Published online Sep 18, 2018. doi: 10.5312/wjo.v9.i9.120
Peer-review started: March 29, 2018
First decision: April 29, 2018
Revised: June 20, 2018
Accepted: June 26, 2018
Article in press: June 27, 2018
Published online: September 18, 2018
Numerous studies have emphasized the association of multiple risk factors, including alcohol consumption, glucocorticoids, trauma, autoimmune diseases, thrombophilia, genetic and metabolic components with secondary osteonecrosis (ON). ON of the femoral head (FH) is a debilitating disease that usually leads to osteoarthritis of the hip joint in young adults and up to now total hip replacement is predestinate in the long term.
Early diagnosis and management aims to suspend the process of joint destruction through enhancement of bone repair and bone renewal. In the early stages of ONFH there are surgical alternatives to restrain the progressive destruction of the subchondral bone such as core decompression, osteotomy, non-vascularized or vascularized bone grafting. This study extended the prospect of use growth and angiogenic factors for the process of repair at the necrotic trabeculae of the FH.
The main aim of this research project was to evaluate the treatment of ONFH with the use of vascular endothelial growth factor (VEGF).
An experimental model of cryosurgically-induced ONFH in canines was used to assess the power of our hypothesis that VEGF could be a crucial therapeutic factor for bone tissue remodeling and reversal of osseous degradation during the treatment of ON. VEGF (2 different doses of 500 μg and 500 ng) was either injected in a single dose or administered continuously in the necrotic area with the use of an osmotic micropump, while in a control group 0.9% sodium chloride (NS) was injected in the necrotic area.
The untreated group had signs of ONFH, whereas the treatment groups with VEGF revealed reversal of the osteonecrosis, except the group treated with NS, that served as control. These findings demonstrate that the bone regeneration process in the osteonecrotic microenvironment could be affected by manipulation of VEGF levels.
We demonstrated that the use of the VEGF affects in a positive and dose dependent manner the necrotic bone and induces the process of osseous regeneration. Since now it is well established by numerous studies that there are strong indications of a cellular and molecular pattern of angiogenic-osteogenic coupling. The restoration of bone vascularity is an absolute parameter in the process of osteoinduction, which is the target of any therapeutic agent against ONFH.
In a reproducible experimental model of ONFH in mature beagles it was found that the treatment with VEGF leads to bone tissue remodeling and new bone formation at the osteonecrotic site and subsequently to reversal of ON. Besides that, the optimal delivery model of VEGF needs to be further studied. Utilizing a well-designed delivery system, like specific slow release scaffolds or gene delivery projects, may potentially lead to better bone regeneration and improve VEGFs therapeutic effect by stabilizing it against rapid degradation. Even if VEGF is sufficient to improve revascularization, recently scientists introduced the use of a combination of growth factors and manipulated progenitor cells to enhance bone repair and bone renewal. Although local VEGF administration is known to enhance new bone formation in ONFH in our study, future studies should further investigate, in a variety of experimental conditions, the role of VEGF as a key molecule and essential player for therapeutic strategies targeting bone reconstruction, so that an even transition to clinical trials may be achieved.