There is evidence that both aging and menopause contribute to bone loss from the proximal femur. The menopause component is more clearly defined, it causes about 20% of the lifetime loss in the femoral neck, and that component occurs in about 7 years. The cause of femoral neck loss prior to menopause is not understood at all, but it represents 30% of lifetime loss. The other 50% of femoral neck loss occurs between age 60 and 90 years. Our hypothesis is that malabsorption of calcium, which starts in the mid sixties, together with secondary hyperparathyroidism plays a pathogenic role. The objectives of these studies are to identify the causes of malabsorption of calcium in a random subset of 100 women before starting the clinical trial. We will measure calcium absorption, vitamin D metabolites and duodenal samples for 1,25 dihydroxy vitamin D receptor concentration. An initial classification of 'aging gut' versus 'kidney' could be made by finding low receptor concentration but normal serum 1,25(OH)2D in the former and the opposite in the latter. However, in the 'kidney' group, there is a possibility of a primary or secondary decrease in 1,25(OH)2D production. To separate primary from secondary, subjects will undergo dynamic stimulation with PTH, presumably the aging kidney (primary) will produce less 1,25(OH)2D than the secondary group. After a year on therapy, the subset (25 from each group) will have all tests repeated and the effect of estrogen or 1alphahydroxyvitamin D2 on receptors, vitamin D levels and absorption followed. Because secondary hyperparathyroidism increases bone turnover, serum osteocalcin, urine hydroxyproline and Pyridinium cross links will be used to follow turnover. Correlations between absorption and bone turnover in the placebo group of 125 subjects will be examined, as well as the effect of improved calcium absorption (after 1alpha-OH-D2 therapy) on bone turnover. Estrogen may have an independent action on bone resorption irrespective of changes in absorption. These studies could identify subsets of elderly subjects who would benefit selectively from estrogen or vitamin D analogues and provide a rational basis for the treatment of bone loss.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010358-04
Application #
2051615
Study Section
Biological and Clinical Aging Review Committee (BCA)
Project Start
1991-09-30
Project End
1996-08-31
Budget Start
1994-09-15
Budget End
1995-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Creighton University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68178
Yalamanchili, Vinod; Gallagher, J Christopher (2012) Treatment with hormone therapy and calcitriol did not affect depression in older postmenopausal women: no interaction with estrogen and vitamin D receptor genotype polymorphisms. Menopause 19:697-703
Sai, Adarsh J; Gallagher, J Christopher; Fang, Xiang (2011) Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-? genotypes. Menopause 18:1101-12
Sai, A J; Walters, R W; Fang, X et al. (2011) Relationship between vitamin D, parathyroid hormone, and bone health. J Clin Endocrinol Metab 96:E436-46
Gallagher, J C; Rapuri, Prema; Smith, Lynette (2007) Falls are associated with decreased renal function and insufficient calcitriol production by the kidney. J Steroid Biochem Mol Biol 103:610-3
Rapuri, Prema B; Gallagher, J Christopher; Smith, Lynette M (2007) Smoking is a risk factor for decreased physical performance in elderly women. J Gerontol A Biol Sci Med Sci 62:93-100
Rapuri, P B; Gallagher, J C; Knezetic, J A et al. (2006) Estrogen receptor alpha gene polymorphisms are associated with changes in bone remodeling markers and treatment response to estrogen. Maturitas 53:371-9
Rapuri, Prema B; Gallagher, J Christopher; Haynatzki, Gleb (2004) Endogenous levels of serum estradiol and sex hormone binding globulin determine bone mineral density, bone remodeling, the rate of bone loss, and response to treatment with estrogen in elderly women. J Clin Endocrinol Metab 89:4954-62
Rapuri, P B; Gallagher, J C; Knezetic, J A et al. (2004) Association between Vitamin D receptor polymorphisms and the rate of bone loss in elderly women-importance of adjusting for dietary and lifestyle factors. J Steroid Biochem Mol Biol 89-90:503-6
Rapuri, P B; Gallagher, J C (2004) Effect of Vitamin D supplement use on serum concentrations of total 25OHD levels in elderly women. J Steroid Biochem Mol Biol 89-90:601-4
Rapuri, Prema B; Gallagher, J Christopher; Haynatzka, Vera (2003) Protein intake: effects on bone mineral density and the rate of bone loss in elderly women. Am J Clin Nutr 77:1517-25

Showing the most recent 10 out of 22 publications