:2762-7
Greenspan, Susan L; Resnick, Neil M; Parker, Robert A (2005) The effect of hormone replacement on physical performance in community-dwelling elderly women. Am J Med 118:1232-9
Greenspan, Susan L; Beck, Thomas J; Resnick, Neil M et al. (2005) Effect of hormone replacement, alendronate, or combination therapy on hip structural geometry: a 3-year, double-blind, placebo-controlled clinical trial. J Bone Miner Res 20:1525-32
Greenspan, Susan L; Resnick, Neil M; Parker, Robert A (2003) Combination therapy with hormone replacement and alendronate for prevention of bone loss in elderly women: a randomized controlled trial. JAMA 289:2525-33
Ferrari, S L; Ahn-Luong, L; Garnero, P et al. (2003) Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women. J Clin Endocrinol Metab 88:255-9
Ferrari, S L; Garnero, P; Emond, S et al. (2001) A functional polymorphic variant in the interleukin-6 gene promoter associated with low bone resorption in postmenopausal women. Arthritis Rheum 44:196-201
Regan, M M; Emond, S K; Attardo, M J et al. (2001) Why do older women discontinue hormone replacement therapy? J Womens Health Gend Based Med 10:343-50

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