Prevention of Bone Loss in Survivors of Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Susan L. Greenspan,
Rajib K. Bhattacharya,
Susan M. Sereika,
Adam Brufsky and
Victor G. Vogel
Departments of Medicine (S.L.G., A.B., V.G.V.), Epidemiology (S.M.S., V.G.V.), Health and Community Systems (S.M.S.), and Biostatistics (S.M.S.) and Magee Women’s Hospital/University of Pittsburgh Breast Program (V.G.V., A.B.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Department of Medicine (R.K.B.), University of Kansas, Kansas City, Kansas 66160
Address all correspondence and requests for reprints to: Susan L. Greenspan, M.D., Professor of Medicine, University of Pittsburgh, 3471 Fifth Avenue, Suite 1110, Pittsburgh, Pennsylvania 15213-3221. E-mail: greenspans{at}dom.pitt.edu.
Background: Few data are available on the safety and efficacyof once-weekly oral bisphosphonate therapy in breast cancersurvivors.
Objective: Our objective was to determine whether risedronate,35 mg weekly, is efficacious and safe in preventing bone lossassociated with chemotherapy-induced menopause.
Design: The study was a randomized, double-blind, placebo-controlledclinical trial over 12 months.
Setting and Participants: Participants included 87 newly postmenopausalwomen with status post chemotherapy, recruited from a breastcancer clinic in an academic medical center.
Intervention: Participants were randomly assigned to receiverisedronate 35 mg/wk or placebo.
Main Outcome Measures: The primary outcomes were the 12-monthchanges in spine and hip bone mineral density. Secondary outcomesincluded changes in markers of bone resorption (urine N-telopeptidecross-linked collagen type I) and formation (osteocalcin, N-terminalpropeptide of type I procollagen, and bone-specific alkalinephosphatase).
Results: After 12 months, bone mineral density increased by1.2% at the spine and 1.3% at the hip in women on risedronatevs. significant decreases for women in the placebo group of0.9% at the spine and 0.8% at the hip (P < 0.01, differencebetween groups). N-telopeptide cross-linked collagen type I,a marker of bone resorption, decreased by 19.3%, and N-terminalpropeptide of type I procollagen, a marker of bone formation,decreased by 26.6% in participants on active therapy comparedwith increases in the control group. Risedronate was well tolerated,and the retention rate was 95% at 1 yr.
Conclusions: Risedronate once weekly prevented bone loss andreduced bone turnover in women with breast cancer treated withchemotherapy. Early measures to prevent bone loss should beconsidered in this cohort of breast cancer survivors.
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