Ashley R. Poynton

Safety profile for the clinical use of bone morphogenetic proteins in the spine.

Study Design. A review was conducted. Objective. To determine the safety profiles of human recombinant bone morphogenetic protein-2 (rhBMP-2) and osteogenic protein-1 (OP-1) used clinically in spine applications. Summary of Background Data. Safety issues associated with the use of bone morphogenetic proteins in spine applications include the possibility of bony overgrowth, interaction with exposed dura, cancer risk, systemic toxicity, reproductive toxicity, immunogenicity, local toxicity, osteoclastic activation, and effects on distal organs. These issues have been given detailed examination in both human and animal studies, and safety data are available for both rhBMP-2 and OP-1. The safety data available for OP-1 are less detailed. Methods. The study involved reviews of published reports and the safety data submitted to the Food and Drug Administration (rhBMP-2 and OP-1) and to the European Agency for the Evaluation of Medicinal Products (OP-1), as well as personal communication with the manufacturers of rhBMP-2 (Medtronic Sofamore Danek, Memphis, TN) and OP-1 (Stryker Biotech, Hopkinton, MA). Results. Application of either rhBMP-2 or OP-1 to raw decorticated bony surfaces leads to new bone formation, which is desirable in the intertransverse or interbody regions. However, new bone formation also may occur if rhBMP-2 or OP-1 comes in contact with laminectomy sites or decompressed neuroforamina, and may lead to restenosis. Inadvertent placement of either rhBMP-2 or OP-1 in the spinal canal leads to formation of bone. Leakage of rhBMP-2 or OP-1 outside the fusion area may lead to adjacent-level fusion. Accurate placement of these factors and adequate retention by their carrier are highly important factors in minimizing these problems. Subdural bone formation occurs if OP-1 is implanted directly beneath the dura. Osteoclastic overstimulation does not appear to be a significant problem with rhBMP-2. However, bone resorption has been associated with OP-1 used in the setting of thoracolumbar fractures. Findings show that RhBMP-2 has an antiproliferative effect on many cancer cells, and no evidence exists that it is carcinogenic. It is unlikely that OP-1 has carcinogenic potential, although fewer data are available. Systemic and local toxicity, significant adverse effects, and harmful effects on distant organs have not been observed in either human or animal studies on rhBMP-2 and OP-1. The benign safety profile of rhBMP-2 may result from its rapid systemic clearance, which results in very little systemic exposure. Systemic exposure to OP-1 also is low. No reproductive toxicity has been observed with either rhBMP-2 or OP-1. However, there is no human safety data. Subclinical immune responses in human subjects to collagen carriers have been reported. Antibody responses to rhBMP-2 have been detected in less than 1% of spine patients. Low titer immune responses have been observed in 38% of patients treated with OP-1. There were no associated clinical adverse effects. Conclusions. Given the available data, both rhBMP-2 and OP-1 appear to be safe provided they are used appropriately, placed accurately, not allowed to come into contact with decompressed areas, and contained in the region of fusion. They must be used with caution in the presence of dural defects.

Kyphoplasty enhances function and structural alignment in multiple myeloma.

We prospectively evaluated 19 patients with multiple myeloma who had kyphoplasty for vertebral compression fractures. Functional status was assessed preoperatively and 3 months postoperatively using the Oswestry Disability Index. Restoration of anterior and midvertebral height was assessed using lateral radiographs. Meaningful improvement occurred in 16 of 19 patients, with a reduction of the average Oswestry Disability Index from 49 ± 16.6 to 32.6 ± 13.6. Partial restoration of anterior vertebral body height was achieved in 76% of levels with an average of 37.8% restoration of the defect. Partial restoration of midvertebral body height was achieved in 91% of levels with an average restoration of 53.4% of the defect. There were no significant complications. These results were compared with results of a cohort of 26 patients with osteoporotic compression fractures treated with kyphoplasty at 37 levels. There was no difference between the groups in terms of Oswestry Disability Index improvement and midvertebral height restoration after 3 months. Greater anterior vertebral height restoration was achieved in the osteoporotic group (51.2% versus 37.8%). Kyphoplasty is a safe treatment modality for myeloma-related vertebral compression fractures. Efficacy in terms of pain relief and functional outcome is comparable with the results in patients with osteoporosis.

Thromboembolic Disease After Combined Anterior/Posterior Reconstruction for Adult Spinal Deformity : A Prospective Cohort Study Using Magnetic Resonance Venography

Study Design. Thromboembolic disease (TED) after anterior/posterior spinal reconstructions was prospectively evaluated in 66 consecutive patients. Objective. Determine the incidence of TED after anterior/posterior spinal reconstruction. Summary of Background Data. Few studies have examined the rate of TED after potentially high-risk combined anterior/posterior reconstructions. Magnetic resonance venography (MRV) is more effective at detecting pelvic deep venous thrombosis (DVT) than conventional screening, but has not been used in these patients. Methods. We undertook a prospective cohort study of 66 consecutive adult patients (mean, 52.7 ± 9.6 years) undergoing combined anterior/posterior spinal reconstructions for spinal deformity. All patients received only mechanical DVT prophylaxis. After surgery, MRV and bilateral lower extremity Doppler ultrasounds were obtained to screen for DVT, and contrast-enhanced spiral computed tomography scans were obtained for clinical suspicion of pulmonary embolism (PE). Results. The total incidence of postoperative TED was 13.6% (9 patients). The overall rate of DVT was 9.1% (6 patients), one-third occurring in the pelvis. PE developed in 7.6% (5 patients). In 2 patients, PE developed less than 48 hours after positive dopplers. In 3 patients, PE developed despite negative screening studies. Right-sided thoracoabdominal approaches were associated with an increased risk of developing DVT (P = 0.03, Odds Ratio 9.8), PE (P = 0.01, Odds Ratio 20), and TED (P = 0.004, Odds Ratio 12). Conclusion. We report a high rate of TED after extensive anterior/posterior spinal reconstructions, for which a right-sided thoracoabdominal approach is an independent risk factor and screening ineffective at preventing PE. These patients should be considered at high risk for postoperative TED.

Bovine thrombin induces an acquired coagulopathy in sensitized patients undergoing revision spinal surgery: a report of two cases.

Study Design. A report of two cases is presented. Objective. To raise awareness of bovine thrombin-induced factor V deficiency. Summary of Background Data. Bovine thrombin is a frequently used hemostatic agent in spinal surgery. Current preparations contain clotting factors in addition to thrombin, particularly factor V, which are immunogenic. Re-exposure of sensitized patients to bovine thrombin products during subsequent surgery may lead to the formation of antibodies that cross-react with human clotting factors, most commonly against factor V. Hemorrhagic complications have been reported in nonspinal patients due to a bovine thrombin-induced factor V deficiency. Methods. Two spinal cases are reported, and the literature is reviewed. Results. In the cases outlined, both patients underwent revision spinal surgery, with re-exposure to bovine thrombin. Both patients developed abnormal coagulation profiles, with an acquired factor V deficiency. No hemorrhagic complications occurred; however, second-stage surgery was delayed in one patient and not undertaken in the other. In both patients, the coagulopathy resolved spontaneously. Conclusions. Bovine thrombin-induced coagulopathy is well recognized in cardiac surgery but has not been reported in spinal surgical patients. Data available from cardiac surgical patients suggests that those who are sensitized to two or more bovine clotting factors are at greatest risk of hemorrhagic complications. The cases we present demonstrate that this phenomenon occurs in spinal surgical patients and serve to raise awareness of the potential danger of bovine thrombin in sensitized patients.

The Natural History and Clinical Syndromes of Degenerative Cervical Spondylosis

Cervical spondylosis is a broad term which describes the age related chronic disc degeneration, which can also affect the cervical vertebrae, the facet and other joints and their associated soft tissue supports. Evidence of spondylitic change is frequently found in many asymptomatic adults. Radiculopathy is a result of intervertebral foramina narrowing. Narrowing of the spinal canal can result in spinal cord compression, ultimately resulting in cervical spondylosis myelopathy. This review article examines the current literature in relation to the cervical spondylosis and describes the three clinical syndromes of axial neck pain, cervical radiculopathy and cervical myelopathy

Nonoperative Modalities to Treat Symptomatic Cervical Spondylosis

Cervical spondylosis is a common and disabling condition. It is generally felt that the initial management should be nonoperative, and these modalities include physiotherapy, analgesia and selective nerve root injections. Surgery should be reserved for moderate to severe myelopathy patients who have failed a period of conservative treatment and patients whose symptoms are not adequately controlled by nonoperative means. A review of the literature supporting various modalities of conservative management is presented, and it is concluded that although effective, nonoperative treatment is labour intensive, requiring regular review and careful selection of medications and physical therapy on a case by case basis.

Orthopedic management of vertebral and long bone fractures in patients with osteoporosis

Because of the evolving demographics of the worlds population, fracture surgeons must become experts in the treatment of fractures in osteoporotic bone. Toward this end, fracture surgeons are learning to modify the classic techniques of internal fixation to adapt them to the elderly population. Screws should be placed into the best quality of bone available, which, in most cases, is an opposing cortex. Screw fixation can be augmented using acrylic cement. When using plate fixation, stable bone contact at the fracture site is the most important factor in reducing strain in the plate. Shortening of the affected bone is advisable to achieve this contact in comminuted fractures. Plates should not be used to bridge areas of comminution in osteoporotic bone. Plates should generally be as long as is compatible with the affected bone, with screws placed as close to and as far away from the fracture site as possible. When confronted with diaphyseal fractures or fractures with metaphyseal-diaphyseal comminution, locked intramedullary nails can be used. Angled blade plates are applicable to osteoporotic metaphyseal fractures but should be used as tension band plates, which require stable load-sharing contact opposite the plate. Antiglide plating and use of tension band wires are also effective strategies for osteoporotic fractures. Finally, to reduce the morbidity of bone graft harvest and to ensure adequate volumes of graft, the use of bone graft substitutes is particularly applicable in elderly patients. All patients with evidence of osteoporosis should be started on a medical regimen to combat further bone loss that includes calcium supplementation with a prescription for antiresorptive agents, including bisphosphonates, calcitonin, or hormone replacement therapy.

Degenerative Cervical Spondylosis: Natural History, Pathogenesis, and Current Management Strategies

Degenerative cervical spondylosis is a common, mostly asymptomatic condition, occurring as a result of age-related degenerative changes in the cervical spine. Symptoms caused by cervical spondylosis can be categorized broadly into three clinical syndromes: axial neck pain, cervical radiculopathy, and cervical myelopathy; with patients commonly having a combination of these syndromes. This special issue contains eleven papers summarizing our present knowledge and understanding of the natural history, pathogenesis, and current management strategies for degenerative cervical spondylosis.

The Evaluation of the Inverted Supinator Reflex in Asymptomatic Patients

Study Design. A prospective study was undertaken over a 6-month period to determine the incidence of the inverted supinator reflex in asymptomatic, neurologically normal individuals. Objective. The objective of our study is to assess asymptomatic patients for the presence of the inverted radial reflex and to determine its clinical relevance. Summary of Background Data. The inverted radial reflex sign is commonly used in clinical practice to assess cervical myelopathy. It is unknown whether the sign correlates with the presence or severity of myelopathy, and no consensus exists regarding the significance of a positive sign in asymptomatic individuals. Methods. Patients attending the Trauma Clinic at our institution were invited to participate. Each patient was examined neurologically and specifically for the presence or absence of the Babinski test, Hoffmans sign, the finger escape sign, static and dynamic Rombergs test, and the inverted supinator reflex. Patients were excluded if they had any history of neck pain, any history of neurosurgical procedure or spinal surgery, any known neurologic disorder or deficit, or if there was any outstanding medicolegal case. Results. We examined 277 patients in 6-month period. The male to female ratio was 1.1:1. The mean age was 27 years (range, 16–78). The incidence of the inverted supinator reflex was 27.6% (75/271). Of the 75 positive patients, the inverted supinator reflex was present bilaterally in 39% (29/75). Nine of 75 patients (10%) had an associated positive Hoffmans sign but had no other signs suggestive of myelopathy. The proportion of patients with a positive inverted supinator reflex reduced with increasing age (Pearson correlation coefficient > 0.80). Conclusion. This study demonstrates that an isolated, inverted supinator reflex may be a variation of normal clinical examination. We believe that an isolated inverted supinator reflex, in the absence of other clinical findings, is not a reliable sign of cervical myelopathy; however, it must be interpreted with caution in the older patient.

Imaging modalities for cervical spondylotic stenosis and myelopathy.

Cervical spondylosis is a spectrum of pathology presenting as neck pain, radiculopathy, and myelopathy or all in combination. Diagnostic imaging is essential to diagnosis and preoperative planning. We discuss the modalities of imaging in common practice. We examine the use of imaging to differentiate among central, subarticular, and lateral stenosis and in the assessment of myelopathy.