The major goal of the proposed research is to investigate the determinants of bone dynamics in young women in order to develop strategies to prevent osteoporosis. Recent studies have confirmed that 1) peak bone density is a predictor of osteoporosis risk; 2) 50% of adult bone mass in females is acquired during adolescence; and 3) for most women, 95% of adult peak bone mass is achieved near the age of 20. The present study (in the first award period) was designed such that he cohort was homogeneous at entry at age 12 with respect to age, race, and pubertal development. BMI and baseline bone density values were used to balance the study groups with respect to genetic influences on bone. In this study, we used a randomized double- blind, placebo-controlled trial and determined that calcium supplementation of 350 mg/d calcium from calcium citrate malate initiated at either age 12 or at age 14 produces a 1.5% annualized increase (p=0.005) in normal bone gain. This increase, if continued for three years and maintained to peak bone mass, should lead to a significant reduction in risk of future osteoporotic fractures. We evaluated the interrelationships among physical activity, physical fitness, nutrient intake, pubertal progression and bone development in girls from age 12 through age 15 and determined that among well-nourished girls cumulative estrogen exposure and dietary calcium intake are the most powerful determinants of bone gain during early and mid-adolescence. We propose to continue to study the subjects from age 16-21 and to determine how dietary, endocrine and lifestyle factors affect bone dynamics and acquisition of peak bone mass. Of the 112 original volunteers, 90 remain in the present cohort and of these 89 (00%) are interested in remaining in the study. During the next 5 years, subjects will not receive calcium supplement or placebo pills;' and we will 1) Determine whether the increase in bone gain due to calcium supplementation from age 12 or from age 14 results increase in adult bone mass; 2) Determine how late adolescent bone gain is related to--a) cumulative adolescent dietary calcium intake; b) physical activity and physical fitness patterns; c) urinary collagen cross-link excretion; d) changes in body composition and anthropometric variables; and e) late adolescent and early adult reproductive hormone levels; 3) Quantify the effect of adolescent menstrual history, cumulative estrogen exposure and cumulative calcium intake on peak bone mass. Continuation of the longitudinal study design is essential to answering these questions. Each subject will be seen yearly. Comprehensive bone and body composition measurements will be made by dual energy x-ray absorptiometry (DEXA). We will also obtain medical and menstrual histories, anthropometric measurements, reproductive hormone measurement from serum samples, nutrient analyses from three day diet records, physical activity assessed by questionnaire, physical fitness measured by cycle ergometry, and bone-specific collagen crosslink excretion measured from urine specimens. The findings from this study will lead to a grater understanding of how modifiable life style factors affect peak bone mass dynamics. Such knowledge is essential to the development of bone health promotion strategies for young American women.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025973-08
Application #
2025241
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1989-12-01
Project End
1999-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Devlin, M J; Stetter, C M; Lin, H-M et al. (2010) Peripubertal estrogen levels and physical activity affect femur geometry in young adult women. Osteoporos Int 21:609-17
Petit, Moira A; Beck, Thomas J; Hughes, Julie M et al. (2008) Proximal femur mechanical adaptation to weight gain in late adolescence: a six-year longitudinal study. J Bone Miner Res 23:180-8
Lloyd, Tom; Petit, Moira A; Lin, Hung-Mo et al. (2004) Lifestyle factors and the development of bone mass and bone strength in young women. J Pediatr 144:776-82
Petit, Moira A; Beck, Thomas J; Lin, Hung-Mo et al. (2004) Femoral bone structural geometry adapts to mechanical loading and is influenced by sex steroids: the Penn State Young Women's Health Study. Bone 35:750-9
Legro, Richard S; Lin, Hung Mo; Demers, Laurence M et al. (2003) Urinary free cortisol increases in adolescent caucasian females during perimenarche. J Clin Endocrinol Metab 88:215-9
Lloyd, Tom; Lin, Hung Mo; Matthews, Amy E et al. (2002) Oral contraceptive use by teenage women does not affect body composition. Obstet Gynecol 100:235-9
Lloyd, Tom; Lin, Hung Mo; Eggli, Douglas F et al. (2002) Adolescent Caucasian mothers have reduced adult hip bone density. Fertil Steril 77:136-40
Lloyd, T; Beck, T J; Lin, H-M et al. (2002) Modifiable determinants of bone status in young women. Bone 30:416-21
Lloyd, T; Taylor, D S; Lin, H M et al. (2000) Oral contraceptive use by teenage women does not affect peak bone mass: a longitudinal study. Fertil Steril 74:734-8
Legro, R S; Lin, H M; Demers, L M et al. (2000) Rapid maturation of the reproductive axis during perimenarche independent of body composition. J Clin Endocrinol Metab 85:1021-5

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