The duration of systemic antibiotic therapy following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, use high concentration targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy in the management of PJI of the hip using our two-stage protocol. A retrospective review of our Institution's prospectively-collected database was performed to identify those patients who were planned to undergo a two-stage hip revision procedure for PJI. All patients had a confirmed diagnosis of PJI as per the major criteria of MSIS 2013, a minimum 5-years follow up and were assessed at the time of review using the MSIS working group outcome-reporting tool (2018). They were then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year).Aim
Method
The duration of systemic antibiotics following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, high concentration of targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy for two-stage hip revision. A retrospective review of our Institution's prospective database was performed to identify all intended two-stage hip revision procedures for PJI. All patients had a confirmed PJI as per MSIS 2013 criteria, minimum 5-years follow up and outcomes according to the MSIS working group outcome-reporting tool; then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year). 383 intended two-stage hip revisions were identified; of which 299 met our inclusion criteria, in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage). Median follow up was 10.7 years (IQR 6.3 – 15.0). 258 (86%) patients proceeded to 2nd stage surgery. 91% success rate was observed for those patients who underwent reimplantation, although dropping to 86% when including the patients who did not proceed to second stage. The median duration of post-operative systemic antibiotics was 5 days (IQR 5–9). No significant difference was observed in patients who received either; < / = 48 hours (86%; n=70) compared to > 48 hours antibiotics (86%; n=229; p=0.96) or </= 5 days of antibiotics (88%; n=202) compared to > 5 days antibiotics (82%; p=0.38). A significant majority had gram-positive (88%) infection with 30% being polymicrobial. Greater success rates were observed with two-stage exchange or gram-positive PJI (86%); than for gram-negative PJI (81%) and polymicrobial infection (74%) (p=0.36). Fungal PJI was observed to have a significantly reduced rate of success (n=3; 33%; p=0.03). Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage to manage PJI of the hip provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs.
The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods.Aims
Methods
No single test is 100% sensitive and specific for the diagnosis of prosthetic joint infection. Joint aspiration is currently the only preoperative investigation that can establish the identity of the infecting organism and its antibiotic susceptibilities. Frequently when attempting to aspirate a joint a ‘dry tap occurs as fluid cannot be aspirated. In this situation, normal saline may be injected into the joint and then reaspirated to provide fluid for culture. The aim of this study was to ascertain the diagnostic accuracy of culture of joint aspiratie with or without saline reaspiration in the event of a dry tap. A retrospective analysis of 580 hip and knee aspirations in patients deemed to have moderate-high risk of infection and ultimately proceeded to revision arthroplasty over 12 years at a large quaternary referral centre where pre operative aspiration is routine. Fluid was aspirated in 313 (54%) cases and dry taps in which saline injection reaspiration was performed occurred in 267 (46%) cases. Overall sensitivity and specificity of diagnostic aspiration were 84% (78–89%) and 85% (81–88%) respectively. Sensitivity and specificity of saline injection-reaspiration after dry tap were 87% (79–82%) and 79% (72–84%) compared to 81% (71–88%) and 90% (85–93%) for direct aspiration. Pre operative joint aspiration and culture is a sensitive and specific test for the confirmation of diagnosis in patients at a moderate to high risk of prosthetic joint infection. Culture of saline injection-reaspiration also provides accurate diagnostic information in the event of a dry tap. Both methods allow susceptibility testing of relevant organisms and are therefore able to guide peri-operative and cement instilled antibiotic therapy. Culture of pre operative joint aspirates provides sensitive and specific diagnostic information including antimicrobial susceptibility results. Saline injection-reaspiration is a useful additional technique in those patients in whom fluid cannot be aspirated.
The management of periprosthetic joint infection is challenging and the duration of systemic antibiotic therapy whether it be during the interval phase or after reimplantation of a new prosthesis is controversial. We report our experience of managing chronic periprosthetic infection of the hip by the two stage exchange procedure. Patients who were scheduled to undergo a two stage revision for chronic periprosthetic infection of the hip were identified from our prospective database. Of 425 patients with microbiologically proven periprosthetic infection, 369 (87%) underwent a two stage procedure, leaving 56 patients who did not proceed to reimplantation. 41 of these were clinically infection free but for personal or medical reasons did not proceed. The remaining 15 had persistent infection. The mean age at the time of the first stage was 68 years (26 – 92 yrs). 256 (61%) patients were alive for review. The mean time between stages was 6.3 months with a mean follow up after the second stage was 65 months (range 5 to 276 months). The success rate of a single 1st stage debridement, confirmed by negative cultures at the time of second stage reimplantation was 94%. 19 patients underwent a repeat 1st stage debridement and were classed as failures of the 1st stage. At the time of final review, 340 (92%) patients were deemed infection free out of those who had completed a 2 stage exchange. The duration of systemic antibiotic treatment after both the 1st and 2nd stages was divided into <48 hrs and >48 hours. There was no significant difference in the success of the 1st stage procedure in patients who received < 48 hours (48% of the patients) as opposed to > 48 hours (p = 0.98, Chi Squared Test, Relative Risk 1.009). Similarly there was no difference in the overall success of the two stage procedure irrespective of the duration of antibiotic therapy with 76% of patients receiving <48hrs of antibiotics after the second stage. Aggressive surgical debridement together with targeted local and short term systemic antibiotic therapy should be the mainstay of treatment in two stage revision surgery.
Tantalum trabecular metal components are increasingly used to reconstruct major bone defects in revision arthroplasty surgery. It is known that some metals such as silver have antibacterial properties. Recent reports have raised the question as to whether Tantalum components are protective against infection in revision surgery. This is based on a retrospective, single institution review, of revision cases comparing tantalum with titanium acetabular implants, which reported a lower incidence of subsequent infection in the tantalum group. This laboratory study aimed to establish if tantalum had any intrinsic antibacterial properties against planktonic bacteria or ability to inhibit biofilm formation. Equal sized pieces of tantalum (Trabecular metal, Zimmer UK) and titanium (Trilogy, Zimmer UK) were sterilised and then incubated with a low dose inoculum of either Staphylococcus aureus or Staphylococcus epidermidis for 24 hours. After serial dilution, colony forming units were quantified on MH agar plates. To establish the ability to inhibit biofilm formation these tantalum and titanium pieces were then washed twice, sonicated and washed again to remove loosely adhered planktonic bacteria. They were then re-incubated for 24 hours prior to quantifying colony forming units. All experiments were performed in triplicateIntroduction
Materials and methods
Data on the outcome of THA in patients under the age of 30 years is sparse. There is a perceived reluctance to offer surgery to young patients on the basis of potential early failure of the implant. We aim to review our experience with THA in this group of patients to establish outcomes in a high volume specialist arthroplasty unit. A retrospective review of prospectively collected data from the Lower Limb Arthroplasty Unit of patients who underwent THA <30 years of age between 1989–2009 was undertaken. Ninety five patients (117 THAs) were identified but 25 patients (27 hips) were excluded for lack of clinical records and 6 patients (9 hips) for follow up of <5 years. Clinical records were reviewed for patients’ age at operation, underlying pathology, details of operation and any failures (revision). Radiographs were reviewed for any evidence of loosening and wear of the components. Functional assessment was also carried out using the modified Hip disability & osteoarthritis outcome score (HOOS), Oxford hip score and EQ5D–5L.Introduction
Material & methods
An extended trochanteric osteotomy (ETO) is a widely used approach for revision hip arthroplasty. Following an ETO it is common practice to use a long stemmed femoral prosthesis at the second stage to bypass the osteotomy. We propose that at the second stage, if the osteotomy has united, it is appropriate to use a standard length prosthesis, which preserves bone stock for any future revisions. We performed a retrospective review of our institution's prospective arthroplasty database, identifying all patients who had undergone an ETO at the first stage revision. A radiograph review was then performed and any subsequent complications recorded. A selection of patients radiographs were individually reviewed by three reviewers and intra-class correlation (ICC) was performed to assess intra-observer reliability.Background
Methods
Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available but significantly more expensive. We investigated whether the antibiotic elution and mechanical strength of ‘home-made’ vancomycin containing bone cement was comparable to commercial vancomycin-impregnated cement. A total of 18 cement discs of constant size, containing either proprietary CopalG+V®; or ‘home-made’ CopalR+G® with vancomycin added by hand, were made. Each disc contained the same antibiotic quantities (0.5g gentamycin, 2g vancomycin) and was immersed in ammonium acetate buffer in a sealed container. Fluid from each container was sampled at eight time points over a two week period. The concentration of gentamicin and vancomycin in the fluid was analysed using high performance liquid chromatography mass spectrometry. The impact strength of each PMMA cement preparation was measured using a Charpy-type impact tester.Introduction
Methods
Local bone-related adverse events occur more frequently following metal-on metal hip resurfacing (MOMHR) versus convention total hip arthroplasty (THA). High local tissue levels of cobalt and chromium may contribute to impaired bone health, however the systemic effects on bone of exposure to elevated metal levels after MOMHR are unknown. In this cross-sectional study we compared whole body bone mineral density (WB-BMD) and biochemical markers of bone turnover in 31 healthy male subjects at a mean of 8 years after MOMHR versus 31 individually age and time since surgery matched male subjects after conventional THA. All subjects had well-functioning prostheses and were in good self-reported health as assessed by Oxford Hip Score and EQ-5D questionnaire. WB-BMD was measured by dual energy x-ray absorptiometry and adjusted for pre-morbid osteoporosis risk factors using the FRAX tool, and for the presence of the metal prostheses using identical exclusion regions. Bone turnover markers were measured on fasting morning serum or 24hr urine collection by electro-chemiluminescent assay. Cobalt and chromium were measured by ICP-MS.Background and objectives
Methods
Measurements of biochemical markers of bone turnover have been explored as a diagnostic tool for the detection of osteolysis after THA, but their predictive value in individual subjects has been poor. One explanation for this low diagnostic utility is that the mechanism of bone resorption in osteolysis may be different to that occurring in other high bone turnover states, such as osteoporosis, where these markers were principally developed. The aim of this study was to examine the role of the biomarkers urinary ααCTX-I and serum CTX-MMP, that are released in pathological rather than physiological bone turnover states, for detecting periprosthetic osteolysis in a case control study of 23 subjects with osteolysis and 26 controls. All samples were collected between the hours of 0800 and 1000 following an overnight fast, and were assayed using standard techniques. The demographic characteristics of the subjects in both groups were similar. Serum CTX-MMP was greater in the osteolysis versus the control group (P=0.001). Urinary ααCTX-I was similar between osteolysis and control groups (P>
0.05). A cut-off value of 5.50ng/mL CTX-MMP had a sensitivity of 91% (95% CI: 72 to 99) and specificity of 69% (48 to 96) detecting osteolysis (P=0.001). The same cut-off had a sensitivity of 100% (100 to 100) and specificity of 63% (44 to 79) for detecting femoral osteolysis (P=0.0004), and a sensitivity of 89% (65 to 98) and specificity of 58% (39 to 75) for identifying pelvic osteolysis (P=0.014). Serum CTX-MMP shows promise for further investigation as a sensitive bio-marker for detecting periprosthetic osteolysis.
In this 2-year randomised clinical trial we examined whether cemented femoral prosthesis geometry affects the pattern of strain-adaptive bone remodelling in the proximal femur after THA. 128 patients undergoing primary THA were randomised to receive a Charnley (shape-closed, no taper), Exeter (force-closed, double-tapered) or C-stem (forced-closed, triple-tapered) prosthesis. All received a cemented Charnley cup. Proximal femoral BMD change over 2 years was measured by DXA. Urine and serum samples were collected at pre-operative baseline and over 1 year post-operatively. N-telopeptides of type-I-collagen (NTX) was measured in urine as a marker of osteoclast activity and Osteocalcin (OC) in serum as a maker of osteoblast activity. Clinical outcome using the Harris and Oxford hip scores, and prosthesis migration measured using digitised radiographs (EBRA-Digital) were measured over 2 years. The baseline characteristics of the subjects in each group were similar (P>
0.05). Decreases in femoral BMD were observed over the first year for all prosthesis designs. Bone loss was greatest (14%) in the proximal medial femur (region 7). The pattern and amount of bone loss observed was similar between all prosthesis designs (P>
0.05). Transient rises in both osteoclast (NTX) and osteoblast (OC) activity also occurred over year 1, and were similar in pattern in the 3 prosthesis groups (p>
0.05). All prostheses showed migration patterns that were true to their design type and similar improvements in clinical hip scores were observed over the 2 year study. Differences in the proposed mechanism of load transfer between prosthesis and host bone in force-closed versus shape-closed femoral prosthesis designs in THA are not major determinants of prosthesis-related remodelling.
The mean age at revision with allograft was 64.3 years (26 to 97). 86 hips (70%) in 74 patients were reviewed both clinically and radiologically. At the time of review 28 patients (29 hips) had died and 5 patients (5 hips) were lost to follow up. Of those patients who had died 18 hips had been followed up to a mean of 66 months (12–145). A further 3 hips were unable to attend for clinical review but had accurate implant-allograft survivorship data. Their data were included in survivorship analysis to the time of last clinical review.
From a consecutive series of 114 patients who had undergone a two-stage exchange without prolonged antibiotic therapy we report the outcome of those patients who continued to have persistent infection.
Seven patients elected not to undergo a further two-stage revision. Five patients have retained their arthroplasty with lifelong suppressive antibiotic therapy. One has a pseudarthrosis and one disarticulation has taken place for inadequate tissue cover.
The adjusted odds ratios for pelvic osteophytes and HO with carriage of the rare FRZB 200 variant were 4.34 (1.01–18.7 p=0.048) and 1.64 (1.05 to 2.54, p=0.028) respectively. The adjusted odds ratio for osteolysis was 0.62 (0.38 to 0.99 p=0.049). There were no bone phenotype associations with the FRZB Arg324Gly variants.
Dual energy X-ray absorptiometry (DXA) is a precise tool for measuring bone mineral density (BMD) around total joint prostheses. The Hologic ‘metal-removal hip’ analysis package (Hologic Inc, Waltham, Massachusetts) is a DOS-based analysis platform that has been previously validated for measurement of pelvic and proximal BMD after total hip arthroplasty (THA). This software has undergone a change in the operating platform to a Windows-based system that has also incorporated changes to DXA image manipulation on-screen. These changes may affect the magnitude of random error (precision) and systematic error (bias) when compared with measurements made using the previously validated DOS-based system. These factors could influence interpretation of longitudinal studies commenced using the DOS system and later completed using the Windows system. The aims of this study were to compare the precision and bias of pelvic and femoral periprosthetic BMD measurements made using the Windows versus the DOS analysis platform of the Hologic ‘metal-removal hip’ software. A total of 29 subjects (17 men and 12 women) with a mean age of 51years (SD±10), who had undergone hybrid THA using a cemented stem and uncemented cup. Subjects underwent duplicate DXA scans of the hemipelvis and proximal femur taken on the same day after a period for repositioning.. Scans were obtained with the patient lying supine in the scanner with the legs in extension and the foot in a neutral position. Scans were carried out using the same Hologic QDR 4500-A fan-beam densitometer in ‘metal-removal hip’ scanning mode. The DXA scan acquisitions were analysed using both the DOS and the Windows versions of the analysis software. The same observer made all analyses (NRS). Pelvic scans were analysed using a four region of interest model and femoral scans were analysed using a seven region of interest model. Precision was expressed as coefficient of variation (CV%) and compared between methods using the F-test. Systematic bias was examined using the Bland and Altman method and paired t-test. The CV% for the pelvic regions of interest (n=4) varied from 3.92 to 8.54 and from 2.36 to 5.96 for the Windows and DOS systems, respectively. The CV% for the net pelvic region was 3.04 and 2.36 for Windows versus DOS, respectively (F- test, p>
0.05). The CV% for the femoral regions of interest (n=7) varied from 1.58 to 4.14 and from 1.84 to 4.65 for the Windows and DOS systems, respectively. The CV% for the net femoral region was 1.75 and 1.51 for Windows versus DOS, respectively (F- test, p>
0.05). Absolute BMD values for the net pelvic region were similar (Bland-Altman, Windows minus DOS value mean = -1.0%, 95% CI −7.5 to 5.6; t-test p.0.05). Absolute BMD values for the net femoral region were also similar (Bland-Altman, Windows minus DOS value mean = 1.3%, 95% CI −8.3 to 10.8; t-test p.0.05). In summary precision of the measurements using the 2 operating systems was similar and there was no systematic bias between methods. These data suggest that scans analysed using each platform may be used interchangeably within the same study subjects, without the need of a calibration correction.
Peri-prosthetic bone loss may contribute to aseptic loosening after THA. The aims of this randomised controlled trial extension study were to study the effect of pamidronate therapy on Peri-prosthetic bone mineral density (BMD) and Peri-prosthetic osteolysis over 5 years after primary THA. 50 patients were enrolled in the study in 1998. All received a hybrid THA (Ultima-TPS stem, Plasmacup) for osteoarthritis. Subjects were randomised to receive either 90mg of pamidronate or placebo by intravenous infusion on the 5th post-operative day. At 5 years 36 patients (41 Hips: placebo n=21, pamidronate n=20) returned for measurement of BMD and clinical and plain radiographic assessment. Five patients had died and nine had withdrawn from the study. The effect of pamidronate in maintaining femoral bone mass in the region of the calcar previously reported at 2 years was maintained at 5 years (Gruen zone 6 pamidronate versus placebo ANOVA P=0.038; Gruen zone 7 ANOVA P=0.048). No differences in pelvic BMD were found between treatment groups at 5 years. Harris hip scores used to evaluate clinical outcome did not show any significant difference between the 2 groups over the 5-year period. (Mann Whitney p>
0.05). Isolated expansile osteolytic lesions were identified on AP radiographs of the hip at 5 years in 4 patients (2 placebo, 2 pamidronate; P>
0.05). One patient had a 5x9mm lytic lesion in the region of the femoral calcar, and 3 patients had pelvic lytic lesions in the region of the acetabular dome (largest measuring 20x10mm). Single-dose peri-operative pamidronate therapy preserves femoral calcar bone mass over a 5 year period after THA. However, although the number of subjects with osteolysis is small, we have seen no difference in the rate of osteolytic lesions between treatment groups. Long term study of this patient group is required to examine the rate of aseptic loosening between the treatment groups.
The pattern and magnitude of pelvic periprosthetic bone loss around cementless metal-backed acetabular implants have previously been described. The pattern of periprosthetic BMD change around cemented all-polyethylene acetabular implants is unreported. The aims of this study were to determine the precision of pelvic BMD measurements around the Charnley cup and to examine the longitudinal pattern of BMD change over the first 2 years after surgery. 19 subjects who had previously received a Charnley cup for osteoarthritis underwent duplicate measurements of pelvic BMD after repositioning using an Hologic QDR 4500A densitometer. Scan analysis was carried out using a 4-region of interest model according to a protocol previously described. In-vivo precision was expressed as coefficient of variation (CV%) for each region of interest. The precision of pelvic periprosthetic BMD measurements were 7.7%, 9.8%, 10.8%, and 9.9% for regions 1 to 4, respectively. Longitudinal BMD changes were measured over a 2 year period in 32 patients (mean age 74 years; 22 women) undergoing cemented THA for unilateral osteoarthritis (17 right-sided). Transient decreases in BMD were observed in regions 2 and 3 (behind the dome of the implant) at 3 months (−9.0% and −13.2%, respectively; P<
0.05) and at 1 year (−8.1% and −9.3%; P<
0.05). By 2 years there had been some recovery in bone mass (BMD−6.9% and −2.6% respectively). No significant changes in BMD for regions 1 and 4 (located at the rim of the implant) were found. The precision of pelvic periprosthetic BMD measurements for the cemented Charnley cup are poorer than those we have previously reported for cementless cups and may be due, in part, to cement artifact. The pattern of BMD change observed for the Charnley implant suggests that load transfer between the implant and the pelvis occurs principally at the implant rim. The magnitude of bone loss is similar to that we have previously reported for cementless metal-backed acetabular implants.
The Exeter (Howmedica Ltd) and Ultima-TPS (Depuy Ltd) implants are both collarless, polished, double-tapered, cemented femoral implants. The Exeter is manufactured in stainless steel and has an excellent long-term survivorship. The Ultima-TPS is manufactured in cobalt-chrome and has been recently introduced. The aim of this study was to compare the early performance of these implants in a 2-year randomised clinical trial. 65 patients with unilateral hip osteoarthritis were randomised to receive either the Exeter or TPS stem. All received a Charnley Cup. Outcome measures included the Oxford Hip Questionnaire, proximal femoral bone mineral density (BMD) measured by dual energy x-ray absorptiometry, and implant subsidence measured using EBRA. At 2 years 43 patients (66%) were reviewed. 22 patients (mean age 70 years, 16 female, BMI 27.9Kg/m2) received the TPS implant, and 21 patients (mean age 70 years, 15 female, BMI 28.9Kg/m2) received the Exeter implant. 19 patients withdrew for reasons unrelated to the study, 2 died, and 1 was withdrawn after deep wound infection. Complete Oxford hip scores were available pre-operatively and at 2 years in 37 patients (n=20 TPS). Median (IQR) pre-operative hip scores were 51 (43 to 54) and 48 (36 to 53) for the TPS and Exeter implants, respectively. At 2 years the hip scores improved to 24 (18 to 31) and 22 (16 to 31), respectively. There were no differences in scores between groups at each time-point. There were no differences in BMD between groups at pre-operative baseline, 3 months, 1 and 2 years (Gruen zones 1–7, all time-points; n=19 TPS, n=13 Exeter implants: P>
0.05). Maximum bone loss was seen in Gruen zone 7 at 2 years for bone implants (TPS-11%, Exeter -14%, P>
0.05). Measurement of subsidence over 2 years using EBRA was possible in 20 patients (n=7 TPS, n=13 Exeter). Mean subsidence at 2 years was 1.62mm for the TPS implant and 1.60mm for the Exeter implant (P>
0.05). There was no plain radiographic evidence of osteolysis in either group. These data suggest that the early performance of the two implants studied is similar. However, long-term survivorship data is required to confirm their equivalency.
In-vitro evidence suggests that wear debris can alter osteoblast function resulting in decreased bone matrix production and negative remodelling balance. FRZB encodes for Secreted Frizzled-Related Protein 3 which may play a role in bone formation and osteoarthritis. This study was undertaken to investigate whether the recently described single nucleotide polymorphisms (SNPs) at positions [+6] and [+109] of the FRZB gene are associated with osteolysis after THA. Genomic DNA was extracted from 481 North European Caucasians at a mean of 12 years following cemented THA for idiopathic osteoarthritis. The control group consisted of 267 subjects and the osteolysis group 214 subjects. The [+6] and [+109] FRZB SNPs were genotyped using standard techniques. For the FRZB [+6] SNP, the rare T allele was significantly over-represented in control versus the osteolysis group (χ2 test for trend, p=0.02,). The odds ratio for osteolysis associated with carriage of the [+6] T-allele versus the [+6] C-allele was 0.58 (95%CI 0.36 to 0.94), p=0.03. The odds ratio for osteolysis associated with carriage of the [+109] G-allele versus the [+109] C-allele was 0.66 (0.38 to 1.12), p=0.15. A number of covariates have previously been described in this cohort and after adjustment for the effects of these covariates, the odds ratio for osteolysis with carriage of the [+6] T-allele was 0.69 (0.42–1.16). We found that the FRZB [+6] T-allele is less common in subjects with osteolysis after THA versus controls, suggesting that allelic variants of genes associated with bone formation pathways may have a role in modulating the risk of osteolysis. However its loss of significance after correction for other factors suggests an interaction between this allele and other risk factors in osteolysis.
The use of prolonged courses of parenteral or oral antibiotic therapy in the management of two stage revision of infected total knee arthroplasty is reported by all major series. We present a series of 59 consecutive patients, all with microbiologically proven deep infection managed at our unit where a prolonged course of antibiotic therapy has not been routinely used. The mean follow-up is 56.4 months (range 24–114 months). Of the 38 patients undergoing a staged exchange, infection was successfully eradicated in 34 patients (89%) with recurrent or persistent infection in 4 (11%). The infection cure rate in our series is similar that reported elsewhere. A prolonged course of antibiotic therapy does not seem to alter the incidence of recurrent or persistent infection. The costs of antibiotic administration are high, both to the patient and care facility. It may be unnecessary.
Phagocytosis of wear particles by perimplant macrophages results in cytokine release and osteoclast activation and osteolysis. Some investigators have proposed that this response may be mediated by adherent endotoxin. The aim of this study was to determine the role of endotoxin in modulating pro-inflammatory cytokine mRNA expression of macrophages when stimulated with titanium particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR) Human peripheral blood mononuclear cells were isolated from healthy subjects and plated in chamber slides. Three types of titanium particles were prepared; commercially pure titanium particles (cpTi), endotoxin stripped particles and endotoxin stripped particles with endotoxin (LPS) added back. Endotoxin levels of 450, 0 and 140 Eu/ml respectively were confirmed by high sensitivity Limulus Amebocyte Lysate assay. Macrophages were stimulated with particle concentrations of 0, 8.3, 83 and 830 particles per cell at time points 0 and 3 hours. LPS (200ng/ml) was used as a positive control. rqRT-PCR was performed using standard techniques. Stimulation of human macrophages with cpTi demonstrated a significant dose dependent increase in TNFα, IL-1A, IL-1B and, IL-6. (Kruskal-Wallis p=0.01, p=0.017, p=0.001 and p=0.013 respectively). IL-18 mRNA levels were not increased (P>
0.05). The expression of mRNA following stimulation with the highest dose of titanium particles was similar to that following LPS stimulation. Endotoxin-free cpTi particles did not elicit any increase in mRNA expression above base line levels (P >
0.05, all cytokines). This lack of response was rescued in endotoxin-stripped particles with LPS added back. Particle dose dependent increases in cytokine mRNA levels were observed for TNFα, IL-1A, IL-1B and, IL-6 mRNA but not IL-18 (p=0.01, p=0.01, p=0.01, p=0.05 and p=0.>
0.05 respectively). Our results show that adherent endotoxin plays a role in modulating particle induced pro-inflammatory cytokine mRNA expression in-vitro. Further study is required in evaluating the role of adherent endotoxin in vivo
Cytokine mediated activation of osteoclasts can lead to peri-implant osteolysis and aseptic loosening. The aim of this study was to determine the IL-1β and TNFα mRNA cytokine expression profile of human macrophages when stimulated with polyethylene particles using relative quantitative real-time polymerase chain reaction (rqRT-PCR). Human peripheral blood monocytes or human monocytes from the cell line THP-1 were used in this study. rqRT-PCR conditions were optimized by stimulating human macrophages with 200ng/ml lipopolysaccharide (LPS). The median CV% value for duplicate measures was 12.6 (range 4.5–54). Stimulation assays were performed using unfractionated endotoxin-free commercial polyethylene particles (median size 7μm); or fractionated particles (size range 0.1–1.2μm). Human macrophages were stimulated with high dose unfractionated polyethylene particles at 0, 3500 or 10500 mm3/cell or with fractionated polyethylene particles at 0 and 100mm3/cell at time points 0 and 3 hours. Low dose unfractionated polyethylene stimulation was performed on THP-1 cells at 0, 50, 100, 1000 and 10000 mm3/cell. In all experiments LPS stimulation was used as a positive control. RNA was extracted and rqRT-PCR was performed using standard techniques High dose unfractionated polyethylene stimulation did not result in a significant difference in cytokine mRNA levels between groups. Using fractionated polyethylene, a small increase in IL-1β mRNA was identified (21% versus maximal stimulation using LPS). Low dose unfractionated polyethylene stimulation of THP-1 cells demonstrated dose dependent decreases in TNFα and IL-1β mRNA expression that was not due to inhibition of RNA extraction or a decrease of cell viability. Endotoxin-free polyethylene particles do not appear to be a major stimulus for IL-1β and TNFα mRNA production as measured by rqRT-PCR. We did observe a small positive effect on IL-1β mRNA expression using a fractionated polyethylene stimulus. However it remains unclear whether this effect is due to fractionation of particles into the submicron range or is due to introduction of endotoxin during the filtration process.
Aseptic loosening due to periprosthetic bone loss is a major cause of implant failure after total hip arthroplasty (THA). Interleukin 1-B (IL-1B) is thought to play a role in aseptic loosening by stimulating the activity of osteoclasts, the main bone resorbing cell type. A restriction fragment length polymorphism due to a C/T single base variation at +3954 in exon 5 of the IL-1B gene has been associated with differences in susceptibility to chronic periodontitis, a condition associated with bone loss. In this study we tested whether carriage of the C and T alleles at this site resulted in differential risk of aseptic loosening in 481 Caucasians (214 failed versus 267 radiologically intact implants) at 11.7± 4.1 years following primary cemented THA for osteoarthritis. Genomic DNA extracted from peripheral blood was genotyped using the Taqman 5′ nuclease method. Carriage rates were calculated and analysed using the 2 test. In the intact implant group the frequency of the T allele was 0.253. The distribution of the C and T alleles was 147:105:15 (CC:CT:TT, respectively). In the failed implant group the frequency of the T allele was 0.241). The distribution of the C and T alleles was 124:77:13. The carriage rate of the T alleles in each group was 44.9% and 42.1%, respectively (odds-ratio P>
0.05). The genotype frequencies were in Hardy-Weinberg equilibrium for both intact and loose implant populations (Chi-squared P>
0.05). Using the multivariate Cox proportional hazards model significant risk factors for loosening of both implant components included gender and age at THA (P<
0.05). However, carriage of the +3954 allele was not a significant independent risk factor for aseptic loosening (P>
0.05). Our data suggests that the IL-1B gene restriction fragment length polymorphism at +3954 does not influence the risk of aseptic loosening after THA.
Polyethylene wear particle-induced osteolysis is a major cause of implant failure after total hip arthroplasty (THA). Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that is thought to play a pivotal role in this process. We have recently shown that carriage of the −238 ‘A’ allele in the TNF gene promoter is associated with a higher rate of osteolysis after THA versus carriage of the [more common] ‘G’ allele. The aim of this study was to determine the effect of this polymorphism on TNF gene transcriptional activation in response to polyethylene particle stimulation using a luciferase reporter gene assay. A 691 bp fragment (−585 to +106) of the TNF gene was amplified by polymerase chain reaction and directionally cloned into the PGL3.basic vector (Promega, Madison, WI). Insert sequences were checked using an ABI 377 DNA sequencer (PE Applied Biosystems, Foster City, CA). RAW264.7 murine macrophage-like cells in rapid growth phase were transfected with plasmids containing either the TNF-238G allele or the TNF-238A allele. pTK-RL (Promega), that expresses the Renilla luciferase gene under the control of Herpes simplex virus minimal promoter, was used as a transfection control. The cells were then either left unstimulated or were induced using polyethylene particles generated from a hip simulator. Lipopolysaccharide (LPS) and LTA (Lipoteichoic acid) were used as positive controls. Luciferase reporter activity was measured after 4 hours (Dual luciferase assay, Promega Corp., Southampton, U.K.) and the relative firefly luciferase activity was calculated. Results were analysed using repeated measures ANOVA. Polyethylene particle stimulation at concentrations of 0, 1, 15, and 30mg/mL resulted in relative luciferase activities (mean (SD)) of 21.4 (2.9), 36.2 (8.2), 45.9 (11.1), and 40.7 (5.1) for the −238A allele; and 19.7 (5.0), 26.4 (8.0), 35.9 (2.3), and 32.4 (2.4) for the −238G allele (ANOVA P=0.01). LPS and LTA stimulation also resulted in increased reporter activity for −238A versus −238G (ANOVA P=0.02 and P=0.04, respectively). The promoter allele TNF-238A results in higher levels of transcriptional activation versus the TNF-238G allele in response to a clinically relevant stimulus, and provides functional evidence for the significance of this polymorphism in the development of osteolysis after THA.
The Huckstep ( Bbraun Medical) interlocking hip prosthesis has been used in the Sheffield Lower Limb Arthroplasty Unit in cases of complex primary and revision hip arthroplasty since 1996. We reviewed the outcomes in cases performed prior to October 2001. Eighty cases were identified. Of these, eight died within one year of surgery, four of which were in the peri operative period. A further thirteen were lost to follow up in the first year due to medical deterioration, move from area or refusal to attend. The remaining 57 patients had a mean time to follow up of 34 months (12–81m). As a primary prosthesis the Huckstep was used to allow corrective osteotomy. In revision cases it was employed to bypass periprosthetic fractures and fragile proximal femoral bone, in cases requiring extended trochanteric osteotomy to facilitate cement removal, and to enable use of bulk proximal femoral allograft. The use of the Huckstep was planned pre operatively in 67 cases and as a salvage option in 13.The design of the implant allowed a stable construct without the need for bone cement which could interpose and prevent bone healing or graft incorporation. It avoids problems incurred in pressurising cement or impaction grafting against fragile bone. Complications included infection requiring further surgery (5), dislocation (5), periprosthetic fracture (2), screw breakage (4), and mechanical failure (2). Eleven patients required further revision surgery. The apparently high complication rate reflects the complex nature of the surgery and the high degree of co morbidity in the elderly patient group. In conclusion, we have found the Huckstep hip prosthesis to be a useful option in cases of complex hip surgery. Whilst the long term outcome is as yet unknown, our short term results show it to have allowed healing of fractures, osteotomy sites and cortical defects, allograft incorporation and replenishing of bone stock, hence facilitating further arthroplasty surgery.
One of the major surgical challenges at revision arthroplasty is the management of bone stock loss in the acetabulum. There are several options available for reconstruction; cemented sockets within thick cement mantles, custom sockets jumbo uncemented sockets, support rings and bone grafting. Slooff and others have shown good results with impaction grafting.(JBJS 80B 1998) If one is to use bone graft, does the preparation of the graft have any effect on the graft itself? There are a number of ways bone can be presented, freeze dried, fresh frozen or frozen irradiated. Concerns have been raised that irradiated bone has an altered and weakened structure. There is a paucity of clinical results on this subject. In this study we present a series of patients using gamma irradiated bone for reconstruction.23% of the cases reconstructions secondary to failure due to sepsis. Between 1987 and 2000 192 revision arthroplasties in 165 patients were performed with irradiated morcellised bone allograft for acetabular reconstruction. Only those patients with a minimum follow up of 24 months were reviewed. Clinical and radiological follow up was achieved in 130 hips in 115 patients. 9 patients had died at a range of 1 to 66 months after surgery. There were 23 (17%) re-revisions of the acetabular component. Of these 13 were for deep sepsis, 5 for persistent early dislocation and 4 for aseptic loosening. Of those hips revised for infection there was a 13% re-revision rate for reinfection. There was only one catastrophic failure of the graft and only three re-revisions for aseptic loosening to date. We feel that impaction grafting of the acetabulum is a useful technique for reconstruction even when the index arthroplasty failed for sepsis. We have found no evidence to show that gamma irradiated bone performs any worse than other types of allograft bone.
Tumour necrosis factor-α (TNF) is thought to play a role in aseptic loosening, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at –238 and –308 in the promoter region of the TNF gene are associated with differences in the susceptibility and severity of several TNF-mediated diseases. We tested whether carriage of the [less common] ‘A’ allele at –238 and –308 are associated with aseptic loosening after THA. 481 Caucasians (214 with failed implants versus 267 with radiologically intact implants) were recruited 11.7± 4.1 years after cemented THA for osteoarthritis. Genomic DNA was extracted from peripheral blood and genotyped for the –238 and –308 polymorphisms using the Taqman® 5′ nuclease method. 500 subjects from the local population were also genotyped using Taqman® to establish the background prevalence of the ‘A’ allele at each site. The carriage rate of –238A was 8.8% in the background population and 10.9% in the THA controls (P>
0.05). –238A carriage in the loosening group was 17.3% (odds ratio 1.72, 95% confidence interval 1.02 to 2.90). Carriage was highest (20.5%) in subjects with loosening of both the femoral and pelvic implant components (odds ratio 2.12; 1.17 to 3.83). The association of –238A with aseptic loosening was independent of age, sex, and amount of implant wear (Cox hazard ratio 1.49 (1.04 to 2.13; P=0.03)). Carriage of –308A was not associated with aseptic loosening. Genetic, as well as environmental factors, influence implant failure after THA. Whether the –238 polymorphism causes the biological change that predisposes to loosening, or is in linkage disequilibrium with such a locus, is not yet known.
An acute phase of periprosthetic bone loss occurs following total hip arthroplasty (THA). Periprosthetic bone loss undermines implant support, may contribute to its failure, and complicates revision surgery as allograft may be required to replace lost bone. We assessed the effect of a single 90mg dose of the bisphosphonate pamidronate on early periprosthetic bone mineral density (BMD), biochemical markers of bone turnover, and clinical outcome in 47 men and women undergoing hybrid THA in a randomised, double-blinded, placebo-controlled trial. The mean (± 95% CI) differences in BMD (area under BMD change.time curve) between those receiving pamidronate and those receiving placebo was 0.91(± 0.51) g.weeks/cm2 for the proximal femur (P=0.002), and 0.80 (±0.60) g.weeks/cm2 for the pelvis (P=0.009). Patients in the pamidronate group had suppression of all biochemical markers of bone turnover compared to placebo (P<
0.05), except for urinary free deoxypyridinoline. Both treatment groups experienced similar improvement in Harris hip and SF-36 UK outcome scores. The frequency of adverse events was similar in each treatment group (placebo 7/24, pamidronate 8/23, P>
0.05). Acute periprosthetic bone loss following THA is due to a transient increase in bone turnover. A single dose infusion of pamidronate in the early post-operative period significantly reduces this bone loss, and is well tolerated.
Factors that allow the generation or ingression of wear particles at the implant-host interface after total hip arthroplasty (THA) may include early migration and periprosthetic bone loss. We have previously shown that a single 90mg dose of the bisphosphonate pamidronate prevents bone loss over 6 months after THA. In this 2 year randomised trial extension study we assessed the longer term effects of this intervention on bone loss and implant migration. Twenty-two patients received 90mg of pamidronate and 22 received placebo at randomisation 5 days after surgery. Femoral and pelvic bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) and implant migration was measured using the EBRA-Digital method over a 104 week period. In the placebo group rapid periprosthetic bone loss occurred over the first 6 months. After this period a partial recovery in bone mass occurred in most regions. Patients in the pamidronate group had significantly less femoral, but not pelvic, bone loss than those give placebo (ANOVA P=0.02). Pamidronate was most effective in preventing bone loss in Gruen zones 6 and 7 (ANOVA P=0.004, and P=0.014, respectively). At week 104 the mean total stem migration was 1.77mm±0.27 and 1.62mm±0.37 for the placebo and pamidronate groups, respectively (P>
0.05). Total cup migration was 0.75mm±0.26 and 0.76mm±0.14, respectively (P>
0.05). Age at surgery accounted for 26% (linear regression r=−0.65, P=0.02) and 38% (r=−0.51, P=0.007) of the variability in stem and cup migration at week 104, with younger subjects experiencing greater migration. Stem migration at week 104 was also inversely related to the Barrack cement mantle grade (r=−0.66, r2 41%, P=0.0003). Implant migration was not significantly related to changes in periprosthetic bone mass. Pamidronate therapy has a significant effect on bone mass, but not implant stability, after THA.Our findings suggest that the major determinants of early migration after THA are young patient age and poor cementing technique.
We aimed to determine whether acute periprosthetic bone loss at 1 year following THA may be predicted by early changes in markers of bone turnover, and prevented by a single 90 mg dose of pamidronate in a randomized trial of 46 men and women undergoing primary THA. Femoral BMD was measured at postoperative baseline, and 6, 12, 26, and 52 weeks later using an Hologic 4500-A densitometer. Markers of bone turnover were measured at preoperative baseline and at 1, 6, 12, and 26 weeks. Patients in the placebo group lost significantly more periprosthetic bone than those in the pamidronate group. The mean (±95% CI) difference in proximal femoral BMD (area under BMD change.time curve) between those receiving pamidronate and those receiving placebo was 1.84 (±1.29) g.weeks/cm2 (P=0.02). A transient increase in all markers of bone turnover was seen in the placebo group, with peaks in osteoclast activity at 6 weeks, and peaks in osteoblast activity 12 weeks. Pamidronate therapy was associated with suppression of all markers of bone turnover with the exception of the resorption marker iFDpd (P<
0.05). Using a multiple regression analysis model the AUC changes in bone markers predicted 42% of proximal femoral BMD change at 1 year (P=0.006). Using only change in 2 of the markers (PINP and iFDpd) at 6 weeks 28% of proximal femoral BMD change at 1 year could be predicted (P=0.01). THA is associated with a transient increase in bone remodelling units and bone loss. The relationship between femoral bone loss and turnover markers in the placebo group suggests that the transient increase in these markers reflects local changes in BMD, and that pamidronate reduces bone loss by preventing increased local bone turnover.
We aimed to determine whether the EBRA method had greater precision and sensitivity for measuring implant migration following total hip arthroplasty (THA) than direct plain radiographic techniques using modern measuring tools. Short-term precision was evaluated in 20 subjects following THA. Consecutive, standardised radiographs of the hip were performed on the same day after repositioning. Prosthetic cup and stem migration were measured from the plain radiographs using a digital calliper following methods described by Ianotti, Malchau, Nunn, Sutherland and Wetherall, and compared to those made using EBRA. Precision was expressed as 95% confidence interval (95%CI = 1.96x Std.dev.). 10 subjects were then followed prospectively with standardised plain radiographs at baseline, 6,12 and 26 weeks after THA. Migration measurements made using EBRA were compared to those made using the most precise plain radiographic method. The 95%CI of all EBRA cup and stem measurements was ±1mm or smaller. Only the Sutherland method had a similar level of precision (95%CI ±1.11 to 1.28 mm: F-Test P>
0.05; all other method comparisons with EBRA P<
0.05). In the longitudinal study cup cranial migration of 0.53 mm (SEM 0.19) and stem subsidence of 1.53 mm (SEM 0.19) were detected using EBRA (2-way ANOVA by rank; P<
0.05 and P<
0.001 respectively). No statistically significant migration of the cup or stem was detected using the Sutherland method. The EBRA method is a precise method for describing implant migration in small groups of patients in the early period following THA, and manual methods lack sufficient precision to be used for this purpose.
We aimed to determine whether development of heterotopic ossification (HO) following THA might be predicted by early changes in biochemical markers of bone turnover. The study cohort consisted of 21 men and women taking part in a randomised trial of the bisphosphonate pamidronate in the prevention of bone loss following THA. All had under gone unilateral THA using the same design of implant and all were assigned to placebo in the trial. The osteoblast activity markers bone-specific alkaline phosphatase (bAP), osteocalcin (Oc), and N-terminal propeptide of type-I procollagen (PINP); and the osteoclast activity markers deoxypyridinoline (iFDpd) and N-telopeptide of type-I collagen (NTx) were measured at baseline, and at 1, 6, 12, and 26 weeks following unilateral THA. The presence of HO was assessed using the Brooker grading by a musculoskeletal radiologist from plain AP radiographs of the hip taken at week 26. A transient increase in all turnover markers occurred following surgery, with peaks in iFDpd, NTx, and PINP at 6 weeks, and peaks in bAP and Oc at 12 weeks. 10 subjects had HO at week 26 (all Brooker grade 1 or 2). Subjects with HO had higher mean peak rises (SEM) in PINP and Oc than those without HO (PINP 81% (10) versus 43% (10), P=0.01; Oc 26% (5) versus 9% (6), P=0.04). Using area under the curve ‘ROC’ analysis, PINP and Oc were equally discriminatory in predicting HO formation (P<
0.05). The optimal cut-off peak rise of >
57% in PINP at 6 weeks following THA had a sensitivity and specificity of 90 and 82, respectively for predicting the development of HO. An increase in PINP of more than 57% 6 weeks following THA is predictive of the development of HO at 26 weeks. This early prediction might allow identification of patients in whom early therapeutic measures could be taken.
The incidence of infection after primary arthroplasty is low. However, with the increasing number of arthroplasties being performed the prevalence of infection is increasing. The pattern of infecting organisms following total joint arthroplasty has changed and gentamicin resistant organisms are becoming increasingly common. Vancomycin added to bone a cement carrier can, with adequate surgical debridement be very effective in the eradication of established resistant infection. We report the results of its use in 33 patients with 26 infected hip and 7 infected knee arthroplasies. 32 patients remain clinically and radiologically free of infection after a mean follow-up of 67 months. There was one recurrence of infection and there were three positive second stage cultures of uncertain significance. Vancomycin is potentially a very useful tool in the management of deep infection following arthroplasty surgery.
In Sheffield the senior author has a long experience in the use of massive circumferential proximal femoral allografts in complex revision hip arthroplasty. Sheffield has a well established bone harvesting and banking service, essential for this type of work. We wish to present the early experience with this technique in the UK. Between April 1992 and November 1998 a total of 33 circumferential proximal femoral allografts were used by one senior surgeon. They were all fresh frozen, cadaveric grafts. This time period was selected to allow a reasonable minimum follow-up period. Seven patients had died and two were lost to follow up, leaving a total of 24 patients to review. A step cut osteotomy was utilised and augmented with a cerclage wire and strut allograft where deemed necessary. The proximal femur was retained where possible. The component was cemented into the allograft only, in the majority of the cases. A cemented, collared prosthesis was used in over 85% of cases. Average follow up was 53 months. By the time of review 2 had undergone further revision, one for sepsis, one for aseptic loosening. A further patient had had revision of the acetabular component in isolation. One patient had recurrent sepsis but is currently being managed non–operatively. One patient required secondary surgery with plate and graft for symptomatic junctional non-union. Other complications included wound drainage, delaying discharge, in three patients and one chronic sciatic nerve palsy. The trochanter was considered radiologically united in 18 patients. Junctional union was considered to have occurred in 17 patients. Allograft resorption of 100% cortical thickness was seen in only 9 patients and in only one zone in 6 of these. Oxford hip scores were collected at follow-up. We recommend this technique in cases where bone loss is catastrophic and in specialist hands only.