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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0532v1 202/2/317    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Idris, M. Articles by Yeh, J Search for Related Content PubMed PubMed Citation Articles by Idris, M. Articles by Yeh, J

M Idris, Endocrinology, IDRO MEDICAL , Bethpage, 11714, United States
J Yeh, Metabolism Laboratory, Winthrop-University Hospital, Mineola, NY 11501, United States

Correspondence: Mohamed Idris, Email: mhidris{at}yahoo.com

ABSTRACT

Long-term aromatase inhibitor use causes bone loss and increases fracture risk secondary to induced estrogen deficiency. We postulated that Alfacalcidol (vitamin D3 analog) could help prevent the Letrozole-induced mineral bone loss. Fifty intact 1 month old female rats were randomly divided into basal group; age matched control group (AMC); Letrozole group (L): oral administration of 2 mg/kg per day; Alfacalcidol group (A): oral administration of 0.1ug/kg per day; and group L+A for a period of 8 weeks. Eight-week administration of Letrozole resulted in a significant increase in body weight, bone length, bone area, bone formation, and bone resorption activities as compared to 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, IGF-1 were significantly higher and serum estrone and estradiol were lower in along with a decrease in ovary+uterus horn weight, as compared to the AMC groups. None of those parameters were affected by Alfacalcidol treatment, except suppression of bone resorption activities and increased trabecular bone mass and femoral BMD, as compared to 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 Letrozole and Alfacalcidol not only enhances bone growth, but also increases bone density, and the effects of Letrozole and Alfacalcidol are independent and additive.