No increased bone formation around alendronate or omeprazole loaded bioactive bone cements in a femoral defect.

Alendronate and omeprazole have been found to influence bone healing by interfering with osteoclastic activity, resulting in increased bone formation. The biological effect of these conventional drugs, incorporated into bioactive bone cement (G2B1), was investigated in a rabbit model. The 2 materials and a control were inserted in defects created in the femoral condyle of rabbits. Implantation time was 6 and 12 weeks. After retrieval, micro-computed tomography and histomorphometry were performed to quantify bone mineral density (BMD) and bone volume (BV) of the implant-surrounding bone mass and the percentage of bone-to-implant contact. BMD and BV were similar in all groups. The percentage of bone-to-implant contact was significantly lower in the alendronate and omeprazole groups than in controls after 6 weeks of implantation. After 12 weeks, this difference in bone contact disappeared for the omeprazole but not for the alendronate implants, which were almost completely surrounded by a fibrous capsule, associated with a limited inflammatory response. In conclusion, in the current study, alendronate and omeprazole did not result in better bone healing when incorporated into bioactive bone cement than did plain control implants. Moreover, an additional cytotoxicity assay revealed that alendronate evoked a toxic response.

Bone regeneration of porous beta-tricalcium phosphate (Conduit TCP) and of biphasic calcium phosphate ceramic (Biosel) in trabecular defects in sheep.

In this study bone regeneration between porous beta-tricalcium phosphate (Conduit TCP) and biphasic calcium phosphate ceramic (Biosel), with a hydroxyapatite/beta-TCP ratio of 75/25, was compared. The ceramic particles were implanted in sheep trabecular bone for 3, 12, and 26 weeks. Histomorphometrical analysis revealed that Conduit degraded significantly during time and only 36% of the material was left at 26 weeks implantation time. Biosel, in contrast, remained nearly intact. The degradation of Conduit was due to dissolution as well as cell-mediated. Biosel showed a high cellular intervention, although this material did not degrade. Both materials were osteoconductive. The amount of newly formed bone appeared greater in the Conduit group after 26 weeks (46% +/- 8% as compared to 37% +/- 8% for Biosel), but this difference was not significant. Bone distribution over the defect was homogeneous in Conduit, whereas Biosel showed significantly more bone in the periphery of the defect after 26 weeks in comparison to the center. In conclusion, both ceramics are biocompatible and osteoconductive. Degradation showed a difference in amount and in cellular events, with more degraded Conduit TCP with less cellular intervention as compared to Biosel.

Antimicrobial efficacy of gentamicin-loaded acrylic bone cements with fusidic acid or clindamycin added.

The increasing gentamicin resistance among bacteria in septic joint arthroplasty has stimulated interest in adding a second antibiotic into gentamicin-loaded bone cement. A first aim of this in vitro study is to investigate whether addition of fusidic acid or clindamycin to gentamicin-loaded bone cement has an additional antimicrobial effect against a collection of 38 clinical isolates, including 16 gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement of the inhibition zone around antibiotic-loaded bone cement discs on agar plates, was used to investigate whether adding a second antibiotic has an additional antimicrobial effect. Second, a selected number of strains was used to study their survival in an interfacial gap made in the different bone cements to mimic the gap between bone and cement as existing near a prosthesis. Gentamicin-loaded bone cement had an antimicrobial activity against 58% of the 38 bacterial strains included in this study, while 68% of the strains were affected by bone cement loaded with a combination of gentamicin and clindamycin. Bone cement loaded with the combination of gentamicin and fusidic acid had antimicrobial activity against 87% of the bacterial strains. In the prosthesis-related gap model, there was a clear trend toward less bacterial survival for gentamicin-loaded bone cement after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid into gentamicin-loaded bone cement yields an additional antimicrobial effect. The combination gentamicin and fusidic acid was effective against a higher number of clinical isolates than the combination of gentamicin with clindamycin, including gentamicin-resistant strains.

Gentamicin-loaded bone cement with clindamycin or fusidic acid added: biofilm formation and antibiotic release.

The formation of staphylococcal biofilms on experimental bone cements, loaded with 0.5 or 1.0 g of active gentamicin and an additional equivalent amount of gentamicin, clindamycin, or fusidic acid was investigated. The biofilms were formed in a modified Robbins device over a 3-day time span and the influence of the additional antibiotics was quantified by expressing the number of colony forming units relative to the corresponding bone cement containing only gentamicin. Combinations of gentamicin with either fusidic acid or clindamycin reduced growth of clinical isolates of both gentamicin-sensitive Staphylococcus aureus and gentamicin-resistant coagulase-negative staphylococci to approximately 28%. To determine whether adding a second antibiotic has influence on the gentamicin release, cement blocks were placed in phosphate buffer and aliquots were taken at designated sampling intervals. The influence of the additional antibiotics was quantified by expressing the percentage released of the total amount of antibiotic incorporated in the different bone cements. After 3 days, all bone cements had released similar percentages of gentamicin, whereas more clindamycin and fusidic acid were released after doubling their concentration in the bone cements. In conclusion, bone cements loaded with combinations of gentamicin and clindamycin or fusidic acid are more effective in preventing biofilm formation than bone cements with gentamicin as a single drug. In addition, the presence of clindamycin or fusidic acid in gentamicin-loaded bone cement has no influence on the total gentamicin release.