The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis.

BACKGROUND: A variety of diagnostic imaging techniques is available for excluding or confirming chronic osteomyelitis. Until now, an evidence-based algorithmic model for choosing the most suitable imaging technique has been lacking. The objective of this study was to determine the accuracy of current imaging modalities in the diagnosis of chronic osteomyelitis. METHODS: A systematic review and meta-analysis of the literature was conducted with a comprehensive search of the MEDLINE, EMBASE, and Current Contents databases to identify clinical studies on chronic osteomyelitis that evaluated diagnostic imaging modalities. The value of each imaging technique was studied by determining its sensitivity and specificity compared with the results of histological analysis, findings on culture, and clinical follow-up of more than six months. RESULTS: A total of twenty-three clinical studies in which the accuracy was described for radiography (two studies), magnetic resonance imaging (five), computed tomography (one), bone scintigraphy (seven), leukocyte scintigraphy (thirteen), gallium scintigraphy (one), combined bone and leukocyte scintigraphy (six), combined bone and gallium scintigraphy (three), and fluorodeoxyglucose positron emission tomography (four) were included in the review. No meta-analysis was performed with respect to computed tomography, gallium scintigraphy, and radiography. Pooled sensitivity demonstrated that fluorodeoxyglucose positron emission tomography was the most sensitive technique, with a sensitivity of 96% (95% confidence interval, 88% to 99%) compared with 82% (95% confidence interval, 70% to 89%) for bone scintigraphy, 61% (95% confidence interval, 43% to 76%) for leukocyte scintigraphy, 78% (95% confidence interval, 72% to 83%) for combined bone and leukocyte scintigraphy, and 84% (95% confidence interval, 69% to 92%) for magnetic resonance imaging. Pooled specificity demonstrated that bone scintigraphy had the lowest specificity, with a specificity of 25% (95% confidence interval, 16% to 36%) compared with 60% (95% confidence interval, 38% to 78%) for magnetic resonance imaging, 77% (95% confidence interval, 63% to 87%) for leukocyte scintigraphy, 84% (95% confidence interval, 75% to 90%) for combined bone and leukocyte scintigraphy, and 91% (95% confidence interval, 81% to 95%) for fluorodeoxyglucose positron emission tomography. The sensitivity of leukocyte scintigraphy in detecting chronic osteomyelitis in the peripheral skeleton was 84% (95% confidence interval, 72% to 91%) compared with 21% (95% confidence interval, 11% to 38%) for its detection of chronic osteomyelitis in the axial skeleton. The specificity of leukocyte scintigraphy in the axial skeleton was 60% (95% confidence interval, 39% to 78%) compared with 80% (95% confidence interval, 61% to 91%) for the peripheral skeleton. CONCLUSIONS: Fluorodeoxyglucose positron emission tomography has the highest diagnostic accuracy for confirming or excluding the diagnosis of chronic osteomyelitis. Leukocyte scintigraphy has an appropriate diagnostic accuracy in the peripheral skeleton, but fluorodeoxyglucose positron emission tomography is superior for detecting chronic osteomyelitis in the axial skeleton.

Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects.

The discovery of bone morphogenetic proteins marks a major step forward in the understanding of bone physiology and in the development of advanced methods in skeletal surgery. The cornerstones for successful growth-factor therapy in skeletal surgery remain biomechanical stability and biological vitality of the bone providing an adequate environment for new bone formation. Knowledge of the biological characteristics, mechanisms of action, and methods of delivery of growth factors will become essential for skeletal surgeons. The current clinical application of bone morphogenetic proteins is safe and efficacious as a result of a well-regulated cascade of events leading to bone formation. Clinical trials have not yet determined whether different clinical indications each require a specific bone-tissue-engineering format or if a single pathway for stimulating bone-healing with growth factors is sufficient.

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture.

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.

Tissue reaction on PLLA versus stainless steel interlocking nails for fracture fixation: an animal study.

In order to develop a biodegradable interlocking nail for fracture fixation, polylactic acid (PLLA) rods were implanted in the femoral bone of young pigs. A midshaft osteotomy was performed in order to mimic a fracture. The tissue response to PLLA rods versus stainless steel rods was studied after 1 and 3 months of implantation. Fracture-healing characteristics and chemical and mechanical properties of the PLLA rods were studied after explantation. Mechanical properties deteriorated during implantation and chemical properties changed significantly in 1 and 3 months of implantation. PLLA and stainless steel induced a similar tissue reaction during the studied implantation time of 3 months.

Bone tissue response to biodegradable polymers used for intra medullary fracture fixation: a long-term in vivo study in sheep femora.

Since the degradability of the synthetic polymers used for fracture fixation is still unclear, a research project with biodegradable interlocking nails with a longterm implantation period has been started. In 21 female sheep a complete mid-shaft osteotomy of the left femur was performed to mimic a fracture of the femoral shaft. For the fixation, an intramedullary stainless-steel interlocking nail, a PLA rod or a PLA/PGA rod was used. After 30 months of implantation the histological results of these three materials were examined. In contrast to most reports the degradation rate of both polymers was much lower than the suggested ultimate period of two years. Even the tissue response was more pronounced than expected and this reaction can imply certain risks for repulsion. One can conclude that the volume quantity of polymeric implant in the bony tissue must be reduced if possible to avoid severe foreign body responses. The immunologic responses and the clinical consequences need more studies. The degradation behavior of the polymer is still not under control.

Biomechanical and histological aspects of fracture healing, stimulated with osteogenic protein-1.

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmp's), such as osteogenic protein-1 (OP-1), but little is known about its effectiveness in stimulation of fracture healing. In this study, biomechanical and histological aspects of fracture healing after an injection of OP-1 in the fracture gap were investigated. In 40 goats, a closed fracture was created in the left tibia. The fractures were stabilized with an external fixator and the animals were assigned to four different groups: no injection, injection of 1 mg OP-1, injection of 1 mg OP-1 with collagenous carrier material, and injection of carrier material alone. Twenty-one animals were sacrificed after 2 weeks and 19 after 4 weeks. Biomechanical testing was perfomed on both explanted tibiae. Four longitudinal samples of the fracture were sawn, processed for histology, and examined by two observers. Biomechanical evaluation showed a higher stiffness and strength at 2 weeks after injection of OP-1. Histological evaluation showed normal fracture healing patterns in all animals without adverse effects of the given injections. These data show that fracture healing can be accelerated with a single injection of OP-1, eventually resulting in normally healed bone.

Plasma exchange in rhabdomyolysis.

The effect of plasma exchange (PE) was evaluated in 4 patients with rhabdomyolysis. A single 21 PE produced a transient fall of creatinine phosphokinase and did not prevent renal failure. Theoretically PE would need to be performed very frequently to remove toxins in appropriate amounts. Since renal failure in myoglobinuira has a relative good prognosis, we do not recommend intensive PE as therapy.

New segmental long bone defect model in sheep: quantitative analysis of healing with dual energy x-ray absorptiometry.

An appropriate animal model is required for the study of treatments that enhance bone healing. A new segmental long bone defect model was developed for this purpose, and dual energy x-ray absorptiometry was used to quantify healing of this bone defect. In 15 sheep, a 3-cm segmental defect was created in the left tibia and fixed with an interlocking intramedullary nail. In seven animals, the defect was left empty for the assessment of the spontaneous healing response. In eight animals serving as a positive control, autologous bone grafting was performed. After 12 weeks, healing was evaluated with radiographs, a torsional test to failure, and dual energy x-ray absorptiometry. The mechanical test results were used for the assessment of unions and nonunions. Radiographic determination of nonunion was not reliably accomplished in this model. By means of dual energy x-ray absorptiometry, bone mineral density and content were measured in the middle of the defect. Bone mineral density was 91+/-7% (mean +/- SEM) and 72+/-6% that of the contralateral intact tibia in, respectively, the autologous bone-grafting and empty defect groups (p = 0.04). For bone mineral content, the values were, respectively, 117+/-18 and 82+/-9% (p = 0.07). Torsional strength and stiffness were also higher, although not significantly, in the group with autologous bone grafting than in that with the empty defect. Bone mineral density and content were closely related to the torsional properties (r2 ranged from 0.76 to 0.85, p < or = 0.0001). Because interlocking intramedullary nailing is a very common fixation method in patients, the newly developed segmental defect model has clinical relevance. The interlocking intramedullary nail provided adequate stability without implant failure. This model may be useful for the study of treatments that affect bone healing, and dual energy x-ray absorptiometry may be somewhat helpful in the analysis of healing of this bone defect.

Loss of bone in the proximal part of the femur following unstable fractures of the leg.

We evaluated the subsequent loss of bone from the proximal part of the ipsilateral and contralateral femora and from the lumbar spine of seven men and nine women who had a fracture of the tibia. The average age was sixty years. All of the fractures were unstable, and the involved leg bore no weight for an average of eight weeks. The bone mineral density was measured with dual-energy x-ray absorptiometry of the lumbar spine and of the femoral neck and the trochanteric region of both hips immediately after the fracture, after the period of immobilization, and at approximately three, six, and twelve months after the fracture. During the period of immobilization, the bone mineral density of the trochanteric region decreased an average of 9 +/- 7 per cent on the side of the fracture, compared with the value immediately after the fracture, but there was no change on the contralateral side (p < 0.01). At twelve months, the average decrease in the trochanteric area was 15 +/- 10 per cent on the side of the fracture, compared with the value immediately after the fracture, but again there had been no change on the uninjured side (p < 0.01). The bone mineral density of the femoral neck on the side of the fracture had decreased 6 +/- 6 per cent at twelve months, compared with a decrease of 2 +/- 4 per cent on the uninjured side (p < 0.05). The bone mineral density of the lumbar spine decreased only during the period of unloading of the fractured leg (1 +/- 2 per cent, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Representative assessment of long bone shaft biomechanical properties: an optimized testing method.

Whole bone bending tests are commonly used in mechanical evaluation of long bones. Reliable information about the midshaft can only be obtained if the bending moment is uniformly distributed along the shaft, and if the distribution of the bending stress is not adversely influenced by rigid clamping of the bone ends. A testing device was developed to determine bending stiffness of long bones in 24 directions, perpendicular to the bone axis. For optimal distribution of bending moment and stress, four-point bending was performed, and bone ends were simply supported, not rigidly clamped. The method was validated by repeated testing of a stainless steel rod, and a sheep femur. Left-right ratios were assessed twice in 2 groups of 5 sheep: one control group, and one group in which the left femur was stabilized with a stainless steel interlocking nail for 2.5 yr, after a midshaft osteotomy. Test results obtained with the steel rod reproducibly were close to predicted values. Measurements with the sheep femurs were reproducible and precise for 3 of the 4 parameters of the bending test. Stiffness parameters were significantly higher in the operated sheep than in the control group. We conclude that the method described here provides accurate and reproducible information, which is representative for the long bone shaft.

A new model for posttraumatic osteomyelitis in rabbits.

A new animal model for posttraumatic osteomyelitis was designed. This model mimics the pathogenesis of the human disease more accurately than models presently available. Femora of New Zealand white rabbits were exposed at the greater trochanter and a stainless steel rod was inserted into the marrow cavity. A Staphylococcus aureus suspension was placed in and around a bone defect, which was drilled midshaft. The disease was evaluated by clinical observation and roentgenographic, hematologic, bacteriologic, and histologic parameters. Osteomyelitis developed in all 24 infected rabbits. None of the five rabbits receiving only an intramedullary rod developed an osteomyelitis. This model proves that an experimental posttraumatic osteomyelitis associated with a foreign body can be reliably induced, even when no infection-promoting chemical agents, small inoculum of bacteria, or minimal bone trauma is present.

How effective is a clerkship as a learning environment?

To assess the educational quality of a traditional clerkship, a questionnaire was administered to 28 students at the end of their 10-week surgical clerkship. The questionnaire contained 116 items on learning objectives, patient problems encountered by students, clinical skills performed, feedback received and amounts of time spent on various activities. The students indicated that they had adequate ability to correctly analyse and manage patient problems. However, the standard deviations and ranges show that individual students' exposure to various patient problems was insufficient. Students generally saw too few emergency patients. The frequencies of performance of diagnostic and therapeutic skills varied widely among students. Most of the feedback received by students was given by residents rather than faculty physicians. Students spent considerable time on activities of limited educational value. It appears that learning during a clerkship occurs rather haphazardly. There are indications that the 'educational exposure' varies substantially from student to student.

Traumatic rupture of the thoracic aorta: time to diagnosis and treatment.

Survival of patients with traumatic rupture of the thoracic aorta (TRTA) depends on early surgical repair. Six cases of TRTA were treated at our institution in 7 years. Time to diagnosis was 1.5, 3, 4, 36, 91 and 140 hours (mean = 46 hours). Diagnosis was made by computed tomography in one and by angiography in five cases. Time from arrival to treatment was 3, 9, 5, 46, 117 and 152 hours (mean = 55 hours). All six patients were treated by clamp and suture technique, with a mean cross clamp time of 48 minutes. Significant delay in diagnosis and treatment occurred in three patients. The reasons for delay were unrecognized signs for TRTA on the initial chest X-ray, a false-negative result of transoesophageal echography and not considering the diagnosis of TRTA. The diagnosis of TRTA requires a high index of suspicion and should always be considered in victims of high impact trauma.

Myocardial contusion as a result of isolated sternal fractures: a fact or a myth?

Isolated sternal fractures are seen with an increasing frequency in traffic road accidents especially after the introduction of the seatbelt legislation. In most cases, the victims are young, otherwise healthy individuals. The medical records of all patients who were treated with a diagnosis of sternal fracture over the past 10 years were retrospectively reviewed. All patients with a radiologic diagnosis of sternal fracture were admitted for cardiac monitoring for at least 24 hours. ECG, determinations of cardiac enzyme levels CK (creatinephosphokinase) and CK-MB and evaluation by a cardiologist were routinely performed. An echocardiography was performed when indicated by the cardiologist. A total of 86 patients had sustained a sternal fracture during the 10-year study period. There were 39 males and 47 females with a mean age of 50 years (range 15-97 years). Serial 12-lead electrocardiograms, which were performed in 83 (97%) patients, revealed no information about myocardial contusion or cardiac arrhythmias with consequent therapy. In eight patients, a significant elevation in cardiac enzyme levels (elevation of CK-MB fraction above 10% of CK) was observed. All were normalized within 24 hours without development of any arrhythmias. Echocardiography was performed in 31 patients. In two patients, dyskinesia of the right ventricle (without enzyme elevations or arrhythmias) was observed. Within 24 hours these abnormalities resolved. The cardiac rhythm was monitored in 61 (71%) patients for a total of 1550 hours. No arrhythmias were observed. The cardiac enzyme studies, ECG and echocardiography revealed no consequent information about arrhythmias. In case of a sternal fracture, we recommend a chest X-ray to exclude other associated intrathoracic injuries. If no abnormalities are identified, admission to hospital is not necessary.

[Bone transplantation and bone replacement materials]. / Bottransplantaten en botvervangende materialen.

There is a growing need for immediately available material with appropriate qualities for reconstruction of large bone defects. Autologous spongy bone grafts are optimal as to biocompatibility, but are in short supply. Allogenic and xenogenic bone grafts evoke an immunological reaction after implantation and are not biocompatible. In the last thirty years ceramic implants and composites have been developed for bone substitution. New calcium phosphate bone substitutes undergo processes of resorption and precipitation of carbonate apatite that play a part in formation of new bone. These materials are easy to use because of their pastelike consistence. Resorption properties are influenced by particle size, crystallinity and composition. So far, no serious adverse reactions were reported. More clinical experience is necessary especially with composites and combinations with antibiotics, bone growth factors and collagen, to specify the place of these modern calcium phosphates in bone replacement and bone substitution.

[Antibiotic prophylaxis in closed fractures is cost-effective if the possibility of a deep infection decreases through this by 0.25%]. / Antibiotische profylaxe bij gesloten fracturen kosten-effectief als de kans op een diepe infectie erdoor afneemt met 0.25%.

This patient-control study was undertaken to assess the cost-effectiveness of prophylaxis of postoperative infections after surgical treatment of closed fractures. The costs of 16 patients with an infection (8 with deep infections, 8 with superficial infections) were investigated and compared with the costs of 16 similar noninfected patients for the parameters hospital stay, antibiotics and surgery. The data were collected from the trauma department of the University Hospital of the Free University of Amsterdam. There were no substantial extra costs in the group of the 8 patients with superficial wound infection compared with their noninfected controls. The mean extra costs for a deep infection in the other 8 patients were Dfl 35,224.-. Considering these results, antibiotic prophylaxis of postoperative wound infections is cost-effective, if it leads to a decrease of the risk of deep wound infections by about 0.25%.

[Reliability of registration of multi-trauma patients]. / De betrouwbaarheid van de registratie van polytrauma-patiënten.

OBJECTIVE: Evaluation of the reliability of diagnostic codification by the Medical Codification Department (MCD) as a method of national hospital identification of multiple injury patients and description of epidemiology and mortality among the multiple injury group studied. DESIGN: Prospective/retrospective and descriptive. SETTING: Free University Hospital, Amsterdam. METHOD: The injuries of 207 severely injured patients presented at the Accident and Emergency department during the year 1992, were coded as an Injury Severity Score (ISS). Those having an ISS > or = 18 were reviewed on cause and outcome of the injury. The diagnose for codification (International Classification of Diseases-9 Clinical Modification) of the MCD, from which an Abbreviated Injury Score (AIS) and the ISS can be calculated, was evaluated. RESULTS: 24 out of the 207 severely injured patients were transferred to other hospitals after stabilisation because of lack of room. Of the remaining 183 patients 124 had an ISS > or = 18.44 (35%) patients died during their stay in hospital. 21 (48%) of them died within 2 hours. 28 (64%) multiple injury patients died during the first 24 hours after admission. Neurological damage was the main cause of death (59%), followed by exsanguination (30%). A traffic accident was the cause of the injuries in 61% and a fall or jump in 27%. The mean ISS of these patients was 29 and the maximum score was 66. Head and neck injuries were present in 80% of the patients. The codification of brain damage by the MCD resulted in several mistakes. Brain damage in multiple injury cases results in a high AIS. Since the ISS is calculated by multiplication of AIS values, small differences in AIS create considerable variations in ISS. CONCLUSION: Multiple injury patients need fast and adequate help because of the high mortality, especially in the first 24 hours. The diagnostic codification of the MCD was found not reliable enough to be used for a hospital identification and registration of multiple injury patients.

[The body-packer syndrome]. / Het 'body-packer'-syndroom.

In four patients, a woman of 35 and men of 27, 38, and 22 years old, body-packer syndrome was diagnosed. Body-packer syndrome is seen in people concealing drugs in special containers within the body; this may lead to rupture with acute intoxication or to ileus. The clinical presentation can be very deceptive. An abdominal X-ray often reveals the packages. If there are no symptoms treatment is with mild laxatives, acute intoxication requires immediate laparotomy. One of the four patients died, the others recovered. Legally (Dutch law), the physician best delivers the drug to the police as a lost object, without revealing the patient's identity.

Destination of debris during intramedullary reaming. An experimental study on sheep femurs.

This study was designed to further explain the better fracture healing in fractures treated with a reamed nail. It investigates the location and quantity of the reaming debris in an ex vivo animal model to test the autograft theory. In 10 cadaveric sheep femurs, a 5-mm semicircular gap was created at the midshaft. The medullary cavity was opened and the reaming debris that dropped from the gap during reaming and the debris from the proximal opening were collected and weighed separately. The mean harvest of reaming debris at the gap was 0.99 g +/- 0.12 g (24%) and from the proximal opening at the medullary cavity 3.08 g +/- 0.31 g (76%) (total 4.07 +/- 0.34 g). This study proves that a significant amount of reaming debris collects at an artificial fracture gap during reaming of the medullary cavity. This finding supports the theory of bone autografting.

Hemiarthroplasty in elderly, debilitated patients with an unstable femoral fracture in the trochanteric region.

The purpose of this study was to evaluate the results of patients with an unstable fracture in the trochanteric region who were treated by hemiarthroplasty. During a 10-year period, 154 of the 308 patients with a trochanteric fracture treated in our hospital had an unstable fracture. In patients with severe comminution and osteoporosis an endoprosthesis was inserted: 5 patients with a subtrochanteric and 17 with a pertrochanteric fracture. Ten patients suffered from central nervous system diseases, and in 10 patients cardiovascular or pulmonary disorders were diagnosed. Pre- and postoperative ambulation levels were classified. Seventeen patients (77%) achieved full weight-bearing mobilization. Five patients never walked again (23%): 2 patients died in the first month (9%). It is concluded that for elderly and debilitated patients with an unstable trochanteric fracture, hemiarthroplasty is an acceptable alternative to osteosynthesis.