There are substantial changes in skeletal metabolism during pregnancy (for fetal skeletal mineralization), lactation (for milk production), and after weaning (to reconstitute mineral stores). Recent evidence indicates considerable reconstitution of skeletal tissues after lactation (""""""""recovery""""""""). The goals of the presently proposed studies are to, first, determine the mechanisms of this anabolic phase in the female, and, second, to utilize this information to develop paradigms and strategies for osteopenias (e.g., postmenopausal osteoporosis). The following Specific Aims are proposed: 1) to determine the """"""""tissue-level"""""""" mechanisms of cancellous and cortical bone loss during lactation and skeletal recovery after lactation. It is hypothesized that tissue-level modeling and remodeling mechanisms protect skeletal structure and function. Changes at different bone compartments and envelopes will be determined using morphometric, chemical and absorptiometric methods in rats; 2) to determine the basic endocrine environment during lactation and recovery after lactation. Endocrine events will be correlated with tissue-level skeletal mechanisms; 3) to test the hypothesis that the re-establishment of an estrus cycle is important in skeletal preservation during and after lactation. It is suggested that re-establishment of the menstrual cycle is important for recovery in the human and this will be modeled with natural estrus initiation or delay (by induction of pseudopregnancy) in rats; 4) to test the hypothesis that physiologically relevant levels of transiently elevated parathyroid hormone (PTH) which occur during lactation are anabolic, rather than catabolic. Shorter-term changes in endogenous PTH will be measured and then these levels will be replicated in a known PTH-responsive model to assess anabolic actions. (The applicant suggests that this could be the first demonstration of a physiologically anabolic role of PTH.); and 5) to test the hypothesis that mechanical loading is a critical determinant of skeletal reconstitution after lactation. For this, an established model of skeletal unloading will be used. Collectively, these studies are intended to provide significant new information on perhaps one of the most anabolic phases in the life-cycle of the adult female skeleton.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR044806-01A1
Application #
2691106
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1998-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Utah
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Miller, Scott C; Bowman, Beth M (2007) Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during the bone remodeling reversal at the end of lactation. Anat Rec (Hoboken) 290:65-73
Miller, Scott C; Anderson, Brian L; Bowman, Beth M (2005) Weaning initiates a rapid and powerful anabolic phase in the rat maternal skeleton. Biol Reprod 73:156-62
Miller, Scott C; Bowman, Beth M (2004) Rapid improvements in cortical bone dynamics and structure after lactation in established breeder rats. Anat Rec A Discov Mol Cell Evol Biol 276:143-9
Wang, Dong; Miller, Scott C; Sima, Monika et al. (2004) The arthrotropism of macromolecules in adjuvant-induced arthritis rat model: a preliminary study. Pharm Res 21:1741-9
Vrotsos, Yannis; Miller, Scott C; Marks Jr, Sandy C (2003) Prostaglandin E--a powerful anabolic agent for generalized or site-specific bone formation. Crit Rev Eukaryot Gene Expr 13:255-63
Shea, Jill E; Miller, Scott C; Poole, David C et al. (2003) Cortical bone dynamics, strength, and densitometry after induction of emphysema in hamsters. J Appl Physiol 95:631-4
Blum, Stephanie C; Heaton, Susanne N; Bowman, Beth M et al. (2003) Dietary soy protein maintains some indices of bone mineral density and bone formation in aged ovariectomized rats. J Nutr 133:1244-9
Miller, S C; Bowman, B M; Siska, C C et al. (2002) Effects of thermal injury on skeletal metabolism in two strains of mice. Calcif Tissue Int 71:429-36
Barry, A B; Baig, A A; Miller, S C et al. (2002) Effect of age on rat bone solubility and crystallinity. Calcif Tissue Int 71:167-71
Bowman, B M; Siska, C C; Miller, S C (2002) Greatly increased cancellous bone formation with rapid improvements in bone structure in the rat maternal skeleton after lactation. J Bone Miner Res 17:1954-60

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