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“Purpose: Osteoporosis causes morbidity and mortality in men. The National Osteoporosis Foundation recommends fracture risk assessment with the online WHO/FRAX (R) tool. Although androgen deprivation therapy for

prostate cancer increases fracture risk, there is limited information about which men require preventative drug therapy. We applied the WHO/FRAX tool to men treated with androgen deprivation therapy for prostate cancer.

Materials and Methods: Information was collected from a practice cohort of men treated with gonadotropin-releasing hormone agonists, and included age, height, weight, Nutlin-3 nmr history of gonadotropin-releasing hormone agonist treatment, dual energy x-ray absorptiometry results, prior bone targeted therapy and clinical risk factors for fracture. Subjects were evaluated with the WHO/FRAX algorithm (http://www.shef.ac.uk/FRAX/).

Results: A total of 363 men treated with androgen deprivation therapy (median age 72 years) were evaluated. By the FRAX algorithm with clinical information (no dual energy x-ray absorptiometry data) the 3% hip fracture risk threshold

for treatment was exceeded by 51.2% of the men (median risk 3.1%). When subjects were grouped by age the treatment threshold was reached by 3.3% of those younger than 70 years, 76.6% of those 70 to 79 years old and by 98.8% Romidepsin mouse of those 80 years old or older. Using FRAX with bone mineral density data in the 93 patients who underwent bone mineral density testing the median 10-year hip fracture risk was 0.9% and the treatment threshold was exceeded by 15% of these subjects.

Conclusions: In this cohort of men receiving androgen deprivation therapy the prevalence of risk sufficient to necessitate drug therapy was high and was strongly influenced

by age. The WHO/FRAX algorithm identifies a greater proportion of men for treatment than the traditional threshold of T score -2.5 or less.”
“Sustained exposure to nicotine is well known to increase the cell surface density of alpha 4 beta 2* neuronal nicotinic receptors both in vivo Megestrol Acetate and in vitro, but the cellular mechanisms mediating this effect are equivocal. Using a pharmacological approach to investigate the effects of nicotine on receptor subunit expression and phosphorylation in SH-EP1 cells expressing human alpha 4 and beta 2 nicotinic receptor subunits, we have demonstrated that incubation with nicotine for 24 h increased the expression of immature and mature forms of both alpha 4 and beta 2 subunits in a concentration-dependent manner, and that inhibition of protein kinase C (PKC), but not cAMP-dependent protein kinase (PKA) inhibited the nicotine-induced increased expression of subunits. Incubation of cells with nicotine for 24 h also increased the phosphorylation of immature forms of alpha 4 subunits similar to that induced by activation of either PKC or PKA. When cells were preincubated with nicotine, the PKC-mediated increased phosphorylation was inhibited; the PKA-mediated phosphorylation was unaltered.