Effect exerted by Teriparatide upon Repair Function of β-tricalcium phosphate to ovariectomised rat's femoral metaphysis defect caused by osteoporosis

Abstract

In this study, we tested the effect of Teriparatide (PTH) in combination with β-tricalcium phosphate (β-TCP) as a bone void filler in an ovariectomised rat distal femoral metaphysis model.β-TCP is a completely resorbable synthetic calcium phosphate and the Teriparatide is a drug that can promote bone formation in the condition of osteoporosis. A critical size defect of 3 mm in diameter, a through-hole bone defect, was drilled into each distal femur of the ovariectomised rats. The hole was filled with β-TCP and the rat was injected PTH Teriparatide (30 μg/kg) in peritoneum 5 times per week. After 4and 8 weeks the animals were killed and the degree of bone healing analysed. In total, 60 animals were investigated. When the β-TCP and PTH were used, histological, biochemistry and histomor-phometric evaluations revealed significantly better bone healing in terms of quantity and quality of the newly formed bone. The Ovariectomised rats which suffer from femur metaphysis defect are cured by embedding β-tricalcuim phosphate and intermittently cured by parathyroid hormone (PTH).

Introduction

There is a clear unsatisfied medical need for the development of novel bone grafts for the treatment of bone defects. Autogenous bone grafts are still considered the “gold standard” for bone replacement, although this method implies limited availability and potential comorbidity [1], [2]. To overcome these limitations, several ceramic calcium phosphates have been developed as synthetic bone substitutes. These materials are proven biocompatible, resorbable, and osteoconductive [3]. Tricalcium phosphate is frequently used for clinical treatment, it is free of imperfections of many biogenic repairing materials and possessed of good function as a filler and support and of good bone conduction, but it does not have good osteoinductivity [4], [5]. Although there are already some cytokines such as rhBMP-2 complex to TCP and other bone biomaterial to treat bone defects, the effect is significant [6], [7]. However, clinical studies and animal experiments of these drugs are not conducted under conditions of osteoporosis; treatment of osteoporosis itself cannot be ignored. Current studies have consistently demonstrated that bone healing for postmenopausal osteoporotic women and osteoporotic animals lacking estrogen is remarkably delayed or impaired [8], [9]. A promising medicine curing osteoporosis-induced bone defect should be in possession of two functions, curative effect for osteoporosis itself and capability of inducing bone formation.

PTH is an exception. Teriparatide, i.e. a recombinant form of parathyroid hormone 1-34 (rh PTH 1-34), is the one and only medicine approved by FDA for curing osteoporosis and stimulating new bone formation. PTH can apparently precipitate bone forming. To be specific, it improves the quantity, quality and density of bone by increasing volume of bone trabecula at hip [10]; meanwhile, it helps to increase the quantity and density of centrum, to enhance bone strength, and to fortify the quantity of femur shaft, cortical thickness and maximum compressive load so that it notably reduces the chance of bone fracture for patients suffering from osteoporosis [11], [12], [13]. PTH has been demonstrated in studies that it can enhance structural allograft healing by anabolic effects on new bone formation via small-vessel angiogenesis, inhibition of angiopoietin-2-mediates arteriogenesis, and enhancement of osteogenic differentiation via bone morphogenetic protein signalling [14]. Interestingly, it has been found that PTH induces bone formation in the proximity of structural femoral bone allograft via intramembranous pathway [15]. Studies have shown that PTH does play a role in promoting bone fractures repair, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts [16], [17]. Osteoporosis bone defect mainly occurs in metaphysis, especially in form of belt-shaped osteoporosis in metaphysis andtransparent belt under osseous articular surface [18], [19].

We designed this experiment. In this study, the performance of the effect for PTH onβ-TCP as a bone void filler in a ovariectomised rat distal femoral metaphysis model of critical size defects were tested.