The effects of adjuvant chemotherapy on bone density in postmenopausal women with early breast cancer



      Adjuvant chemotherapy for breast cancer can have adverse effects on bone. We investigated the effects of adjuvant chemotherapy on bone mineral density in postmenopausal women with early-stage breast cancer.


      We performed a chart review of all our breast center patients who had spine or hip bone density measured by dual-energy X-ray absorptiometry at our institution after treatment for stage I or II breast cancer. Patients who had other causes of metabolic bone disease were excluded. Multivariate regression analysis was used to adjust for confounding factors. Results were expressed as age-adjusted standard deviation units (Z scores).


      Of the 130 eligible women, 36 (28%) received adjuvant chemotherapy and 94 (72%) did not. Mean adjusted bone density scores in both the hip (0.65 SD units; 95% confidence interval [CI]: 0.32 to 0.98 SD units; P = 0.0002) and spine (0.60 SD units; 95% CI: 0.01 to 1.19 SD units; P = 0.05) were significantly lower in patients who had received adjuvant chemotherapy compared with those who had not.


      Women who were postmenopausal when they developed breast cancer and who received adjuvant chemotherapy had lower bone density than those who did not. Whether this effect is caused by adjuvant chemotherapy remains to be determined.


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        • Greenlee R.T
        • Murray T
        • Bolden S
        • Wingo P.A
        Cancer statistics, 2000.
        CA Cancer J Clin. 2000; 50: 7-33
        • Hudis C.A
        • Norton L
        Adjuvant drug therapy for operable breast cancer.
        Semin Oncol. 1996; 23: 475-493
        • Bines J
        • Oleske D.M
        • Cobleigh M.A
        Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast cancer.
        J Clin Oncol. 1996; 14: 1718-1729
        • Bruning P.F
        • Pit M.J
        • de Jong-Bakker M
        • et al.
        Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer.
        Br J Cancer. 1990; 61: 308-310
        • Shapiro C.L
        • Leboff M
        Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in women with early-stage breast cancer.
        J Clin Oncol. 2001; 19: 3306-3311
        • Headley J.A
        • Theriault R
        • LeBlanc A.D
        • et al.
        Pilot study of bone mineral density in breast cancer patients treated with adjuvant chemotherapy.
        Cancer Invest. 1998; 16: 6-11
        • Pfeilschifter J
        • Diel I.J
        Osteoporosis due to cancer treatment: pathogenesis and management.
        J Clin Oncol. 2000; 18: 1570-1593
        • Ries L.A.G
        • Kosary C.L
        • Hankey B.F
        • Miller B.A
        SEER Cancer Statistics Review 1973–1996. National Cancer Institute, Bethesda, MD1999
        • Looker A.C
        • Wahner H.W
        • Dunn W.L
        • et al.
        Proximal femur bone mineral levels of US adults.
        Osteoporos Int. 1995; 5: 389-409
        • Neter J.K.M
        • Nachtsheim C.J
        • Wasserman W
        Applied Linear Statistical Models. 4th ed. McGraw-Hill, Boston1997
        • Marshall D
        • Johnell O
        • Wedel H
        Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures.
        BMJ. 1996; 312: 1254-1259
        • National Osteoporosis Foundation
        Physician’s Guide to Prevention and Treatment of Osteoporosis. National Osteoporosis Foundation, Washington, DC1998: 1-29
        • Cauley J.A
        • Lucas F.L
        • Kuller L.H
        • et al.
        Bone mineral density and risk of breast cancer in older women: the study of osteoporotic fractures.
        JAMA. 1996; 276: 1404-1408
        • Zhang Y
        • Kiel D.P
        • Kreger B.E
        • et al.
        Bone mass and the risk of breast cancer among postmenopausal women.
        N Engl J Med. 1997; 336: 611-617
        • Rozenberg S
        • Ham H
        • Liebens F
        Screening mammography in elderly women. Research on breast cancer in older women consortium [letter].
        JAMA. 2000; 283: 3203
        • Zmuda J.M
        • Cauley J.A
        • Ljung B.M
        • et al.
        Bone mass and breast cancer risk in older women: differences by stage at diagnosis.
        J Natl Cancer Inst. 2001; 93: 930-936
        • Orwoll E.S
        • Bauer D.C
        • Vogt T.M
        • Fox K.M
        Axial bone mass in older women.
        Ann Intern Med. 1996; 124: 187-196
        • Drinkwater B.L
        Exercise in the prevention of osteoporosis.
        Osteoporos Int. 1993; 3: 169-171
        • Scheven B.A
        • van der Veen M.J
        • Damen C.A
        • et al.
        Effects of methotrexate on human osteoblasts in vitro: modulation by 1,25-dihydroxyvitamin D3.
        J Bone Miner Res. 1995; 10: 874-880
        • van der Veen M.J
        • Scheven B.A
        • van Roy J.L
        • et al.
        In vitro effects of methotrexate on human articular cartilage and bone-derived osteoblasts.
        Br J Rheumatol. 1996; 35: 342-349
        • May K.P
        • Mercill D
        • McDermott M.T
        • West S.G.I
        The effect of methotrexate on mouse bone cells in culture.
        Arthritis Rheum. 1996; 39: 489-494
        • Wang T.M
        • Shih C
        Study of histomorphometric changes of the mandibular condyles in neonatal and juvenile rats after administration of cyclophosphamide.
        Acta Anat. 1986; 127: 93-99
        • Banfi A
        • Podesta M
        • Fazzuoli L
        • et al.
        High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors.
        Cancer. 2001; 92: 2419-2428
        • Longcope C
        • Hunter R
        • Franz C
        Steroid secretion by the postmenopausal ovary.
        Am J Obstet Gynecol. 1980; 138: 564-568
        • Riis B.J
        • Rodbro P
        • Christiansen C
        The role of serum concentrations of sex steroids and bone turnover in the development and occurrence of postmenopausal osteoporosis.
        Calcif Tissue Int. 1986; 38: 318-322
        • Stone K
        • Bauer D.C
        • Black D.M
        • et al.
        Hormonal predictors of bone loss in elderly women.
        J Bone Miner Res. 1998; 13: 1167-1174
        • Davidson B.J
        • Riggs B.L
        • Wahner H.W
        • Judd H.L
        Endogenous cortisol and sex steroids in patients with osteoporotic spinal fractures.
        Obstet Gynecol. 1983; 61: 275-278
        • Cummings S.R
        • Browner W.S
        • Bauer D
        • et al.
        Endogenous hormones and the risk of hip and vertebral fractures among older women.
        N Engl J Med. 1998; 339: 733-738
        • Ettinger B
        • Pressman A
        • Sklarin P
        • et al.
        Associations between low levels of serum estradiol, bone density, and fractures among elderly women.
        J Clin Endocrinol Metab. 1998; 83: 2239-2243
        • Dnistrian A.M
        • Schwartz M.K
        • Fracchia A.A
        • et al.
        Endocrine consequences of CMF adjuvant therapy in premenopausal and postmenopausal breast cancer patients.
        Cancer. 1983; 51: 803-807
        • Bhatavdekar J.M
        • Shah N.G
        • Patel D.D
        • et al.
        Endocrine function in premenopausal and postmenopausal advanced breast cancer patients treated with CMF or tamoxifen.
        Neoplasma. 1992; 39: 123-127
        • Mincey B.A
        • Moraghan T.J
        • Perez A.E
        Prevention and treatment of osteoporosis in women with breast cancer.
        Mayo Clin Proc. 2000; 75: 821-829
        • Kanis J.A
        • McCloskey E.V
        • Powles T
        • et al.
        A high incidence of vertebral fracture in women with breast cancer.
        Br J Cancer. 1999; 79: 1179-1181
        • Orloff J.J
        • Wu T.L
        • Stewart A.F
        Parathyroid hormone-like proteins.
        Endocr Rev. 1989; 10: 476-495
        • Powell G.J
        • Southby J
        • Danks J.A
        • et al.
        Localization of parathyroid hormone-related protein in breast cancer metastases.
        Cancer Res. 1991; 51: 3059-3061
        • Delmas P.D
        • Balena R
        • Confravreux E
        • et al.
        Bisphosphonate risedronate prevents bone loss in women with artificial menopause due to chemotherapy of breast cancer.
        J Clin Oncol. 1997; 15: 955-962
        • Powles T.J
        • McCloskey E
        • Paterson A.H
        • et al.
        Oral clodronate and reduction in loss of bone mineral density in women with operable primary breast cancer.
        J Natl Cancer Inst. 1998; 90: 704-708
        • Saarto T
        • Blomqvist C
        • Valimaki M
        • et al.
        Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens.
        Br J Cancer. 1997; 75: 602-605
        • Diel I.J
        • Solomayer E.F
        • Costa S.D
        • et al.
        Reduction in new metastases in breast cancer with adjuvant clodronate treatment.
        N Engl J Med. 1998; 339: 357-363
        • Hillner B.E
        • Ingle J.N
        • Berenson J.R
        • et al.
        American Society of Clinical Oncology.
        J Clin Oncol. 2000; 18: 1378-1391