Maternal efficiency during reproduction is essential for species propagation. The mammalian skeleton provides mineral for the fetal skeleton during pregnancy and milk production during lactation. Dramatic changes occur in the maternal skeleton during the reproductive cycle and some may serve to protect skeletal integrity. The post-lactation period is particularly 'anabolic', but mechanistically not understood. To further define the maternal skeletal adaptations and mechanisms that occur during and after the reproductive cycle, the following aims are proposed. 1). To determine the cellular and tissue events in the skeleton during the transition from late pregnancy to lactation. We hypothesize that the increases in resorption in late pregnancy and sustained during lactation are the result of an increased rate of osteoclast formation, prolongation of lifespan and a decrease in apoptosis. 2) To determine the cellular and tissue events in the skeleton that occur during the transition from lactation to post-weaning. The hypothesis is that increases in bone formation are associated with an increased rate of osteoblast formation but decreased resorption is the result of decreased osteoclast activity, decreased formation but increased apoptosis. 3) To determine if the post-weaning increase in calcitonin (CT) levels is correlated with decreased osteoclastic functions, and establishes the """"""""milieu"""""""" for the post-lactational recovery phase. We suspect correlation with decreases in prolactin, but increased estrogen and initiation of estrus. 4) Is there a change in the remodeling period during the reproductive cycle in mammals? This will be determined from archived materials from a species that has intracortical bone remodeling. 5) Does moderate skeletal loading improve bone mass, structure, strength and dynamics during the post-lactation 'recovery' phase? Our hypothesis is that skeletal loading will have synergistic effects on skeletal mass and structure during this period. These studies will provide new knowledge on perhaps the most dynamic and """"""""anabolic"""""""" period in the life of the adult female skeleton and may provide new insights into treatments of diseases after reproductive capacity has ended.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044806-05
Application #
6532968
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Program Officer
Mcgowan, Joan A
Project Start
1998-08-01
Project End
2005-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
5
Fiscal Year
2002
Total Cost
$225,000
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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