Project Details


Osteoporosis affects 20% of the female population over 65 years of age and
there is an 80% excess mortality after an osteoporotic fracture. The
preservation of bone mass as well as achieving a peak bone mass are
fundamental to preventing this disease state. The risk of osteoporosis
increases in women of low body weight or those who have a history of weight
loss. In addition, recent studies have shown that in obese subjects, bone
mineral density (BMD) decreases after moderate weight loss. Such findings
are of particular concern due to the large number of American women (up to
40%) who are following a weight loss regimen. During weight reduction, the
loss in lean body mass is dependent on the total caloric deficit and the
protein intake. There is limited information about the loss of other
proteins, such as collagen, which makes up approximately one third of the
protein in the body and is primarily in bone. Collagen has a slow rate of
turnover and therefore has generally been thought to be spared during semi-
starvation. Our preliminary data, however, suggest the Opposite. We found
that the rate of collagen cross-link excretion (as a measure of collagen
turnover which represents bone resorption) doubles during a moderate weight
loss regimen of about 1100 kcal/d. Moreover, the increased rate of bone
resorption was greater in postmenopausal than premenopausal women. Subjects
were counseled to consume about 800 mg of calcium/d, however their actual
intake averaged about 500 mg/d. Thus, it is not clear whether calories
and/or calcium might be responsible for the marked increased in bone
resorption. The proposed investigation will explore the nutritional
regulation of bone turnover during moderate weight reduction. Specifically,
we will test the hypothesis that a low calcium intake during weight
reduction accelerates the rate of bone turnover. Two recently developed
measures of bone turnover, collagen cross-link excretion and serum
osteocalcin levels, both of which are sensitive and specific for short-term
studies, will be used to examine bone resorption and synthesis,
respectively. We will determine whether the rate of weight loss, the
absolute weight loss, or the level of calcium intake influence the rate of
bone turnover and BMD. In addition, in order to address the mechanisms by
which bone turnover is altered, the effect of weight loss and calcium
intake on the hormonal regulators of bone turnover will be assessed.
Complementary studies in a rat model will be used to further explore how
nutritional parameters regulate bone composition, histology, and
biomechanical properties. Importantly, these rodent studies will directly
assess the relationship between biochemical and clinical indexes of bone
health with the incidence of bone fractures. The long-term goals of this
research program are to determine nutritional influences on cartilaginous
tissues which can be applied in the prevention and treatment of
Effective start/end date9/30/948/31/99


  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging
  • National Institute on Aging


  • Rheumatology


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