Maintenance of cortical bone in human parathyroid hormone(1-84)-treated ovariectomized rats

The purpose of this cross-sectional study,vas to evaluate the effects of hu man parathyroid hormone(1-84) (hPTH) followed by maintenance treatment with 17 beta -estradiol (E-2), risedronate (Ris), or a reduced dose of hPTH (Lo wPTH) on cortical hone in the ovariectomized (ovx) rat. Eight groups of ovx and one group of intact female rats (3.5 months) were left untreated for 1 1 weeks. For the following 12 weeks, four groups received subcutaneous inje ctions of hPTH (75 mug/kg per day on 3 days/week) and four groups received vehicle, Treatments,were then changed to E-2 (10 mug/kg per day on 2 days/w eek), Ris (3 mug/kg per day on 3 days/week), LowPTH (25 mug/kg per day on 3 days/week), or,vehicle. Bone tissue was collected at weeks -11 (baseline), 0 (ovx effect), 12 (hPTH effect), 24, 36, and 48 (maintenance effect). Bon e mineral density (BMD) and bone mineral content (BMC) of the diaphyseal fe mur and total cross-sectional area (Tt.Ar), marrow: area (Ma.Ar), cortical area (Ct.Ar), and periosteal and endocortical bone formation of the tibia w ere measured. Ovariectomy resulted in loner BMD (,weeks 0-48), unaffected B MC, and greater Tt.Ar (weeks 12 and 36), Ma.Ar (week 48), and Ct.Ar (weeks 0 and 12) compared with intact rats, Endocortical and periosteal bone forma tion were greater in the ovx than in the intact rats up to 23 weeks postova riectomy. Treatment of ovx rats with hPTH for 12 weeks resulted in greater cortical BMD, BMC, and endocortical hone formation than in intact or ovx co ntrols. In ovx rats pretreated with hPTH and then treated with Ris for 36 w eeks, BMD and BMC were greater and Ma.Ar was smaller than in ovx controls, In ovx rats pretreated with hPTH and then treated with LowPTH, BMD, BMC, Ct .Ar, and endocortical bone formation were greater and Ma.Ar was smaller tha n in ovx controls. Treatment of hPTH-pretreated rats with E-2 for 36 weeks did not affect cortical BMD, BMC, and Ct.Ar, although periosteal bone forma tion was lower in the E-2 group compared with the ovx group. Thus, in ovari ectomized rats, cortical bone gained by 12 weeks of hPTH treatment was main tained for up to 36 weeks by treatment with risedronate or low-dose hPTH, b ut not with 17 beta -estradiol. (Bone 28:251-260; 2001) (C) 2001 by Elsevie r Science Inc, All rights reserved.