Summary Lumbar bone mineral density (BMD) determination by dual photon absorptiometry was used to study the influence of adjuvant chemotherapy for premenopausal breast cancer on the risk of premature osteoporosis. Six cycles of combination chemotherapy caused ovarian failure in 31 of 44 (71 %) women, amenorrhoea mostly already beginning during treatment. In contrast, only seven of 44 (16%) women, who were pair-matched for age and year of breast cancer surgery and had not been treated with chemotherapy, were post-menopausal at the time of measurement. The mean interval after breast surgery was 3.5 years. The significantly decreased BMD in the treated group (1.17 compared to 1.29 g cm-2) could only be explained by the high incidence of menopause in these women, which on average occurred 10 years prematurely. Extrapolation of these findings suggests that adjuvant chemotherapy may precipitate osteoporotic fractures by some 10 years in a considerable proportion of women cured of premenopausal breast cancer.Gradual loss of bone matrix and mineral is a consequence of ageing leading to osteoporosis. In general, women start off with less peak adult bone mass than men and consequently develop more symptoms from osteoporosis. As a result a considerable proportion of women suffer from spontaneous fractures in later life (Gordan, 1978;Nordin, 1980; NIH Consensus Statement, 1984). Various data suggest that in osteoporosis there is a disproportionately greater loss of trabecular bone from the axial skeleton compared to cortical bone from appendicular sites (Riggs et al., 1981).The average annual loss of bone mass measured by bone mineral density (BMD) in women before menopause amounts to 1-2%, but may rise to some 6-8% during the first 2-5 years after menopause (Krolner & Pors Nielsen, 1982;Genant et al., 1982). This dramatic temporary increase in the rate of bone loss around natural menopause or after bilateral ovariectomy has been ascribed to a ceasing protection from bone loss by ovarian hormones (Riggs et al., 1981(Riggs et al., , 1982(Riggs et al., , 1986Genant et al., 1982;Johnston et al., 1985;Richelson et al., 1984). Oestrogen replacement therapy effectively prevents osteoporosis in post-menopausal women if started within a few years after menopause (Riis, 1987;Lindsay et al., 1976;Christiansen et al., 1980;Recker et al., 1977).Adjuvant chemotherapy in premenopausal women treated for breast cancer frequently leads to diminished ovarian function and premature menopause (Henderson, 1987). Since early menopause is one of the strongest predictors of osteoporosis (Richelson et al., 1984), we anticipated that the widely used adjuvant chemotherapy regimen of cyclophosphamide, methotrexate and 5-fluorouracil (CMF), might seriously precipitate osteoporosis.To investigate this possibility we have compared the bone mineral density of the lumbar spine between women who had been treated with adjuvant CMF and women, matched for age and time of premenopausal breast cancer surgery, who received no such treatment. Patients were consi...

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