Osteoporosis, an illness resulting in weak and brittle bones, will soon cause over $25 billion dollars of economic damage to the US economy each year. For decades, menopausal osteoporosis was thought to be effect of bone turnover as a result of the loss of estrogen due to depletion of ovarian follicles. Recent research, however, has shown that the hormone primarily responsible for estrogen synthesis, follicle stimulating hormone (FSH), can contribute to bone degeneration. What is unclear is the specific mechanism by which FSH has this effect. We hypothesized that FSH may contribute to monocyte differentiation to osteoclasts. To test this, we used the RAW 246.7 murine monocyte cell line which can differentiate into osteoclasts in the presence of RANKL. We were able to find evidence of FSH-dependent signaling in cells FSH treated cells with or without RANKL. In particular, time dependent activation of the cyclic AMP Response Element Binding Protein (CREB) was observed along with other proteins utilized by FSH signaling and osteoclast differentiation. Interestingly, RANKL treatment changed the pattern of phosphorylation of CREB and the related transcription factor ATF1. Since CREB partially regulates osteoclast differentiation and function this could be one part of the mechanism by which FSH stimulates osteoclastogenesis and bone demineralization. With this in mind, future therapies targeting FSH action could be developed to prevent the onset of osteoporosis.