Date of Award

2017

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Bioengineering

First Advisor

X. Sherry Liu

Abstract

Pregnancy and lactation induce dramatic changes in maternal bone structure and mechanics, as a result of the increased calcium demand caused by fetal/infant growth. After weaning, the maternal skeleton enters an anabolic phase where reproductive bone losses are partially, but incompletely, recovered. However, clinical studies have indicated that reproductive history does not increase the long-term risk of developing osteoporosis or fracture, forming a paradox. This thesis aimed to thoroughly characterize the effects of pregnancy, lactation, and weaning on maternal bone structure and mechanics, and to investigate structural compensations that allow for the maintenance of the mechanical integrity of the female skeleton in the face of permanent, reproduction-induced alterations in skeletal phenotype. We used a rat model, combined with in vivo micro-computed tomography (µCT) imaging techniques, to track the immediate and long-term effects of reproduction on maternal bone at multiple skeletal sites. Our findings indicated that, although reproduction induces dramatic structural changes, many of which remain long after weaning, the maternal physiology also comprises several innate compensatory mechanisms that allow for the maintenance of skeletal mechanical integrity throughout the lifespan despite permanent, reproduction-induced skeletal deficits. We identified three such adaptations: 1) Changes in cortical bone structure and alterations in the load-sharing between the trabecular and cortical compartments allowed for the maintenance of whole-bone mechanics despite trabecular bone loss. 2) Location-specific differences in the extent of reproductive bone loss and post-weaning recovery resulted in a lower degree of microstructural deterioration at trabecular sites that play a critical load-bearing role. 3) Females appeared to start off with more bone than mechanically necessary, which allowed for a buffer to offset future reproductive bone loss. Furthermore, our final investigation of the effects of reproductive history on bone loss patterns later in life indicated a protective effect of reproduction on future estrogen-deficiency-induced bone loss, as rats with a history of pregnancy and lactation underwent lower rates of bone loss after ovariectomy than virgin rats with no prior history of reproduction. Overall, this work forms a strong foundation upon which to base further studies into the impacts of pregnancy, lactation, and weaning on maternal skeletal health.

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