Intermittent Administration of Human Parathyroid Hormone before Osteosynthesis Stimulates Cancellous Bone Union in Ovariectomized Rats

Abstract

It has been reported that intermittent administration of human parathyroid hormone (h-PTH) promotes bone healing after surgery for osteoporotic fractures. If bone healing is promoted by the administration of h-PTH during pre-operative waiting period, we can prevent prolonged bed rest. Therefore, we evaluated the effects of pre-operative h-PTH treatment on cancellous bone union and its mechanism for fracture healing in ovariectomized rats as a model for osteoporosis. Ovariectomized 7-month-old female Sprague-Dawley rats underwent an osteotomy of the proximal tibia as a fracture model, and h-PTH (30 µg/kg body weight) or vehicle was administered as a pre-operative treatment for one week. After the one-week treatment, tibiae were fixed with wire for osteosynthesis, and h-PTH or vehicle was administered for 1 or 3 weeks following wire fixation. In addition to bone histomorphometry, we used alcian blue/hematoxylin stained sections for evaluating cartilage volume and immunostained sections for analyzing the expression of proliferating cell nuclear antigen (PCNA) for cell proliferation and that of Sox9 and Runx2, differentiation markers for cartilage cells and osteoblasts, respectively. Pre-operative treatment with PTH significantly increased bone volume. Pre-operative and pre-to post-operative treatment with PTH for 2 weeks significantly promoted bone union. Pre-operative treatment with PTH significantly increased cartilage volume, and pre-to post-operative treatment with PTH for 2 weeks significantly increased the percentage of cells positive for Runx2 (p < 0.01), but not PCNA or Sox9. Pre-operative administration of h-PTH enhances bone union by promoting cartilage formation and cell differentiation to osteoblasts, but not by promoting cell proliferation.

Effects of Intermittent Administration of Parathyroid Hormone and Parathyroid Hormone‐Related Protein on Fracture Healing: A Narrative Review of Animal and Human Studies

“…The results of the study supported that PTH therapy promoted fracture healing in gonadectomized osteopenic animals. Later, Nozaka and colleagues and Tsuchie and colleagues reported that PTH therapy exerted its beneficial effects on healing not only in long bone shaft fractures but also in cancellous bone osteotomy in gonadectomized osteopenic animals …”

In vivo effects of two novel ALN-EP4a conjugate drugs on bone in the ovariectomized rat model for reversing postmenopausal bone loss

“…Currently, the only clinically approved anabolic therapy for the treatment of osteoporosis is teriparatide (Forteo™), which is a recombinant form of parathyroid hormone (PTH). Past studies have shown that intermittent administration of PTH has significant bone anabolic effects on rats and humans [8][9][10]. Unfortunately, treatments with Forteo™ require daily injection and long-term use of PTH has been associated with osteogenic sarcoma in rats [11][12][13], and thus, its use may be limited due to safety concerns.…”

The Role of Parathyroid Hormone in Fracture Healing

“…33 Together with other studies, PTH shows beneficial effects on healing of fractures in the setting of osteoporosis. [34][35][36][37][38][39] Drugs, such as glucocorticoids, can induce a state of osteopenia within the bones. That is to say that steroids increase bone loss by inhibiting osteoblast formation and function, decreasing collagen synthesis, and decreasing intestinal calcium absorption.…”