Abstract
BackgroundOsteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation.MethodsThe osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests).ResultsThe mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p < 0.05). At 6 and 12 weeks, the highest levels of OC and OPN markers were found in the OPG-chitosan gel group, followed by the chitosan gel group. The number of osteoclasts in the OPG-chitosan gel group was lower than the other groups. The results of the liver and kidney functional tests indicated no signs of harmful systemic effects of treatment. In conclusion, the OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications.
Highlights
The gold standard for bone regeneration is an autologous bone graft
We demonstrated that OPG is released from the OPG-chitosan gel in vivo, and it is possible that the controlled release of OPG at the defect site enhances the recruitment of active osteoblasts and suppresses the recruitment of osteoclasts, thereby improving bone regeneration
We conclude that the bioresorbable OPG-chitosan material induced the formation of a significant quantity of bone in a critical-sized parietal bone defect in a rabbit model
Summary
The gold standard for bone regeneration is an autologous bone graft. the procurement of autogenous bone comes with some disadvantages, such as creating an additional surgical area, significant morbidity, and limited source material. The first clinical trial evaluated the efficacy of recombinant Fc-OPG, used systemically as a drug for the treatment of osteoporosis in postmenopausal women (Bekker et al, 2001) and another study evaluated a different formulation of OPG, known as AMGN-0007, in patients with lytic bone lesions associated with multiple myeloma or breast carcinoma (Body et al, 2003). Both of these studies reported that Fc-OPG treatment resulted in reduced bone turnover markers when administered at a low dose, and had a longer antiresorptive effect when administered at an equivalent dose. The OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications
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