PATHOPHYSIOLOGY OF INVOLUTIONAL OSTEOPOROSIS

  • Oursler, Merry Jo (PI)
  • Riggs, Lawrence B. (PI)
  • Melton, Joseph L. (PI)
  • Mann, Kenneth (PI)
  • O'Fallon, William (PI)
  • Riggs, B. Lawrence (PI)
  • Melton, Joseph (PI)
  • Ofallon, William M. (PI)
  • Melton, Joseph (PI)
  • Melton, Joseph L. (PI)
  • Mann, Kenneth (PI)
  • Riggs, Lawrence B. (PI)
  • O'Fallon, William (PI)
  • Ofallon, William M. (PI)
  • Melton, Joseph (PI)
  • Lawrence Riggs, B. (PI)
  • Melton, Joseph (PI)
  • Khosla, Sundeep (PI)
  • Spelsberg, Thomas C (PI)
  • Monroe, David G (PI)
  • Amin, Shreyasee (PI)

Project: Research project

Project Details

Description

Osteoporosis is a multifactorial disorder. Our overall objective is to
develop a more coherent understanding of the etiology and pathophysiology
of the age-related bone loss that leads to osteoporosis. We will pursue
this objective using two strategies. First, we will study normal women to
understand better the two most important causes of involutional bone loss -
- estrogen deficiency and age-related processes. These studies will allow
us to elucidate mechanisms of bone loss in the general population during
the latent period before osteoporosis has occurred. Second, we will study
mechanisms of one loss in a women who have already developed postmenopausal
osteoporosis. These studies will allow us to determine if mechanisms of
bone loss in osteoporotic women differ substantially from those in
comparable women without osteoporosis. These issues will be addressed by
carrying out 8 experimental protocols encompassed in 3 specific aims.
Specific Aim #1 is to define more completely the pathophysiologic
mechanism(s) by which estrogen deficiency causes negative calcium (Ca)
balance and bone loss in normal postmenopausal women by a) elucidating
mechanism(s) for decreased intestinal Ca absorption (Protocol 1), b)
elucidating mechanism(s) for increased renal Ca excretion (Protocol 2), and
c) assessing the relationship among estrogen deficiency, bone turnover, and
production of bone-resorbing cytokines (Protocol 3). Specific Aim #2 is to
define further the causal mechanism(s) for age-related bone loss in normal
elderly women y a) determining if they have intestinal resistance to
vitamin D action (Protocol 4), b) determining if the previously observed
nocturnal increases in serum parathyroid hormone with aging are related to
Ca deficiency (Protocol 5), and c) determining if estrogen deficiency
continues to contribute to increased bone turnover late in life (Protocol
5), and c) determining if estrogen deficiency continues to contribute to
increased bone turnover late in life (Protocol 6). After studying normal
individuals to address the first two specific aims, in studies addressing
Specific Aim #3, we will search for potentially unique abnormalities in
women with postmenopausal osteoporosis that could account for their
increased rate of bone turnover and bone loss by a) searching for a defect
in parathyroid hormone-mediated renal Ca transport that might explain
previously observed abnormalities in renal Ca conservation in these women
(Protocol 7) and b) defining the mechanisms of bone loss that we seek to
uncover is needed to develop more rational strategies for the prevention
and treatment of osteoporosis.
StatusFinished
Effective start/end date9/1/844/30/20

ASJC

  • Medicine(all)