Abstract
Steroid-associated osteonecrosis (SAON) might induce bone collapse and subsequently lead to joint arthroplasty. Core decompression (CD) is regarded as an effective therapy for early-stage SAON, but the prognosis is unsatisfactory due to incomplete bone repair. Parathyroid hormone[1–34] (PTH[1–34]) has demonstrated positive efficacy in promoting bone formation. We therefore evaluated the effects of PTH on improving the effects of CD in Early-Stage SAON. Distal femoral CD was performed two weeks after osteonecrosis induction or vehicle injection, with ten of the ON-induced rabbits being subjected to six-week PTH[1–34] treatment and the others, including ON-induced and non-induced rabbits, being treated with vehicle. MRI confirmed that intermittent PTH administration improved SAON after CD therapy. Micro-CT showed increased bone formation within the tunnel. Bone repair was enhanced with decreased empty osteocyte lacunae and necrosis foci area, resulting in enhanced peak load and stiffness of the tunnel. Additionally, PTH enlarged the mean diameter of vessels in the marrow and increased the number of vessels within the tunnels, as well as elevated the expression of BMP-2, RUNX2, IGF-1, bFGF and VEGF, together with serum OCN and VEGF levels. Therefore, PTH[1–34] enhances the efficacy of CD on osteogenesis and neovascularization, thus promoting bone and blood vessels repair in the SAON model.
Highlights
This confirmed that osteonecrosis in the distal femurs was established successfully, while no changes were observed in the sham group
This study demonstrated that: (1) Parathyroid hormone (PTH)[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] improved the efficacy of Core decompression (CD) in the treatment of Steroid-associated osteonecrosis (SAON); (2) PTH[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] enhanced the effects of CD on osteogenesis under steroid administration, by increasing the number of osteoblasts, decreasing the number of necrosis foci and empty lacunae, thereby resulting in better biomechanical properties; (3) Neovascularization was improved by PTH[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] administration after CD by increasing blood vessel number in the bone tunnel and enlarging the diameter of vessels in the bone marrow; (4) PTH[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] upregulated the expression of BMP-2 and vascular endothelial growth factor (VEGF) protein in distal femurs, as well as increased serum OCN and VEGF levels
Larger diameter of vessels in the marrow was observed, but unexpectedly, we found no significant difference in the number of vessels between the SAON-CD group and the SAON-CD-PTH group in the marrow, even though PTH could increase the proliferation of endothelial cells
Summary
The experimental protocol was approved by the Institutional Animal Care and Use Committee of the Second Affiliated Hospital, School of Medicine, Zhejiang University (Register ID No.: 2015–391; Date: 7 May 2015). The whole experiment was performed according to the Guide for the Care and Use of Laboratory promulgated by the United States National Institutes of Health. Animals were held in a facility under a temperature range from 18 ̊C to 25 ̊C and regular day/night cycle, being allowed free access to food and water. Rabbits were monitored daily to evaluate the signs of pain, distress, or moribundity visually and their weights were measured three times a week. Animals, exhibiting the signs above or 10% acute weight reduction, were to be humanely euthanized prior the experimental endpoint. All animals were euthanized by an overdose of pentobarbital (90 mg/kg, Sigma Chemical Co., St. Louis, MO, USA) at the endpoint. All efforts were made to minimize suffering during the whole experiment
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