4. Study justification 4.1 Background 4.1.1 Introduction Bone substitution is becoming more relevant in an age where the prevalence of bone disorders and conditions has a steep upward trend and where the population grows older, is more obese and has low physical activity. The expectations are aiming for a worldwide doubled incidence. (15) Because of the histological compatibility and the immunogenic advantage, autologic bone grafts nowadays still serve as the golden standard in bone substitution. Moreover, autografts have several key components to achieve osteoinduction (i.e., bone morphogenetic proteins (BMPs), osteogenesis (i.e., osteoprogenitor cells) and osteoconduction (i.e., three-dimensional and porous matrix). Autografts do involve harvesting bone, with can be obtained from the patient’s iliac crest, …show more content…
In the 1990’s multiple studies suggested that the protein recombinant human bone-morphogenetic protein-2 (rhBMP-2), which was used in the InFUSEtm implant, had these effects. There were uncertainties regarding selection of the carriers, dosing, and safety. (2) The bone inducing effectiveness in humans was proven and accepted. Several initial review articles concerning the safety of the usage of these bone inducers, were lost in the mass, due to the many industry-sponsored trails. These, probably biased, trails showed all the same: no adverse effects associated with rhBMP-2. In the end it appeared that there were ten to fifty times higher risk of adverse events associated with rhBMP-2. (2) The risk of another InFUSEtm-debacle, the cost-effectiveness, stability issues and shelf-life of just 12-24 months. Made the route to the medical market very hard for new comparable uses of proteins in bone substitution. A FDA-approval for this kind of product is hard to get these days after these medical errors (2, 6,