Anabolic effect of high doses of human parathyroid hormone (1–38) in mature intact female rats

Abstract

Adult female retired breeder Wistar rats were treated with placebo or with synthetic human parathyroid hormone (hPTH) fragment (1–38) by subcutaneous injection at doses ranging from 50 to 1000 μg/kg, 5 days per week, for 2–8 weeks. One group of rats received hPTH‐(1–38), 400 μg/kg, 5 days per week for 4 weeks, followed by 4 weeks placebo. The effects on bone mass and structure were evaluated by histomorphometric analysis of cross sections of femoral metaphyses. The effects on bone formation were evaluated by measuring uptake of [H]tetracycline into femora and by qualitative evaluation of histologic sections after labeling with calcein and tetracycline. All doses of hPTH‐(1–38) were anabolic. Lamellar bone formation was stimulated on all surfaces, and cancellous bone mass was increased as a result of trabecular thickening. Small quantities of woven bone were also formed in marrow cavities after treatment with 400 or 1000 μg/kg. Treatment with 1000 μg/kg had an effect on measured parameters similar to that with 400 μg/kg, and there was no evidence for a diminution of the anabolic effect at high doses. Animals treated with hPTH‐(1–38) for 4 weeks followed by 4 weeks placebo tended to have less bone than those that received hPTH‐(1–38) for 8 weeks but had significantly more bone than placebo‐treated rats. In conclusion, daily injection of hPTH‐(1–38) for 2–8 weeks at doses ranging from 50 to 1000 μg/kg had an anabolic effect on both cortical and trabecular bone in the femur of mature female intact rats. After withdrawal of treatment, the bone formation rate fell below levels in untreated animals, but bone mass remained higher.