Effect of Anastrozole Therapy on Bone Formation and Growth of Orchiectomized Pubertal Male Rats: Anastrozole Effect on Bone Formation and Growth

Abstract

Our study was designed to evaluate the effect of aromatase inhibition in orchidectomized rats and determine the effect of lack of estrogen and gonadal androgen in bone. Thirty male Sprague Dawley rats age six weeks were used for the study, 20 of them were bilaterally orchidectomized, and 10 of them served as wild-type controls. The orchidectomized rats were randomly subdivided into two different groups. The first group consisted of ten Orchidectomized Control Rats (ORX) and the second composed of ten Orchidectomized Rats Treated with Anastrozole (ANA). The duration of the study was six weeks (age 7 weeks to 13 weeks). The ANA group showed an increased longitudinal growth rate (p < 0.009) and femoral length (p < 0.04) compared to ORX. The T.Ar was increased by 29% (p < 0.005) and Tb.Sp decreased by 49.7% (p < 0.004) compared to ORX, with no difference in TB.Th. The periosteal BFR (p < 0.02) and CT.Ar (p < 0.03) were also increased in ANA compared to ORX. Interestingly, the maximal (breaking) load of the femur was 17.5% higher in ANA than ORX (p < 0.001) and was similar to controls (p < 0.6). Surprisingly anastrozole improved bone fragility, mainly by reducing bone modeling in the cancellous bone and possibly by increasing periosteal BFR in the cortical bone. We hypothesized that these results could be secondary to an increase in non-gonadal androgen production, increased IGF-1 receptor expression at the bone level or possibly a combination of both.