Analysis of the effects of physiological perturbations on the bone remodeling process
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The skeletal system is a dynamic organ that provides support, protection, aids in the production of all blood cells, and serves as a calcium ion reservoir. It is constantly undergoing a process called ‘remodeling’, which occurs through the actions of osteoclast and osteoblast cells. The former is responsible for breaking down bone whereas the latter secretes an organic matrix for bone synthesis. Two experiments were conducted to analyze the effects of physiological perturbations on the bone remodeling process. Specifically, the impact of aging and selective serotonin re-uptake inhibitor administration coupled with lactation on bone morphology and composition were observed. The bony skeleton is not a stagnant organ, rather it undergoes functional, mechanical, and compositional changes throughout life. Thus, we wanted to determine the consequences age had on various bone parameters and found a decrease in bone volume fraction (BV/TV), trabecular number (Tb.N), cortical thickness (C.Th), and an increase in periosteal area, endosteal area, and cortical porosity (C.Po). In regards to pregnancy, post-partum depression is a common condition. As a result, many women utilize selective serotonin re-uptake inhibitors (SSRIs) to combat the negative symptoms associated with it. Serotonin is an important hormone involved in mood regulation and the mammary-derived form has a role in lactation. It induces the production of parathyroid hormone-related protein, which is essential for regulating maternal calcium. Because the calcium source for milk production is derived from the maternal bone, we were interested in the impact peri-partum usage of SSRIs had on maternal bone mineral density. Additionally, we sought to understand the effect that circulating SSRIs had on the bone formation of pups. Analysis revealed age-related decreases in BV/TV, Tb.N, trabecular thickness (Tb.Th), C.Th and increases in trabecular spacing (Tb.Sp) and C.Po, with the effects being exacerbated in cohorts treated with a SSRI during lactation. We did not observe, however, any change in trabecular bone mineral density (Tb.BMD) or cortical bone mineral density (C.BMD) over time. In regards to the pups, we observed similar results to those of the dams in addition to a significant reduction in femur length. With the data obtained from the two projects, we hope that they bring awareness to potential consequences that physiological perturbations may have on the bone remodeling process. Both experiments have clinical correlations to humans. Further understanding the relationship between aging and bone may aid in developing methodologies to prevent age-related changes. On the other hand, analyzing the effects that SSRI usage has on maternal and child bone density may result in alternative methods to combat post-partum depression.