Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue, compared with autologous iliac crest graft in lumbar fusion surgery.

BACKGROUND CONTEXT: Although autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs. PURPOSE: This study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy. STUDY DESIGN/SETTING: A prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial. PATIENT SAMPLE: A total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4-L5 degenerative spondylolisthesis and/or with L4-L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Spinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment. METHODS: Patients who underwent L4-L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups. RESULTS: Seventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups. CONCLUSIONS: Compared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study.

Validity of creatine kinase as an indicator of muscle injury in spine surgery and its relation with postoperative pain.

PURPOSE: To confirm the validity of postoperative creatine kinase (CK) values as an indicator of muscle lesion, assess the relationship of CK with variables indicating surgical invasiveness and investigate an association between CK values and excessive postoperative pain. MATERIAL AND METHODS: The study included 96 patients (mean age 62.8 years) who underwent instrumented spine fusion for degenerative lumbosacral disease. Serum CK concentration was determined on the first postoperative day. All patients received intravenous paracetamol and metamizole, and in cases of intense pain, rescue analgesia with iv meperidine. Patients were categorized according to whether or not they required rescue analgesia. Data on the number of levels fused, the duration of surgery, and operative bleeding were recorded in each patient. RESULTS: CK values were higher in men and in younger patients. Significant correlations were found between CK and the number of fused levels and duration of surgery. Only 17.7% of patients required rescue analgesia. CK levels did not significantly differ between patients who did not need rescue analgesia (1135 IU/L) and those who did (1421.5 IU/L). CONCLUSIONS: Serum CK concentration is a valid marker of surgical muscle injury and is affected by the age and sex. Factors such as the magnitude and duration of surgery show a relationship with postoperative CK values. The incidence of severe postoperative pain is not significantly related to CK level.

Evaluation of health-related quality of life in patients candidate for spine and other musculoskeletal surgery.

INTRODUCTION: Despite the high prevalence of musculoskeletal diseases, in Spain there are few data about how these conditions affect the quality of life of individuals. The objective of this study was to assess the quality of life (QOL) of patients candidate for orthopedic surgical treatment using an age-gender adjusted method of QOL scores. MATERIALS AND METHODS: The SF-36 Health Survey was administered to 538 patients candidate for surgery between surgical treatment was classified in four groups (lumbar disease, cervical disease, knee arthroplasty, and hip arthroplasty). Associated morbidities were collected retrospectively for all cases using the Charlson co-morbidity index. Univariate, bivariate, and multivariate statistical analyses were done to compare the four groups to each other, to the general population mean, and to the age and gender-adjusted population mean. RESULTS: 234 men and 304 women whose mean age was 58.78 years (19-89) were assessed. Patients candidate for some kind or lumbar surgery had the worst scores in all physical and mental scales as compared to the other disease groups. Patients candidate for knee arthroplasty, had the best quality of life scores in all scales, compared to the other disease groups. Medical conditions had no influence over the summary measures. CONCLUSION: Presenting the results of SF-36 in standard deviations from the age- and gender-adjusted population mean (T values) leads to a better appreciation of the differences between the various diseases. Patients candidate for surgery of the lumbar spine had a worse QOL, while the QOL in patients candidate for knee arthroplasty was the least affected.