Alfacalcidol prevents aromatase inhibitor (Letrozole)-induced bone mineral loss in young growing female rats.
Long-term aromatase inhibitor use causes bone loss and increases fracture risk secondary to induced estrogen deficiency. We postulated that alfacalcidol (A; vitamin D(3) analog) could help prevent the Letrozole (L)-induced mineral bone loss. Fifty intact 1-month-old female rats were randomly divided into basal group; age-matched control group (AMC); L group: oral administration of 2 mg/kg per day; A group: oral administration of 0.1 microg/kg per day; and group L+A for a period of 8 weeks. Eight-week administration of L resulted in a significant increase in body weight, bone length, bone area, bone formation, and bone resorption activities when compared with the AMC group. However, the bone mass and bone mineral density (BMD) were significantly lower than the AMC group. Serum levels of testosterone, LH, FSH, and IGF-1 were significantly higher and serum estrone and estradiol were lower along with a decrease in ovary+uterus horn weight, when compared with the AMC groups. None of those parameters were affected by A treatment, except suppression of bone resorption activities and increased trabecular bone mass and femoral BMD, when compared with the AMC group. Results of L+A combined intervention showed that bone length, bone area, and bone formation activities were higher than the AMC group, and the bone resorption activities were lower and BMD was significantly higher than that of the L group. This study demonstrates that the combined intervention of L and A not only enhances bone growth, but also increases bone density, and the effects of L and A are independent and additive.
Mohamed
Idris
I
Metabolism Laboratory, Winthrop-University Hospital, Mineola, New York 11501, USA. mhidris@yahoo.com
Yeh
James K
JK
D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001846:Bone Development / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced* / Q000517:prevention & control*; D004357:Drug Synergism; D005260:Female; D005269:Femur / Q000187:drug effects; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D000077289:Letrozole; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology*
D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D006887:Hydroxycholecalciferols; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; C008088:alfacalcidol