SAN DIEGO—Postmenopausal women with breast cancer receiving an aromatase inhibitor (AI) may experience significant bone loss and may need to have their bone health monitored more closely, according to new data presented at the Endocrine Society’s 92nd Annual Meeting and Expo.
Researchers at the University of Connecticut have found that women with normal or mild/moderate bone mineral density (BMD) at initiation of AI treatment appear to have significant bone loss at the lumbar spine, femoral neck, and total hip over the first year of therapy. Markers of bone turnover, including serum C-telopeptide collagen crosslinks (sCTx) and serum procollagen type 1 amino-terminal propeptide (P1NP), increased over the first year of treatment. Wo men with the greatest increase in vitamin D levels had the lowest increase in markers for bone turnover.
Currently, AIs are considered first-line therapy for the treatment of hormone-sensitive breast cancer. Large clinical trials have shown, however, that a reduction in serum estrogen levels by these medications leads to substantial bone loss. Antiresorptive medications are available to prevent this type of bone loss, but they are expensive and they also have significant side effects. Treating all women with breast cancer with an antiresorptive agent while they are receiving letrozole or anastrozole may not be the most cost-effective and appropriate approach.
Researchers at the University of Connecticut hypothesized that women who demonstrate high bone turnover, as reflected by bone turnover markers in the first 3 to 6 months on treatment, will have greater bone loss. The current study evaluated women during their first year of treatment with anastrozole or letrozole, receiving adequate calcium and vitamin D. All the subjects had normal or moderately low bone mass at the start of the study. The investigators looked at whether early changes in bone turn over markers correlated with bone loss at 1 year.
“We found there were declines in bone density at 3 months and 6 months after treatment with aromatase inhibitors. The interesting thing we found is that women who had the greatest increase in vitamin D levels from baseline to 6 months had the least increase in uNTx, which is a bone resorption marker,” said study coinvestigator Faryal Mirza, MD, an assistant professor of medicine at the University of Connecticut Health Center, Farmington. “This would suggest that replacement with vitamin D may be a good way to decrease bone loss as a result of aromatase inhibitor therapy.”
Mirza and her colleagues reported at this meeting on the first 13 women who have completed the study. They hope to soon have more data on the remaining subjects in the trial. The investigators measured hormones and bone turnover markers at baseline, 1, 3, 6, and 12 months. The hormones included estradiol (E2) and sex hormone–binding globulin. BMD was measured at baseline and then again at 6 and 12 months at the lumbar spine, femoral neck, and total hip using dual-energy x-ray absorptiometry.
The researchers found that lumbar spine BMD declined by 2% and total hip BMD decreased by 1.4% at 6 months and by 3.4% and 2.0%, respectively, at 12 months. The patients with the highest E2 levels had the lowest sCTx, and the patients with the largest increase in serum vitamin D levels were found to have the least increase at 3 months in uNTx from baseline.
“This is a small study and it needs to be validated in a larger subset of patients,” said Mirza in an interview with The Oncology Pharmacist. “To our knowledge, this is the first study to show this. A lot of women are receiving aromatase inhibitors and so this is a very important issue, and the risk of fracture has to be addressed.”
She said this study is an important first step for identifying which women on AIs should or should not be put on a bisphosphonate. Mirza said that it is hoped that this study can point to ways of treating bone loss while delaying the need for bisphosphonates in this patient population.