Osteoporosis is a major public health problem, with over 50% of Caucasian women and nearly 20% of Caucasian men at risk for an osteoporotic fracture in their lifetime (NIH Osteoporosis and Related Bone Diseases - National Resource Center). While some of the predictors of peak bone mass (PBM) include genetic predisposition and environmental factors, such as physical activity and diet, peak bone mass is also influenced by rapid changes in reproductive hormone levels for both genders, especially estrogen and progesterone during the accelerated growth period. Despite its well-studied effects in the reproductive system, progesterone's effects on bone metabolism remain largely unknown. In our laboratory, mice whose nuclear progesterone receptors (PR) were rendered nonfunctional (PRKO) exhibited a rapid gain of bone mass (age 1-3 months) and greater peak bone mass but with a sex difference in magnitude of increase (3- fold higher PBM in females and +50% in males) in comparison to their wild type (WT) litter mates (Yao et al. 2009). Thus, the presence of progesterone nuclear receptors exerts inhibitory effects on bone formation during the period of rapid bone acquisition, and this inhibition is more profound in female mice. Based on our preliminary observations, we hypothesize that progesterone signaling inhibits bone formation during the rapid bone growth period such that peak bone mass is lower in females than in males. We further hypothesize that inhibition of progesterone signaling in osteoblasts during the period of rapid bone acquisition period accelerates achievement of peak bone mass, especially for females. To test our hypotheses, we propose the following specific aims:
Specific Aim 1 : To investigate the direct effects of PR deletion on osteoblast and bone formation and compare these effects in female and male mice.
Specific Aim 2 : To determine if the inhibition of PR in vivo will lead to an uncoupling of bone turnover, we will monitor bone architecture and bone turnover changes following these interventions to determine how these interventions affect peak bone mass acquisition and if the responses would be differ between the sexes.

Public Health Relevance

Osteoporosis is a major public health problem that currently affects 44 million Americans. Progesterone is known for its effects on the reproductive system, but its physiological roles in skeletal metabolism remains unclear. This study aims to clarify differences in peak bone mass acquisition between sexes with the overall goal of explaining sex differences in musculoskeletal diseases across the lifespan.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Davis
United States
Zip Code
Chaudhari, Abhijit J; Leahy, Richard M; Wise, Barton L et al. (2014) Global point signature for shape analysis of carpal bones. Phys Med Biol 59:961-73
Katzman, Wendy B; Miller-Martinez, Dana; Marshall, Lynn M et al. (2014) Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the Osteoporotic Fractures in Men (MrOS) research group. BMC Musculoskelet Disord 15:19
Nardo, Lorenzo; Lane, Nancy E; Parimi, Neeta et al. (2014) Diffuse idiopathic skeletal hyperostosis association with thoracic spine kyphosis: a cross-sectional study for the Health Aging and Body Composition Study. Spine (Phila Pa 1976) 39:E1418-24
Wise, Barton L; Parimi, Neeta; Zhang, Yuqing et al. (2014) Frailty and hip osteoarthritis in men in the MrOS cohort. J Gerontol A Biol Sci Med Sci 69:602-8
Boissonneault, A; Lynch, J A; Wise, B L et al. (2014) Association of hip and pelvic geometry with tibiofemoral osteoarthritis: multicenter osteoarthritis study (MOST). Osteoarthritis Cartilage 22:1129-35
Amugongo, Sarah K; Yao, Wei; Jia, Junjing et al. (2014) Effect of sequential treatments with alendronate, parathyroid hormone (1-34) and raloxifene on cortical bone mass and strength in ovariectomized rats. Bone 67:257-68
Nelson, Amanda E; Liu, Felix; Lynch, John A et al. (2014) Association of incident symptomatic hip osteoarthritis with differences in hip shape by active shape modeling: the Johnston County Osteoarthritis Project. Arthritis Care Res (Hoboken) 66:74-81
Siris, E S; Adler, R; Bilezikian, J et al. (2014) The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int 25:1439-43
Bansal, Symron; Katzman, Wendy B; Giangregorio, Lora M (2014) Exercise for improving age-related hyperkyphotic posture: a systematic review. Arch Phys Med Rehabil 95:129-40
Chaganti, R K; Tolstykh, I; Javaid, M K et al. (2014) High plasma levels of vitamin C and E are associated with incident radiographic knee osteoarthritis. Osteoarthritis Cartilage 22:190-6

Showing the most recent 10 out of 18 publications