The introduction of new treatments needs to be both clinically effective and cost effective. Clinicians tend to be unaware of the importance of the latter, and how health economic assessments are undertaken, especially in a public health system where the inclusion of funded treatments is made on a national basis. The purpose of this study was to determine the cost savings from a societal perspective in the use of recombinant human Bone Morphogenetic Protein -2 (rhBMP-2) in grade III A and B open tibia fractures treated with a locked intramedullary nail and soft-tissue management in the UK, Germany, and France. Healthcare system (direct healthcare costs) and costs for productivity losses (indirect health-care costs) were calculated using the raw data from the Bone Morphogenetic Protein Evaluation Group in Surgery for Tibial Trauma “BESTT study”. Return-to-work time for estimation of productivity losses was assumed to correspond with the time of fracture healing. For calculation of secondary interventions costs and productivity losses the respective 2007/08 national tariffs for surgical procedures and average national wages for the UK, Germany, and France were used. From a societal perspective, overall savings per case of €7911 for the UK, €9270 for Germany, and €9291 were calculated. Those savings largely offset the upfront price of rhBMP-2 of €2266(£1,790) in the UK, €2970 in Germany, and €2950 in France. Total net savings can be estimated to be €9.6 million for the UK, €14.5 million for Germany, and €11.4 million for France. For all three countries reduced productivity losses are the key driver for the overall savings. In summary, despite the apparent high direct cost of rhBMP-2 in grade III A and B open tibia fractures, at a national level there are net cost-savings from a societal perspective for all three countries.
Gentamicin was described with negative effects on bone formation. Arginin-Glycin-Aspartat (RGD) sequences play a key role in the adhesion of osteoblasts and have proven to improve implant integration. We have already shown a significant reduction in infection rates by a combined gentamicin-hydroxyapatite (HA) and gentamicin-RGD-hydroxyapatite coating in a rabbit infection model for cementless joint prostheses. The purpose of the study was to assess whether the gentamicin-HA coating had a negative effect on the implant integration and new bone formation, compared to pure HA coating, and whether this could be enhanced by additional gentamicin-RGD-HA coating. There were 5 study groups (8 animals per group) with 5 different stainless steel K-wires: uncoated, HA coated, gentamicin-HA, RGD-coated, gentamicin-RGD-HA coated. A 2.0 mm K-wire with one type of coating was introduced into the intramedullary canal of the tibia. The tibiae were harvested after 12 weeks and standardised longitudinal and transverse sections were performed to study new bone formation around the implant and implant bone contact. New bone formation and osseointegration of the implant surface was assessed using histomorphometrical methods by computerised semi-quantitative analysis and histological methods. There were no significant differences between the HA and the gentamicin-HA group although new bone formation and implant bone contact were always higher for the pure HA coating. Additional RGD coating on the gentamicin-RGD-HA coating did not show significant improvement of bone formation and implant integration compared to gentamicin-HA. There was a very similar histological appearance of new bone formation between all groups with very low frequency of giant cells, indicating good biocompatibility. Gentamicin-HA coating did not have significant negative effects on bone formation and bone implant contact, compared to pure HA coating. In combination with the excellent ability to reduce infection rates, gentamicin-HA coating may have a high interest in cement-less arthroplasty.
Infections in total joint arthroplasty, particularly with multiresistant bacteria, are a serious problem. A new nanoparticulate silver cement had previously shown good biocompatibility combined with good in vitro antimicrobial activity against multiresistant bacteria. The purpose of the current study was to evaluate the antibacterial activity of nanoparticulate silver cement against biofilm-building methicillin-resistant S. aureus (MRSA) in a rabbit model and to compare it to that of gentamicin-loaded cement. Gentamicin cement or nanoparticulate silver bone cement was injected into the proximal half of one femur in 10 animals, respectively. Before hardening of the cement 107 or 108 colony forming units of MRSA with high gentamicin resistance were inoculated at the cement bone interface in 5 rabbits of each group. The animals were euthanized after 14 days and both the cement adjacent bone and the cement itself were studied using microbiological and histological methods. Infection was defined as positive culture growth from the bone and/or cement samples. Infections rates were 100% for the gentamicin group (10 of 10 animals had infection) and 30% for the NanoSilver group (3 of 10 animals). Thus, nanoparticulate silver bone cement significantly reduced infection rates by 70%. Nanoparticulate silver cement exhibited good antimicrobial activity in the prophylaxis of cement-related infections with MRSA and is therefore a promising alternative in total joint arthroplasty.