The effect of medroxyprogesterone acetate on bone metabolism in the oophorectomized, tamoxifen-treated rat

Abstract

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.