Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer.
OBJECTIVE
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.


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 > or = 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.


CONCLUSIONS
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.
Shapiro
C L
CL
The Authur G. James Cancer Hospital and Richard J. Solove Research Institute, Ohio State University, Columbus 43210, USA. shapiro-1@medctr.osu.edu
Manola
J
J
Leboff
M
M
D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D000568:Amenorrhea / Q000139:chemically induced*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000139:chemically induced*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D017697:Premenopause
D000970:Antineoplastic Agents; D015675:Osteocalcin; D005640:Follicle Stimulating Hormone; D000469:Alkaline Phosphatase