Aim

In the current study we aim to characterize the use of cationic host defense peptides (HDPs) as alternative antibacterial agents to include into novel antibacterial coatings for orthopedic implants.

Staphyloccous aureus represent one the most challenging cause of infections to treat by traditional antibacterial therapies. Thanks to their lack of microbial resistance described so far, HDPs represent an attractive therapeutic alternative to antibiotics. Furthermore, HDPs have been showed to control infections via a dual function: direct antimicrobial activity and regulation of immune response. However, HDPs functions characterization and comparison is controversial, as changing test conditions or cell type used might yield different effects from the same peptide. Therefore, before moving towards the development of HDP-based coatings, we need to characterize and compare the immunomodulatory and antibacterial functions under the same conditions in vitro of 3 well-known cathelicidins: human LL-37, chicken CATH-2, and bovine-derived IDR-1018.

Aim

“Implant associated Staphylococcus aureus or S. epidermidis infections are often difficult to treat due to the formation of biofilms on prosthetic material. Biofilms are bacterial communities adhered to a surface with a self-made extracellular polymeric substance that surrounds resident bacteria. In contrast to planktonic bacteria, bacteria in a biofilm are in an adherent, dormant state and are insensitive to most antibiotics. In addition, bacteria in a biofilm are protected from phagocytic cells of the immune system. Therefore, complete surgical removal and replacement of the prosthetic implant is often necessary to treat this type of infections. Neutrophils play a crucial role in clearing bacterial pathogens. They recognize planktonic bacteria via immunoglobulin (Ig) and complement opsonisation. In this project, we aim to evaluate the role of IgG and complement in the recognition and clearance of staphylococcal biofilms by human neutrophils. Furthermore, we evaluate if monoclonal antibodies (mAbs) targeting biofilm structures can enhance recognition and clearance of staphylococcal biofilms by the human immune system.”

Summary

The M2a-38^tm metal on metal total hip arthroplasty showed a high incidence of pseudotumors and an unexpected high revision rate in our thoroughly screened cross sectional cohort.

Introduction: In uncemented total hip arthroplasty (THA) stem sizing and stem insertion affect the fit and fill of the prosthesis in the medullary canal. This study investigates how tightness of the stem fit influences bone remodelling and if there is a correlation between radiological and clinical Results: Methods: In a retrospective study a consecutive series of 64 patients following uncemented THA with a proximally coated anatomic stem (ABG-II, Stryker) was followed-up for 5 years using the Merle d’Aubigne (MdA) clinical score. Radiographic analysis of bone remodelling features per Gruen zone (R1 to R7) was performed on AP and lateral x-rays at 5 years. Femoral fit was measured at three levels (proximal, mid-stem, distal) on the direct postop x-ray using the femoral fit ratio (f) of Kim and Kim (tight femoral fit: f≥0.8, non-tight: f< 0.8). The medullary canals were categorised according to Noble (normal, stove pipe, champagne flute). Bone remodelling was compared to literature values of the ABG-I stem and correlated to clinical findings.

Results: The MdA improved from 9.6 pre-op to 17.1 at 5 years with no difference between tight and non-tight implants. Lateral thigh pain (LTP) occurred in 10/64 cases (3 requiring medication). Patients with LTP had significantly lower proximal (0.75 vs 0.80) and distal fit & fill (0.72 vs 0.79. LTP was equally frequent with a normal or varus position.

Proximal bone resorption occurred in 27% (R1) or 34% (R7) which is lower than the values reported for the ABG-I stem (R1: 48%, R7: 45%). Bone resorption was significantly higher with tight than non-tight mid-stem fit (69% vs 27%, p=0.04). The same trend was true for tight distal fit (56% vs 37%).

Cancellous densifications were frequent at mid-stem level (R2: 83%, R6:88%) but much less distally (R3: 44%, R5:25%). No influence of fit & fill was measured.

Cortical densifications were noted in 16% (ABG-I 15%) overall with a higher proportion measured for tight distal fit (25%) than loose distal fit (6%, p=0.07). A similar observation was made for cortical thickening (11% overall, tight:non-tight=16%:6%). Pedestal formation (17% overall) was more likely with a non-tight proximal fit (23% vs 12%) and mid-stem fit (20% vs 8%)

A proximal tight fit was achieved more frequently with normal (55%) and stovepipe femora (50%) than champagne flute femora which had the highest proportion of tight distal fit (85%).

Discussion: At 5 years femoral implant fit influenced bone remodelling reactions which are in agreement with the design philosophy of proximally press-fitting anatomic stems. However, implant fit could not be correlated to clinical outcome yet. This may require a longer follow-up.

As LTP occurred with non-tight fit it seems that elastic mismatch is not the main cause.

Less proximal bone resorption and less distal densifications confirm the design changes from ABG-I to ABG-II.

Introduction: Investigating the correlations between bone ongrowth and HA resorption on coated implants is important to understand the contribution of resorbable coatings on implant fixation and periprosthetic bone remodelling. It is only possible histomorphometrically and this study measured bone apposition and residual HA on hip stems of one single design.

Methods: Post-mortem retrievals of 13 ABG-I (Stryker) hip stems from 13 patients (10f, 3m, age: 58–86yrs, uneventful THA, death unrelated to hip diseases). The time from implantation (stem in-vivo) ranged between 3.3 to 11.2yrs.

Three cross sections were cut from the metaphyseal femur and surrounding bone proximal to Gruen zones 2 and 6 (regions with HA coating). The three sections were A (proximal), B (mid-part) and C (distal). Sections were prepared using the Donath technique and then paragon stained for quantitative histomorphometry using an Axioskop microscope (Carl Zeiss, Germany) with image analysing (SAMBA, France).

For each segment the total implant perimeter, percentage of implant perimeter covered by bone and the total percentage of residual HA coating were measured. Bone implant contact was defined as direct ongrowth of bone to the coating or the titanium surface.

Results: HA resorption increased significantly with the time in-vivo as measured by the residual HA (e.g. < 6yrs: Avg.=36.7%, > 6yrs: Avg.=10.1%, p=0.02). This correlation was true for all sections A, B and C (p=0.02–0.03). Beyond 8yrs HA was almost gone.

Bone ongrowth ranged between 18%–56% and was independent of the time in-vivo. Bone ongrowth was most strongly correlated to patient age with younger patients having significantly higher bone ongrowth (p=0.001). Bone ongrowth was correlated with HA-resorption only in the most proximal zone A (p=0.001) with lower ongrowth associated with lower levels of residual HA. However, HA resorption was not significantly correlated with patient age.

HA resorption was significantly higher most proximally with less residual HA (13.0%) than mid-stem (22.6%, p=0.05) and distal (28.1%, p=0.05). Metaphyseal stem level and bone ongrowth were not significantly correlated in this manner.

Discussion: HA resorption increased with implantation time and was nearly completed at 8yrs. As bone ongrowth was independent of time in-vivo and independent of HA resorption on the mid-part and distal coated stem sections there is evidence that long term implant fixation is not diminished while the HA coating is being resorbed.

Bone ongrowth but not HA resorption was strongly correlated to patient age indicating that the bone remodelling process is more affected by individual bone health than it can be stimulated by HA coating.

HA resorption increased significantly from the distal to mid-stem and the most proximal coating level in the same way as stress shielding and thus osteoclastic stimulation goes up.

Introduction. Periprosthetic femoral fractures (PPF) have become more common as the population at risk, patients with joint arthroplasty, has increased. The choice of treatment depends on the location of the fracture relative to the implant, the residual fixation of the implant and patient factors such as deficient bone stock or osteopenia. The Vancouver classification categorises types of PPF and identifies strategies for its management. However, the Vancouver classification is mainly based and focused on cemented implants. Recently a modified algorithm for the management of PPF based on the Vancouver classification has been published. We analysed PPF with a single type of uncemented hip stem and compared our treatment to the most recent management algorithm.

Methods. From a consecutive series of 619 uncemented proximal hydroxyapatatite coated ABG-I prostheses, 14 patients (2.3%) sustained a PPF after an adequate trauma. The mean time between the index operation and the fracture was 6.9 years(range: 2.0 to 13.7 years). The mean age of the patients at the time of fracture was 79 years (range 59–87). The fracture patterns and state of stem fixation were analysed.

Results. In 5 patients the fracture was limited to the proximal Gruen zones 1 and 7 with the stem still firmly fixed (type A). Fracture treatment was conservative but in one patient the greater trochanter had to be reat-tached. Six B1,two B2 fractures and one B3 fracture were seen. Compared to the Vancouver classification we observed a different pattern in the type B fractures. No fractures at the tip of the stem were seen as common and characteristic in cemented implants. Three B1 fractures were operated due to fracture displacement and three were treated conservately. THe B2 and B3 fractures were managed with long uncemented revision stems because of a disrupted bone-prosthesis interface. Type C fractures were not seen. All fractures healed well.

Conclusion. The ABG-I shows a bone remodelling pattern consisting of mid stem bone condensation and proximal bone resorption, which leads to a high bone density gradient. This gradient acts as a stress riser and thus can be a preferred location for the initiation of a fracture. This pattern is distinctly different from the fracture types observed for cemented implants. . As a result the ABG-I stem was modified to the ABG-II design permitting more proximal and less mid-stem load transfer, smoothening the bone density gradient.

This study confirms that the Vancouver classification and the modified algorithm for the management of PPF are a simple,reproducible classification system also for the uncemented treatment modality. Conservative treatment is a valid option in case of a stable implant, while in case of a loose implant surgical intervention is mandatory.

Introduction: After total hip arthroplasty (THA) the periprosthetic bone is loaded in an unphysiological manner (stress shielding), a major cause for periprosthetic bone resorption and aseptic loosening. Design, material and surface properties of the implant influence the stress shielding effect. This study investigates whether the design changes from the successful ABG-I to the ABG-II stem can be verified in perioprosthetic bone remodelling using Dual-Energy X-ray Absorptiometry (DEXA).

Methods: 51 THA patients (22f, 29m, avg. age: 60.8 years) were randomised to either ABG-I or ABG-II. DEXA measurements were performed preoperatively and 10 days (baseline), 3 weeks, 3, 6, 12 and 24 months postoperatively using standard Gruen zone analysis. At the same time clinical Merle d’Aubigne (MdA) scores were measured. Changes in bone mineral density (BMD) were expressed as percentage changes from the baseline for each of the Gruen zones (R).

Results: The average MdA score (25 ABG-I, 26 ABG-II) increased from 10.3 preoperatively to 17.3 at 24 months postoperative. The improvement was higher for ABG-II (7.5) than ABG-I (6.5) but not significant (p=0.15). During the first three postoperative months the average BMD of all zones combined dropped steeply for both the ABG-I (−5.5%) and ABG-II (−4.5%, n.s.). Beyond 3 months, the overall BMD change (zones combined) continued to develop without significant difference between both implant designs (plateau and slight recovery) but the individual zones showed distinct differences. The average BMD loss in the proximal Gruen zones was much lower for ABG-II (R1: −7.9%, R7: −3.7%) than for ABG-I (R1: −9.3%, R7: −11.9%) while distally the situation was reversed with better bone preservation for the ABG-I (R3: −2.9%, R4: −1.5%, R5: −1.7%) than for the ABG-II (R3: −6.0%, R4: −2.8%, R5: −4.6%). In the mid-stem region a transitional area was identified with better bone preservation for ABG-II in Gruen zone 6 (+2.7% vs −1.4%) and for ABG-I in Gruen zone 2 (-4.9% vs 7.9%). However, the p-values (two-sided t-test) ranged from 0.05–0.35 at statistically non-significant levels.

Discussion: The steep initial bone loss for both stem designs and all Gruen zones combined indicates that during this early postoperative phase surgical trauma and reduced loading dominate the bone remodelling process and not the type of implant. The different development of proximal and distal BMD for ABG-I and II in the period thereafter demonstrates the long-term effect of implant design verifies the design improvements (less proximal stress shielding). A parallel study identified the dominant influence of preoperative BMD on BMD loss. This explains our high standard deviation and the lack of statistical significance. The study is now expanded with patients matched for preoperative BMD.