In September 2005, a multidisciplinary meeting took place in Nice, France, to discuss the current needs for skeletal intervention (SI), under the auspices of CIRSE and SIR societies. Professor Kieran Murphy, Johns Hopkins Hospital, Baltimore, MD, was the driving force behind this project, and this article seeks to outline the proceedings from the meeting, which will be published later in 2007.
A panel comprised of experts was put together by the Cooperative Alliance for Interventional Radiology Research (CAIRR), the clinical trials network of the Society of Interventional Radiology Foundation, in partnership with the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) Foundation. The rationale for the meeting was to establish a prioritised research agenda for SI that includes basic science and technology research, pilot clinical studies, and pivotal clinical trials.
Chaired by Drs Kieran Murphy and Dimitrios A Kelekis (Eugendion University Hospital, Athens, Greece), a skeletal intervention research consensus panel (SI RCP) was created from a list of leading scientists developed by the SI RCP Chair, CAIRR Advisory Council, and the CIRSE Foundation Board of Directors. The Panel included members from interventional radiology (six), orthopaedics (three), internal medicine (one), and physics (one).
The meeting was structured into four parts per standard CAIRR RCP process:
1) introductory presentations;
2) moderated roundtable Panel discussion with comments from industry and governmental representatives;
3) research topic prioritisation; and
4) preliminary clinical research protocol development.
Oral presentations provided a summary of the previously reported outcomes from research involving skeletal intervention therapies. These presentations included findings of epidemiology of osteoporosis, bone architecture: implications for intervention, medical therapy of osteoporosis, kyphoplasty, vertebroplasty, percutaneous disc interventions, skeletal pain management, ablative and other therapies for skeletal malignancy, and skeletal imaging.
According to researchers, there is a growing body of clinical evidence from 17 years of experience that vertebroplasty and kyphoplasty procedures are effective treatments. However, there are weaknesses in the peer reviewed vertebroplasty and kyphoplasty scientific literature, and currently there are only a few studies that achieve level one evidence by Cochrane review/analysis. These gaps in the scientific literature have brought into question the efficacy and benefit of minimally invasive skeletal intervention procedures.
Data collection and analysis
Throughout the meeting, the Panelist's comments were recorded into a list of proposed SI research topics, and each Panel member and industry attendee prioritised the topics from each composite list with a scoring system used in previous CAIRR RCPs.
Panel presentations
During the meeting, select panel members were asked to present on empirical research in their area of expertise. These presentations aimed to educate all panel and audience members on the most vital topics facing SI research, and to create dialogue among the panelists.
Vertebroplasty and kyphoplasty
It was discussed that future studies and registries involving vertebroplasty and kyphoplasty should provide more data that may help answer many important questions that are still outstanding. Physicians ultimately need to know when to use these techniques, as current indications and exact mechanisms are not clearly defined.
Further scientific evidence is also needed to identify how much restoration of strength and shape of the vertebrae is needed. This is because there appears to be an increased risk of adjacent fractures when bone elasticity is lowered.
Other points up for discussion concerned the long-term effects of percutaneous olymethylmethacrylate (PMMA) on the surrounding bone architecture. It was suggested that performing a clinical trial using the absolute minimum injection of 1-2mL to study lowest effective volume to decrease complications might serve as an adequate alternative to the current 8mL treatment standard. It was recommended that a long-term prospective randomised trial medical/vertebroplasty/kyphoplasty study is needed, although it was acknowledged that this may be difficult to achieve due to low study enrollment.
Percutaneous disc interventions
The Panel then addressed the issue of disc interventions. It was noted that studies have revealed the importance of defining which type of percutaneous technique should be used according to specific indications. According to the Cochrane systematic review of the treatment of lumbar disc herniation, there is moderate evidence demonstrating that automated percutaneous discectomy produces poorer clinical outcomes than standard discectomy or chymopapain.
Skeletal pain management
In addressing skeletal pain management, a study conducted at the Johns Hopkins hospital was discussed. An evaluation of 205 consecutive percutaneous vertebroplasty procedures found that 44% of patients had a complete improvement of pain, 46% reported significant pain improvement, 5% reported minimal improvement, 5% reported that their pain level was unchanged, and no patients reported increased pain after undergoing a percutaneous vertebroplasty procedure. The patient pool included 86% who were osteoporotic, and 12% who were neoplastic. Parameters of the study excluded prospective patients who had coagulopathy or an infection, but did not place limits on age, height or elapsed time from the fracture. Patients included in the study did have to exhibit pain resistance to medical management.
Epidemiology and medical therapy of osteoporosis
A recent study of 1,407 residents from Rancho Bernardo, CA, aimed to obtain epidemiological data for prevalence of osteoarthritis disease of the spine in the general population as well as for prevalence/incidence of non-traumatic vertebral fractures. The middle class study population, comprised of ambulatory Caucasian adults, aged 50-96 years old, had their radiographs of the lateral thoracic and lumbar spine read and scored. The radiographs were scored for: vertebral fractures using Genant method, osteophy and disc space narrowing, aortic calcification, and diffusion of idiopathic skeletal hyperostosis (DISH). It was found that no major complications occurred during the study, and none of the three minor complications were related to cement leakage. In summary, the positive outcomes in this study provide additional evidence that percutaneous vertebroplasty may performed safely without prior angiographic evaluation of the vertebral venous system.
Skeletal imaging
Moving to skeletal imaging, a study of visual assessment of vertebral fracture using lateral dual X-ray absorptiometry scan found that vertebral fracture assessment (VFA) was discussed that showed good sensitivity (>80%) in identifying moderate/severe deformities and excellent negative predictive value (>90%) in distinguishing subjects without from those with vertebral deformities on a per subject basis. Subjects included 80 postmenopausal women (28 osteoporotic, 40 osteopenic), aged 61 to 84 years. A comparison of VFA results to radiography found that of 987 non-fractured vertebral bodies evaluated by lateral vertebral assessment (LVA), the densitometrists correctly identified 960 as normal. Only 2.8% were incorrectly classified as fractured. All but one (94%) of grade 2 or 3 fractures were correctly identified using LVA. Of 22 grade 1 compression fractures present in evaluable vertebral bodies, 11 were detected by LVA. It was surmised that through continued research, this type of assessment may further exhibit its benefits in the clinical evaluation of patients at risk of osteoporosis, or during the clinical study patient selection period.
Ablative and other therapies for skeletal malignancy
Interventional oncology is an emerging field and when percutaneous procedures are elected to eliminate spinal tumours, interventional radiologists can choose among available therapeutic modalities, which are classified in three categories: cementoplasty, radiofrequency (RF) ablation, and cementoplasty combined with RF ablation. For spinal and acetabular metastases, cementoplasty is the preferred technique. In case of large invasion of soft tissue surrounding the vertebral body, or acetabulum, RF ablation can be combined with vertebroplasty. According to many studies, RF ablation is an excellent alternative to painful osteolytic bone metastases, in part because single or few localisations are required during the procedure. In addition, RF ablation is able to produce a much more predictable lesion than alcohol. While RF ablation can be an effective treatment, it does not come without limitations. The monopolar technique is contraindicated if the lesion is too close to neurological structures or sensitive organs, such as the colon or intestine. In these cases, the bipolar technique can be used for a precise limitation of the coagulation.
Discussion
During the Panel discussion, there was considerable interest in vertebroplasty, kyphoplasty, disease information and the development and utility of outcome databases. Specifically, there was consensus that comparisons between the benefits and maladies associated with vertebroplasty and kyphoplasty should be documented through a data collection registry. Developing a central databank where researchers are able to submit their outcomes would be of benefit to the field of spinal intervention through data analysis and dissemination of best practices. Additionally, large quantities of data on vertebroplasty and kyphoplasty therapies could be used to develop inclusion criteria and comment on the current state of outcomes assessment.
Discussion also focused on additional benefits of informatics, including the possibility of marketing an established database and its findings to both industry and insurance companies. Primarily, a large database of qualitative and quantitative information regarding spinal intervention outcomes would enable physicians, particularly those who are at smaller practices and do not have the benefit of a robust research institution, to easily reference best practices when faced with the predicament of deciding on the best course of treatment for patients with specific symptoms.
The Panel discussed future research considerations to provide a framework to stimulate growth is areas including further critical research discussions and protocol development to address some of the SI researched questions identified by the RCP, and engaging the FDA and NIH in funding and study design related to clinical studies.
It was also revealed that the Panel considers a prospective randomised study of intervention versus medical management for osteoporotic compression fracture, with crossover to intervention for those who fail medical therapy, to represent the most important clinical SI research priority.
The proceedings from the SI meeting will be published later this year.
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