The objective of this proposal to document the changes in bone mass, structure and remodeling that occur during pregnancy, lactation and post- weaning in a nonhuman primate (Macaca nemestrina) model. The hypothesis to be tested is that pregnancy and lactation can result in irreversible bone loss in very young skeletally immature females. As a result, early reproducing females will not achieve peak bone mass. Low peak bone mass is a major risk factor for the development of post-menopausal osteoporosis, and the proposed research will elucidate some of the factors that contribute to the attainment and maintenance of peak bone mass. The methods to be used include bone densitometry, tetracycline labeling of bone, bone biopsy and biochemical measures of bone remodeling. nutrient intake and estrogenic status.
The specific aims are: (1) To describe with densitometric measurements the general pattern of bone loss and gain throughout a 12-month reproductive cycle (pregnancy, lactation, weaning) and post-weaning in a sample of 151 females followed prospectively; (2) to document with histomorphometry the static and kinetic parameters of bone remodeling and trabecular structure at early pregnancy and post-weaning; (3) to correlate with the histomorphometric data changes in levels of serum hormones and bone markers that regulate and/or reflect bone formation between primiparous immature females (greater than or equal to 4.50 yr. less than or equal to 6.5 yr.) vs. primiparous precocious immature females (less than or equal to 4.5 yrs); (5) to test, by comparison with 55 age- matched nulliparous females, whether primiparous precocious immature females achieve the predicted level of bone mass post-weaning, and (6) to test whether the bone mass of precocious immature females differs from that of their more mature cohorts at parity 3. The possibility of irreversible bone loss in the precocious immature reproductive female is central to defining the biological risks associated with early reproduction by human teenagers. Females who do not achieve optional peak bone mass are at high risk for fractures in the post-menopausal phase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR040813-03
Application #
2080268
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1992-02-01
Project End
1996-01-31
Budget Start
1994-02-01
Budget End
1995-01-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Washington
Department
Social Sciences
Type
Schools of Arts and Sciences
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kramer, Patricia Ann; Newell-Morris, Laura L; Simkin, Peter A (2002) Spinal degenerative disk disease (DDD) in female macaque monkeys: epidemiology and comparison with women. J Orthop Res 20:399-408
Lipkin, E W; Aumann, C A; Newell-Morris, L L (2001) Evidence for common controls over inheritance of bone quantity and body size from segregation analysis in a pedigreed colony of nonhuman primates (Macaca nemestrina). Bone 29:249-57
Ott, S M; Lipkin, E W; Newell-Morris, L (1999) Bone physiology during pregnancy and lactation in young macaques. J Bone Miner Res 14:1779-88
Ott, S M; O'Hanlan, M; Lipkin, E W et al. (1997) Evaluation of vertebral volumetric vs. areal bone mineral density during growth. Bone 20:553-6