Isserow J A, Rucinski B, Romero D F, Mann G N, Liu C C, Epstein S
Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania 19141.
Endocrinology. 1995 Feb;136(2):713-9. doi: 10.1210/endo.136.2.7835304.
Tamoxifen (TAM) is used primarily in the management of breast cancer, and it also has bone-sparing effects similar to estrogen. In breast cancer patients TAM may have a potential role in the prevention and management of osteoporosis. TAM therapy is associated with uterine hyperplasia, and medroxyprogesterone acetate (MPA) added to the regimen provides protection against this. Due to the potential combined use of MPA and TAM in the clinical setting, this study was conducted to assess whether MPA acted synergistically, dampened, or enhanced the TAM effect on bone. Seventy-five female rats (60 oophorectomized; Ox), were randomized into five groups and received either TAM (0.1 mg/kg.day) and/or MPA (0.3 mg/kg.day) therapy over 28 days as follows: 1) sham; 2) Ox; 3) Ox plus TAM; 4) Ox plus MPA; and 5) Ox plus TAM plus MPA. Blood was sampled on days 0, 14, and 28 for measurement of ionized calcium, PTH, 1,25-dihydroxyvitamin D, osteocalcin, and insulin-like growth factor 1. TAM-treated rats showed a reduction in body weight serum osteocalcin, PTH, and insulin-like growth factor 1. Histomorphometric analysis of the proximal tibia showed less cancellous bone volume in Ox rats, and the effect was attenuated by TAM. MPA alone had no significant effect on cancellous bone volume. All the bone formation parameters evaluated (bone formation rate, mineral apposition rate, percent calcein-labeled surface, and number of osteoblasts) were higher in Ox rats compared with sham-operated rats and were lower in TAM-treated rats compared with Ox rats. These parameters were not changed by MPA, alone or in combination with TAM. The number of osteoclasts was higher in Ox rats compared with sham-operated rats and was reduced by TAM. MPA therapy alone or in combination with TAM did not affect number of osteoclasts. These results suggest that MPA neither dampened nor enhanced the effect of TAM on bone.
他莫昔芬（TAM）主要用于乳腺癌的治疗，并且它还具有与雌激素类似的保护骨骼的作用。在乳腺癌患者中，TAM可能在骨质疏松症的预防和治疗中发挥潜在作用。TAM治疗与子宫增生有关，在治疗方案中添加醋酸甲羟孕酮（MPA）可预防这种情况。由于在临床环境中可能联合使用MPA和TAM，因此进行了本研究以评估MPA是否协同、减弱或增强了TAM对骨骼的作用。75只雌性大鼠（60只卵巢切除；Ox）被随机分为五组，并在28天内接受以下TAM（0.1mg/kg·天）和/或MPA（0.3mg/kg·天）治疗：1）假手术组；2）卵巢切除组；3）卵巢切除加TAM组；4）卵巢切除加MPA组；5）卵巢切除加TAM加MPA组。在第0、14和28天采集血液，用于测量离子钙、甲状旁腺激素、1,25-二羟基维生素D、骨钙素和胰岛素样生长因子1。接受TAM治疗的大鼠体重、血清骨钙素、甲状旁腺激素和胰岛素样生长因子1均降低。胫骨近端的组织形态计量学分析显示，卵巢切除大鼠的松质骨体积减少，而TAM可减弱这种作用。单独使用MPA对松质骨体积无显著影响。与假手术大鼠相比，所有评估的骨形成参数（骨形成率、矿物质沉积率、钙黄绿素标记表面百分比和成骨细胞数量）在卵巢切除大鼠中更高，与卵巢切除大鼠相比，接受TAM治疗的大鼠中更低。这些参数不受MPA单独或与TAM联合使用的影响。与假手术大鼠相比，卵巢切除大鼠中的破骨细胞数量更高，而TAM可减少破骨细胞数量。单独使用MPA治疗或与TAM联合使用均不影响破骨细胞数量。这些结果表明，MPA既没有减弱也没有增强TAM对骨骼的作用。
