Intermittent administration of human parathyroid hormone enhances bone formation and union at the site of cancellous bone osteotomy in normal and ovariectomized rats

Abstract

Intermittent administration of human parathyroid hormone (hPTH) has an anabolic effect on bone in animals and humans and is expected to be a potent agent for the treatment of osteoporosis. However, little is known about the effects of hPTH on cancellous bone healing after cancellous bone fractures or osteotomies. We evaluated whether hPTH enhanced bone union at the site of cancellous bone osteotomy and further elucidated the possible mechanisms of hPTH effects on cancellous bone healing. After a bilateral ovariectomy (OVX) or sham operation in mature female rats, cancellous bone osteotomy was performed on the right proximal tibia. After once-a-week administration of hPTH (1–34) (100 μg/kg) or its vehicle for 4 weeks, bilateral tibiae including osteotomy and non-osteotomy sites were harvested. Along with conventional bone histomorphometry, cancellous bone union at the osteotomy site and the rate of proliferating cells immunostained with proliferating cell nuclear antigen (PCNA) and adipocytes in the surrounding bone marrow were evaluated. hPTH increased cancellous bone volume by stimulating bone formation in both normal and OVX rats and suppressed adipocyte volume ( p < 0.05). The percentage of PCNA-positive cells at the osteotomy site after PTH treatment was 2- to 3-fold higher than that of vehicle treatment controls both in sham-operated and OVX rats ( p < 0.05). The magnitude of increase in the percentage of PCNA-positive cells after PTH treatment at the osteotomy site was two times higher than that at the non-osteotomy site. Furthermore, PTH treatment increased cancellous bone union after osteotomy both in sham-operated and OVX rats ( p < 0.05). These results suggest that hPTH enhances cancellous bone healing at the site of osteotomy with, at least in part, a local regulating action that increases osteoblastogenesis and decreases adipocytogenesis at and around the osteotomy.