Role of low levels of endogenous estrogen in regulation of bone resorption in late postmenopausal women.
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.
Heshmati
Hassan M
HM
Division of Endocrinology and Metabolism, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Khosla
Sundeep
S
Robins
Simon P
SP
O'Fallon
W Michael
WM
Melton
L Joseph
LJ
Riggs
B Lawrence
BL
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
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D004958:Estradiol; D000077289:Letrozole