Effect of Chemotherapy Appears to Trigger Bone Loss in Breast Cancer Patients (dateline July 18, 2001)

Breast cancer patients treated with chemotherapy are at risk for significant bone loss, according to a new study. The high rate of bone loss occurred after only six months of chemotherapy in women in the study who experienced ovarian failure, a common side effect of chemotherapy that leads to premature menopause. The researchers say their study underscores the need to administer bone density screening tests to women who undergo chemotherapy to better address the issue of bone loss and help prevent osteoporosis, a degenerative bone disease.

The study, which was published in the July 15, 2001 issue of the Journal of Clinical Oncology, involved 49 pre-menopausal women with Stage I or Stage II  breast cancer who were to be treated with chemotherapy. All of the women were evaluated four weeks after beginning chemotherapy and again at six and 12-month intervals. Due to chemotherapy, Dr. Charles L. Shapiro and his colleagues from Ohio State University found that 35 of the women experienced ovarian failure, which put them into premature menopause. However, the surprising fact of the study was that the women who experienced ovarian failure lost up to 8% of bone density within 12 months of treatment.

Bone loss commonly occurs in women who have already reached menopause. Before a woman reaches her mid-30s, her body gains more bone than it loses. Around age 35, this process balances out. However, around 50 years of age when a woman reaches menopause, her ovaries stop producing estrogen. At this time, the rate of bone loss is accelerated. If bone loss becomes severe, a woman may develop osteoporosis, a condition in which low bone density causes the bones to break easily.

Dr. Shapiro and his colleagues were alarmed to find that the women who experienced ovarian failure in the study lost a significant amount of bone density (8%). In comparison, women who reach menopause naturally tend to lose only about 1% to 2% of bone density in the spine per year. It appears as though chemotherapy-induced ovarian failure results in a faster rate of bone loss than natural menopause. The researchers were also surprised that bone loss began to occur in as little as six months after chemotherapy began. Most previous studies began to evaluate bone loss in women after 12 months of treatment.

Experts believe that it is the effect of chemotherapy, ovarian failure, that causes accelerated bone loss in chemotherapy patients, not the treatment itself. In the study, the majority of patients were treated with chemotherapy that consisted of the drugs cyclophosphamide (brand name, Cytoxan), methotrexate (brand names, Amethopterin, Mexate, Folex), and fluorauracil (brand name, Fluorouracil, 5-Fu, Adrucil). This therapy is commonly called CMF. Some of the women received cyclophosphamide and doxorubicin (brand name, Adriamycin) with or without fluorouracil or paclitaxel (brand name, Taxol). In addition, 11 of the women were also treated with tamoxifen (brand name, Nolvadex) after chemotherapy.

Because chemotherapy is often a highly effective treatment for breast cancer, Dr. Shapiro and his colleagues are not advocating that women stop receiving chemotherapy. Instead, they suggest that chemotherapy patients be closely monitored with bone density tests. These women should also discuss with their physicians calcium and vitamin D consumption, moderate weight-bearing exercises, and other activities to help prevent bone loss prior to chemotherapy. Click here to learn more about preventing osteoporosis.

Originally, Dr. Shapiro and his colleagues had planned to continue their study to test whether a calcium nasal spray would decrease bone loss after 12 months of chemotherapy. However, an independent monitoring committee decided that the amount of bone loss in the chemotherapy patients was so severe that it would not be ethical to continue the study, since some of the women would have to be given a placebo (an inactive substance) instead of the calcium nasal spray.

Dr. Shapiro plans to begin a new clinical trial that will test the effectiveness of the drug Zometa (generic name, bisphosphonate zolendronic acid) in preventing bone loss in pre-menopausal chemotherapy patients. Physicians note that tamoxifen and raloxifene (brand name, Evista) are associated with an increase in bone density in post-menopausal women. Tamoxifen is used to treat breast cancer patients while raloxifene is FDA approved to help prevent osteoporosis. Researchers are also investigating whether raloxifene helps prevent breast cancer in women at high risk for the disease.

Additional Resources and References

• The study, "Ovarian Failure After Adjuvant Chemotherapy is Associated with Rapid Bone Loss in Women with Early-Stage Breast Cancer," is published in the July 15, 2001 issue of the Journal of Clinical Oncology (Vol. 19, Issue 14, 3306-3311). An abstract of the study is available at http://www.jco.org/
• The July 12, 2001 Reuters Health report, "Substantial Bone Loss Associated with Breast Cancer Chemotherapy," is available within 30 days of publication at http://www.reutershealth.com/
• To learn more about chemotherapy, please visit http://www.imaginis.com/breasthealth/chemo.asp
• To learn more about osteoporosis, please visit http://www.imaginis.com/osteoporosis/
• To learn more about menopause, please visit http://www.imaginis.com/womenshealth/menopause.asp