Vitamin D deficiency exacerbates bone loss associated with exemestane

After two years of exemestane, vitamin D-deficient postmenopausal women experienced a 4.7% reduction in BMD in the femoral neck.

Per E. Lønning

ATLANTA — A randomized study revealed that low blood levels of vitamin D may worsen the bone loss experienced by postmenopausal women with breast cancer during adjuvant treatment with aromatase inhibitors.

“Our findings support the use of vitamin D as well as calcium supplementation for postmenopausal women in general, and for those receiving aromatase inhibitors in particular,” said Per E. Lønning, MD, PhD, professor at Haukeland University Hospital in Bergen, Norway. “Women should have adequate vitamin D levels before starting exemestane therapy.”

The study was presented here at the 2006 ASCO Annual Meeting.

Lønning and colleagues analyzed baseline blood levels of various biomarkers involved in bone metabolism to determine their influence on bone loss. They evaluated 59 patients with breast cancer who received exemestane for two years, and 62 who received placebo.

Compared with the desired levels of vitamin D (minimum of 30 ng/mL), most women in both groups suffered from vitamin D deficiency at baseline: 52 patients in the exemestane group had a mean vitamin D level of 21.6 ng/mL (20 ng/mL to 23.3 ng/mL), and 56 patients in the placebo group had a mean level of 22.6 ng/ml (21.2 ng/mL to 24.1 ng/mL). Researchers speculated that geographical circumstances (ie, Norway’s relatively shorter periods of sunlight) could have contributed to the high number of vitamin D deficient women in both groups.

After two years, bone loss in the femoral neck in vitamin D deficient women was greater in the exemestane group (4.7% reduction in bone mineral density [BMD]) compared with the placebo group (3% BMD decrease). In women with adequate vitamin D levels, however, femoral bone loss was similar between the two groups (3.6% decrease for exemestane, 3.3% decrease for placebo).

The mean BMD change was similar in the lumbar spine of vitamin D deficient women: 52 women on exemestane experienced a 3.4% decrease in BMD compared with a 2.4% decrease in BMD observed in 59 women on placebo. In women with adequate levels of vitamin D, seven patients on exemestane had a 4.3% mean BMD decrease and six patients on placebo had a 0.6% decrease.

Researchers said longer follow-up is necessary to confirm their findings.

Prior research had shown that bone loss in the femoral neck of postmenopausal women with early-stage breast cancer on exemestane for two years was worse and they had a nonsignificant increased bone loss in the lumbar spine compared with women on placebo.

In a study of 147 postmenopausal women with early-stage breast cancer who were randomized to receive either exemestane for two years or placebo, exemestane increased the annual bone loss from the femoral neck (2.72%) compared with placebo (1.48%; P=.024) with a nonsignificant increase in bone loss in the lumbar spine (exemestane 2.17% vs. placebo 1.84%). The annual bone loss was higher than expected in the placebo arm, researchers said.

Vitamin D deficiency could be the most important factor elevating bone loss among patients treated with exemestane as well as in the placebo group.

For more information:

• Lønning PE, Geisler J, Krag LE, et al. Vitamin D deficiency: A threat to bone health in breast cancer patients during adjuvant treatment with aromatase inhibitors. Abstract 554. Presented at: 2006 ASCO Annual Meeting; June 2-6; Atlanta.
• Lønning PE, Geisler J, Krag LE, et al. Effects of exemestane administered for two years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol. 2005;23:5126-5137.