Antibacterial coating of implants: are we missing something?

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user's cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma. Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199-206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.

Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier.

Living in biofilms is probably the most common condition for bacteria and fungi and biofilm-related infections account for the majority of bacterial infectious diseases worldwide. Among others biofilm-related infections, those associated with implanted biomaterials have an enormous and still largely underestimated impact in orthopaedics and trauma, cardio-surgery and several other surgical disciplines. Given the limited efficacy of existing antibiotics in the prevention and treatment of bacterial biofilms, new strategies are needed to protect implants and host tissues, overcoming the striking ability of the microorganisms to adhere on different surfaces and to immediately protect themselves by forming the biofilm matrix. Adhesion is a necessary first step in microbial colonization and pathogenesis and provides a potential target for new preventive and treatment approach. Among various polymers, tested as antibacterial coatings, hyaluronic acid and some of its composites do offer a well-established long-term safety profile and a proven ability to reduce bacterial adhesion and biofilm formation. Aim of the present review is to summarize the available evidence concerning the antiadhesion/antibiofilm activity of hyaluronic acid and some of its derivatives to reduce/prevent bacterial adhesion and biofilm formation in various experimental and clinical settings.

Does cemented or cementless single-stage exchange arthroplasty of chronic periprosthetic hip infections provide similar infection rates to a two-stage? A systematic review.

BACKGROUND: The best surgical modality for treating chronic periprosthetic hip infections remains controversial, with a lack of randomised controlled studies. The aim of this systematic review is to compare the infection recurrence rate after a single-stage versus a two-stage exchange arthroplasty, and the rate of cemented versus cementless single-stage exchange arthroplasty for chronic periprosthetic hip infections. METHODS: We searched for eligible studies published up to December 2015. Full text or abstract in English were reviewed. We included studies reporting the infection recurrence rate as the outcome of interest following single- or two-stage exchange arthroplasty, or both, with a minimum follow-up of 12 months. Two reviewers independently abstracted data and appraised quality assessment. RESULTS: After study selection, 90 observational studies were included. The majority of studies were focused on a two-stage hip exchange arthroplasty (65 %), 18 % on a single-stage exchange, and only a 17 % were comparative studies. There was no statistically significant difference between a single-stage versus a two-stage exchange in terms of recurrence of infection in controlled studies (pooled odds ratio of 1.37 [95 % CI = 0.68-2.74, I2 = 45.5 %]). Similarly, the recurrence infection rate in cementless versus cemented single-stage hip exchanges failed to demonstrate a significant difference, due to the substantial heterogeneity among the studies. CONCLUSION: Despite the methodological limitations and the heterogeneity between single cohorts studies, if we considered only the available controlled studies no superiority was demonstrated between a single- and two-stage exchange at a minimum of 12 months follow-up. The overalapping of confidence intervals related to single-stage cementless and cemented hip exchanges, showed no superiority of either technique.

Leucocyte esterase, glucose and C-reactive protein in the diagnosis of prosthetic joint infections: a prospective study.

Analysis of joint fluid is of paramount importance for the diagnosis of prosthetic joint infections. Different markers of inflammation and/or infection in joint fluid have been proposed for diagnosis of these infections. In this study we evaluated the performance of leucocyte esterase, C-reactive protein (CRP) and glucose assays in synovial fluids from 129 patients with septic (n = 27) or aseptic (n = 102) prosthetic joint failure. Samples were collected in serum tubes and centrifuged to limit the presence of corpuscle interfering with the assays. Determinations of leucocyte esterase and glucose were carried out by means of enzymatic colorimetric reactions performed on strips for urine analysis. Tests were considered positive when graded + or ++ whereas traces or absence of colour were considered negative. CRP was measured using an automated turbidimetric method and considered suggestive for infections when >10 mg/L. Leucocyte esterase was positive in 25/27 infected patients and negative in 99/102 not infected patients (sensitivity 92.6%, specificity 97.0%). CRP was higher than the threshold in 22/27 infected patients and in 6/102 not infected patients (sensitivity: 81.5%; specificity: 94.1%) whereas glucose showed the lowest sensitivity (77.8%) and specificity (81.4%), being negative in 21/27 and 19/102 infected and not infected patients, respectively. CRP led to a correct diagnosis in 19 of 22 patients with discordant esterase and glucose results. In conclusion, evaluation of leucocyte esterase, glucose and CRP may represent a useful tool for rapid diagnosis of prosthetic joint infections.

Does exchange arthroplasty of an infected shoulder prosthesis provide better eradication rate and better functional outcome, compared to a permanent spacer or resection arthroplasty? a systematic review.

BACKGROUND: The best surgical modality for treating chronic periprosthetic shoulder infections has not been established, with a lack of randomised comparative studies. This systematic review compares the infection eradication rate and functional outcomes after single- or two-stage shoulder exchange arthroplasty, to permanent spacer implant or resection arthroplasty. METHODS: Full-text papers and those with an abstract in English published from January 2000 to June 2014, identified through international databases, such as EMBASE and PubMed, were reviewed. Those reporting the success rate of infection eradication after a single-stage exchange, two-stage exchange, resection arthroplasty or permanent spacer implant, with a minimum follow-up of 6 months and sample size of 5 patients were included. RESULTS: Eight original articles reporting the results after resection arthroplasty (n = 83), 6 on single-stage exchange (n = 75), 13 on two-stage exchange (n = 142) and 8 papers on permanent spacer (n = 68) were included. The average infection eradication rate was 86.7 % at a mean follow-up of 39.8 months (SD 20.8) after resection arthroplasty, 94.7 % at 46.8 months (SD 17.6) after a single-stage exchange, 90.8 % at 37.9 months (SD 12.8) after two-stage exchange, and 95.6 % at 31.0 months (SD 9.8) following a permanent spacer implant. The difference was not statistically significant (p = 0.650). Regarding functional outcome, patients treated with single-stage exchange had statistically significant better postoperative Constant scores (mean 51, SD 13) than patients undergoing a two-stage exchange (mean 44, SD 9), resection arthroplasty (mean 32, SD 7) or a permanent spacer implant (mean 31, SD 9) (p = 0.029). However, when considering studies comparing pre- and post-operative Constant scores, the difference was not statistically significant. CONCLUSION: This systematic review failed to demonstrate a clear difference in infection eradication and functional improvement between all four treatment modalities for established periprosthetic shoulder infection. The relatively low number of patients and the methodological limitations of the studies available point out the need for well designed multi-center trials to further assess the best treatment option of peri-prosthetic shoulder infection.

Calcium-Based, Antibiotic-Loaded Bone Substitute as an Implant Coating: A Pilot Clinical Study.

Background: Implant-related infections remain a major complication after orthopaedic surgery. Antibacterial coating of implants may prevent bacterial adhesion and biofilm formation. However, in spite of extensive preclinical research in the field, antibacterial coatings to protect orthopaedic implants in the clinical setting remain particularly few. The aim of the present study is to evaluate the safety of a calcium-based, antibiotic-loaded bone substitute as an antibacterial coating of cementless joint prosthesis. Methods: From March 2013 to August 2015, 20 consecutive patients scheduled for cementless or hybrid two-stage revision surgery for peri-prosthetic joint infection were included in this prospective, observational, pilot study. Cerament G or Cerament V, a gentamicin or vancomycin-loaded calcium-based resorbable bone substitute (60% calcium sulphate, 40% hydroxyapatite), was applied at surgery on the stem surface of hip (n=7) or knee (n=13) revision prosthesis. After surgery, all patients underwent clinical (HHS or KSS and SF-12 score), laboratory and radiographic evaluation at 3, 6 and 12 months and yearly thereafter. Results: At a minimum of 12 months follow-up, 19/20 (95%) patients showed no recurrence of infection and no signs of radiographic loosening of the stem. No adverse events were associated with the use of Cerament G or V. Conclusions: This is the first pilot clinical study on the short-term safety of using a calcium-based, gentamicin or vancomycin-loaded bone substitute as a surface coating on cementless prosthetic implants. If confirmed by larger studies and at longer follow-ups, these findings may open a new prospective to protect intra-operatively orthopedic implants from bacterial adhesion, through the use of resorbable, osteoconductive, antibiotic carriers.

ANTIBIOTIC-LOADED REGENOSS FOR THE TREATMENT OF SEPTIC BONE DEFECTS: IN VITRO STUDY AND PRELIMINARY CLINICAL EXPERIENCE.

Bone and joint infections are a difficult to treat condition, often associated with bone loss. Although the management of septic bone defects may currently be achieved through various treatment modalities, there is a continuous need for bone substitutes able at the same time to favour bone repair and to provide local antibacterial protection. RegenOss, a biomimetic and resorbable bone substitute, has been previously shown to be highly biocompatible and osteoconductive. Aims of the present study were to test the in vitro ability of RegenOss to act as a local carrier of antibiotics and to investigate its clinical safety and efficacy in a continuous series of patients, affected by bone loss in active or previous infection. In vitro study was performed by adding vancomycin, levofloxacin or meropenem and assessing elution properties of RegenOss at fixed time intervals by means of a microbiological assay. At 48 hours, 98.5% of meropenem, 94.1% of levofloxacin and 76.3% of vancomycin were recovered in the medium, while all antibiotics were completely eluted at seven days. Clinical safety and efficacy of vancomicyn- or vancomicyn and meropenem-loaded RegenOss had been tested in 13 consecutive patients. After the surgical procedure, each patient underwent clinical, laboratory and radiographic evaluation at 3, 6, 12, 18 and 24 months. No adverse events associated with the use of RegenOss were observed. Twelve patients showed no infection recurrence and ten satisfactory bone healing at follow-up. In conclusion, this study shows the ability of RegenOss to act as local carrier when loaded with three different antibiotics with a complete elution in one week. The clinical use of antibiotic-loaded RegenOss appears safe in this preliminary clinical series, while larger studies are needed to confirm the efficacy of the intra-operative combination of this biomimetic bone substitute with various antibacterials in the treatment of septic bone defects.

Prolonging culture to 15 days improves bacterial detection in bone and joint infections.

Since the optimal incubation period of cultures for diagnosis of bone and joint infections is still a matter of debate, the present study aimed to evaluate the effects of different incubation periods (5 and 15 days) on microbial isolation. Samples from 387 patients with bone and joint infections (including prosthetic ones) were analyzed from March 2012 to February 2014. In 197 patients (51 %) growth was obtained within 48 hrs, while in 124 (32 %) and 66 (17 %) patients cultures yielded positive results within and after 5 days of incubation, respectively. Of 449 microorganisms isolated, 247 grew within 48 hrs, 131 within the first 5 days of incubation while 71 were isolated after 5 days. Staphylococcus aureus was the most frequently isolated pathogen within 48 hrs, while Propionibacteria were prevalently isolated after 5 days of incubation. Interestingly, about 25 % of microorganisms isolated after 5 days of incubation were coagulase-negative staphylococci. Extending incubation period of broth cultures improves isolation rates of pathogens involved in bone and joint infections thus improving management of these infections.

A comparative study of the use of bioactive glass S53P4 and antibiotic-loaded calcium-based bone substitutes in the treatment of chronic osteomyelitis: a retrospective comparative study.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed. In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups. After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate. Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Behaviour of perioperative values of haemoglobin, haematocrit and red blood cells in elderly patients undergoing lower limb arthroplasty: a retrospective cohort study on non-transfused patients.

Little is known on how elderly patients recover pre-operative haemoglobin, haematocrit and red blood cell levels after total hip and knee arthroplasties. In this study we aimed to evaluate blood loss and recovery blood levels in relation to gender, type of surgery and preoperative haemoglobin values. We conducted a retrospective cohort study on 187 patients over 65 years of age who underwent total knee or total hip arthroplasty between January 2008 and December 2009. Preoperative blood analysis was carried out within 40 days prior to intervention followed by a 15-day postoperative follow-up. Haemoglobin recovery values in anaemic patients versus healthy patients was also estimated. All tested values decreased significantly during the first 3-5 postoperative days. Haemoglobin levels decreased statistically significantly more in males than in females, while no significant differences were observed for haematocrit and erythrocytes. Recovery of haemoglobin values did not differ significantly between healthy patients and patients with preoperative haemoglobin below 120 g/L. Furthermore, our data showed a higher blood loss in total hip arthroplasty, whilst recovery rates showed to be higher after a total knee arthroplasty procedure. In conclusion, the type of intervention and gender played an important role in blood loss and recovery rates in total joint arthroplasty.

Two-stage revision of septic knee prosthesis with articulating knee spacers yields better infection eradication rate than one-stage or two-stage revision with static spacers.

PURPOSE: The best method for treating chronic periprosthetic knee infection remains controversial. Randomized, comparative studies on treatment modalities are lacking. This systematic review of the literature compares the infection eradication rate after two-stage versus one-stage revision and static versus articulating spacers in two-stage procedures. METHODS: We reviewed full-text papers and those with an abstract in English published from 1966 through 2011 that reported the success rate of infection eradication after one-stage or two-stage revision with two different types of spacers. RESULTS: In all, 6 original articles reporting the results after one-stage knee exchange arthoplasty (n = 204) and 38 papers reporting on two-stage revision (n = 1,421) were reviewed. The average success rate in the eradication of infection was 89.8% after a two-stage revision and 81.9% after a one-stage procedure at a mean follow-up of 44.7 and 40.7 months, respectively. The average infection eradication rate after a two-stage procedure was slightly, although significantly, higher when an articulating spacer rather than a static spacer was used (91.2 versus 87%). CONCLUSIONS: The methodological limitations of this study and the heterogeneous material in the studies reviewed notwithstanding, this systematic review shows that, on average, a two-stage procedure is associated with a higher rate of eradication of infection than one-stage revision for septic knee prosthesis and that articulating spacers are associated with a lower recurrence of infection than static spacers at a comparable mean duration of follow-up. LEVEL OF EVIDENCE: IV.

Gait analysis in patients with a preformed articulated knee spacer.

Two-stage revision is one of the most widely accepted procedures to eradicate infection and restore function in infected knee prosthesis; while the use of an articulated spacers is advocated by many as a means to preserve function between stages, no data are available regarding gait parameters after spacer implant. The aim of present study was to assess and compare the gait parameters of patients with articulated knee spacers with a normal reference population and with the sound limb. Computerised gait analysis, was performed 8 to 14 weeks after the infected knee prosthesis had been removed and a preformed, articulated, knee spacer had been implanted, in 10 consecutive patients. Kinematic data show a mean gait velocity reduction of 70% and a decrease of the range of motion of the operated knee of 59%, compared with controls. While ground reaction forces were only slightly reduced, frontal and sagittal moments and calculated powers around the affected knees were near zero or zero. Our findings point out the ability of a preformed articulated spacer to preserve, although reduced, the normal gait parameters and joint range of motion and the capacity of the human body to provide useful postural modifications, even in the absence of the proprioceptive input from a normal knee or from a traditional total knee replacement.

Telethermographic findings after uncomplicated and septic total knee replacement.

Thermal imaging with infrared thermography is a noninvasive approach to monitoring surgical site healing and detecting septic complications. The aim of this study was to set reference values for telethermographic patterns of wound healing after total knee replacement (TKR) not complicated by infection and to compare them against thermograms from patients with knee prosthesis infection. Forty consecutive patients operated for TKR underwent telethermography of the operated and the contralateral knee before and up to 12 months after uncomplicated surgery. The imaging data sets were then compared against those obtained starting 8 months after TKR in 15 other patients with diagnosed periprosthetic infection. Presurgical assessment thermograms showed no difference between the affected and the healthy knees. At assessment 3 days postoperative, the temperature of the operated knee had increased markedly, with a peak differential temperature (operated minus non-operated knee joint temperature) of 3.4±0.7°C; measurement at 90 days after surgery showed a return to baseline knee joint temperature in the patients with uncomplicated surgery. In the patients with septic complications, the mean differential temperature was 1.6±0.6°C (range, 1.1-2.5°C). Thermal imaging showed a measurable, reproducible telethermographic pattern of surgical site healing in patients with uncomplicated TKR and an elevated mean differential temperature >1.0°C in those with persistent prosthesis infection.

Iron status evaluation as a marker of postoperative joint infection: a pilot study.

We evaluated the effect of different inflammatory conditions on iron status and, as a consequence, the possible use of iron markers as indicators of infection in the diagnosis of postoperative prosthetic orthopaedic joint infections. The study population was consisted of 26 patients undergoing revision of total hip or total knee joint arthroplasty and subdivided into three groups according to the cause of prosthesis implant failure: 10 as having had previous infection (Group A), 10 patients were categorized as having infection (Group B); and the remaining 6 (Group C) as not having infection. These patients were assayed for mean corpuscular haemoglobin concentration (MCHC) and serum values of iron (Fe), ferritin (Fer), transferrin (Tf), soluble transferrin receptor (sTfR), and transferrin saturation (sat Tf). Septic patients display statistically significant lower serum iron concentration, higher sTfR and ferritin levels, lower, but not statistically significant, MCHC compared to non septic ones. Little differences were observed for Tf, sat Tf, tibc, TfR index, among the three groups of patients. Our study suggests that iron status parameters, in particular serum iron, ferritin, sTfR and TfR index, could be useful tools for the early detection and the diagnosis of orthopaedic prosthetic joint infections.

Modulation of biofilm of strains isolated from patients with chronic obstructive pulmonary disease by levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone.

The ability of levofloxacin, moxifloxacin, ciprofloxacin, amoxicillin/clavulanic acid and ceftriaxone to interfere on biofilm produced by Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae isolated from patients with chronic obstructive pulmonary disease was evaluated. The effects of antibiotics were evaluated on formation of biofilm (at 1/2, 1/4 and 1/8 X MIC) and on preformed biofilm (at epithelial lining fluid peak concentrations) by means of a spectrophotometric method. Levofloxacin was the most active compound followed by ciprofloxacin, moxifloxacin and amoxicillin/clavulanic acid and ceftriaxone. Levofloxacin may contribute to clear the reservoir of pathogens involved in chronic obstructive pulmonary disease, thus leading to decreased occurrence of acute exacerbations.

Evaluation of zebrafish Danio rerio as a model for enteric septicemia of catfish (ESC).

Zebrafish (also known as zebra danio) Danio rerio were injected intramuscularly with Edwardsiella ictaluri at doses of 6 x 10(3), 6 x 10(4), or 6 x 10(5) colony-forming units per gram (CFU/g) or sterile phosphate-buffered saline (sham) or were not injected. Mortality occurred from 2 to 5 d postinjection (dpi) at rates of 0, 76.6, and 81.3% for the low, medium, and high doses, respectively, and E. ictaluri was isolated from dead fish. Survivors were sampled at 10 dpi and E. ictaluri was not isolated. Sham-injected and noninjected controls did not suffer mortality. Histopathology trials were performed in which zebrafish were injected with 1 x 10(4) CFU/g or sham-injected and sampled at 12, 24, 48, 72, and 96 h postinjection for histological interpretation. Collectively, these zebrafish demonstrated increasing severity of splenic, hepatic, cardiac, and renal interstitial necrosis over time. To evaluate the progression of chronic infection, zebrafish were injected with 1 x 10(2) CFU/g and held for 1 month postinjection. Beginning at 12 dpi and continuing for an additional 2 weeks, zebrafish demonstrated abnormal spiraling and circling swimming behaviors. Histopathology demonstrated necrotizing encephalitis. In immersion trials, zebrafish were exposed to low, medium, and high doses (averaging 1.16 x 10(5), 1.16 x 10(6), and 1.16 x 10(7) CFU/mL of tank water) of E. ictaluri for 2 h. Mortality occurred from 5 to 9 d postexposure at rates of 0, 3.3, and 13.3% for the low, medium, and high doses, respectively; E. ictaluri was isolated from dead fish. Channel catfish Ictalurus punctatus exposed to the medium doses suffered 100% mortality, and E. ictaluri was isolated from these fish. This study demonstrates the potential use of zebrafish as a model for E. ictaluri pathogenesis.

A new method to reduce pin-prick pain of intra-muscular and subcutaneous injections.

AIM: Although about 10% of the normal population is thought to be needle-phobic, no method to reduce pin-prick pain is currently available for large scale application. We describe a new simple and easy-to-do method to reduce pin-prick pain through the pressure of multiple blunt pins at the injection site. METHODS: Two-hundred and twelve patients were randomly assigned to 2 groups. The treated group (n= 106) received intramuscular and subcutaneous injections with the application of the blunt pins and the control group (n= 106) with a placebo device. Pain was tested with the visual analogue scale on a 0 (no pain)-10 (maximum pain) scale. RESULTS: After intramuscular injections a significant (P< 0.0001) pain reduction in the treated group compared to placebo was observed: 1.90+/-1.27 versus 5.16+/-1.37 (mean pain reduction: 63.2%); 88.5% of the patients in the treated group and 11.4% in placebo group rated the pain as = or < 3. After subcutaneous injections mean reported pain in the treated group compared to placebo was: 0.32+/-0.51 versus 2.61+/-0.77 (mean pain reduction: 87.7%) (P< 0.0001); 95.1% of the patients in the treated group and 9.8% in the placebo rated the pain as = or <1. No side effects were observed. CONCLUSIONS: Multiple blunt pins pressure on the skin, at the time of intramuscular or subcutaneous injection is able to significantly reduce pin-prick pain. The underlying physiological mechanisms are briefly discussed.

Analysis of the gait of adults who had residua of congenital dysplasia of the hip.

Twenty-one adult subjects who had symptomatic residua of unilateral congenital dysplasia of the hip, with various degrees of degenerative changes, were studied with respect to the physical and radiographic findings and gait performance. Three-dimensional body reconstruction; the Trendelenburg sign; spatiotemporal parameters of stride; ground-reaction forces; kinematics of the hip, knee, and ankle; moments of forces; and joint powers were evaluated bilaterally. The kinematic and kinetic parameters of the affected limb were compared with those of the unaffected limb and with those of the limbs of normal control subjects. Correlations between changes in selected gait parameters and the clinical and radiographic signs of impairment of the hip were demonstrated. The results are discussed in relation to the possible mechanisms underlying the observed alterations and in view of possible operative interventions.

Prophylaxis with indomethacin for heterotopic ossification after Chiari osteotomy of the pelvis.

One hundred patients who had painful dysplasia of the hip were treated with a Chiari osteotomy of the pelvis, and the postoperative radiographs were reviewed for the development of heterotopic ossification. Sixty patients did not receive indomethacin postoperatively, and eighteen (30 per cent) had heterotopic ossification of at least class 1; forty patients received indomethacin for two weeks postoperatively, and only three (8 per cent) of them had heterotopic ossification. This difference was significant (p < 0.025). No class-3 or 4 heterotopic ossification was seen in the patients who were given indomethacin. The prevalence of side-effects was relatively low, and no delayed union of the osteotomy was observed in any patient. We concluded that indomethacin, in the dosage schedule and regimen that we used, provides effective prophylaxis for heterotopic ossification after a Chiari pelvic osteotomy.