In pre-menopausal women, chemotherapy to treat early-stage breast cancer can cause the ovaries to shut down, either temporarily or permanently. Because the ovaries produce most of the estrogen in a pre-menopausal woman's body, shutting down the ovaries causes a big drop in estrogen levels. Estrogen helps keep bones strong, so a drop in estrogen levels during and after chemotherapy can cause bone loss, which makes bones weak.
The small study reviewed here found that giving Zometa (chemical name: zoledronic acid) during and after chemotherapy for early-stage breast cancer kept bone density stable in pre-menopausal women. The women who didn't get Zometa during and after chemotherapy had some bone loss.
Spine and hip bone strength was determined by measuring bone mineral density. Bone mineral density is lower in weaker bones and higher in stronger bones. The researchers measured bone mineral density three times in the study:
The women who got Zometa didn't lose a significant amount of bone in the year after chemotherapy; their bone mineral density measurement was the same each time it was measured.
The women who got a placebo instead of Zometa had some loss of bone in the year after chemotherapy:
Blood tests also showed that the women who didn't get Zometa were experiencing bone loss.
Another part of this research showed that Zometa can prevent bone loss in pre-menopausal women who get hormonal therapy medicine to treat breast cancer.
This study does have some weaknesses. The women received Zometa intravenously every 3 months, but it's not clear if that schedule is the best. It was also difficult to get women to participate in the study and to keep those who did decide to participate. This might be why the study was small (101 women).
Zometa belongs to a group of medicines called bisphosphonates. Bisphosphonates help prevent bone loss and can build bone strength. Other bisphosphonates are:
Some bisphosphonates, such as Fosamax and Actonel, are pills taken by mouth. Zometa, Aredia, and Bonefos are given intravenously. Besides Zometa, research has shown that Aredia, Bonefos, and Fosamax have some ability to protect bones during and after chemotherapy for breast cancer.
If you're a pre-menopausal woman and chemotherapy is part of your treatment plan for early-stage breast cancer, ask your doctor how chemotherapy might affect your bones and the steps you can take to minimize any effects.
Visit the Breastcancer.org Bone Health section to learn more about measuring bone health, how breast cancer treatment can affect your bones, and ways you can keep your bones healthy and strong during and after treatment.
NEW YORK, Aug. 18 (MedPage Today) -- In premenopausal breast cancer patients, zoledronic acid (Zometa) was able to stave off chemotherapy-induced bone loss, investigators here found.
Bone mineral density remained stable in patients who received the bisphosphonate drug during adjuvant chemotherapy, Dawn L. Hershman, M.D., of Columbia University here, and colleagues, reported online in the Journal of Clinical Oncology.
In contrast, patients randomized to placebo had significant bone loss at six and 12 months.
"The results have important implications for the growing number of young breast cancer survivors who will enter menopause early and experience both a prolonged period of estrogen deficiency and an increased risk of osteoporotic fracture," the authors concluded.
Questions about the optimal timing, dosage, and duration of bisphosphonate therapy remain unanswered and might never be answered, they continued, because of the necessarily long duration needed to complete clinical studies that could address those issues.
Young women with early-stage breast cancer often have temporary or permanent cessation of menses. Chemotherapy-induced estrogen deficiency may stimulate loss of bone mineral, increasing the risk of osteoporosis, the authors noted.
The bisphosphonate drugs clodronate and pamidronate (Aredia) have demonstrated efficacy for reducing chemotherapy-related bone loss. However, significant bone loss persisted at two years in a study of clodronate, which has relatively weak activity, the authors continued.
The more potent drug alendronate (Fosamax) can cause potentially severe adverse gastrointestinal effects, a particular concern for women receiving chemotherapy, they said.
Intravenous zoledronic acid has been shown to prevent bone loss in premenopausal women receiving combined endocrine therapy. Investigators continued the examination of the drug's efficacy in a study involving premenopausal women with early-stage breast cancer treated with adjuvant chemotherapy.
The study involved 101 women (mean age 42), about 90% of whom reported regular menses at baseline. The patients were randomized to zoledronic acid or placebo and followed for a year, which included the period of treatment with chemotherapy.
Bone mineral density was assessed by dual-energy x-ray absorptiometry (DEXA) at baseline and after six and 12 months. The primary endpoint was the percent change in lumbar spine bone mineral density at six and 12 months.
DEXA scans revealed lumbar spine bone loss of 2.2% at six months and 4.1% at 12 months in the placebo group.
Additionally, loss of total hip bone mineral density, a secondary endpoint, was 0.8% at six months and 2.6% at 12 months. Bone mineral loss was associated with significant increases in biomarkers of bone turnover, the authors reported.
In contrast, patients treated with zoledronic acid had stable bone mineral density throughout the 12 months (P<0.0001 versus placebo).
None of the DEXA-assessed sites had significant changes in bone mass from baseline. Biomarker assessment showed that bone turnover was either suppressed or attenuated.
The researchers noted several limitations to the study, including the fact that every-three-month dosing may not be necessary. They also noted that the expansion of the study to external sites resulted in a higher than expected ineligibility rate, poorer patient retention, and questions about the quality of the bone mineral density data.
In addition, they said, accrual was slow because patients "had difficulty deciding whether to participate before initiating chemotherapy, and dropout was higher than expected for the same reason."
The study received funding from the National Institutes of Health.
Dr. Hershman and coauthor Elizabeth Shane, M.D., both disclosed that they have received research funding from Novartis.
Additional source: Journal of Clinical OncologySource reference: Hershman DL et al. "Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer" J Clin Oncol 2008; 26: DOI: 10.1200/JCO.2008.16.4707.
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