title: Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women.
abstract: Although median levels of bone turnover are increased in postmenopausal women, it is unclear whether the low circulating levels of endogenous estrogen exert a regulatory role on these levels. This issue was evaluated by assessing the effect of a blockade of estrogen synthesis on bone turnover markers in 42 normal women (mean age +/- SD, 69 +/- 5 years) randomly assigned to groups receiving the potent aromatase inhibitor letrozole or placebo for 6 months. Letrozole treatment reduced serum estrone (E1) and estradiol (E2) to near undetectable levels (p < 0.0001). This treatment did not affect bone formation markers but, as compared with the placebo group, increased bone resorption markers (urine 24-h pyridinoline [PYD] by 13.3% [p < 0.05] and 24-h urine deoxypyridinoline [DPD] by 14.2% [p < 0.05]) and decreased serum parathyroid hormone (PTH) by 22% (p = 0.002). These data indicate that in late postmenopausal women even the low serum estrogen levels present exert a restraining effect on bone turnover and support the concept that variations in these low levels may contribute to differences in their rate of bone loss.
authors.affiliation: Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Heshmati
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Simon P
authors.initials: SP
authors.lastname: Robins
authors.forename: W Michael
authors.initials: WM
authors.lastname: O'Fallon
authors.forename: L Joseph
authors.initials: LJ
authors.lastname: Melton
authors.forename: B Lawrence
authors.initials: BL
authors.lastname: Riggs
mesh_terms: D000368:Aged; D047072:Aromatase Inhibitors; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000097:blood* / Q000139:chemically induced; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008593:Menopause / Q000097:blood; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D015663:Osteoporosis, Postmenopausal / Q000097:blood; D011446:Prospective Studies; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D004958:Estradiol; D000077289:Letrozole