The Less Potent Estrogenic Effect of Tamoxifen on Bone in Ovariectomized Rats With Established Osteopenia

Abstract.

The longitudinal effects of tamoxifen (TAM) treatment on bone metabolism, spinal bone mineral density (BMD), and bone mineral content (BMC) were compared with those of estrogen in ovariectomized (OVX) rats with established osteopenia. The 6-month-old rats were divided into Sham (n = 8) and OVX (n = 24) groups. First, the OVX rats were allowed to lose bone for 6 weeks. Six weeks after ovariectomy they were divided into three groups: (1) OVX rats treated with solvent vehicle (OVX+Vehicle), (2) OVX rats injected with TAM subcutaneously six times a week at a dosage of 1.0 mg/kg body weight (OVX+TAM), (3) OVX rats injected with 17-β estradiol subcutaneously six times a week at a dosage of 0.1 mg/kg body weight (OVX+ET). The longitudinal effects of TAM and estrogen on bone were studied by dual energy X-ray absorptiometry (DXA) and biochemical markers including urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr). Ovariectomy resulted in a significant increase in urinary Pyr, Dpyr, and a significant decrease in spine BMD and BMC. TAM treatment completely inhibited the further bone loss in OVX rats with established osteopenia, however, estrogen increased spine BMD and BMC significantly compared with OVX+Vehicle, OVX+TAM, and baseline of treatment. Both TAM and estrogen treatment decreased urinary Pyr and Dpyr significantly in OVX rats. Our findings indicate that TAM acts as an estrogen agonist with respect to effects on spine BMD, BMC, and bone resorption in OVX rats with established osteopenia, but fails to restore spine BMD and BMC to the extent observed with estrogen in this study.