Role of physical activity in new onset fractures after percutaneous vertebroplasty.

BACKGROUND: Increased mobility and physical activity after successful vertebral augmentation procedure might increase the risk of new-onset fractures. PURPOSE: To determine whether new-onset fracture following vertebroplasty is associated with specific type of physical activity. MATERIAL AND METHODS: A total of 107 patients underwent at least two procedures of percutaneous vertebroplasty. Among them, 30 patients who sustained a post-vertebroplasty fracture(s), were stratified by fracture-causing activity and examined the incidence of the initial and post-vertebroplasty fractures, time to post-vertebroplasty fractures, duration of anti-osteoporotic therapy, T-score, and body mass index. RESULTS: The following percentages correspond to patients with fractures sustained pre- and post-vertebroplasty, respectively; spontaneous fractures in 17% and 7% (P = 0.20), sitting in 7% and 3% (P = 0.50), walking or standing in 7% and 20% (P = 0.10), housework in 3% and 3% (P > 0.99), coughing or sneezing in 0% and 20% (P = 0.003), exercise in 7% and 17% (P = 0.20), lifting in 10% and 17% (P = 0.40) and falling in 50% and 13% (P = 0.002). Different levels of activity were not significantly associated with time to incidence of post-vertebroplasty fractures. Anti-osteoporotic medications were administered to 33% of patients before vertebroplasty and 37% after the vertebroplasty (P = 0.78); medications were administered to these groups for 16 and 25 months, respectively (P = 0.39). CONCLUSION: A significantly elevated risk of new onset fracture with increased physical activity was not identified. However, patients should be carefully counseled after vertebroplasty to optimize medical therapy for osteoporosis and also to use extreme care when engaging in even moderate physical activity.

Impact of pain question modifiers on spine augmentation outcome.

PURPOSE: To determine whether the reported pain severity changed significantly on the basis of specific types of pain questions posed to patients with spine augmentation. MATERIALS AND METHODS: Institutional review board approval and patient consent were obtained for this HIPAA-compliant, prospective study. Patients presenting for consideration of spine augmentation between November 2008 and May 2009 were enrolled. Twenty-four patients were asked at initial presentation and at 30 days to grade their severity of back pain on a 10-point numeric rating scale in response to nine pain questions modified by the relative severity (most vs least severe), by activity (at rest vs with activity), and over time (previous day vs previous week). Statistical analysis included paired t tests to detect any differences in responses to the questions at both time points. RESULTS: Of the 24 patients, 15 (63%) underwent spine augmentation. For patients undergoing spine augmentation, baseline mean numeric rating score for "worst pain with activity over the past week" was 8.9 ± 1.5 (standard deviation), compared with 2.9 ± 2.7 for "least pain at rest over the past day" (P = .001). Interval change between baseline and 30-day assessments was relatively small for all nine questions (mean, 1.6; range, 0.2-2.2); the mean difference for eight of the nine questions did not reach statistical significance. The modifiers worst versus least and with activity versus at rest had a significant impact on the reported severity, while previous week versus previous day had minimal impact. CONCLUSION: Wide variation in the reported pain can be achieved simply by modifying specific pain questions to patients with spine augmentation.

Incident vertebral fractures in patients not undergoing vertebroplasty.

PURPOSE: To determine whether vertebroplasty increases the risk of new (ie, incident) vertebral fractures by comparing the rates of incident fractures among a group of patients with painful vertebral fractures who did not undergo vertebroplasty with a group of patients who did. MATERIALS AND METHODS: A retrospective chart review was performed to identify new-onset fractures after initial vertebroplasty evaluation in two groups, including patients who underwent vertebroplasty within 1 week of initial evaluation (group 1) and those who did not (group 2). Group 2 was further limited to patients with acute or subacute prevalent fractures (group 2A) after exclusion of those with exclusively chronic prevalent fractures. Survival analyses were performed to compare time to diagnosis and frequency of incident fractures in these three groups of patients. RESULTS: Group 1 included 269 patients, group 2 included 107 patients, and group 2A included 82 patients. Compared with group 2, incident fractures in group 1 occurred significantly earlier (log-rank statistic, 0.01) and more frequently (hazard ratio, 2.9; 95% CI, 1.2-8.4). CONCLUSIONS: Among patients with acute or subacute vertebral fractures presenting for consideration of vertebroplasty, those who undergo the procedure experience more and earlier incident fractures than those who do not, but the observed differences failed to reach statistical significance. Further work is needed in this area to better define relative risks of incident fracture between treated and nontreated patients.

The effect of operator variability and experience in vertebroplasty outcomes.

PURPOSE: To determine if operator variability, prior vertebroplasty experience, or acquired vertebroplasty experience affects clinical outcomes. MATERIALS AND METHODS: Informed consent was obtained from all patients and all data were handled in a manner consistent with institutional review board guidelines and the Health Insurance Portability and Accountability Act. Outcomes from 841 vertebroplasties, sorted by operator, were studied; two operators had previous vertebroplasty experience and five were neurointerventionalists who were initially new to the procedure. Objective (Roland-Morris Disability Questionnaire [RDQ] and analog pain scales) and subjective (mobility, narcotic use) scores were monitored before and after vertebroplasty at specified intervals following treatment. Perioperative cement volume utilization, complications, and number of treated levels were recorded. Random-effects and repeated-measures analyses of variance were used to assess operator differences and variability in clinical outcomes while generalized linear mixed-model regression analyses were used to track changes in clinical outcomes over time. RESULTS: All operators provided similar average durable clinical improvements in postoperative pain and disability with nonsignificant interoperator variability. However, generalized linear model regression suggests that four of five initially novice operators showed significant changes in several procedural measures and clinical outcomes over the study timeframe, including cement volume utilization (reduction of 3.64 to 4.63 cm(3)), 1 week RDQ score (reduction of 4.79 to 8.62 points) and postoperative rest pain (reduction of 1.18 to 2.03 points). CONCLUSION: Changes over time in measured outcomes suggest the presence of a training effect among novice operators. Cement volume utilization and immediate postprocedural pain decrease with experience but long-term clinical outcomes are insensitive to operator experience.

A randomized trial of vertebroplasty for osteoporotic spinal fractures.

BACKGROUND: Vertebroplasty is commonly used to treat painful, osteoporotic vertebral compression fractures. METHODS: In this multicenter trial, we randomly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement (control group). The primary outcomes were scores on the modified Roland-Morris Disability Questionnaire (RDQ) (on a scale of 0 to 23, with higher scores indicating greater disability) and patients' ratings of average pain intensity during the preceding 24 hours at 1 month (on a scale of 0 to 10, with higher scores indicating more severe pain). Patients were allowed to cross over to the other study group after 1 month. RESULTS: All patients underwent the assigned intervention (68 vertebroplasties and 63 simulated procedures). The baseline characteristics were similar in the two groups. At 1 month, there was no significant difference between the vertebroplasty group and the control group in either the RDQ score (difference, 0.7; 95% confidence interval [CI], -1.3 to 2.8; P=0.49) or the pain rating (difference, 0.7; 95% CI, -0.3 to 1.7; P=0.19). Both groups had immediate improvement in disability and pain scores after the intervention. Although the two groups did not differ significantly on any secondary outcome measure at 1 month, there was a trend toward a higher rate of clinically meaningful improvement in pain (a 30% decrease from baseline) in the vertebroplasty group (64% vs. 48%, P=0.06). At 3 months, there was a higher crossover rate in the control group than in the vertebroplasty group (51% vs. 13%, P<0.001) [corrected]. There was one serious adverse event in each group. CONCLUSIONS: Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group. (ClinicalTrials.gov number, NCT00068822.)

Bisphosphonates are not associated with vertebral osteonecrosis.

Intravertebral clefts are considered markers for osteonecrosis. We tested the hypothesis that bisphosphonate therapy was associated with vertebral osteonecrosis. A retrospective review of a vertebroplasty database was performed. Exposure to, duration of, and type of bisphosphonate therapy was documented. Radiographs were reviewed to identify intravertebral gas-filled or fluid-filled clefts, which are considered a marker for vertebral osteonecrosis. Proportion of patients with and without clefts was compared between the group exposed to bisphosphonates and the unexposed group using Chi-squared test. Duration of bisphosphonate exposure was compared between patients with and without clefts using Student's t-test. After exclusion of 16 patients with malignancy and 21 with chronic steroid therapy 237 patients were identified. Sixty-seven (28%) of the total cohort of patients were prescribed bisphosphonate therapy. Overall, clefts were present in 68 (29%) of the 237 patients. Among the 67 patients exposed to bisphosphonate therapy, 15 patients (22%) had clefts. Among the 170 patients not exposed to bisphosphonate therapy, 53 patients (31%) had clefts (P = 0.17 compared to bisphosphonate therapy group). Mean duration of bisphosphonate therapy among patients with clefts was 52 +/- 63 weeks and among patients without clefts was 57 +/- 79 weeks (P = 0.80). Intravertebral clefts are not associated with bisphosphonate therapy. If these clefts indicate osteonecrosis, then bisphosphonate therapy does not appear to be associated with vertebral osteonecrosis.

INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of percutaneous vertebroplasty.

BACKGROUND: The treatment of painful osteoporotic vertebral compression fractures has historically been limited to several weeks of bed rest, anti-inflammatory and analgesic medications, calcitonin injections, or external bracing. Percutaneous vertebroplasty (the injection of bone cement into the fractured vertebral body) is a relatively new procedure used to treat these fractures. There is increasing interest to examine the efficacy and safety of percutaneous vertebroplasty and to study the possibility of a placebo effect or whether the pain relief is from local anesthetics placed directly on the bone during the vertebroplasty procedure. METHODS/DESIGNS: Our goal is to test the hypothesis that patients with painful osteoporotic vertebral compression fractures who undergo vertebroplasty have less disability and pain at 1 month than patients who undergo a control intervention. The control intervention is placement of local anesthesia near the fracture, without placement of cement. One hundred sixty-six patients with painful osteoporotic vertebral compression fractures will be recruited over 5 years from US and foreign sites performing the vertebroplasty procedure. We will exclude patients with malignant tumor deposit (multiple myeloma), tumor mass or tumor extension into the epidural space at the level of the fracture. We will randomly assign participants to receive either vertebroplasty or the control intervention. Subjects will complete a battery of validated, standardized measures of pain, functional disability, and health related quality of life at baseline and at post-randomization time points (days 1, 2, 3, and 14, and months 1, 3, 6, and 12). Both subjects and research interviewers performing the follow-up assessments will be blinded to the randomization assignment. Subjects will have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end of the study (month 12) to determine subsequent fracture rates. Our co-primary outcomes are the modified Roland score and pain numerical rating scale at 1 month. DISCUSSION: Although extensively utilized throughout North America for palliation of pain, vertebroplasty still has not undergone rigorous study. The study outlined above represents the first randomized, controlled study that can account for a placebo effect in the setting of vertebroplasty. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81871888.

Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire.

BACKGROUND AND PURPOSE: Vertebroplasty is rapidly disseminating as a treatment for vertebral compression fractures, but its efficacy has not been assessed with a well-validated, back pain-specific instrument. We report the use of the Roland-Morris Disability Questionnaire (RDQ) in patients undergoing vertebroplasty for painful osteoporotic compression fractures. METHODS: Retrospective review of patients treated with vertebroplasty who completed the RDQ and 2 verbal pain scales (0-10) for pain at rest and pain with activity at baseline, 1 week, 1 month, 6 months, and 1 year post-vertebroplasty. Changes in outcome measures were analyzed by using a paired t test and correlations were assessed with Spearman rho. Multiple linear regression was used to analyze the relationship between baseline scores and independent variables. RESULTS: One hundred thirteen patients were treated at 164 vertebral levels. At baseline, RDQ scores were associated with rest and activity pain (P < .001 and P = .002, respectively) but were not associated with other independent variables. All 3 outcome scores decreased by 1 week and remained improved through maximal follow-up (P < .001). RDQ scores improved by a mean of 7.0 points at 1 week and remained improved at 1 year (P = .02). RDQ scores correlated with both rest and activity pain, but the absolute correlation was slightly better (+0.15 on average) with activity pain. CONCLUSIONS: Patients who underwent vertebroplasty experienced relief of back pain and symptoms, as shown by improvement in verbal pain and RDQ scores. The RDQ correlates well with measures of pain, shows clinically significant improvement and is responsive to changes across time. More important, the RDQ provides an easily administered, well-validated, back pain-specific outcome measure that could be adopted to assess vertebroplasty outcomes.

Vertebroplasty in the inpatient population.

BACKGROUND AND PURPOSE: Vertebroplasty is frequently offered to patients hospitalized for refractory pain due to vertebral fractures, because it is assumed that the procedure will facilitate resolution of pain and a rapid hospital discharge. We report our experience with inpatient vertebroplasty, with attention to rapidity of discharge and relevant clinical parameters. METHODS: We retrospectively reviewed the duration of hospitalization in patients admitted with primary diagnoses of back pain or vertebral fracture who were treated with vertebroplasty. We cataloged outcomes in the form of verbal pain scales (graded 0-10), in-hospital medication use (graded 0-6), and posthospitalization medication use. Outcomes were assessed at baseline and at 1 week, 1 month, 6 months, 1 year, and 2 years postvertebroplasty. RESULTS: We identified 66 such patients who had a median total hospital stay of 6.0 days (range, 1-26 days). Median length of stay before and after vertebroplasty were 4.0 (range, 1-24 days) and 1.5 days (range, 0-7 days), respectively. Ten (15%) patients were discharged the day of vertebroplasty. By days 2 and 3, 33 (50%) and 48 (72.7%) of the 66 patients had been discharged. Patients who received vertebroplasty earlier in the course of hospitalization demonstrated greater decreases in medication strength by discharge (P = .045). There was significant improvement in all outcome measures by 1 week, with continued improvement at 1 and 6 months. CONCLUSION: This study confirms that vertebroplasty facilitates a rapid hospital discharge as well as long-term improvement in patients admitted for refractory pain. Vertebroplasty administered earlier in hospitalization also leads to greater decreases in analgesic requirements.

Hemostatic gene polymorphisms and the prevalence of thrombotic complications in polycythemia vera and essential thrombocythemia.

Patients with polycythemia vera and essential thrombocythemia are at risk for thrombotic and bleeding complications. Currently, no diagnostic test can predict thrombohemorrhagic complications. In a prospective study of 86 patients with polycythemia vera (43 patients) or essential thrombocythemia (43 patients), we examined the possible role of polymorphisms of platelet adhesion receptors [glycoprotein (GP) Ibalpha, GPIa, GPIIIa) and clotting factor II (prothrombin's G20210A mutation) and clotting factor V (Leiden mutation) in determining the risk of thrombotic or bleeding complications. Except for an association between vasomotor symptoms and prothrombin mutation (P < 0.001), no significant correlation between polymorphism of clotting factors and thrombohemorrhagic complications was identified. When the entire patient cohort was considered, the polymorphisms of platelet adhesion receptors were not associated with the risk for thrombotic or bleeding complications. However, among patients with polycythemia vera, the presence of the PlA2 allele of GPIIIa was associated with an increased risk of arterial thrombosis. In view of previous studies linking the presence of the PlA2 allele of GPIIIa to a higher risk for coronary artery thrombosis, our data have physiologic relevance. However, they need to be confirmed in a larger study.

A phase 2 trial of combination low-dose thalidomide and prednisone for the treatment of myelofibrosis with myeloid metaplasia.

Single-agent thalidomide (THAL) at "conventional" doses (> 100 mg/d) has been evaluated in myelofibrosis with myeloid metaplasia (MMM) based on its antiangiogenic properties and the prominent neoangiogenesis that occurs in MMM. THAL monotherapy at such doses produces approximately a 20% response rate in anemia but is poorly tolerated (an adverse dropout rate of > 50% in 3 months). To improve efficacy and tolerability, we prospectively treated 21 symptomatic patients (hemoglobin level < 10 g/dL or symptomatic splenomegaly) with MMM with low-dose THAL (50 mg/d) along with a 3-month oral prednisone (PRED) taper (beginning at 0.5 mg/kg/d). THAL-PRED was well tolerated in all enrolled patients, with 20 patients (95%) able to complete 3 months of treatment. An objective clinical response was demonstrated in 13 (62%) patients, all improvements in anemia. Among 10 patients who were dependent on erythrocyte transfusions, 7 (70%) improved and 4 (40%) became transfusion independent. Among 8 patients with thrombocytopenia (platelet count < 100 x 10(9)/L), 6 (75%) experienced a 50% or higher increase in their platelet count. In 4 of 21 patients (19%), spleen size decreased by more than 50%. Responses observed were mostly durable after discontinuation of the PRED. The dose of THAL in this study (50 mg/d) was better tolerated than the higher doses used in previous studies. Adverse events associated with corticosteroid therapy were mild and transient. Clinical responses did not correlate with improvements in either intramedullary fibrosis or angiogenesis. THAL-PRED is well tolerated and preliminarily appears to be a promising drug regimen for treating cytopenias in patients with MMM.

Phase 2 trial of imatinib mesylate in myelofibrosis with myeloid metaplasia.

In a phase 2 study, 23 patients with myelofibrosis with myeloid metaplasia were treated with imatinib mesylate at a constant dose of 400 mg/d. Treatment was held in 16 patients (70%), after 1 to 12 weeks, because of side effects (neutropenia, 6 patients; musculoskeletal pain, 5 patients; thrombocytosis, 4 patients; edema, 3 patients; diarrhea and hyperbilirubinemia, 1 patient). Including patients in whom retreatment at a reduced dose was possible, 11 patients (48%) were able to continue treatment beyond 3 months. None of the patients experienced a response in anemia, and only 2 had partial responses in splenomegaly. A greater than 50% increase in platelet count was documented in 11 (48%) patients, but not in those with baseline platelet counts of less than 100 x 10(9)/L. In vitro, imatinib mesylate caused variable degrees of growth suppression of myeloid and erythroid progenitors that unfortunately did not translate into clinical benefit.