Effect of Intermittent Administration of Parathyroid Hormone on Fracture Healing in Ovariectomized Rats

Woo, Kim Hyun; Jahng, Jun Seop

Abstract

PURPOSE: This study was designed to compare fracture healing in normal and ovariectomized rat, and to evaluate the effect of intermittent administration of parathyroid hormone on fracture healing in osteopenic animal model,
MATERIALS AND METHODS
Four-months-old mature female Sprague-Dawley rats were randomly elivided into 5 groups. Group I underwent a sham operation, and others (Group II-V) were ovariectomized. At three months after ovariectomy or sham operation, standardized bilateral transverse tibial fractures were created and intramedullary nailings with Kirschner wire were performed. The rats were then treated with daily subcutaneous injection of placebo in Groups I and II, 17beta-estradiol in Group III, low doses of recombinant human PTH (1-84) in Group IV, and high doses of recombinant human PTH (1-84) in Group V for 4 weeks. At day 30 of post-fracture the animals were sacrificed and fracture healing was assessed with histologic/histomorphometric analysis and three-point bending mechanical testing.
RESULTS
On histologic/histomorphometric evaluation of sham operation group, the fracture callus mainly consisted of dense trabecular bone. On the other hand, Groups II and III seemed to have much looser cancellous network, abundant in fibrous marrow. In parathyroid hormone-treated g roups, external callus consisted of more dense trabecular, woven bone than that of Groups II or III, and especially the high doses of parathyroid hormone-treated group was comparable to the sham operation group in terms of per cent trabecular bone volume (Group I>V>IV>III=II, P<0.05). Mechanical testing indicated that ultimate load was reduced in Group II and III compared to sham operated or parathyroid hormone-treated groups (Group I=V>IV>III=II, P<0.05). Other significant differences were the increase in absorbed energy at ultimate load of Groups I and V (Group I=V>IV=III=II, P<0.05), and increase in ultimate stress of Groups I and V (Group I=V>IV=II=III, P<0.05).
CONCLUSIONS
On the basis of this study, it may be concluded that fracture healing is delayed in the ovariectomy-induced osteopenic rat model. Our experiment also showed dose-related stimulation of parathyroid hormone in the strength of fracture, and that antiresorptive agents such as estrogen had no effect. Further study is needed in large animal model, and attention should be focused on systemic/long-term effect of parathyroid hormone and its relationship with local growth factors in fracture healing.