JOURNAL OF BONE AND MINERAL RESEARCH zyxwvutsr Volume 10, Number 10, 1995 Blackwell Science, Inc. Intermittent Treatment with Human Parathyroid Hormone (hPTH[ 1-34]) Increased Trabecular Bone Volume but Not'Connectivity in Osteopenic Rats N.E. LANE,' J.M. THOMPSON,' GORDON J. STREWLER,' and J.H. KINNEY2 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 zyxwvu [ 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 preFTH-treatment OVX group was sacrificed. The remaining OVX animals were randomized into four groups of zyx 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 zyx pg/kg of body weight (BW)/day and were sacrificed on day 84 post-OW. 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 zyxwv (p < 0.05). The trabecular bone volume was equal to or greater than the Sham-operated animals in both hFTH(1-34) 40 and 400 pg/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 trabec- ulae. 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 zyxwvutsr be given before a significant distance between trabeculae has developed. Further studies will need to be done to refute or confirm our hypothesis. (J Bone Miner Res 1995;101470-1477) INTRODUCTION ST~OPOROSIS is A DisEAsE characterized by low bone mass 0 and microarchitectural deterioration of bone tissue that leads to increased bone fragility and a consequent increased risk of fractures."," It most often occurs in older estrogen- deplete postmenopausal women.(2) Two basic means have been proposed to treat the bone loss of osteoporosis: the inhibition of bone resorption and the promotion of bone formation. Estrogen,'3' ~alcitonin,(~) and bisphosphonates(','' have been successful in preventing further bone loss but they are not able to restore substantially bone mass in the presence of established osteoporosis. Recently, treatment with intermit- tent parathyroid hormone 1-34 (FTH[1-34]) has been shown to significantly increase bone mass in osteoporotic animals and humans,"-") and to improve biomechanicd strength and pre- serve trabecular bone connectivity in an animal model of osteoporosis.(X.") Intermittent PTH injections appear to in- crease bone mass by adding bone to existing trabeculae. To date, trabecular bone connectivity is generally esti- mated from mathematical models derived from from two- dimensional (2D) histologic data.(x.'4,'') Since trabecular 'Department of Medicine, University of California at San Francisco, San Francisco, California. 'Department of Chemistry and Material Science, Lawrence Livermore National Ldboratories, Livermore, California. 1470