Tohoku J. Exp. Med., 2013 Jan, 229(1)

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

HIROYUKI TSUCHIE,¹ NAOHISA MIYAKOSHI,¹ YUJI KASUKAWA,¹ HIROSHI AONUMA¹ and YOICHI SHIMADA¹

¹Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita City, Akita, Japan

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.

keywords —— cancellous bone union; intermittent administration; osteoporosis; parathyroid hormone; pre-operative period

© 2013 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2013, 229, 19-28

Correspondence: Hiroyuki Tsuchie, Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan.

e-mail: tuchikiti@yahoo.co.jp