title: Adjuvant therapies of bone graft around non-cemented experimental orthopedic implants stereological methods and experiments in dogs.
abstract: Revision arthroplasty is a challenging aspect of the otherwise quite successful area of joint replacement surgery. The instable interaction between implant and host bone has often initiated a destructive process of inflammation and osteolysis, rendering the revision site sclerotic and with insufficient bone stock. One way of dealing with this is to build up a bed of tightly packed morselized bone graft to support the revision implant in a procedure often referred to as impaction grafting. Fresh frozen morselized femoral head allograft is the gold standard material for impaction grafting of the large defects usually involved in revision arthroplasty. The clinical outcome does not match that of primary arthroplasties. Implant subsidence is greater, implant survival shorter, and the bone graft is often not incorporated into living bone. The studies constituting this thesis have investigated ways of improving early implant fixation and bone graft incorporation. All studies used the same experimental canine model of early fixation and osseointegration of uncemented implant components inserted into a bed of impacted bone graft. Study I compared bone grafted implants where the morselized allograft was used alone or had been added rhBMP-2, the bisphosphonate pamidronate or a combination of the two. The main object was to see wether the previously observed growth factor related accelerated allograft resorption could be counteracted by the addition of an anti-catabolic drug. The study also compared HA-coated and non-coated porous Ti implants. The untreated control implants had better mechanical fixation than all other treatment groups. RhBMP-2 raised the total metabolic turnover of bone within the allograft with a net negative result on implant fixation. Pamidronate virtually blocked bone metabolism, also when combined with rhBMP-2. The HA-coated implants had more than twice as good mechanical fixation and improved osseointegration compared to the corresponding Ti implants. Study II investigated the addition of a bovine bone matrix lyophilisate (Colloss) to the allograft in three different doses. The main object was to see, whether the addition of a biological delivery device of low-dose osteogenic growth factors could provide a sufficient signal to increase the bioactivity of the bone graft without also yielding mechanical instability through increased allograft resorption. Allograft resorption increased with increased signal dose, but not to the extent that it affected implant fixation negatively at the observational time point. Mechanical implant fixation was doubled, and implant osseointegration and graft incorporation were improved. Study III compared a beta-TCP ceramic bone graft substitute (Ossaplast) with and without an osteogenic signal (Colloss E) to morselized allograft with and without the same signal. The object was to investigate, whether the addition of an osteogenic stimulus to a bio ceramic could replace biological allograft bone. The addition of an osteogenic signal improved early osseointegration of implants grafted with beta-TCP granules and increased their mechanical implant fixation to a level comparable to the allografted implants. All studies I-III confirmed that the topical addition of an osteogenic signal could increase implant osseointegration and the formation of new bone within a grafted defect. Another striking observation was the near-complete absence of fibrous tissue in the treated groups. The osseointegration of ceramic bone grafts improves when both the osteoconductive as well as the osteogenic components of bone are substituted. The effect on implant fixation of devices and pharmaceuticals that influence bone metabolism can be difficult to predict, as shown in study I. There seems to be a therapeutic window for these substances. This must be further explored prior to clinical use, as the adverse effects of overdosing bone anabolic and anti-catabolic substances can be detrimental.
authors.affiliation: Orthopaedic Research Laboratory, Dept. of Orthopaedics, Aarhus University Hospital, Denmark. baas@ki.au.dk
authors.forename: Jørgen
authors.initials: J
authors.lastname: Baas
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D007592:Joint Diseases / Q000601:surgery*; D010014:Osteolysis / Q000188:drug therapy*; D011475:Prosthesis Failure; D019919:Prosthesis Implantation / Q000009:adverse effects*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic