Antiestrogens are used in the treatment, and sometimes even in the prophylaxis, of
breast cancer.
Tamoxifen is the most commonly used
antiestrogen, but
toremifene is gaining in popularity. We compared here the effects of
tamoxifen and
toremifene on bone metabolism and density in 30 postmenopausal patients with
breast cancer, who were randomized to receive
tamoxifen (20 mg/day, n = 16) or
toremifene (40 mg/day, n = 14) for 1 yr.
Biochemical markers of
bone resorption [urinary
hydroxyproline, serum cross-linked carboxyterminal telopeptide of
type I collagen, urinary cross-linked
aminoterminal telopeptide of type I collagen (NTx)] and bone formation [serum bone-specific
alkaline phosphatase,
osteocalcin, and aminoterminal and carboxyterminal propeptide of
type I procollagen] were assessed before treatment and at 6 and 12 months of the
antiestrogen regimen. Bone mineral density (BMD) in the lumbar spine and proximal femur (neck, trochanter, and Ward's triangle) was measured using dual-energy x-ray absorptiometry before treatment and at 12 months of treatment. Urinary NTx decreased after 6 months' use of
tamoxifen (mean fall: 33%) and of
toremifene (mean fall: 16%). Use of
tamoxifen was associated with a significant decrease in
osteocalcin (mean fall: 25%) and aminoterminal propeptide of
type I procollagen (mean fall: 22%), whereas
toremifene failed to influence these markers.
Tamoxifen increased BMD, on average, by 2% in the lumbar spine, 1% in the femoral neck, and 5% in Ward's triangle.
Toremifene failed to increase BMD at any site measured, and in contrast, a slight trend toward a fall (-0.3 to -0.9%) in BMD was seen in patients treated with
toremifene. Falls in urinary NTx, from baseline to 6 months, correlated significantly with changes in the lumbar spine BMD (r = -0.57, P = 0.0002) in the whole patient series. We conclude that
tamoxifen (20 mg/day) increases BMD in postmenopausal
breast cancer patients, whereas
toremifene (40 mg/day) merely prevents the increasing age-associated fall in BMD. More prolonged studies on bone metabolism, comparing these two
antiestrogens, are needed; but even now, clinicians should be aware of these differences between
tamoxifen and
toremifene.