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.

Bone Mineral Density and Lipid Changes During 5 Years of Follow-up in a Study of Prevention of Breast Cancer with Toremifene in Healthy, High-risk Pre- and Post-menopausal Women

“…These limitations notwithstanding, however, we consider that these data indicate, at a minimum, that toremifene 60 mg/day has no obvious bonedepleting effect in postmenopausal women. This conclusion, which is broadly in conformity with studies of tamoxifen [20][21][22], is supported by the observation that BMD in women randomised to toremifene was either stable or slightly increased during the first 3 years of the study (when patient numbers were relatively large), whereas in other studies a spontaneous reduction in BMD has been seen in postmenopausal women not using HRT [19].…”

Effects of toremifene (TOR) and tamoxifen (TAM) on serum lipids

“…TAM is known to exhibit favorable actions on the lipid/bone metabolic systems as minor effects [3,4]. This agent is considered to prevent coronary disease and osteoporosis.…”

Crossover trial for lipid abnormality in postmenopausal breast cancer patients during selective estrogen receptor modulators (SERMs) administrations

“…They not only develop antagonist actions in breast cancer tissues but also act as agonists in other tissues. They are also known to give favorable effects to the metabolism of lipids and bones as their secondary action [1,2]. In particular, coronary artery diseases in which lipid metabolism is deeply involved account for about 1/3 of deaths in postmenopausal women, and the prevention of these diseases is an important issue.…”