THE EFFECT OF MEDROXYPROGESTERONE ACETATE ON BONE METABOLISM IN THE OOPHORECTOMIZED, TAMOXIFEN-TREATED RAT

Tamoxifen (TAM) is used primarily in the management of breast cancer, and it also has bane-sparing effects similar to estrogen. In breast ca ncer patients TAM may have a potential role in the prevention and mana gement of osteoporosis. TAM therapy is associated with uterine hyperpl asia, and medroxyprogesterone acetate (MPA) added to the regimen provi des protection against this. Due to the potential combined use of MPA. and TAM in the clinical setting, this study was conducted to assess w hether MPA acted synergistically, dampened, or enhanced the TAM effect on bone. Seventy-five female rats (60 oophorectomized; Ox), were rand omized 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 osteocal cin, 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 eff ect on cancellous bone volume. All the bone formation parameters evalu ated (bone formation rate, mineral apposition rate, percent calcein-la beled surface, and number of osteoblasts) were higher in Ox rats compa red with sham-operated rats and were lower in TAM-treated rats compare d 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 d one or in combination with TAM did not affect number of osteoclasts. T hese results suggest that MPA neither dampened nor enhanced the effect of TAM on bone.