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 osteoporosis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG012161-02
Application #
2053600
Study Section
Nutrition Study Section (NTN)
Project Start
1994-09-30
Project End
1999-08-31
Budget Start
1995-09-20
Budget End
1996-08-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Rutgers University
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
038633251
City
New Brunswick
State
NJ
Country
United States
Zip Code
08901
Rosanoff, Andrea; Dai, Qi; Shapses, Sue A (2016) Essential Nutrient Interactions: Does Low or Suboptimal Magnesium Status Interact with Vitamin D and/or Calcium Status? Adv Nutr 7:25-43
Chang, B; Schlussel, Y; Sukumar, D et al. (2015) Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction. Bone 81:138-144
Pop, L Claudia; Shapses, Sue A; Chang, Brian et al. (2015) VITAMIN D-BINDING PROTEIN IN HEALTHY PRE- AND POSTMENOPAUSAL WOMEN: RELATIONSHIP WITH ESTRADIOL CONCENTRATIONS. Endocr Pract 21:936-42
Von Thun, Nancy L; Sukumar, Deeptha; Heymsfield, Steven B et al. (2014) Does bone loss begin after weight loss ends? Results 2 years after weight loss or regain in postmenopausal women. Menopause 21:501-8
Jacobs, Thomas P; Kaufman, Martin; Jones, Glenville et al. (2014) A lifetime of hypercalcemia and hypercalciuria, finally explained. J Clin Endocrinol Metab 99:708-12
Shapses, S A; Sukumar, D; Schneider, S H et al. (2012) Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity. Osteoporos Int 23:2607-14
Douard, Veronique; Suzuki, Takuji; Sabbagh, Yves et al. (2012) Dietary fructose inhibits lactation-induced adaptations in rat 1,25-(OH)?D? synthesis and calcium transport. FASEB J 26:707-21
Sukumar, D; Partridge, N C; Wang, X et al. (2011) The high serum monocyte chemoattractant protein-1 in obesity is influenced by high parathyroid hormone and not adiposity. J Clin Endocrinol Metab 96:1852-8
Douard, Veronique; Asgerally, Abbas; Sabbagh, Yves et al. (2010) Dietary fructose inhibits intestinal calcium absorption and induces vitamin D insufficiency in CKD. J Am Soc Nephrol 21:261-71
Hawkins, Jaleah; Cifuentes, Mariana; Pleshko, Nancy L et al. (2010) Energy restriction is associated with lower bone mineral density of the tibia and femur in lean but not obese female rats. J Nutr 140:31-7

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