The Role of FSH in Osteoporosis & Ensuing Susceptibility to Fractures
Abstract
Around 10 million Americans suffer from osteoporosis, a disease that leads to over 1.5 million fractures every year and costs the national health care system between 17 to 20 billion dollars annually. Osteoporosis is a systemic disease that occurs when the rate of bone reabsorption (breakdown to retrieve calcium) surpasses the rate of bone regeneration. Our research stems from the observation that bone loss is more commonly seen in elderly women rather than in men: 80% of Americans with osteoporosis are women. Although previous studies suggest that the decrease in estrogen levels following menopause is the cause of bone loss, more recent research has proved that the highest rate of bone loss occurs during perimenopause when serum FSH levels spike which occurs before estrogen levels drop. In the past couple of years, research from Professor Cohen’s lab has concluded that osteoclast differentiation increases in the presence of FSH. If this is due to the presence of FSH receptors in osteoclasts, these would present as a critical target for pharmaceutical intervention. To explore this hypothesis a mouse osteoclast progenitor cell line was treated with RANK-Ligand to stimulate differentiation into osteoclasts. The osteoclasts were then treated with FSH in a time course. Some were pre-treated with negative allosteric modulators (NAMs) to prevent FSH activation of its receptor. The activation of the FSHRs in osteoclasts was measured using a western blot analysis. The data collected over the course of this experiment suggests that FSH receptors are present in osteoclasts. However, the presence of negative allosteric modulators did not seem to have particularly affected the hormone’s ability to activate signaling. Further investigation of the pathways through which FSH promotes the differentiation and proliferation of osteoblasts is needed to understand and identify new approaches for how they can be disrupted and prevent or minimize osteoporosis.