Systemic antibiotics are not required for successful two-stage revision hip arthroplasty.

The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into 'successful' or 'unsuccessful'. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs.

The antimicrobial activity and biocompatibility of a controlled gentamicin-releasing single-layer sol-gel coating on hydroxyapatite-coated titanium.

AIMS: 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. METHODS: 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. RESULTS: The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. CONCLUSION: In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522-529.

Review of total hip arthroplasty in patients younger than 30 years: mid- to long-term results.

BACKGROUND: 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. The aim of this study was to review clinical and radiological outcomes of THA in patients under the age of 30 years in a high-volume specialist arthroplasty unit. METHODS: A retrospective review of patients between 1989 and 2009 was undertaken. 95 patients (118 THAs) were identified but 17 patients were excluded for lack of clinical records or for follow-up under 5 years. Clinical records were reviewed for demographics, underlying pathology, details of operation and failures. Radiographs were reviewed for evidence of loosening and wear of the components. Functional assessment was carried out using the modified Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score and EQ-5D-5L. RESULTS: Mean age was 25 (16-30) years and 65% patients were females. The most common underlying pathologies were development dysplasia of the hip (29%) and juvenile rheumatoid arthritis (25%). Mean follow-up was 12.6 (5-24) years, during which 19 patients (25%) were revised. The majority of the revisions were for aseptic loosening of the acetabular component. CONCLUSIONS: Surgeons are cautious when considering THA in very young patients despite the significant documented improvement in function and quality of life after THA. This study reports on the mid- to long-term results of THA which will be valuable when advising young patients on the prospects of revision surgery at the time of primary THA.

"Combined Diagnostic Tool" APPlication to a Retrospective Series of Patients Undergoing Total Joint Revision Surgery.

Background: Differentiating between septic and aseptic joint prosthesis may be challenging, since no single test is able to confirm or rule out infection. The choice and interpretation of the panel of tests performed in any case often relies on empirical evaluation and poorly validated scores. The "Combined Diagnostic Tool (CDT)" App, a smartphone application for iOS, was developed to allow to automatically calculate the probability of having a of periprosthetic joint infection, on the basis of the relative sensitivity and specificity of the positive and negative diagnostic tests performed in any given patient. Objective: The aim of the present study was to apply the CDT software to investigate the ability of the tests routinely performed in three high-volume European centers to diagnose a periprosthetic infection. Methods: This three-center retrospective study included 120 consecutive patients undergoing total hip or knee revision, and included 65 infected patients (Group A) and 55 patients without infection (Group B). The following parameters were evaluated: number and type of positive and negative diagnostic tests performed pre-, intra- and post-operatively and resultant probability calculated by the CDT App of having a peri-prosthetic joint infection, based on pre-, intra- and post-operative combined tests. Results: Serological tests were the most common performed, with an average 2.7 tests per patient for Group A and 2.2 for Group B, followed by joint aspiration (0.9 and 0.8 tests per patient, respectively) and imaging techniques (0.5 and 0.2 test per patient). Mean CDT App calculated probability of having an infection based on pre-operative tests was 79.4% for patients in Group A and 35.7 in Group B. Twenty-nine patients in Group A had > 10% chance of not having an infection, and 29 of Group B had > 10% chance of having an infection. Conclusion: This is the first retrospective study focused on investigating the number and type of tests commonly performed prior to joint revision surgery and aimed at evaluating their combined ability to diagnose a peri-prosthetic infection. CDT App allowed us to demonstrate that, on average, the routine combination of commonly used tests is unable to diagnose pre-operatively a peri-prosthetic infection with a probability higher than 90%.

One-stage or two-stage revision surgery for prosthetic hip joint infection--the INFORM trial: a study protocol for a randomised controlled trial.

BACKGROUND: Periprosthetic joint infection (PJI) affects approximately 1% of patients following total hip replacement (THR) and often results in severe physical and emotional suffering. Current surgical treatment options are debridement, antibiotics and implant retention; revision THR; excision of the joint and amputation. Revision surgery can be done as either a one-stage or two-stage operation. Both types of surgery are well-established practice in the NHS and result in similar rates of re-infection, but little is known about the impact of these treatments from the patient's perspective. The main aim of this randomised controlled trial is to determine whether there is a difference in patient-reported outcome measures 18 months after randomisation for one-stage or two-stage revision surgery. METHODS/DESIGN: INFORM (INFection ORthopaedic Management) is an open, two-arm, multi-centre, randomised, superiority trial. We aim to randomise 148 patients with eligible PJI of the hip from approximately seven secondary care NHS orthopaedic units from across England and Wales. Patients will be randomised via a web-based system to receive either a one-stage revision or a two-stage revision THR. Blinding is not possible due to the nature of the intervention. All patients will be followed up for 18 months. The primary outcome is the WOMAC Index, which assesses hip pain, function and stiffness, collected by questionnaire at 18 months. Secondary outcomes include the following: cost-effectiveness, complications, re-infection rates, objective hip function assessment and quality of life. A nested qualitative study will explore patients' and surgeons' experiences, including their views about trial participation and randomisation. DISCUSSION: INFORM is the first ever randomised trial to compare two widely accepted surgical interventions for the treatment of PJI: one-stage and two-stage revision THR. The results of the trial will benefit patients in the future as the main focus is on patient-reported outcomes: pain, function and wellbeing in the long term. Patients state that these outcomes are more important than those that are clinically derived (such as re-infection) and have been commonly used in previous non-randomised studies. Results from the INFORM trial will also benefit clinicians and NHS managers by enabling the comparison of these key interventions in terms of patients' complication rates, health and social resource use and their overall cost-effectiveness. TRIAL REGISTRATION: Current controlled trials ISRCTN10956306 (registered on 29 January 2015); UKCRN ID 18159.

Re-infection outcomes following one- and two-stage surgical revision of infected hip prosthesis in unselected patients: protocol for a systematic review and an individual participant data meta-analysis.

BACKGROUND: Several aggregate published reviews have compared the effectiveness of one- and two-stage surgical revision to prevent re-infection following prosthetic hip infection and have reported inconsistent results. In addition, there were several features of these previous reviews which limited the validity of the findings. In the absence of a well-designed clinical trial, we propose the Global Infection Orthopaedic Management (INFORM) collaboration, a worldwide collaborative systematic review and meta-analysis of individual participant data (IPD) to address the existing uncertainties. METHODS: Cohort studies (prospective or retrospective) and randomised controlled trials conducted in unselected patients with infection treated exclusively by one- or two-stage revision and reporting re-infection outcomes within 2 years of revision will be retrieved by searching the following databases: MEDLINE, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Registry Platform. Reference lists of relevant studies will be manually scanned and there will be email contact with investigators of grey literature and conference abstracts. Investigators will be invited to join the Global INFORM collaboration and share their individual level data. The primary outcome of the analyses will be incidence of re-infection within 2 years of commencement of revision surgery. Primary analyses will be conducted comparing the one-stage to the two-stage surgical revision. IPD analyses will be based on Cox proportional hazard (PH) models estimated for each study separately. Study-specific log hazard ratios will be combined using random-effects meta-analysis with fixed-effects meta-analysis in subsidiary analyses. Hazard ratios for re-infection according to different individual level characteristics such as sex, age groups, body mass index and comorbidities will also be assessed. DISCUSSION: The analyses will enable a consistent approach to the definition of re-infection outcomes, more detailed analyses under a broader range of circumstances and exploration of potential sources of heterogeneity and produce much more valid and precise estimates of re-infection outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2015: CRD42015016664.

Temocillin: a new candidate antibiotic for local antimicrobial delivery in orthopaedic surgery?

OBJECTIVES: To assess the performance of the Gram-negative-specific antibiotic temocillin in polymethylmethacrylate bone cement pre-loaded with gentamicin, as a strategy for local antibiotic delivery. METHODS: Temocillin was added at varying concentrations to commercial gentamicin-loaded bone cement. The elution of the antibiotic from cement samples over a 2 week period was quantified by LC-MS. The eluted temocillin was purified by fast protein liquid chromatography and the MICs for a number of antibiotic-resistant Escherichia coli were determined. The impact strength of antibiotic-loaded samples was determined using a Charpy-type impact testing apparatus. RESULTS: LC-MS data showed temocillin eluted to clinically significant concentrations within 1 h in this laboratory system and the eluted temocillin retained antimicrobial activity against all organisms tested. Impact strength analysis showed no significant difference between cement samples with or without temocillin. CONCLUSIONS: Temocillin can be added to bone cement and retains its antimicrobial activity after elution. The addition of up to 10% temocillin did not affect the impact strength of the cement. The results show that temocillin is a promising candidate for use in antibiotic-loaded bone cement.

Metal-on-metal hip prostheses and systemic health: a cross-sectional association study 8 years after implantation.

There is public concern over the long term systemic health effects of metal released from hip replacement prostheses that use large-diameter metal-on-metal bearings. However, to date there has been no systematic study to determine which organs may be at risk, or the magnitude of any effect. We undertook a detailed cross-sectional health screen at a mean of 8 years after surgery in 35 asymptomatic patients who had previously received a metal-on-metal hip resurfacing (MoMHR) versus 35 individually age and sex matched asymptomatic patients who had received a conventional hip replacement. Total body bone mineral density was 5% higher (mean difference 0.05 g/cm², P = 0.02) and bone turnover was 14% lower (TRAP 5b, mean difference -0.56IU/L, P = 0.006; osteocalcin, mean difference -3.08 ng/mL, P = 0.03) in the hip resurfacing versus conventional hip replacement group. Cardiac ejection fraction was 7% lower (mean absolute difference -5%, P = 0.04) and left ventricular end-diastolic diameter was 6% larger (mean difference 2.7 mm, P = 0.007) in the hip resurfacing group versus those patients who received a conventional hip replacement. The urinary fractional excretion of metal was low (cobalt 5%, chromium 1.5%) in patients with MoMHR, but creatinine clearance was normal. Diuretic prescription was associated with a 40% increase in the fractional excretion of chromium (mean difference 0.5%, P = 0.03). There was no evidence of difference in neuropsychological, renal tubular, hepatic or endocrine function between groups (P>0.05). Our findings of differences in bone and cardiac function between patient groups suggest that chronic exposure to low elevated metal concentrations in patients with well-functioning MoMHR prostheses may have systemic effects. Long-term epidemiological studies in patients with well-functioning metal on metal hip prostheses should include musculoskeletal and cardiac endpoints to quantitate the risk of clinical disease.

Effect of sliding-taper compared with composite-beam cemented femoral prosthesis loading regime on proximal femoral bone remodeling: a randomized clinical trial.

BACKGROUND: This two-year randomized clinical trial was performed to examine whether the geometry of the cemented femoral prosthesis affects the pattern of strain-adaptive bone remodeling in the proximal aspect of the femur after primary total hip arthroplasty. METHODS: One hundred and twenty patients were randomized to receive a Charnley (composite-beam), Exeter (double-tapered), or C-Stem (triple-tapered) prosthesis. The change in proximal femoral bone mineral density over two years was measured by dual x-ray absorptiometry (DXA). Bone turnover markers were measured in urine and serum samples collected at the preoperative baseline and during the first postoperative year. N-telopeptide of type-I collagen was measured in urine as a marker of osteoclast activity, and osteocalcin was measured in serum as a marker of osteoblast activity. Clinical outcome was measured with use of the Harris and Oxford hip scores and prosthesis migration was measured with use of digitized radiographs during the first two postoperative years. RESULTS: The baseline characteristics of the subjects in each group were similar (p > 0.05). Decreases in femoral bone mineral density were observed over the first year for all prosthesis designs, with no further loss during the second year. The decreases were similar in regional distribution and magnitude between the composite-beam and sliding-taper designs (p > 0.05). Bone loss was greatest (14%) in the proximal medial aspect of the femur (Gruen zone 7). Transient increases in both N-telopeptide of type-I collagen and osteocalcin activity also occurred over the first year, and these increases were similar in pattern among the three prosthesis groups (p > 0.05). All prostheses showed migration patterns that were consistent with their design type, and similar improvements in clinical hip scores were observed over the two-year course of the study. CONCLUSIONS: Differences in the mechanism of load transfer between the prosthesis and host bone in composite-beam or sliding-taper cemented femoral prosthesis designs were not a major determinant of proximal femoral bone loss after total hip arthroplasty, and the design that included a third taper exhibited a remodeling profile that was similar to those of the double-tapered design.

Iliopsoas tendonitis caused by overhang of a collared femoral prosthesis.

Pain after total hip arthroplasty can be due to a variety of causes, one of the less common being iliopsoas tendonitis. We report an unusual case of iliopsoas tendonitis caused by overhang of the femoral calcar by a collared femoral prosthesis resulting in impingement on the iliopsoas tendon. An ultrasound-guided corticosteroid and local anesthetic diagnostic injection to the site of impingement confirmed the diagnosis with temporary symptom relief. Revision of the femoral stem to a collarless prosthesis resulted in immediate and complete resolution of symptoms.

Polymorphisms in the interleukin-1 receptor antagonist and interleukin-6 genes affect risk of osteolysis in patients with total hip arthroplasty.

OBJECTIVE: To determine whether osteolysis after total hip arthroplasty (THA) is associated with common polymorphisms within the genes encoding the interleukin-1 (IL-1) family and IL-6, and to determine whether polymorphisms that are associated with osteolysis affect in vitro messenger RNA (mRNA) expression in human peripheral blood mononuclear cells (PBMCs) in response to wear particles. METHODS: Unrelated white subjects of North European descent (n=612) were recruited a mean of 11 years after cemented THA for primary osteoarthritis. Of these subjects, 272 had previous osteolysis and 340 had no radiographic evidence of osteolysis (control group). Genomic DNA was genotyped for the following single-nucleotide polymorphisms (SNPs): IL1A +4845, IL1B +3954, IL1B -3737, IL1B -511, IL1RA +2018, IL6 -174, IL6 -572, and IL6 -597. In a subset of 60 subjects, PBMCs were extracted and stimulated with titanium particles and/or endotoxin, and cytokine mRNA expression was measured using quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: The odds ratio (OR) for osteolysis associated with carriage of the IL1RA +2018C allele was 0.66 (95% confidence interval [95% CI] 0.48-0.91) (P=0.012). The remaining SNPs were not individually associated with osteolysis. The uncommon IL6 haplotype -174G/-572G/-597A (osteolysis group frequency 2.4%, control group frequency 0.8%) was associated with osteolysis (P=0.02, calculated using Haploview software). The IL1RA +2018CC genotype was associated with increased mRNA expression compared with the +2018TT genotype in both unstimulated and stimulated PBMCs (P=0.01 by analysis of variance, after Bonferroni correction). CONCLUSION: The IL1RA +2018C allele is associated with a decreased risk of osteolysis after THA and with increased IL-1 receptor antagonist mRNA expression in vitro. An uncommon haplotype within the promoter region of the gene for IL-6 is positively associated with osteolysis.

The use of total femoral arthroplasty as a limb salvage procedure: the Sheffield experience.

Over the last 25 years, 14 patients have undergone total femoral arthroplasty (TFA) after complications of revision arthroplasty surgery. These patients had previously undergone extensive surgery, which had failed, and required salvage surgery. The alternatives would have been amputation or hip disarticulation. A retrospective review of medical records and radiographs was undertaken, and clinical outcome was evaluated using the Musculoskeletal Tumour Society criteria. Before TFA, all patients had previously undergone multiple operations (range, 2-10). In 88% of cases, reconstructive options were not only limited by the availability of minimal host bone but also by deep sepsis. Results were encouraging, with most of the patients having greater mobility and less pain after surgery. A third of the patients achieved a 75% improvement in function. We believe that TFA has a definite role in the management of complex problems after extensive hip and knee revision arthroplasty surgery.

Accuracy of joint aspiration for the preoperative diagnosis of infection in total hip arthroplasty.

The aim of this study was to assess the diagnostic accuracy of radiology department-based hip aspiration for the diagnosis of infection after total hip arthroplasty. Patient selection criteria were devised so that only patients with moderate to high risk of infection were selected for hip aspiration. Seventy-three patients are included in this study, all of whom underwent revision hip surgery after aspiration. Culture results of hip aspirates were compared with the intraoperative tissue cultures at the time of revision surgery, which was used as the gold standard for diagnosing infection. Seventeen patients (23%) had infected hip joints at operative culture. The sensitivity and specificity, positive and negative predictive values, and accuracy of the hip aspiration were 0.82 and 0.91, 0.74 and 0.94, and 0.89, respectively. We conclude that hip aspiration carried out in the radiology department is reliable, but appropriate patient selection is important to obtain accurate results.

Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: a randomized trial.

In this trial we studied the effect of pamidronate on periprosthetic bone turnover and pelvic implant migration over 2 years after hybrid total hip arthroplasty (THA). Twenty-two patients received 90 mg of pamidronate and 22 received placebo at randomization 5 days after surgery. Rapid periprosthetic bone loss occurred in the placebo group over the first 6 months and was accompanied by transient increases in biochemical markers of bone turnover. Partial recovery in bone mass occurred in most regions after this period. No recovery of bone mass occurred at the femoral calcar or the medial wall of the acetabulum. Femoral calcar bone loss at 2 years was strongly predicted by acute biomarker changes at week 6. Pamidronate therapy reduced femoral bone loss in the region of the femoral calcar (P = 0.01), but did not affect pelvic bone loss. Pamidronate therapy also inhibited the transient rise in biochemical markers of bone turnover during this period. Pamidronate therapy did not affect acetabular cup migration. Cup migration was inversely related to subject age, but unrelated to initial post-operative bone mineral density, or subsequent bone loss. In summary, early periprosthetic bone loss is associated with a transient expansion of the bone remodeling space. Bisphosphonate therapy reduces femoral calcar bone loss and bone turnover after THA, but did not influence cup migration in this study. Acute changes in biochemical markers predict femoral periprosthetic bone loss.

The value of hip aspiration versus tissue biopsy in diagnosing infection before exchange hip arthroplasty surgery.

The exclusion of infection is the most important factor in determining treatment options in a failed hip arthroplasty. Preoperative biopsy in the form of aspiration or tissue biopsy can be used to diagnose infection. Preoperative aspiration and tissue drill biopsy were performed in 273 consecutive patients under general anesthesia 3 months before exchange arthroplasty surgery. The results of the preoperative aspiration and tissue biopsy cultures were compared with the definitive intraoperative tissue cultures obtained at surgery. Seventy-one of 273 (26%) hips were infected. Overall accuracy of aspiration was 90.1% and tissue biopsy 87.9%. The sensitivity and specificity was 80% and 94% for aspiration and 83% and 90% for tissue biopsy. Positive predictive value and negative predictive values were 81.4% and 93.1% for aspiration and 73.8% and 93.8% for tissue biopsy. The more invasive tissue drill biopsy offers no advantage over aspiration in terms of bacterial accuracy and results in more false positives.

Variation in the TNF gene promoter and risk of osteolysis after total hip arthroplasty.

UNLABELLED: Genetic factors may influence implant failure caused by osteolysis after THA. In an association study of 481 subjects after THA, we found that carriage of the TNF-238A allele was associated with an increased incidence of osteolysis versus noncarriage (odds ratio, 1.7) and was independent of other risk factors. Genetic and environmental factors influence implant survival after THA. INTRODUCTION: Tumor necrosis factor (TNF) is thought to play a role in osteolysis, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at -238 and -308 in the TNF gene promoter are associated with differences in susceptibility to several TNF-mediated diseases. We tested whether these polymorphisms are associated with osteolysis after THA. MATERIALS AND METHODS: A total of 481 whites (214 with failed versus 267 with intact implants) were recruited 11.7 +/- 4 years after cemented THA. Genomic DNA was extracted from peripheral blood and genotyped for the -238 and -308 polymorphisms using the Taqman 5' nuclease method. Healthy controls (n = 500) from the background population were also genotyped to establish the local prevalence of these alleles. RESULTS: The carriage of -238A was 8.8% in the background population and 10.9% in the THA controls (p > 0.05). Carriage of -238A in the osteolysis group was 17.3% (odds ratio, 1.7; 95% CI, 1.0-2.9). Carriage was highest (20.5%) in patients with more widespread osteolysis (OR, 2.1; 1.2-3.8). The association of -238A with osteolysis was independent of other risk factors for osteolysis (logistic regression analysis: OR, 1.8; 1.0-3.2). Carriage of -308A was not associated with osteolysis. CONCLUSION: Genetic, as well as environmental factors, influence implant failure after THA. Whether the TNF-238 polymorphism causes a biological change that predisposes to loosening or is in linkage disequilibrium with such a locus is not yet known.

Bone mineral density and biochemical markers of bone turnover in aseptic loosening after total hip arthroplasty.

The aims of this study were to determine whether subjects with aseptic loosening after total hip arthroplasty (THA) have regional differences in periprosthetic bone mineral density (BMD) and systemic biochemical markers of bone turnover compared to subjects with successful implants.Proximal femoral and pelvic BMD were measured by dual energy X-ray absorptiometry and bone turnover markers were assayed in 49 subjects 12.6+/-4.3 (mean+/-SD) years after cemented THA. Femoral BMD was lower in Gruen zones 2, 5, 6, and 7 in subjects with a loose femoral implant (n=17) compared to those (n=32) with fixed femoral implants (P<0.05 all comparisons). This BMD difference was greatest (-31%, P=0.02) in the proximal and medial region of the femur. Subjects with femoral loosening had higher levels of the bone resorption marker N-telopeptides of type-I collagen (P=0.02) than those with a fixed femoral implant. No differences in pelvic BMD or bone turnover markers were found between subjects with loose (n=18) versus fixed (n=31) pelvic implants. This study suggests that failure of femoral components after cemented THA is associated with region-specific decreases in BMD and an increase in urinary excretion of N-telopeptide cross-links of type-I collagen. These surrogate outcome markers may be of value in monitoring response to antiresorptive therapies used to treat periprosthetic osteolysis, although the diagnosis of aseptic loosening remains clinical and radiological.