Prior hip or knee prosthetic joint infection in another joint increases risk three-fold of prosthetic joint infection after primary total knee arthroplasty: a matched control study.

AIMS: There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls. PATIENTS AND METHODS: We retrospectively reviewed 95 patients (102 primary TKAs) treated between 2000 and 2014 with a history of PJI in another TKA or THA. A total of 50 patients (53%) were female. Mean age was 69 years (45 to 88) with a mean body mass index (BMI) of 36 kg/m2 (22 to 59). In total, 27% of patients were on chronic antibiotic suppression. Mean follow-up was six years (2 to 16). We 1:3 matched these (for age, sex, BMI, and surgical year) to 306 primary TKAs performed in 306 patients with a THA or TKA of another joint without a subsequent PJI. Competing risk with death was used for statistical analysis. Multivariate analysis was followed to evaluate risk factors for PJI in the study cohort. RESULTS: The cumulative incidence of PJI in the study cohort (6.1%) was significantly higher than the matched cohort (2.6%) at ten years (hazard ratio (HR) 3.3; 95% confidence interval 1.18 to 8.97; p = 0.02). Host grade in the study group was not a significant risk factor for PJI. Patients on chronic suppression had a higher rate of PJI (HR 15; p = 0.002), with six of the seven patients developing PJI in the study group being on chronic suppression. The new infecting microorganism was the same as the previous in only two of seven patients. CONCLUSION: In this matched cohort study, patients undergoing a clean primary TKA with a history of TKA or THA PJI in another joint had a three-fold higher risk of PJI compared with matched controls with ten-year cumulative incidence of 6.1%. The risk of PJI was 15-fold higher in patients on chronic antibiotic suppression; further investigation into reasons for this and mitigation strategies are recommended. Cite this article: Bone Joint J 2019;101-B(7 Supple C):91-97.

2019 John Charnley Award: Increased risk of prosthetic joint infection following primary total knee and hip arthroplasty with the use of alternative antibiotics to cefazolin: the value of allergy testing for antibiotic prophylaxis.

AIMS: The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. PATIENTS AND METHODS: We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. RESULTS: Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. CONCLUSION: PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9-15.

Lumbar fusion involving the sacrum increases dislocation risk in primary total hip arthroplasty.

AIMS: Concurrent hip and spine pathologies can alter the biomechanics of spinopelvic mobility in primary total hip arthroplasty (THA). This study examines how differences in pelvic orientation of patients with spine fusions can increase the risk of dislocation risk after THA. PATIENTS AND METHODS: We identified 84 patients (97 THAs) between 1998 and 2015 who had undergone spinal fusion prior to primary THA. Patients were stratified into three groups depending on the length of lumbar fusion and whether or not the sacrum was involved. Mean age was 71 years (40 to 87) and 54 patients (56%) were female. The mean body mass index (BMI) was 30 kg/m2 (19 to 45). Mean follow-up was six years (2 to 17). Patients were 1:2 matched to patients with primary THAs without spine fusion. Hazard ratios (HR) were calculated. RESULTS: Dislocation in the fusion group was 5.2% at one year versus 1.7% in controls but this did not reach statistical significance (HR 1.9; p = 0.33). Compared with controls, there was no significant difference in rate of dislocation in patients without a sacral fusion. When the sacrum was involved, the rate of dislocation was significantly higher than in controls (HR 4.5; p = 0.03), with a trend to more dislocations in longer lumbosacral fusions. Patient demographics and surgical characteristics of THA (i.e. surgical approach and femoral head diameter) did not significantly impact risk of dislocation (p > 0.05). Significant radiological differences were measured in mean anterior pelvic tilt between the one-level lumbar fusion group (22°), the multiple-level fusion group (27°), and the sacral fusion group (32°; p < 0.01). Ten-year survival was 93% in the fusion group and 95% in controls (HR 1.2; p = 0.8). CONCLUSION: Lumbosacral spinal fusions prior to THA increase the risk of dislocation within the first six months. Fusions involving the sacrum with multiple levels of lumbar involvement notably increased the risk of postoperative dislocation compared with a control group and other lumbar fusions. Surgeons should take care with component positioning and may consider higher stability implants in this high-risk cohort.

Irrigation and debridement with chronic antibiotic suppression for the management of infected total knee arthroplasty: A Contemporary Analysis.

AIMS: The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure. PATIENTS AND METHODS: This was a single-centre retrospective review of 134 infected primary TKAs that were treated with IDCR. Infections within four weeks of the procedure were defined as acute postoperative infections, and those occurring more than four weeks after the procedure with symptoms for less than three weeks were defined as acute haematogenous infections. Patients were treated with intravenous antibiotics for four to six weeks, followed by chronic oral antibiotic suppression. Estimates of survival were made using a competing risk analysis. The mean follow-up was five years (2.1 to 13). RESULTS: The infection was an acute postoperative infection in 23 TKAs and an acute haematogenous infection in 111 TKAs. The incidence of subsequent infection was 36% in those with an acute postoperative infection and 33% in those with a haematogenous infection, five years postoperatively (p = 0.40). Age < 60 years increased the risk of subsequent infection (hazard ratio (HR) 2.4; p = 0.009) and removal of the components (HR 2.8; p = 0.007). Infection with a staphylococcal species increased the risk of subsequent infection (HR 3.6; p < 0.001), and removal of the components (HR 3.2; p = 0.002). Musculoskeletal Infection Society host type and local extremity grade, body mass index (BMI), the duration of symptoms, gender, and the presence of a monoblock tibial component had no significant effect on the outcome. CONCLUSION: In a rigorously defined group of acute periprosthetic infections after TKA treated with IDCR and chronic antibiotic suppression, the infection-free survival at five years was 66%. The greatest risk factor for failure was an infection with a staphylococcal species, followed by age of < 60 years. Cite this article: Bone Joint J 2018;100-B:1471-76.

The use of highly crosslinked polyethylene in total knee arthroplasty.

Advances in polyethylene (PE) in total hip arthroplasty have led to interest and increased use of highly crosslinked PE (HXLPE) in total knee arthroplasty (TKA). Biomechanical data suggest improved wear characteristics for HXLPE inserts over conventional PE in TKA. Short-term results from registry data and few clinical trials are promising. Our aim is to present a review of the history of HXLPEs, the use of HXLPE inserts in TKA, concerns regarding potential mechanical complications, and a thorough review of the available biomechanical and clinical data. Cite this article: Bone Joint J 2017;99-B:996-1002.

Joint registries: what can we learn in 2016?

AIMS: To demonstrate, with concrete examples, the value of in-depth exploration and comparison of data published in National Joint Arthroplasty registry reports. PATIENTS AND METHODS: The author reviewed published current reports of National Joint Arthroplasty registries for findings of current significance to current orthopaedic practice. RESULTS: A total of six observations that demonstrate actionable or unexpected findings from joint registries are described. These include: one third to one half of all arthroplasty failures in the first decade occur in the first one to two years; infection rates after arthroplasty have not declined in the last three decades; infection after TKA is more common in men than women; outcomes of TKA are more variable in young compared with older patients; new technologies (uncemented implants and crosslinked polyethylene) have improved results of THA and a real-time shift in use of ceramic femoral heads is occurring in THA. CONCLUSION: These six observations may be used to better understand current practice, stimulate practice improvements or suggest topics for further study. Cite this article: Bone Joint J 2017;99-B(1 Supple A):3-7.

What is the lifetime risk of revision for patients undergoing total hip arthroplasty? a 40-year observational study of patients treated with the Charnley cemented total hip arthroplasty.

AIMS: The purpose of this study was to determine the lifetime risk of revision surgery for patients undergoing Charnley cemented total hip arthroplasty (THA), with 40-year follow up, using death as a competing risk. MATERIALS AND METHODS: We retrospectively reviewed 2000 cemented Charnley THAs, with 51 living hips available at 40 years. RESULTS: The cumulative risk of revision or removal for any reason was 13% (95% confidence interval (CI) 12 to 15). Patients aged under 50 years at the time of surgery had a 35% (95% CI 28 to 42) risk of revision or removal for any reason (Hazard Ratio (HR) 3.6; 95% CI 2.5 to 5.2; p < 0.001), patients 50 to 59 years old had a 20% risk (95% CI 16 to 24) (HR 2.1; 95% CI 1.5 to 2.8; p < 0.0001), patients aged 60 to 69 years had a 9% risk (95% CI 7 to 11) (reference point), and patients ≥ 70 years old had a 5% risk (95% CI 4 to 7) (HR 0.96; 95% CI 0.6 to 1.5; p = 0.86) during their lifetime. Men had a higher risk of revision or removal for any reason (HR 2.1; 95% CI 1.7 to 2.7; p < 0.001). CONCLUSION: With almost all the patients in this series followed up till either death or revision, we have been able to develop a 'rule of thumb' for lifetime likelihood of revision or implant removal for the Charnley THA: one in three for patients < 50 years, one in five for patients 50 to 59 years, one in ten for patients 60 to 69 years, and one in 20 for patients ≥ 70 years. The results provide a benchmark for comparison of outcomes, for the newer designs of THA. Cite this article: Bone Joint J 2016;98-B:1436-40.

Epidemiology of periprosthetic femoral fractures in 5417 revision total hip arthroplasties: a 40-year experience.

AIMS: The goals of this study were to define the risk factors, characteristics, and chronology of fractures in 5417 revision total hip arthroplasties (THAs). PATIENTS AND METHODS: From our hospital's prospectively collected database we identified all patients who had undergone a revision THA between 1969 and 2011 which involved the femoral stem. The patients' medical records and radiographs were examined and the relevant data extracted. Post-operative periprosthetic fractures were classified using the Vancouver system. A total of 5417 revision THAs were identified. RESULTS: There were 668 intra-operative fractures, giving an incidence of 12%. Fractures were three times more common with uncemented stems (19%) than with cemented stems (6%) (p < 0.001). The incidence of intra-operative femoral fracture varied by uncemented stem type: fully-coated (20%); proximally-coated (19%); modular fluted tapered (16%) (p < 0.05). Most fractures occurred during the insertion of the femoral component (35%). One-third involved the diaphysis and 26% were of the calcar: 69% were undisplaced. There were 281 post-operative fractures of the femur (20-year probability = 11%). There was no difference in risk for cemented and uncemented stems. Post-operative fractures were more common in men < 70 years (p = 0.02). Periprosthetic fractures occurred earlier after uncemented revision of the femoral component, but later after a cemented revision. The most common fracture type was a Vancouver B1 (31%). Of all post-operative fractures, 24% underwent open reduction and internal fixation and 15% revision arthroplasty. CONCLUSION: In revision THA, intra-operative fractures occurred three times more often with an uncemented stem. Many were undisplaced diaphyseal fractures treated with cerclage fixation. While the risk of post-operative fracture is similar between uncemented and cemented components, they occur at notably different times depending on the type of stem fixation. TAKE HOME MESSAGE: In revision THA, intra-operative periprosthetic femoral fractures occur three times more often with uncemented stems. Many are non-displaced diaphyseal fractures treated with cerclage fixation. While postoperative fracture risks are equivalent between uncemented and cemented components, they occur at notably different time periods based on stem fixation type.

Epidemiology of periprosthetic fracture of the femur in 32 644 primary total hip arthroplasties: a 40-year experience.

AIM AND METHODS: The goals of this study were to define the risk factors, nature, chronology, and treatment strategies adopted for periprosthetic femoral fractures in 32 644 primary total hip arthroplasties (THAs). RESULTS: There were 564 intra-operative fractures (1.7%); 529 during uncemented stem placement (3.0%) and 35 during cemented stem placement (0.23%). Intra-operative fractures were more common in females and patients over 65 years (p < 0.001). The majority occurred during placement of the femoral component (60%), and involved the calcar (69%). There were 557 post-operative fractures (20-year probability: 3.5%; 95% confidence interval (CI) 3.2 to 3.9); 335 fractures after placement of an uncemented stem (20-year probability: 7.7%; 95% CI 6.2 to 9.1) and 222 after placement of a cemented stem (20-year probability: 2.1%; 95% CI 1.8 to 2.5). The probability of a post-operative fracture within 30 days after an uncemented stem was ten times higher than a cemented stem. The most common post-operative fracture type was a Vancouver AG (32%; n = 135), with 67% occurring after a fall. In all, 36% (n = 152) were treated with revision arthroplasty. CONCLUSION: In summary, intra-operative fractures occur 14 times more often with uncemented stems. Female patients over 65 years of age are at highest risk. Post-operative fractures are also most common with uncemented stems, but are independent of age or gender. Cumulative risk of post-operative periprosthetic femur fracture was 3.5% at 20 years. TAKE HOME MESSAGE: Intra-operative fractures occur 14 times more often with uncemented stems, particularly with female patients over 65 years of age, while post-operative fracture risk is independent of age or gender, but still increased with uncemented stems.

Revision total hip arthroplasty in patients with extensive proximal femoral bone loss using a fluted tapered modular femoral component.

Revision total hip arthroplasty (THA) is challenging when there is severe loss of bone in the proximal femur. The purpose of this study was to evaluate the clinical and radiographic outcomes of revision THA in patients with severe proximal femoral bone loss treated with a fluted, tapered, modular femoral component. Between January 1998 and December 2004, 92 revision THAs were performed in 92 patients using a single fluted, tapered, modular femoral stem design. Pre-operative diagnoses included aseptic loosening, infection and peri-prosthetic fracture. Bone loss was categorised pre-operatively as Paprosky types III-IV, or Vancouver B3 in patients with a peri-prosthetic fracture. The mean clinical follow-up was 6.4 years (2 to 12). A total of 47 patients had peri-operative complications, 27 of whom required further surgery. However, most of these further operations involved retention of a well-fixed femoral stem, and 88/92 femoral components (97%) remained in situ. Of the four components requiring revision, three were revised for infection and were well fixed at the time of revision; only one (1%) was revised for aseptic loosening. The most common complications were post-operative instability (17 hips, 19%) and intra-operative femoral fracture during insertion of the stem (11 hips, 12%). Diaphyseal stress shielding was noted in 20 hips (22%). There were no fractures of the femoral component. At the final follow-up 78% of patients had minimal or no pain. Revision THA in patients with extensive proximal femoral bone loss using the Link MP fluted, tapered, modular stem led to a high rate of osseointegration of the stem at mid-term follow-up. Cite this article: Bone Joint J 2015; 97-B:312-17.

Acetabular fractures: the role of total hip replacement.

Total hip replacement (THR) after acetabular fracture presents unique challenges to the orthopaedic surgeon. The majority of patients can be treated with a standard THR, resulting in a very reasonable outcome. Technical challenges however include infection, residual pelvic deformity, acetabular bone loss with ununited fractures, osteonecrosis of bone fragments, retained metalwork, heterotopic ossification, dealing with the sciatic nerve, and the difficulties of obtaining long-term acetabular component fixation. Indications for an acute THR include young patients with both femoral head and acetabular involvement with severe comminution that cannot be reconstructed, and the elderly, with severe bony comminution. The outcomes of THR for established post-traumatic arthritis include excellent pain relief and functional improvements. The use of modern implants and alternative bearing surfaces should improve outcomes further.

Hemodynamic flow improves rat hepatocyte morphology, function, and metabolic activity in vitro.

In vitro primary hepatocyte systems typically elicit drug induction and toxicity responses at concentrations much higher than corresponding in vivo or clinical plasma C(max) levels, contributing to poor in vitro-in vivo correlations. This may be partly due to the absence of physiological parameters that maintain metabolic phenotype in vivo. We hypothesized that restoring hemodynamics and media transport would improve hepatocyte architecture and metabolic function in vitro compared with nonflow cultures. Rat hepatocytes were cultured for 2 wk either in nonflow collagen gel sandwiches with 48-h media changes or under controlled hemodynamics mimicking sinusoidal circulation within a perfused Transwell device. Phenotypic, functional, and metabolic parameters were assessed at multiple times. Hepatocytes in the devices exhibited polarized morphology, retention of differentiation markers [E-cadherin and hepatocyte nuclear factor-4α (HNF-4α)], the canalicular transporter [multidrug-resistant protein-2 (Mrp-2)], and significantly higher levels of liver function compared with nonflow cultures over 2 wk (albumin ~4-fold and urea ~5-fold). Gene expression of cytochrome P450 (CYP) enzymes was significantly higher (fold increase over nonflow: CYP1A1: 53.5 ± 10.3; CYP1A2: 64.0 ± 15.1; CYP2B1: 15.2 ± 2.9; CYP2B2: 2.7 ± 0.8; CYP3A2: 4.0 ± 1.4) and translated to significantly higher basal enzyme activity (device vs. nonflow: CYP1A: 6.26 ± 2.41 vs. 0.42 ± 0.015; CYP1B: 3.47 ± 1.66 vs. 0.4 ± 0.09; CYP3A: 11.65 ± 4.70 vs. 2.43 ± 0.56) while retaining inducibility by 3-methylcholanthrene and dexamethasone (fold increase over DMSO: CYP1A = 27.33 and CYP3A = 4.94). These responses were observed at concentrations closer to plasma levels documented in vivo in rats. The retention of in vivo-like hepatocyte phenotype and metabolic function coupled with drug response at more physiological concentrations emphasizes the importance of restoring in vivo physiological transport parameters in vitro.

Genetic association analysis of vitamin D pathway with obesity traits.

OBJECTIVE: Observational studies have examined the link between vitamin D deficiency and obesity traits. Some studies have reported associations between vitamin D pathway genes such as VDR, GC and CYP27B1 with body mass index (BMI) and waist circumference (WC); however, the findings have been inconsistent. Therefore, we investigated the involvement of vitamin D metabolic pathway genes in obesity-related traits in a large population-based study. METHODS: We undertook a comprehensive analysis between 100 tagging single nucleotide polymorphisms (tagSNPs) in genes encoding for DHCR7, CYP2R1, VDBP, CYP27B1, CYP27A1, CYP24A1, VDR and RXRG, and obesity traits in 5224 participants (aged 45 years) in the 1958 British birth cohort (1958BC). We further extended our analyses to investigate the associations between SNPs and obesity traits using the summary statistics from the GIANT (Genetic Investigation of Anthropometric Traits) consortium (n=123 865). RESULTS: In the 1958BC (n=5224), after Bonferroni correction, none of the tagSNPs were associated with obesity traits except for one tagSNP from CYP24A1 that was associated with waist-hip ratio (WHR) (rs2296239, P=0.001). However, the CYP24A1 SNP was not associated with BMI-adjusted WHR (WHRadj) in the 1958BC (rs2296239, P=1.00) and GIANT results (n=123 865, P=0.18). There was also no evidence for an interaction between the tagSNPs and obesity on BMI, WC, WHR and WHRadj in the 1958BC. In the GIANT consortium, none of the tagSNPs were associated with obesity traits. CONCLUSIONS: Despite a very large study, our findings suggest that the vitamin D pathway genes are unlikely to have a major role in obesity-related traits in the general population.

Hip and knee arthroplasty 2011: what's new, what's true, does it matter? Evidence based issues.

This conversation represents an attempt by several arthroplasty surgeons to critique several abstracts presented over the last year as well as to use them as a jumping off point for trying to figure out where they fit in into our current understanding of multiple issues in modern hip and knee arthroplasty.

Serum 25-hydroxyvitamin D and IgE - a significant but nonlinear relationship.

BACKGROUND: Hormonal vitamin D system affects the determination of T-cell responses. It is unknown if there is an association between vitamin D status and allergic conditions. Our aim was to investigate differences in serum IgE concentrations by vitamin D status [measured by 25(OH)D] and by a genetic variation in a key vitamin D activation enzyme (CYP27B1) previously shown to be associated with type 1 diabetes. METHODS: 9377 participants in the 1958 British birth cohort completed a biomedical assessment at 45 years of age ; 7288 eligible participants had data on 25(OH)D and IgE, with 6429 having further information on CYP27B1 genotype ()1260C>A). RESULTS: There was a nonlinear association between 25(OH)D and IgE (P-value for curvature = 0.0001). Compared with the reference group with the lowest IgE concentrations [25(OH)D 100-125 nmol/l], IgE concentrations were 29% higher (95% CI 9-48%) for participants with the 25(OH)D <25 nmol/l, and 56% higher (95% CI 17-95%) for participants with 25(OH)D >135 nmol/l (adjusted for sex, month, smoking, alcohol consumption, time spent outside, geographical location, social class, PC/TV time, physical activity, body mass index and waist circumference). CYP27B1 genotype was associated with both 25(OH)D (difference for A vs. C allele: 1.88%, 95% CI 0.37-3.4%, P = 0.01) and IgE concentrations ()6.59%, )11.6% to )1.42%, P = 0.01). CONCLUSIONS: These data suggest that there may be a threshold effect with both low and high 25(OH)D levels associated with elevated IgE concentrations. The same CYP27B1 allele that is protective of diabetes was associated with increased IgE concentrations.

Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional population survey.

BACKGROUND: Identified aetiological factors for chronic widespread pain (CWP) are largely related to emotional and behavioural factors, but current management leads to modest improvement in symptoms. Vitamin D deficiency has been suggested as a new modifiable risk factor for CWP. OBJECTIVE: To examine the association between vitamin D status (measured by 25-hydroxyvitamin D (25(OH)D)) and CWP in a nationwide population sample of white British adults, accounting for potential mediating and confounding lifestyle factors. METHODS: 9377 participants born 1 week in March 1958, in England, Scotland or Wales and completing a biomedical assessment at age 45; 6824 eligible participants had data on 25(OH)D and completed pain manikins. RESULTS: Prevalence of CWP varied by 25(OH)D concentration in women but not in men, with the lowest prevalence observed for women with 75-99 nmol/l (14.4% for <25 nmol/l, 14.8% for 25-49 nmol/l, 11.6% for 50-74 nmo/l, 8.2% for 75-99 nmol/l and 9.8% for participants with > or =100 nmol/l). There was an interaction between 25(OH)D concentration and gender in relation to CWP (interaction, p = 0.006), which was not fully explained by differences in lifestyle or social factors (adjusted interaction, p = 0.03). For women, the association between 25(OH)D concentration and CWP persisted after full adjustment (odds ratio (OR) for <75 nmol/l vs 75-99 nmol/l 1.57, 95% CI 1.09 to 2.26), while no evidence for an association was apparent in men (OR = 1.03, 95% CI 0.75 to 1.43). CONCLUSION: Current vitamin D status was associated with CWP in women but not in men. Follow-up studies are needed to evaluate whether higher vitamin D intake might have beneficial effects on the risk of CWP.

Decrease in particle-induced osteolysis in obese (ob/ob) mice.

There may be variability in the susceptibility of different individuals to osteolysis from wear debris, and it is not clear whether some individuals may have a genetic predisposition for a more marked osteolytic response. The purpose of this study in mice was to determine whether genetically determined obesity can alter the response to particulate debris. Polyethylene particles were implanted onto the calvaria of seven wild-type mice and seven obese mice (ob/ob). Calvaria from unimplanted wild-type and obese mice served as controls. Calvaria were harvested after 7 days, stained with toluidine blue and for tartrate-specific alkaline phosphatase, and analyzed by histomorphometry. The osteoclast number per mm total bone perimeter was 8.000+/-3.464 in wild-type animals with particles and 2.857+/-1.676 in ob/ob animals with particles (p=0.002; Fisher's PLSD). Bone resorption was 1.895+/-0.713 mm/mm(2) in wild-type animals with particles and 1.265+/-0.494 mm/mm(2) in ob/ob animals with particles (p=0.0438; Fisher's PLSD). Particles induced a diminished osteolytic response in genetically determined obese mice, suggesting that obesity may have a protective role against particle-induced bone resorption-similar to obesity and osteoporosis. These important new findings may help to stimulate clinical studies which may define criteria to better identify patients at risk to develop particle-induced osteolysis.

In vivo evaluation of novel hyaluronan/chitosan microparticulate delivery systems for the nasal delivery of gentamicin in rabbits.

Biodegradable microparticles containing gentamicin were prepared using chitosan hydroglutamate (CH), hyaluronic acid (HA) and a combination of both polymers by a solvent evaporation method. These formulations were administered nasally via an insufflator. Gentamicin was also administered nasally into rabbits as a solution and powder (a physical mixture of gentamicin and lactose), intravenously (IV) and intramuscularly (IM). The resultant serum levels of gentamicin were determined by Fluorescence Polarisation Immunoassay (FPIA). The bioavailability of gentamicin was poor when administered as a nasal solution (1.1%) and dry powder (2.1%) when compared with IV. However, the microparticulate systems composed of CH and HA/CH considerably enhanced the bioavailability of gentamicin (31.4 and 42.9%, respectively,) with HA microparticles inducing a less significant enhancement (23.3%). Previous in vitro dissolution and frog palate studies indicated that these microparticulate formulations were all mucoadhesive and demonstrated prolonged drug release. Such findings were translated into an increase in the bioavailability of gentamicin when compared with a simple nasal solution in vivo. When HA and CH were combined in the HA/CH formulation, the polymers appeared to improve the absorption of incorporated gentamicin synergistically in comparison to the individual polymers, suggesting a promising nasal delivery system.

Primary uncemented total hip arthroplasty in patients <40 years old: 10- to 14-year results using first-generation proximally porous-coated implants.

Eighty-two consecutive primary first-generation uncemented total hip arthroplasties (72 patients) performed in patients <40 years old were reviewed with minimum follow-up of 10 years. Of 82 hips, 24 (29.3%) have been revised to date. The estimated survival free of aseptic revision or radiographic failure was 81.3% at 10 years for the acetabular components. The estimated survival free of aseptic revision or radiographic failure was 84.9% at 10 years for the femoral component. In this exclusively young patient cohort, there was a high failure rate of the acetabular component and the femoral component. The data in this report can serve as a baseline for comparison of newer implants and operative methods.