PATHOPHYSIOLOGY OF SENILE TYPE 11 OSTEOPOROSIS

Project: Research project

Description

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.
StatusFinished
Effective start/end date9/30/918/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $177,406.00
  • National Institutes of Health: $293,108.00
  • National Institutes of Health

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Osteoporosis
Femur Neck
Menopause
Vitamin D
Calcium
Estrogens
Bone Remodeling
Kidney
Bone and Bones
Calcitriol Receptors
Secondary Hyperparathyroidism
Hydroxyproline
Femur
Therapeutics
Placebos
Urine
Serum