The study, under the direction of Dr. Charles L. Shapiro, director of breast medical oncology at the Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and colleagues at the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston, examined 49 premenopausal women with stage I or II breast cancer. Baseline measures of bone density, estradiol, follicle-stimulating hormone (FSH) and the markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase were taken within four weeks of beginning adjuvant chemotherapy. Similar measures were taken at six and 12 months after chemotherapy began.
Researchers found 35 of the women (71 percent) lost ovarian function at the end of one year, and, as expected, experienced increases in FSH and decreases in estradiol, changes normally associated with menopause.
What was unexpected, however, was that these same women revealed rapid and dramatic bone loss as early as six months, especially in the femur and spine, and it continued to escalate until the 12 month end point. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function.
"This is truly significant," says Shapiro. "To put it in perspective, a normal post-menopausal woman experiences 1-2 percent bone loss in the spine over the course of a year. The women in our study experienced bone loss four-fold that amount, up to 8 percent in just one year." Shapiro says the bone loss at 12 months was so significant that they had to drop a part of the study that randomized some of the participants to treatment with a nasal spray, calcitonin, and others to a placebo. "An independent monitoring committee examined the 12-month data, and determined it would be unethical to place women on a placebo given the magnitude of the bone loss they were experiencing," Shapiro says.
Previous studies have demonstrated bone loss frequently occurs following chemotherapy, but this study reveals it occurs much earlier than in prior studies. "The results of this study support a role for bone density scans in those women who develop chemotherapy-induced ovarian failure or early menopause, and earlier intervention with calcium, vitamin D, weight-bearing exercise and counseling about the relationship between cigarette smoking, alcohol and bone loss," says Shapiro.
Shapiro says a class of drugs known as bisphosphonates have been shown to mitigate bone loss in women with early stage breast cancer receiving adjuvant chemotherapy. Based on those findings, a Cancer and Leukemia Group B (CALGB) national trial is set to open soon evaluating whether bisphosphonate zolendronic acid (Zometa) will prevent bone loss in premenopausal women receiving adjuvant chemotherapy.
Journal
Journal of Clinical Oncology