During pregnancy and breastfeeding, the maternal skeleton serves as an important source of calcium for fetal/infant growth. This results in a substantial loss of maternal bone mass. However, at the same time, the skeleton must also continue to perform its mechanical function, bearing the loads applied during everyday activities. This balance is achieved through adaptations during pregnancy and lactation and partial recovery of bone mass after weaning, which allow the mechanical strength of the maternal skeleton to be preserved. The mechanisms behind the skeleton's amazing ability to balance these metabolic and mechanical functions during female reproduction are not clear. By elucidating the underlying mechanisms, this Faculty Early Career Development (CAREER) Program project will increase our scientific knowledge on the changes in bone structure, mechanical properties, and bone cells' responses to mechanical forces that occur as a result of childbearing. Through the education program, this project will inspire interest in bone biology and mechanics among high school students, foster interdisciplinary learning and research in musculoskeletal engineering and science in undergraduate students, and enhance communication with the general public on the educational context of bone biology, structure and mechanics.
The first objective of this project is to quantify the effects of physiological load-bearing and determine the effects of bone's mechano-sensitivity on skeletal responses to pregnancy and lactation. Trabecular and cortical bone structure, mechanics, and remodeling activities will be compared among multiple skeletal sites that undergo various amounts of load-bearing during daily activities. The extent of bone formation in response to a range of low to high peak strains applied through axial tibial loading in virgin rats and rats at different reproductive stages will be compared. The second objective of the project is to define mechanisms by which pregnancy and lactation modulate the osteocyte micro-mechanical environment and mechano-sensitivity. This will be achieved by integrating advanced imaging, mechanical testing, and simulation techniques for assessment of changes in lacunar and canalicular structure, peri-lacunar bone tissue material properties, and load-induced fluid flow stimulation experienced by osteocytes and their processes in response to different stages of female reproduction. The proposed study will discover and understand novel functions of the osteocyte in modulating its micro-mechanical environment and mechano-sensitivity to maintain the integrity of the maternal skeleton, and provide insight into prevention and management of osteoporosis during pregnancy and lactation.
