EFFECTS OF LONG-TERM DIABETES AND OR HIGH-DOSE 17-BETA-ESTRADIOL ON BONE-FORMATION, BONE-MINERAL DENSITY, AND STRENGTH IN OVARIECTOMIZED RATS/

Long-term diabetes in female rats preserves the bone mineral density ( BMD) but impairs the strength of the femur, In this study, we have com pared the effects of diabetes and high-dose 17 beta-estradiol (E-2), t wo conditions of low bone formation, in ovariectomized (ovx) rats, Spo ntaneously diabetic BB rats were ovx 0-3 days after onset, and nondiab etic ovx littermates were used as controls; the rats were either untre ated or treated with E-2 (30 mu g/day, subcutaneously), for 6 or 12 we eks (n = 9 in each of the eight groups), Analysis included: plasma 1,2 5-dihydroxyvitamin D-3, insulin-like growth factor-I (IGF-I), and oste ocalcin concentrations; histomorphometry of the proximal tibial metaph ysis (PTM); and DXA and biomechanical testing of the femur, Both E-2 t reatment and diabetes markedly lowered plasma IGF-I and osteocalcin co ncentrations, as well as dynamic morphometric parameters of bone forma tion in the PTM, Plasma IGF-I and osteocalcin were correlated (R-2 = 0 .55; p < 0.0001), E-2 treatment in both control and diabetic ovx rats increased the trabecular bone volume in the PTR I and the BMD in the m etaphysis of the distal femur; there was no difference between control and diabetic rats, however, The diaphyseal area and BMC were decrease d in E-2-treated or/and diabetic ovx rats, but the diaphyseal BMD rema ined unchanged compared with untreated ovx rats, The biomechanical pro perties of the whole femur (strength, angular deformation, and stiffne ss) were decreased in E-2-treated and diabetic E-2-treated ovx rats af ter 12 weeks. The data indicate that in situations of chronic low bone formation, whole bone strength does not reflect total BMD but correla tes better with bone size and bone mineral content measurements. (C) 1 997 by Elsevier Science Inc.