Fred C. Bakker

Treatment of traumatic thoracolumbar spine fractures: a multicenter prospective randomized study of operative versus nonsurgical treatment.

Study Design. Multicenter prospective randomized trial. Objective. To test the hypotheses that thoracolumbar AO Type A spine fractures without neurologic deficit, managed with short-segment posterior stabilization will show an improved radiographic outcome and at least the same functional outcome as compared with nonsurgically treated thoracolumbar fractures. Summary of Background Data. There are various opinions regarding the ideal management of thoracolumbar Type A spine fractures without neurologic deficit. Both operative and nonsurgical approaches are advocated. Methods. Patients were randomized for operative or nonsurgical treatment. Data sampling involved demographics, fracture classifications, radiographic evaluation, and functional outcome. Results. Sixteen patients received nonsurgical therapy, and 18 received surgical treatment. Follow-up was completed for 32 (94%) of the patients after a mean of 4.3 years. At the end of follow-up, both local and regional kyphotic deformity was significantly less in the operatively treated group. All functional outcome scores (VAS Pain, VAS Spine Score, and RMDQ-24) showed significantly better results in the operative group. The percentage of patients returning to their original jobs was found to be significantly higher in the operative treated group. Conclusions. Patients with a Type A3 thoracolumbar spine fracture without neurologic deficit should be treated by short-segment posterior stabilization.

Properties of calcium phosphate ceramics in relation to their in vivo behavior.

B one replacement has been under investigation for many centuries. The first report on bone replacement comes from the bronze age, when a skull defect was treated by implantation of a bone autograft. However, the first successful treatment of a bone defect with a bone graft was performed by the Dutch surgeon Job van Meek’ren in 1668. After that, it took many centuries before the first large series of bone transplants was reported. Since that time, the advantages and disadvantages of bone transplantation have become clearly understood. The need for bone replacement is evident in traumatology and orthopedics. Loss of bone caused by trauma, infection, or tumor resection poses great problems on both the treating surgeon and the patient. Treatment of these conditions often includes the implantation of autogenous bone transplant material, but this method leads to significant consequences for the patient. Harvesting autogenous bone grafts causes comorbidity in 6 to 20% of patients, such as persistent pain, hypersensitivity, or anesthesia, and 3 to 9% have more serious problems. Artificial bone replacement materials can avoid these consequences. Since the first use of plaster of paris as an artificial bone replacement material in 1894, different groups of artificial bone replacement materials have been developed over the years. Glass ceramics, metal ceramics, polymers, and calcium phosphate ceramics, such as hydroxyapatite (HA) and tricalciumphosphate (TCP) have been investigated extensively. These materials have different properties and, therefore, display different interactions with the host tissue. Factors such as porosity, osteoconductivity, and biocompatibility seem to become increasingly important in the development of new artificial bone replacement materials. This paper focuses on the relation between the properties of bone replacement materials, especially calcium phosphate ceramics, and the host tissue, to provide some clarity in the processes involved in the incorporation of these materials in bone tissue. Developments in the combination of osteogenic or osteoinductive substances and calcium phosphate ceramics will be discussed as well. POROSITY

Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow

Hydroxyapatite is a synthetic bone graft, which is used for the treatment of bone defects and nonunions. However, it is a rather inert material with no or little intrinsic osteoinductive activity. Recombinant human osteogenic protein‐1 (rhOP‐1) is a very potent biological agent, that enhances osteogenesis during bone repair. Bone marrow contains mesenchymal stem cells, which are capable of new bone formation. Biosynthetic bone grafts were created by the addition of rhOP‐1 or bone marrow to granular porous hydroxyapatite. The performance of these grafts was tested in a sheep model and compared to the results of autograft, which is clinically the standard treatment of bone defects and nonunions. A 3 cm segmental bone defect was made in the tibia and fixed with an interlocking intramedullary nail. There were five treatment groups: no implant (n = 6), autograft (n = 8), hydroxyapatite alone (n = 8), hydroxyapatite loaded with rhOP‐1 (n = 8), and hydroxyapatite loaded with autologous bone marrow (n = 8). At 12 weeks, healing of the defect was evaluated with radiographs, a torsional test to failure, and histological examination of longitudinal sections through the defect. Torsional strength and stiffness of the healing tibiae were about two to three times higher for autograft and hydroxyapatite plus rhOP‐1 or bone marrow compared to hydroxyapatite alone and empty defects. The mean values of both combination groups were comparable to those of autograft. There were more unions in defects with hydroxyapatite plus rhOP‐1 than in defects with hydroxyapatite alone. Although the differences were not significant, histological examination revealed that there was more often bony bridging of the defect in both combination groups and the autograft group than in the group with hydroxyapatite alone. Healing of bone defects, treated with porous hydroxyapatite, can be enhanced by the addition of rhOP‐1 or autologous bone marrow. The results of these composite biosynthetic grafts are equivalent to those of autograft.

The reliability of plain radiography in experimental fracture healing

Abstract Objective. To investigate the reliability of radiographs in the evaluation of healing of closed fractures. Design. A closed midshaft tibial fracture was created in 40 goats and stabilized with an external fixator. The animals were assigned to four groups: no injection, injection of 1 mg osteogenic protein-1 (OP-1), 1 mg OP-1 with collagenous carrier, or carrier alone. Radiographs were performed weekly until the animals were killed after 2 and 4 weeks. Healing was evaluated using radiographs, biomechanical testing, and histological examination. All radiographs were examined by two independent observers. Interobserver agreement was calculated and radiographic scores were compared with mechanical and histological scores using regression analysis. Results. Regression analysis showed poor correlation between radiogra-phic scores and biomechanical and histological data. Correlation coefficients varied between 0.39 and 0.63. Good agreement between the obser-vers was seen in only three parameters: visibility of the fracture line, weightbearing ability, and a combined healing parameter. Conclusion. Plain radiography provides poor parameters for monitoring the fracture healing process.

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

Fracture healing could be stimulated with osteoinductive bone morphogenetic proteins (bmps), 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.

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.

Reaming debris in osteotomized sheep tibiae.

BACKGROUND Reamed nailing gives better fracture healing than unreamed nailing in operative treatment of fractures and nonunions. This study investigates the effect of isolated reaming debris on fracture healing in an animal model. METHODS Thirty sheep were treated with an osteotomy of the tibia with 5-mm distraction. In one group, the osteotomy gap was left empty; in the second group, the gap was packed with reaming debris from the ipsilateral femur; and in the third group, the gap was packed with cancellous bone from the iliac crest. At follow-up, callus volume was measured on standard radiographs. RESULTS After 3 weeks, callus volume from the reaming debris group as well as the iliac crest group had increased significantly compared with the empty group. CONCLUSION This study shows that isolated reaming debris supports callus building as much as conventional bone grafting, which might explain why fractures heal with more callus formation when treated with reamed nailing compared with unreamed nailing.

Randomized clinical trial comparing the effect of computed tomography in the trauma room versus the radiology department on injury outcomes

Computed tomography (CT) of injured patients in the radiology department requires potentially dangerous and time‐consuming patient transports and transfers. It was hypothesized that CT in the trauma room would improve patient outcome and workflow.

Internet-Based Early Intervention to Prevent Posttraumatic Stress Disorder in Injury Patients: Randomized Controlled Trial

Background Posttraumatic stress disorder (PTSD) develops in 10-20% of injury patients. We developed a novel, self-guided Internet-based intervention (called Trauma TIPS) based on techniques from cognitive behavioral therapy (CBT) to prevent the onset of PTSD symptoms. Objective To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients. Methods Adult, level 1 trauma center patients were randomly assigned to receive the fully automated Trauma TIPS Internet intervention (n=151) or to receive no early intervention (n=149). Trauma TIPS consisted of psychoeducation, in vivo exposure, and stress management techniques. Both groups were free to use care as usual (nonprotocolized talks with hospital staff). PTSD symptom severity was assessed at 1, 3, 6, and 12 months post injury with a clinical interview (Clinician-Administered PTSD Scale) by blinded trained interviewers and self-report instrument (Impact of Event Scale—Revised). Secondary outcomes were acute anxiety and arousal (assessed online), self-reported depressive and anxiety symptoms (Hospital Anxiety and Depression Scale), and mental health care utilization. Intervention usage was documented. Results The mean number of intervention logins was 1.7, SD 2.5, median 1, interquartile range (IQR) 1-2. Thirty-four patients in the intervention group did not log in (22.5%), 63 (41.7%) logged in once, and 54 (35.8%) logged in multiple times (mean 3.6, SD 3.5, median 3, IQR 2-4). On clinician-assessed and self-reported PTSD symptoms, both the intervention and control group showed a significant decrease over time (P<.001) without significant differences in trend. PTSD at 12 months was diagnosed in 4.7% of controls and 4.4% of intervention group patients. There were no group differences on anxiety or depressive symptoms over time. Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms (n=20) (P<.001). Conclusions Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients. Moreover, uptake was relatively low since one-fifth of individuals did not log in to the intervention. Future research should therefore focus on innovative strategies to increase intervention usage, for example, adding gameplay, embedding it in a blended care context, and targeting high-risk individuals who are more likely to benefit from the intervention. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 57754429; http://www.controlled-trials.com/ISRCTN57754429 (Archived by WebCite at http://webcitation.org/6FeJtJJyD).

Resorbable calcium phosphate particles as a carrier material for bone marrow in an ovine segmental defect

Resorbable calcium phosphate ceramics are only osteoconductive; therefore, their combination with osteogenic substances may lead to stimulation of bone healing. In the present study this combination, using autologous bone marrow, was investigated. In 31 sheep, a 3-cm tibial segmental defect was created and stabilized with an intramedullary nail. The animals were divided into four groups: empty defects (group 1, n = 7), and defects filled with 10-mL dense resorbable calcium phosphate particles (group 2, n = 8), with 10-mL particles soaked in bone marrow (group 3, n = 8), or with 10-mL autologous bone (group 4, n = 8). On evaluation after 12 weeks, significantly higher values were seen in group 3 than in group 2 for callus volume (p = .016), bone mineral density ratio (p = .03), bone mineral content ratio (p = .04), torsional strength (p = .005), and torsional stiffness (p = .01). For all end points, the outcome of group 3 was lower than that of group 4. In the histology, there was direct contact between newly formed bone and remnants of the particles. There were no signs of inflammatory reactions. Although a stimulatory effect of bone marrow was seen, the combination of resorbable calcium phosphate particles with bone marrow does not provide an alternative for autologous bone grafting.