The effect of adjuvant
tamoxifen treatment on bone mineral density (BMD) and bone turnover markers was studied in postmenopausal
breast cancer patients. The relationship of
tamoxifen's effect with the genetic polymorphisms of
estrogen receptor (ER)-alpha and ER-beta gene was also studied. Twenty-one postmenopausal
breast cancer patients were given
tamoxifen (20 mg/day) as the adjuvant treatment after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry) and
bone resorption (
deoxypyridinoline,
aminoterminal telopeptide of type I collagen, and carboxyterminal telopeptide of
type I collagen) and formation (propeptide of
type I procollagen,
osteocalcin, and bone-specific
alkaline phosphatase) markers were examined at baseline (before the surgery), 6 and 12 months after the start of
tamoxifen treatment. Genetic polymorphisms analyzed were TA dinucleotide repeats polymorphism in the promoter region and PvuII and XbaI restriction fragment length polymorphism for the ER-alpha gene and the CA dinucleotide repeats polymorphism in the intron 5 for the ER-beta gene.
Tamoxifen significantly increased BMD of the lumbar spine at both 6 (P<0.01) and 12 months (P<0.01) after the start of
tamoxifen as compared with that at baseline. The mean percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All
bone resorption and formation markers significantly decreased at both 6 and 12 months. Among the four genetic polymorphisms studied, only ER-beta CA repeat polymorphism was found to be significantly associated with BMD at 12 months, i.e. BMD of the 21 CA repeats allele carriers was significantly higher than that of the non-carriers (P=0.025). These results suggest that
tamoxifen increases BMD of the lumbar supine by reducing the bone turnover in postmenopausal
breast cancer patients, and this bone restoring effect of
tamoxifen is more marked in ER-beta 21 CA repeats allele carriers than non-carriers.