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Ovarian Failure After Adjuvant Chemotherapy Is Associated With Rapid Bone Loss in Women With Early-Stage Breast Cancer

From the Division of Adult Oncology and Department of Biostatistical Science, Dana-Farber Cancer Institute; Skeletal Health and Osteoporosis, Brigham and Women’s Hospital, Boston, MA; and Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University, Columbus, OH.

Address reprint requests to Charles L. Shapiro, MD, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University, Starling-Loving Hall B421, 320 West 10th Ave, Columbus, OH 43210; email: shapiro-1{at}medctr.osu.edu

PURPOSE: We sought to evaluate the effects of chemotherapy-induced ovarian failure on bone loss and markers of skeletal turnover in a prospective longitudinal study of young women with breast cancer receiving adjuvant chemotherapy.

PATIENTS AND METHODS: Forty-nine premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated within 4 weeks of starting chemotherapy (baseline), and 6 and 12 months after starting chemotherapy with dual-energy absorptiometry and markers of skeletal turnover osteocalcin and bone-specific alkaline phosphatase. Chemotherapy-induced ovarian failure was defined as a negative pregnancy test, greater than 3 months of amenorrhea, and a follicle-stimulating hormone 30 MIU/mL at the 12-month evaluation.

RESULTS: Among the 35 women who were defined as having ovarian failure, highly significant bone loss was observed in the lumbar spine by 6 months and increased further at 12 months. The median percentage decrease of bone mineral density in the spine from 0 to 6 months and 6 to 12 months was -4.0 (range, -10.4 to +1.0; P = .0001) and -3.7 (range, -10.1 to 9.2; P = .0001), respectively. In contrast, there were no significant decreases in bone mineral density in the 14 patients who retained ovarian function. Serum osteocalcin and bone specific alkaline phosphatase, markers of skeletal turnover, increased significantly in the women who developed ovarian failure.

CONCLUSION: Chemotherapy-induced ovarian failure causes rapid and highly significant bone loss in the spine. This may have implications for long-term breast cancer survivors who may be at higher risk for osteopenia, and subsequently osteoporosis. Women with breast cancer who develop chemotherapy-induced ovarian failure should have their bone density monitored and treatments to attenuate bone loss should be evaluated.

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