Marttunen M B, Hietanen P, Tiitinen A, Ylikorkala O
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Finland.
J Clin Endocrinol Metab. 1998 Apr;83(4):1158-62. doi: 10.1210/jcem.83.4.4688.
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.
抗雌激素药物用于乳腺癌的治疗，有时甚至用于预防。他莫昔芬是最常用的抗雌激素药物，但托瑞米芬的使用正日益普遍。我们在此比较了他莫昔芬和托瑞米芬对30例绝经后乳腺癌患者骨代谢和骨密度的影响，这些患者被随机分为两组，分别接受他莫昔芬（20毫克/天，n = 16）或托瑞米芬（40毫克/天，n = 14）治疗1年。在治疗前以及抗雌激素治疗方案的6个月和12个月时，评估骨吸收的生化标志物[尿羟脯氨酸、血清I型胶原交联羧基末端肽、尿I型胶原交联氨基末端肽（NTx）]和骨形成标志物[血清骨特异性碱性磷酸酶、骨钙素以及I型前胶原氨基末端和羧基末端前肽]。使用双能X线吸收法在治疗前和治疗12个月时测量腰椎和股骨近端（颈部、大转子和Ward三角区）的骨矿物质密度（BMD）。使用他莫昔芬6个月后尿NTx下降（平均下降：33%），使用托瑞米芬后尿NTx下降（平均下降：16%）。使用他莫昔芬与骨钙素显著下降（平均下降：25%）和I型前胶原氨基末端前肽显著下降（平均下降：22%）相关，而托瑞米芬未能影响这些标志物。他莫昔芬使腰椎BMD平均增加2%，股骨颈增加1%，Ward三角区增加5%。托瑞米芬在任何测量部位均未能增加BMD，相反，接受托瑞米芬治疗的患者中观察到BMD有轻微下降趋势（-0.3%至-0.9%）。在整个患者系列中，从基线到6个月尿NTx的下降与腰椎BMD的变化显著相关（r = -0.57，P = 0.0002）。我们得出结论，他莫昔芬（20毫克/天）可增加绝经后乳腺癌患者的BMD，而托瑞米芬（40毫克/天）仅能预防与年龄相关的BMD下降。需要对这两种抗雌激素药物进行更长期的骨代谢研究比较；但即便如此，临床医生现在就应知晓他莫昔芬和托瑞米芬之间的这些差异。
