Intermittent treatment with human parathyroid hormone (hPTH[1-34]) increased trabecular bone volume but not connectivity in osteopenic rats

Abstract

Previous studies have determined that intermittent parathyroid hormone (PTH) therapy increases bone mass and improves biomechanical strength in osteopenic animal models. The purpose of this investigation was to determine if intermittent human parathyroid hormone (hPTH[1–34]) therapy increased trabecular bone volume and connectivity in a rat model of established osteopenia using three-dimensional (3D) ex vivo in situ morphometry by X-ray tomographic methods (XTM). Six-month-old retired Sprague-Dawley breeder rats were used. Thirty animals were ovariectomized (OVX) and six were Sham operated. On day 56, post-OVX, a prePTH-treatment OVX group was sacrificed. The remaining OVX animals were randomized into four groups of six animals each, given injections 5 out of every 7 days for 28 days of either vehicle or hPTH(1-34) at 4, 40, or 400 μg/kg of body weight (BW)/day and were sacrificed on day 84 post-OVX. At sacrifice, the left proximal tibias were harvested for XTM scans. hPTH(1-34) at medium and high doses significantly increased trabecular bone volume and trabecular thickness compared with ovariectomized animals treated with vehicle (p < 0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hPTH(1–34) 40 and 400 μg/kg of BW treatment groups. Trabecular bone connectivity decreased by nearly 50% compared to the Sham-operated group at day 84 post-OVX and did not increase with any of the hPTH(1-34) treatments. Intermittent hPTH(1-34) treatment in osteopenic OVX rats increased trabecular bone volume to control levels or higher by thickening existing trabecule. Human PTH(1–34) did not re-establish connectivity when therapy was started after 50% of the trabecular connectivity was lost. We hypothesize that to re-establish trabecular connectivity, a therapeutic intervention would have to be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis.