Comparison of effects of tamoxifen and toremifene on bone biochemistry and bone mineral density in postmenopausal breast cancer patients

Abstract

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.