| Osteoporosis and cardiovascular disease (CVD) are common age-related conditions, which are major public health problems leading to an increase in mortality, morbidity, and disability. There have been several connections found between CVD and osteoporosis such as common genetic factors, risk factors, and pathological mechanisms. There is a direct effect of estrogen and Neuropeptide Y antagonist on CVD and osteoporosis that is demonstrated by the manifestation of estrogen receptors on osteoblasts, osteoclasts, and vascular endothelial and smooth muscle cells. Loss of estrogen has been found to be involved in the pathogenesis of atherosclerosis and bone loss through modulation of other factors including cytokines and oxidized lipids. The goal of this proposed research was to determine if sustained delivery of estrogen and antagonizing NPY is capable of regulating bone cell function while improving cardiovascular panels. Osteoblast and osteoclast cells were treated for periods of 24, 48 and 72 hours in the presence of estrogen, or an antagonist to neuropeptide Y. Following the incubation, cell viability, cell function, and morphology were determined. The results indicated a significant increase in osteoblast proliferation and alkaline phosphate production in cells treated with estrogen and antagonist to NPY without evidence of cellular damage. Estrogen did not affect osteoclast cell numbers, while neuropeptide Y antagonist reduced osteoclast numbers. The data shows Y antagonist may be a useful and safe compound that could be used in the treatment of osteoporotic fractures. Ovariectomized Sprague Dawley rats were administered estradiol and NPY antagonist at a rate of 5ng/day over an eight-week period. Body weights, estradiol levels, cholesterol levels, and bone strength were determined at 2, 4, and 8 weeks following sustained delivery of estradiol and NPY antagonist and compared with intact control and ovariectomized control animals. Estrogen and NPY antagonist replacement resulted in improved cholesterol panels without significant changes in bone flexural strength or improvements in bone porosity. Additional long term studies are needed to determine if the benefits of estrogen replacement outweigh the inherent risks associated with hormone replacement therapies. |
