Percutaneous Kyphoplasty For Vertebral Fractures Caused By Osteoporosis And Malignancy

Back pain and related problems have substantial public health impact within the Medicare population each year, including discomfort, loss of mobility, and serious morbidity. CMS has identified this important issue for long-term examination. Disease conditions interest include disc degeneration, spinal stenosis, spondylolisthesis, and vertebral compression fractures.

Vertebral body compression fractures of the spine are among the most common fracture types in patients who have osteoporosis. Compression fractures of the spine are also caused by osteolytic destruction, secondary to malignancy. Pain and loss of function are the most common symptoms.

Percutaneous vertebroplasty is a minimally invasive treatment that inserts bone cement into the compressed and fractured vertebrae to provide mechanical stabilization. Kyphoplasty is a variation of vertebroplasty. Kyphoplasty uses an inflatable balloon to expand the compressed vertebral body, in an attempt to restore its natural height before injecting a cement-like substance into the vertebral cavity.

As an initial step, CMS will review the scientific evidence on the effectiveness of surgical management of vertebral compression fractures, particularly vertebroplasty and kyphoplasty procedures, in the Medicare population. We will refer this issue to the Medicare Coverage Advisory Committee (MCAC). Committee members will be given presentations on the current literature and also receive public comments to aid in the discussions and recommendations regarding the quality of the evidence on verterbroplasty and kyphoplasty procedures.

We expect to hold additional future meetings of the Medicare Coverage Advisory Committee regarding other back pain treatments and will post future notices in the Federal Register.

DRAFT

PERCUTANEOUS KYPHOPLASTY FOR VERTEBRAL FRACTURES CAUSED BY OSTEOPOROSIS AND MALIGNANCY

ASSESSMENT OBJECTIVE

This Assessment evaluates the available evidence to determine whether kyphoplasty (KP) is demonstrated to be an effective treatment. This procedure uses a specialized bone tamp with an inflatable balloon to expand a collapsed vertebral body as close as possible to its natural height before introducing the mechanical fixation by injecting bone cement into the expanded cavity. The primary uses reported in the literature include: (1) osteoporotic vertebral compression fracture and (2) vertebral fractures caused by osteolytic destruction secondary to malignancy. Beneficial effects of interest would include relief of associated symptoms (e.g., pain) as well as improvement in ability to function (e.g., mobility and activities of daily living). Adverse effects would include complications associated with kyphoplasty.

BACKGROUND

Osteoporotic Vertebral Compression Fracture

Vertebral fractures are among the most common fractures in patients who have osteoporosis (Ross 1997). It is estimated that up to 50% of women and approximately 25% of men will have a vertebral fracture at some point in their lives. Multiple vertebral fractures may be expected in about half of these cases (Ross 1997). While the incidence of vertebral fracture is high, the minority of vertebral fractures (about one-third) actually reaches clinical diagnosis (Ross 1997).

Acute vertebral fracture may present with pain, although clinically silent fractures may account for one-half of all radiographically visible vertebral fractures (Ross 1997). Pain management in the acute setting is not standardized. Common management strategies include bed rest, activity modification, and local and/or systemic analgesics. Calcitonin has also been suggested to reduce pain in the acute setting. Postural bracing of the spine is another option, but this has not been reported recently in the literature (Lin and Lane 2002).

Chronic pain, usually following multiple vertebral fractures, does not tend to respond to the management strategies described for acute pain. The source of chronic pain after vertebral compression fracture is not thought to be the vertebrae itself but is believed to relate predominantly to strain on muscles and ligaments secondary to kyphosis. This type of pain frequently is not improved with analgesics and may be better addressed through exercise (Ross 1997).

Vertebral Metastasis/Multiple Myeloma Lesions

Metastatic disease involving the spine generally involves the vertebral bodies with pain being the most frequent complaint (Healey 1997). Pain may be caused by any number of factors such as intraosseous tumor, vertebral fracture with associated segment instability, or extraosseous tumor producing spinal or nerve root compression. Such compression may also cause neurologic dysfunction.

Prognosis in patients with vertebral metastasis is variable and relates to a number of factors such as the patient’s underlying functional status and primary tumor, as well as anatomic location of the metastasis. Restored ambulation has been associated with increased survival (Healey 1997).

Palliative treatment options include radiation therapy, chemotherapy, and/or surgical resection with fixation for stabilization. The pain associated with metastasis alone is usually quite responsive to radiation therapy. The pain due to fractures caused by osteolytic destruction due to the metastases are often more difficult to manage. External bracing devices may be used as well; however, long-term use may be difficult for patients. Nonsurgical intervention may be preferable in patients with limited expected survival and poor functional status.

While radiation and chemotherapy are frequently effective in reducing tumor burden and associated symptoms, pain relief may be delayed days to weeks depending on tumor response and the presence of fracture. Further these approaches rely on bone remodeling to regain vertebral body strength, which may necessitate supportive bracing to minimize the risk of vertebral collapse during healing.

Percutaneous Approaches to Treating Vertebral Fractures

Percutaneous vertebroplasty (PVP) is a minimally invasive treatment involving percutaneous needle injection of bone cement into a diseased vertebral body. The procedure was first reported by investigators from France in 1987 as a treatment for complicated vertebral body hemangioma (Galibert et al. 1987). Since that time, the PVP technique has been further investigated, both within the U.S. and in Europe, as a treatment option to provide mechanical support and symptomatic relief in other conditions involving fractures due to osteolytic destruction of the spine. Osteolytic destruction of one or more vertebral bodies may be caused by a variety of conditions. However, osteoporosis, vertebral metastasis, and vertebral involvement by multiple myeloma are the most commonly reported uses of PVP in the literature. Other reported uses for PVP include treatment for symptomatic or aggressive vertebral hemangiomas, Langerhans cell histiocytosis (also known as eosinophilic granuloma) or vertebral lymphoma (Cardon et al. 1994, Martin et al. 1999).

PVP may provide an analgesic effect through mechanical stabilization of a fractured or otherwise weakened vertebral body (Deramond et al. 1998). Thermal damage to intraosseous nerve fibers is another possible mechanism of effect, since the cement used in the procedure, polymethyl methacrylate (PMMA), undergoes a heat-releasing (exothermic) reaction when it hardens. One study performed PVP injections in cadaveric vertebrae and measured resultant in vitro temperature changes (Deramond 1999). The results of this study indicate a possible role of thermal necrosis as an explanation for the pain relief observed after PVP. However, differences between in vivo conditions and the cadaveric study conditions preclude definitive conclusions. Chemical or vascular effects have also been discussed (Cotten and Duquesnoy 1997), but at present the mechanism of analgesic effect is not well understood.

PVP involves injection of a cement-like substance, most commonly PMMA, into a diseased vertebral body. PMMA is made radiopaque by the addition of barium sulfate powder and tantalum powder. The injection is performed by introducing a needle (usually 10–15 gauge, depending on the spinal level) through a transpedicular or paravertebral approach into the vertebral body. Either fluoroscopic or computed tomographic (CT) guidance is used to guide needle placement.

Kyphoplasty

Kyphoplasty is a relatively recent variation of PVP. This procedure uses a specialized bone tamp with an inflatable balloon to expand a collapsed vertebral body as close as possible to its natural height. The vertebral body then undergoes mechanical fixation by injecting PMMA into the expanded cavity. The expansion of a cavity by the balloon tamp permits infusion of PMMA into the cavity under lower pressure than PMMA injection during PVP; however, PMMA leakage can still occur outside the vertebral cavity (Garfin et al. 2001). Kyphoplasty can be performed under general or local anesthesia with conscious sedation. The procedure requires more time than PVP.

The reduction of kyphotic deformity of the spine that KP provides is postulated to provide additional health benefits. Kyphotic deformity can interfere with pulmonary function via loss in lung volume and may lead to early satiety and abdominal compression, though such impairments may not occur until kyphosis becomes severe (Ingram and Braunwald 2001; Ross 1997).

Complications of Kyphoplasty. Adverse effects of kyphoplasty include localized bleeding, infection, and/or resultant pain or neurological symptoms following leakage of injected material. Injected material may also leak into the systemic venous system with the potential for pulmonary embolism. In addition, complications from patient positioning and anesthesia for the procedure may include rib fracture, systemic infection, or even death.

Most case reports of complications due to cement leakage have been reported in conjunction with PVP rather than kyphoplasty. Case reports of major neurological complications have been reported following PMMA leakage into the surrounding neurological structures (Harrington 2001; Wenger and Markwalder 2002; Ratliff et al. 2001; Wilkes et al. 1994), although some of these complications resolved after surgical removal of PMMA.

Concern has also been raised about possible increases in fractures in the vertebral bodies adjacent to where kyphoplasty has been recently performed (Fribourg et al. 2004).

FDA Status

Kyphoplasty is a surgical procedure and, as such, is not subject to U.S. Food and Drug Administration (FDA) approval.

Kyphoplasty requires the use of an inflatable bone tamp. One such tamp, the KyphX® inflatable bone tamp, received 510(k) marketing clearance from the FDA in July 1998.

Polymethyl methacrylate (PMMA) bone cement was available as a drug product prior to enactment of the FDA’s device regulation and was at first considered what the FDA terms a “transitional device.” It was transitioned to a class III device requiring premarketing applications. Several orthopedic companies have received approval of their bone cement products for purposes other than vertebroplasty or kyphoplasty since 1976. On October 1999, PMMA was reclassified from class III to class II which requires future 510(k) submissions to meet “special controls” instead of “general controls” to assure safety and effectiveness. FDA issued a guidance document on July 17, 2002 (accessed September 6, 2002 at http://www.fda.gov/cdrh/ode/guidance/668.pdf) that outlines the types of special controls required and describes the following recommended labeling information:

Kyphon, Inc. has received 510(k) clearance for their bone cement product to be used for vertebroplasty and kyphoplasty as of April 1, 2004. Continuing concern about other cement and bone void filling products led to an FDA Public Health Web Notification that notes the types of complications that can occur with these products, and offers advice to physicians regarding use of such products. FDA requires hospitals and facilities to report deaths and serious injuries associated with the use of such medical devices (U.S. Food and Drug Administration 2004). Use of cement products not receiving FDA clearance specifically for vertebroplasty represents an off-label use.

METHODS

Search Methods

Studies of kyphoplasty were identified through a computerized online search of the MEDLINE (via PubMed) database through April 15, 2005, using various textwords, including: "kyphoplast*"; "cementoplast*"; and "methylmethacrylate" combined with ("vertebral" OR "spinal"). To identify more recent studies, the MEDLINE search was supplemented by searches of Current Contents, by manual searches of the most recent issues of the pertinent journals, and by reading the reference lists in the most recently published papers.

Study Selection

Studies were included in the Assessment "Review of Evidence" if the study had these characteristics:

• Full-length article published in the English language
• Population consists of patients with vertebral fractures due to osteoporosis or malignancy
• Patient population is a consecutive series of patients, or near-consecutive series ( ≤90%)
• Treatment uses kyphoplasty
• Reports on relevant clinical outcomes of pain, functional status, or quality of life
• Pre- and post-procedure values for outcomes are reported, as quantitative or categorical measures
• Sample size is ≤20 patients for studies on osteoporosis; ≤10 for malignancy

Abstracts were not systematically included in the study selection process, and results of case series reported in abstract form only are not included in the review. One nonrandomized, comparative trial published in German was brought to our attention by a reviewer, and this study was translated and included in the Assessment. An unpublished systematic review prepared by Kyphon was also reviewed. The studies cited in the Kyphon systematic review were all case series; no comparative studies were included. The studies overlapped with those cited in this Assessment, but were slightly different, as different selection criteria were used. Overall, however, this review did not add new evidence and would not change the conclusion of this Assessment.

FORMULATION OF THE ASSESSMENT

Patient Indications

1. Patients who have painful vertebral body compression fracture(s) associated with osteoporosis. This indication does not include patients with evidence of spinal cord compression or compromise. Clinical history and appropriate use of imaging tests, which may include MRI, should be used to exclude other causes of back pain and to locate the vertebral bone that is causing the pain. The fracture must be anatomically suited for the procedure.
2. Patients who have painful vertebral fractures associated with osteolytic destruction from malignant disease (e.g., bone metastasis). This indication does not include patients with evidence of spinal cord compression or compromise.

Technologies to Be Compared

Patient Indication #1. For these patients, the usual comparator is continued medical management. The initial treatment for osteoporotic vertebral body compression fractures includes conservative measures such as bed rest, use of an immobilization/bracing device, and analgesic medication, sometimes including narcotic analgesics. Second-line treatment alternatives in this setting are not well established and may include exercise, continued conservative treatment, or other methods of pain relief. Vertebroplasty is also an alternative procedure.

Patient Indication #2. These patients seek palliation from pain. Because these patients have limited remaining life span and may have poor health due to the underlying malignant disease, treatment choices are complex. Osteolytic vertebral body destruction may result in pain and/or instability with the potential for neurological compromise from tumor growth and vertebral collapse. Patients may simply be medically managed. Destructive lesions due to malignancy may be treated with local radiation therapy to shrink the tumor and relieve pain. The effectiveness of radiation therapy in reducing pain may be delayed several days to weeks and some tumors may not be radiation sensitive. In addition, prior radiation therapy in that same spinal location may contraindicate further radiation therapy due to dose limitations. For patients with local spinal instability from extensive destruction, surgical stabilization may be an option; however, patients with extensive malignancy may not be considered suitable candidates for aggressive surgical intervention. Vertebroplasty is also a treatment alternative.

Health Outcomes

Patient Indication #1. The primary health outcomes of interest include pain and ability to function particularly with regard to activities of daily living. Beneficial effects of treatment would include reduction in pain and increased ability to function, which is primarily achieved through decreased pain and increased mobility. Although kyphosis is improved among some patients undergoing KP, this is an intermediate outcome unless actual health outcomes result from this improvement.

Potential harmful effects include complications associated with the procedure or the associated anesthesia.

Patient Indication #2. The primary health outcomes of interest include pain and ability to function, similar to Patient Indication #1. However, fast response is important for this indication, and durability of relief may be less important given the patients’ limited remaining life span.

Specific Assessment Question

1. What are the effects of kyphoplasty on health outcomes for each indication?

2. How do the outcomes of kyphoplasty compare with outcomes of alternative treatments?

REVIEW OF EVIDENCE

Overview

The available published evidence describing the outcomes of kyphoplasty consists mostly of uncontrolled studies including case reports and small case series. We were able to find 2 nonrandomized studies comparing kyphoplasty to continued conservative management. The case series are mostly retrospective, and it is difficult to determine the criteria for patient selection for the procedure. In the uncontrolled studies, reported outcomes most commonly included measures of pain, degree of analgesic use, and procedure related adverse events. Few studies report functional status or activities of daily living. Studies on kyphoplasty also report changes in the degree of thoracic curvature or vertebral height but this is an intermediate outcome that has not yet been correlated to symptomatic improvements such as improved pulmonary or gastrointestinal function. Many studies are limited with regard to reporting detail of outcome measures and results with significant amounts of missing follow-up data in many studies. Most studies are retrospective in nature, and the length of follow-up is relatively short in many studies.

Comparison of reported outcomes across observational studies (historical comparisons) is not reliable because known and unknown differences in patient populations are likely to have a confounding influence on observed outcomes. Furthermore, differences in study methods, concurrent treatments, outcome measures used, and differences in reporting limit the feasibility of performing historical comparisons. Finally, studies that enroll subjects who are experiencing severe pain at the time of enrollment and compare results before and after the intervention do not take into consideration the potential for severe pain to display regression to the mean over time. Chronic pain may display a waxing and waning pattern and, pain from osteoporotic compression fractures may improve over time without intervention as the fracture heals.

What are the effects of kyphoplasty on health outcomes?

Patient Indication #1. Patients who have symptomatic vertebral body compression fracture(s) associated with osteoporosis

Eight published case series studies enrolling 385 patients were found that met selection criteria. Characteristics of the studies are shown in Table 1. A few studies included a few patients with vertebral fractures due to malignancy, but these patients’ outcomes were not reported separately. All studies enrolled patients with severe pain, but they varied with respect to the duration of the pain prior to the procedure. Most studies used some form of VAS to report pain outcomes.

The results are generally consistent in that all show statistically significant decreases in pain from an initial starting value between 7–9 on the VAS to about 2–4 after the procedure (Table 2). Such pain relief appears to be lasting in the 4 studies that reported long-term outcomes, although most of the studies had large losses to follow-up. Only one study by Berlemann et al. (2004) retained most of the patients at the end of long-term follow-up. This study showed continued pain relief out to 1 year after the procedure.

Table 1. Kyphoplasty for Osteoporotic Vertebral Fractures*– Study Characteristics

*Some studies include a few patients with malignant disease that are not reported separately
Abbreviations: See Appendix Table

Table 2. Kyphoplasty for Osteoporotic Vertebral Fractures – Outcomes [PDF, 332KB]

In terms of other outcomes, results generally showed improvement after kyphoplasty. Lieberman et al. (2001) and Coumans et al. (2003) reported statistically significant improvements in several subscores of the SF-36, including physical function, mental health, pain, vitality and social function. Ledlie et al. (2003) showed that the proportion of patients fully ambulatory increased after the procedure, but the study had progressive losses to follow up over time. Crandall et al. (2004) showed decreases in the amount of medication use over time.

In terms of adverse outcomes (Table 3), leakage of the cement outside the vertebral body is a common occurrence, occurring between 6% and 38% in 6 studies that reported its occurrence. Among all the series, there was only 1 patient who had symptoms due to the leak. Other adverse effects such as pulmonary embolus, myocardial infarction, and congestive heart failure infrequently occurred.

In sum, the case series show a consistent improvement in pain scores and other functional scores when compared to baseline. Evidence regarding the durability of benefit is weakened by the losses to follow up reported in most studies, but is consistent with effectiveness at least to 1 year. The major limitation of this body of evidence is that there is no control group; thus, placebo effects and natural history may account for some or all of the apparent benefits of treatment. Retrospective studies raise concerns about unknown selection biases which may affect the results. Findings from an observational study and a pilot randomized trial of vertebroplasty raise concern that placebo or natural history effects may be occurring. These findings will be described and summarized later in the Assessment.

Patient Indication #2. Patients who have symptomatic vertebral fractures associated with osteolytic destruction (e.g., bone metastasis). This indication does not include patients with evidence of spinal cord compromise.

Three studies were found reporting a total of 52 patients for this indication (Tables 4 and 5). Two of the studies (Dudeney et al. 2002; Lane et al. 2004) included only patients with multiple myeloma. Each of the studies reports a different set of outcomes. Dudeney et al. (2002) reports improvements in several SF-36 subscales, including physical function, pain, vitality and social function. Fourney et al. (2003) reported improvements in pain score from a mean of 8 preoperatively to 2 postoperatively. Lane et al. (2004) reported improvement in the Oswestry Disability Index score from 48.94 to 32.6 at 3 months. Qualitatively, these improvements appear to be similar to the degree of pain relief that occurs in patients with osteoporotic vertebral fractures who undergo kyphoplasty.

Table 3. Adverse Events of Kyphoplasty

¹Adverse event rates based on % pts with complication

Key: Leak all cement leaks, with or without any clinical symptoms
Bleed postoperative, clinically significant bleeding
Leak-Sx cement leaks causing clinical symptoms
PE pulmonary embolus
CHF congestive heart failure
MI myocardial infarction
Rib Fx rib fracture
Other Abbreviations: See Appendix Table

Table 4. Kyphoplasty for Vertebral Fractures Due to Malignancy – Study Characteristics

Abbreviations: See Appendix Table

Table 5. Kyphoplasty for Vertebral Fractures Due to Malignancy– Outcomes

¹ p-values for pre- post- (within-group) comparisons unless otherwise specified

Abbreviations: See Appendix Table

In terms of adverse events, leakage of cement occurred in 11%, 0%, and 26%, in the 3 studies. None of the leaks caused symptoms. Fourney et al. (2003) reported that over time, 14% of patients had recurrent fractures at other sites. Without a control group, it is not possible to attribute these fractures to the kyphoplasty procedure.

Similar to the situation for kyphoplasty performed for osteoporotic fractures, the major limitation of this body of evidence is that there is no control group; thus placebo effects and natural history may account for some or all of the apparent benefits of treatment.

How do the outcomes of kyphoplasty compare with outcomes of alternative treatments?

There were 2 nonrandomized comparison studies of kyphoplasty for treatment of osteoporotic fractures. Kasperk et al. (2005) enrolled 60 patients with vertebral fractures present for greater than 12 months. All patients were evaluated as being suitable for having kyphoplasty. Patients were then offered kyphoplasty; those who refused became the control group. The patients had no statistically significant differences in characteristics at baseline. In the principal clinical outcomes, the kyphoplasty group had greater improvements in VAS pain score and EVOS functional score than the control group. There were slight reductions in the use of opiate medication in both groups (formal statistical analysis not reported) and fewer back-pain-related physician visits in the kyphoplasty group. In other secondary analyses, they found no correlation between the degree of kyphosis correction and pain or functional outcomes, and no difference in treatment effect across subgroups.

The other comparative study by Komp et al. (2004) compared 19 patients receiving kyphoplasty to 17 patients receiving conservative therapy. This study was published in a German-language journal in a brief format (3 pages) compared to most studies in this Assessment. Patients presented, on average, 34 days after the injury thought to have caused the fracture, and all patients had “functionally unstable fractures” as revealed by images of the vertebral body at flexion and extension. The results were reported without formal statistical testing, but show an improvement in the kyphoplasty group in the VAS pain scale from 91 to 25 at 6 months (uncertain group measure, probably mean or median). The control group showed less improvement from 91 to 83 at 6 months. The pain score as evaluated by NASS score (North American Spine Score) showed similar results, as did functional status as assessed by the Oswestry disability scale.

In sum, these 2 nonrandomized studies are suggestive of a benefit of kyphoplasty when compared to conservative management. These 2 studies enrolled different types of patients with respect to age of fracture; the study by Kasperk et al. (2005) enrolling patients with greater than -year old fractures, and Komp et al. (2004) enrolling patients with acute fractures who met specific radiologic criteria for instability. The brief format of the Komp study does not allow an assessment of the similarity of the kyphoplasty and control groups. Contrary to a nonrandomized study of vertebroplasty by Diamond et al. (2003), the control groups in this study did not improve appreciably over a period of weeks to months.

Lack of randomized trial data raises concerns as to whether natural history, regression to the mean, or placebo effects may be responsible for some or all of the apparent benefit of kyphoplasty. The small size and lack of randomization of the comparative studies published so far may suffer from differences in confounding factors between those patients who accepted and those who refused kyphoplasty.

Comparative Studies of Vertebroplasty and Medical Treatment

With the lack of randomized trials of kyphoplasty, a possible concern is whether placebo or natural history effects may be responsible for some of the observed improvements in symptoms. Results of 2 studies of vertebroplasty, a closely related procedure, will be briefly reviewed here.

Diamond et al. (2003) enrolled 79 consecutive patients with acute vertebral fractures. All patients were offered vertebroplasty, and those who declined were followed as a comparison group. The two groups had balanced baseline characteristics. At 24 hours, the group undergoing PVP (n=55) had much improved pain compared to the control group (n=24). However, at 6 weeks and between 6 and 12 months, there were no differences between groups in pain score. The control group had an identical mean pain score to the PVP group at the end of follow-up. Similar findings were shown for the Barthel index of physical functioning. At long-term follow-up, there was still slightly higher functioning in the group undergoing PVP, but no difference in the percent improvement from baseline between groups. The authors interpret these findings as demonstrating that PVP produced faster resolution of symptoms than conservative management.

In a study presented at the American Society of Neuroradiology Meeting in 2002, Kallmes et al. reported the findings of a small pilot study in 5 patients with subacute vertebral body compression fractures (i.e., less than 2 months in duration). This sham-controlled randomized trial permitted blinded crossover after 14 days if a patient failed to respond to initial treatment. Three patients were initially assigned to receive the sham procedure and 2 were assigned to receive PVP, but one sham patient suffered a new compression fracture 48 hours after the sham treatment and was excluded from the analysis. Thus, results are available in 4 subjects.

Both subjects initially treated with the sham procedure had minimal relief after treatment and crossed over to PVP, but results after PVP were similar with minimal pain relief observed. Both subjects who initially underwent PVP had minimal relief in symptoms and crossed over to receive the sham procedure. One of these patients reported complete pain relief after the sham procedure. All 5 patients were asked to guess which procedure they had received in order to assess how well the blinding had worked and all guessed that they had received the sham procedure on the first treatment session.

This study provides anecdotal support for the concern that nonspecific placebo effects may be important in determining the results following PVP. Therefore, controlled, comparative studies are important to establish the clinical effectiveness of either vertebroplasty or kyphoplasty due to the potential influence of nonspecific treatment effects (placebo effect) as well as the influence of heterogeneous patient populations and variable natural history of symptomatic vertebral body lesions. The results of the observational study by Diamond et al. (2003) are also consistent with a placebo effect of a surgical intervention.

SUMMARY OF APPLICATION OF THE TECHNOLOGY EVALUATION CRITERIA

Following is a summary of the available evidence on percutaneous kyphoplasty for vertebral fractures from osteoporosis or malignancy according to the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.

1. The technology must have final approval from the appropriate governmental regulatory bodies.

Kyphoplasty is a surgical procedure and, as such, is not subject to U.S. Food and Drug Administration (FDA) approval. Kyphon, Inc. has received 510(k) marketing clearance for a bone cement product to be used in vertebroplasty and kyphoplasty. Kyphoplasty also requires the use of an inflatable bone tamp. One such tamp, the KyphX® inflatable bone tamp, received 510(k) marketing clearance from the FDA in July 1998. Other bone cements and bone void filling products used represent an off-label use of such products.

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.

The available evidence is not sufficient to permit conclusions of the effect of kyphoplasty on health outcomes.

The published evidence describing the outcomes of kyphoplasty consists mostly of uncontrolled studies. These uncontrolled studies were mostly retrospective and enrolled heterogeneous patient populations. Such studies cannot eliminate placebo and natural history effects as explanations for the apparent effectiveness of PVP. Two studies of vertebroplasty, a closely related procedure, raise concern about such effects. In a nonrandomized study, patients undergoing PVP had immediate pain relief from the procedure. However, at 6 weeks of follow-up and at 6-12 months follow-up, there was no difference between the group undergoing PVP and another group of patients that had not undergone PVP. In another pilot study reported only in abstract form, patients did not respond to PVP, but did respond to a sham procedure. These studies raise concern that nonspecific placebo effects may be important in determining results following PVP.

The published literature on outcomes of kyphoplasty consists mostly of case series studies. For the indication of osteoporosis, 8 case studies meeting selection criteria were reviewed that evaluated outcomes of 385 patients. Results were generally consistent in showing significant decreases in pain from an initial preoperative level of 7 to 9 on a visual analog scale (VAS) and decreasing to 2 to 4 within one day of the procedure. For the indication of osteolytic destruction due to metastasis, 3 studies were reviewed, evaluating a total of 52 patients. Outcome measures varied between these three studies, but all showed improvements either in VAS pain score, several aspects of physical functioning as measured by SF-36, or improvement in a disability score.

Two nonrandomized studies comparing kyphoplasty to conservative management showed that patients receiving kyphoplasty had greater improvements in pain and function compared to patients on conservative treatment. In these 2 studies, the control groups showed minimal improvement in pain and function over the period of observation, which contrasts with the comparative study of PVP, in which the control group improved over time. Differences in patient presentation and selection for treatment could be responsible for the differences observed. These studies point out the uncertainty of the natural history of vertebral fractures, and that controlled studies would help determine the efficacy of kyphoplasty.

Because of the results of the comparative studies of vertebroplasty suggest possible placebo or natural history effects, case series studies are insufficient to make conclusions about the effect of kyphoplasty on health outcomes. The nonrandomized studies of kyphoplasty may suggest a benefit to the procedure, but cannot rule out placebo and confounding effects to explain the results.

3. The technology must improve the net health outcome.

4. The technology must be as beneficial as any established alternatives.

The available evidence does not permit conclusions regarding the effect of percutaneous kyphoplasty on health outcomes or compared with alternatives.

5. The improvement must be attainable outside the investigational settings.

It has not yet been demonstrated whether percutaneous kyphoplasty improves health outcomes in the investigational setting. Therefore, it cannot be demonstrated whether improvement is attainable outside the investigational settings.

For the above reasons, percutaneous kyphoplasty for vertebral fractures from osteoporosis or malignancy does not meet the TEC criteria.

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APPENDIX

Table of Abbreviations