Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise.

Background: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. Methods: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. Results: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. Conclusion: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis.

The effect of fatty infiltration, revision surgery, and sex on lumbar multifidus passive mechanical properties.

Purpose: Previous research has demonstrated increased stiffness in the multifidus muscle compared to other paraspinal muscles at the fiber bundle level. We aimed to compare single fiber and fiber bundle passive mechanical properties of multifidus muscle: (1) in 40 patients undergoing primary versus revision surgery and (2) in muscle with mild versus severe fatty infiltration. Methods: The degree of muscle fatty infiltration was graded using the patients' spine magnetic resonance images. Average single fiber and fiber bundle passive mechanical properties across three tests were compared between primary (N = 30) and revision (N = 10) surgery status, between mild and severe fatty infiltration levels, between sexes, and with age from passive stress-strain tests of excised multifidus muscle intraoperative biopsies. Results: At the single fiber level, elastic modulus was unaffected by degree of fatty infiltration or surgery status. Female sex (p = 0.001) and younger age (p = 0.04) were associated with lower multifidus fiber elastic modulus. At the fiber bundle level, which includes connective tissue around fibers, severe fatty infiltration (p = 0.01) and younger age (p = 0.06) were associated with lower elastic modulus. Primary surgery also demonstrated a moderate, but non-significant effect for lower elastic modulus (p = 0.10). Conclusions: Our results demonstrate that female sex is the primary driver for reduced single fiber elastic modulus of the multifidus, while severity of fatty infiltration is the primary driver for reduced elastic modulus at the level of the fiber bundle in individuals with lumbar spine pathology.

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology.

PURPOSE: The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS: Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS: Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION: Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences.

Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology.

BACKGROUND: Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS: Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS: Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION: Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population.

Regional differences between superficial and deep lumbar multifidus in patients with chronic lumbar spine pathology.

BACKGROUND: Due to its unique arrangement, the deep and superficial fibers of the multifidus may have differential roles for maintaining spine stabilization and lumbar posture; the superficial multifidus is responsible for lumbar extension and the deep multifidus for intersegmental stability. In patients with chronic lumbar spine pathology, muscle activation patterns have been shown to be attenuated or delayed in the deep, but not superficial, multifidus. This has been interpreted as pain differentially influencing the deep region. However, it is unclear if degenerative changes affecting the composition and function of the multifidus differs between the superficial and deep regions, an alternative explanation for these electrophysiological changes. Therefore, the goal of this study was to investigate macrostructural and microstructural differences between the superficial and deep regions of the multifidus muscle in patients with lumbar spine pathology. METHODS: In 16 patients undergoing lumbar spinal surgery for degenerative conditions, multifidus biopsies were acquired at two distinct locations: 1) the most superficial portion of muscle adjacent to the spinous process and 2) approximately 1 cm lateral to the spinous process and deeper at the spinolaminar border of the affected vertebral level. Structural features related to muscle function were histologically compared between these superficial and deep regions, including tissue composition, fat fraction, fiber cross sectional area, fiber type, regeneration, degeneration, vascularity and inflammation. RESULTS: No significant differences in fat signal fraction, muscle area, fiber cross sectional area, muscle regeneration, muscle degeneration, or vascularization were found between the superficial and deep regions of the multifidus. Total collagen content between the two regions was the same. However, the superficial region of the multifidus was found to have less loose and more dense collagen than the deep region. CONCLUSIONS: The results of our study did not support that the deep region of the multifidus is more degenerated in patients with lumbar spine pathology, as gross degenerative changes in muscle microstructure and macrostructure were the same in the superficial and deep regions of the multifidus. In these patients, the multifidus is not protected in order to maintain mobility and structural stability of the spine.

Expert review with meta-analysis of randomized and nonrandomized controlled studies of Barricaid annular closure in patients at high risk for lumbar disc reherniation.

Introduction: Patients with lumbar disc herniation and associated sciatica are often referred for lumbar discectomy. The surgical defect in the annulus fibrosus is typically left unrepaired after lumbar discectomy. Patients with large postsurgical annular defects (≥6 mm width) have a higher risk of symptom recurrence and reoperation compared to those with small defects. In these high-risk patients, a treatment gap exists due to the lack of effective treatments for durable annulus fibrosus repair.Areas covered: This article highlights the therapeutic need and summarizes the clinical results of a bone-anchored annular closure device (Barricaid) that was designed to fill the treatment gap in patients with large postsurgical annular defects. Clinical results were summarized by means of a systematic review with meta-analysis of two randomized and two nonrandomized controlled studies.Expert opinion: Professional societal recommendations and clinical study results support the adoption of bone-anchored annular closure for use in properly selected patients undergoing lumbar discectomy who are at high-risk for reherniation due to a large postsurgical defect in the annulus fibrosus. The risks of symptomatic reherniation and reoperation are approximately 50% lower in patients treated with lumbar discectomy and the Barricaid device compared to lumbar discectomy only, representing a clinically effective treatment strategy.

Contribution of Lumbar Spine Pathology and Age to Paraspinal Muscle Size and Fatty Infiltration.

STUDY DESIGN: Retrospective chart analysis of 199 individuals aged 18 to 80 years scheduled for lumbar spine surgery. OBJECTIVE: The purpose of this study was to quantify changes in muscle cross-sectional area (CSA) and fat signal fraction (FSF) with age in men and women with lumbar spine pathology and compare them to published normative data. SUMMARY OF BACKGROUND DATA: Pathological changes in lumbar paraspinal muscle are often confounded by age-related decline in muscle size (CSA) and quality (fatty infiltration). Individuals with pathology have been shown to have decreased CSA and fatty infiltration of both the multifidus and erector spinae muscles, but the magnitude of these changes in the context of normal aging is unknown. METHODS: Individuals aged 18 to 80 years who were scheduled for lumbar surgery for diagnoses associated with lumbar spine pain or pathology were included. Muscle CSA and FSF of the multifidus and erector spinae were measured from preoperative T2-weighted magnetic resonance images at the L4 level. Univariate and multiple linear regression analyses were performed for each outcome using age and sex as predictor variables. Statistical comparisons of univariate regression parameters (slope and intercept) to published normative data were also performed. RESULTS: There was no change in CSA with age in either sex (P > 0.05), but women had lower CSAs than men in both muscles (P < 0.0001). There was an increase in FSF with age in erector spinae and multifidus muscles in both sexes (P < 0.0001). Multifidus FSF values were higher in women with lumbar spine pathology than published values for healthy controls (P = 0.03), and slopes tended to be steeper with pathology for both muscles in women (P < 0.08) but not in men (P > 0.31). CONCLUSION: Lumbar muscle fat content, but not CSA, changes with age in individuals with pathology. In women, this increase is more profound than age-related increases in healthy individuals. LEVEL OF EVIDENCE: 3.

Patient perceptions of physician reimbursement for spine surgery.

STUDY DESIGN: Anonymous patient survey. OBJECTIVE: To determine what patients think surgeons should be paid to perform elective spine surgical procedures, and gauge awareness of actual Medicare reimbursement. SUMMARY OF BACKGROUND DATA: With increasing transparency, the public may become aware of physician reimbursements and may be a part of the debate regarding appropriate reimbursement. It is unknown what patients perceive that spinal surgeons deserve to be, or are actually, paid to perform spinal procedures. METHODS: Two hundred anonymous surveys were given to consecutive patients in an outpatient office setting by means of convenience sampling. Patients were asked how much they think physicians are and should be reimbursed for typical spine procedures; and they were asked about their opinions of the actual reimbursement amount for these procedures. It was made explicit that the fee in question included only the surgeon's reimbursement and not that of the hospital. Data were tabulated, statistical comparisons were made, and results were correlated with demographic information. RESULTS: On average, respondents thought that surgeons should be paid $21,299 for performing a lumbar discectomy and estimated that Medicare actually pays $12,336 (actual average reimbursement $971). Similar disparities were seen for the other procedures.The vast majority of respondents thought that the average Medicare reimbursement for spine procedures was too low. For example, 92.2% of patients thought that $971 for a lumbar discectomy was "too low," 6.1% thought it was "about right," and only 1.6% thought that $971 was "too high." CONCLUSION: Patients think that orthopedic spine surgeons should be compensated over 10 to 20 times more than current Medicare reimbursement rates. Patients overestimate the actual amount that Medicare reimburses by a factor of approximately 7 to 10. Less than 10% of patients think that the current Medicare payment is about right, and less than 2% think that surgeons are overpaid.

An attempt at clinically defining and assessing minimally invasive surgery compared with traditional "open" spinal surgery.

BACKGROUND: The goal of this editorial and literature review is to define the term "minimally invasive surgery" (MIS) as it relates to the spine and characterize methods of measuring parameters of a spine MIS technique. METHODS: This report is an analysis of 105,845 cases of spinal surgery in unmatched series and 95,161 cases in paired series of open compared with MIS procedures performed by the same surgeons to develop quantitative criteria to analyze the success of MIS. RESULTS: A lower rate of deep infection proved to be a key differentiator of spinal MIS. In unmatched series the infection rate for 105,845 open traditional procedures ranged from 2.9% to 4.3%, whereas for MIS, the incidence of infection ranged from 0% to 0.22%. For matched paired series with the open and MIS procedures performed by the same surgeons, the rate of infection in open procedures ranged from 1.5% to 10%, but for spine MIS, the rate of deep infection was much lower, at 0% to 0.2%. The published ranges for open versus MIS infection rates do not overlap or even intersect, which is a clear indication of the superiority of MIS for one specific clinical outcome measure (MIS proves superior to open spine procedures in terms of lower infection rate). CONCLUSIONS: It is difficult, if not impossible, to validate that an operative procedure is "less invasive" or "more minimally invasive" than traditional surgical procedures unless one can establish a commonly accepted definition of MIS. Once a consensus definition or precise definition of MIS is agreed upon, the comparison shows a higher infection rate with traditional spinal exposures versus MIS spine procedures.

The economics of minimally invasive spine surgery: the value perspective.

STUDY DESIGN: Review of the literature. OBJECTIVE: To summarize current cost and clinical efficacy data in minimally invasive spine (MIS) surgery. SUMMARY OF BACKGROUND DATA: Cost effectiveness (CE), using cost per quality-adjusted life-years gained, has been shown for lumbar discectomy, decompressive laminectomy, and for instrumented and noninstrumented lumbar fusions in several high-quality studies using conventional, open surgical procedures. Currently, comparisons of costs and clinical outcomes of MIS surgery to open (or nonoperative) approaches are rare and of lesser quality, but suggest that a potential for cost benefits exist using less-invasive surgical approaches. METHODS: A literature review was performed using the database of the National Center for Biotechnology Information (NCBI), PUBMED/Medline. RESULTS: Reports of clinical results of MIS approaches are far more common than economic evaluations. MIS techniques can be classified as endoscopic or nonendoscopic. Although endoscopic approaches decrease some approach morbidities, the high cost of instrumentation, steep learning curves, and new complication profiles introduced have prevented widespread adoption. Additionally, the high costs have not been shown to be justified by superior clinical benefits. Nonendoscopic MIS approaches, such as percutaneous posterior or lateral, and mini-open lateral and anterior approaches, use direct visualization, standard operative techniques, and report lower complication rates, reduced length of stay, and faster recovery time. For newer MIS and mini-open techniques, significantly lower acute and subacute costs were observed compared with open techniques, mainly due to lower rates of complications, shorter length of stay, and less blood loss, as well as fewer discharges to rehab. Although this suggests that certain MIS procedures produce early cost benefits, the quality of the existing data are low. CONCLUSION: Although the CE of MIS surgery is yet to be carefully studied, the few economic studies that do exist suggest that MIS has the potential to be a cost-effective intervention, but only if improved clinical outcomes are maintained (durable). Longer follow-up and better outcome and cost data are needed to determine if incremental CE exists with MIS techniques, versus open or nonsurgical interventions.

An evidence-based approach to spine surgery.

Health care reform will emphasize evidence-based medicine to provide the highest quality care. Recent literature has emerged in spinal surgery that has profoundly increased the evidence base for several spinal procedures. There is now good evidence from randomized controlled trials that surgical treatment of symptomatic lumbar disc herniation, decompression for spinal stenosis, and decompression and fusion for degenerative spondylolisthesis all offer significant clinical benefit in the face of serious back and radicular pain when compared with nonsurgical care. Studies of nonsurgical and surgical treatments for chronic low back pain are inconclusive, limited by study design/methodology. Continuing to increase study quality in the field of spine surgery is more important now than ever before. Optimizing diagnostic specificity, surgical indications, and measuring outcomes with validated instruments should help the spine care community acquire essential data to provide the highest quality evidence-based care, while simultaneously eliminating procedures that lack evidence of efficacy or value.

Biopsy of osteoporotic vertebral compression fractures during kyphoplasty: unsuspected histologic findings of chronic osteitis without clinical evidence of osteomyelitis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate biopsy results obtained during vertebral augmentation (kyphoplasty) for presumed/confirmed osteoporotic vertebral compression fractures (VCFs). SUMMARY OF BACKGROUND DATA: Kyphoplasty to augment vertebrae in osteoporotic VCFs is well established. When VCF etiology is in question, bone biopsy can be performed at that time. Biopsy results, however, can be misleading without careful clinical correlation. METHODS: From July 2003 to July 2006, 94 vertebral biopsies were obtained from 66 patients during kyphoplasty for VCFs. Average patient age was 73 (range, 22-99), including 47 females and 19 males. There were 48 one-level, 17 two-level, and 4 three-level biopsies. Biopsy levels included: T6 (3), T7 (7), T8 (7), T9 (3), T10 (3), T11 (8), T12 (21), L1 (18), L2 (13), L3 (8), L4 (2), L5 (1). Histologic/immunohistochemical evaluations were performed. RESULTS: All specimens showed features of fracture in various stages of bony healing. Initially, 13 of 66 (19.7%) cases were read by a surgical pathologist as chronic inflammation, with 6 having features suggestive of chronic osteomyelitis, including polyclonal plasma cells, necrosis, and lymphoplasmacytic infiltrate. For this study, these biopsies were evaluated by an independent surgical pathologist (N.W.). Re-review showed 7 of the 13 cases were consistent with osteoporotic VCF healing in various stages with adjacent trilineage hematopoiesis. Six of 13 (46%), were read as containing fragmented bony spicules, fibrotic and fatty marrow, lymphoplasmacytic inflammation, and aggregates of mature, polyclonal plasma cells, suggesting the possibility of chronic osteomyelitis. However, at average follow-up of 37 months (range, 21-57 months), no patient demonstrated clinical and/or laboratory evidence of infection. Additionally, biopsies from 4 patients confirmed suspected or unsuspected malignancy, or confirmed no recurrence of malignant disease. CONCLUSION: Patients undergoing first-time vertebral augmentation should be considered for vertebral biopsy. Tissue examination is useful and may reveal pathologic fracture or possible infection. However, if infection is reported, clinical and laboratory correlation are important to make a diagnosis of osteomyelitis.

Spine surgeons survey on attitudes regarding osteoporosis and osteomalacia screening and treatment for fractures, fusion surgery, and pseudoarthrosis.

COMMENTARY ON: Dipaola CP, Bible JE, Biswas D, et al. Survey of spine surgeons on attitudes regarding osteoporosis and osteomalacia screening and treatment for fractures, fusion surgery, and pseudoarthrosis. Spine J 2009;9:537-44 (this issue).

Bone morphogenetic protein-2 (BMP-2) in the treatment of pyogenic vertebral osteomyelitis.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To present results of recombinant human bone morphogenetic protein-2 (rhBMP-2) use in medically nonresponsive pyogenic vertebral osteomyelitis (PVO), treated by anterior/posterior debridement and instrumented fusion in the cervical, thoracic, and lumbosacral spine. SUMMARY OF BACKGROUND DATA: Surgical options for PVO vary, as do their outcomes, and can be complicated by recurrence, pseudarthrosis, and death. Although rhBMP-2 use in spinal fusion is increasing, its utility in PVO is unknown. Additionally, use in areas of infection is listed as a contraindication, although this is not supported by laboratory (animal) studies or clinical studies in long bones. METHODS: Between 2003 and 2005, 14 patients who underwent circumferential fusion for PVO were included in this study. Average patient age was 54 years (range, 27-77 years). Eight (57%) patients had 3 or more vertebral bodies involved. Diagnostic studies included radiographs, CT, MRI, and markers of infection [(C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood count (WBC)]. All patients underwent anterior fusion with rhBMP-2 inserted in structural allograft (11 patients) or titanium cylindrical cages (3 patients), followed by posterior instrumented fusion with autogenous iliac crest graft (8 occurring on the same day). Follow-up averaged 22 months (range, 11-30 months). All were studied with plain radiographs, including flexion-extension lateral films and fine cut CT scans with reconstruction. Pain ratings were recorded by visual analog scores (VAS). RESULTS: Clinical resolution of infections, normalization of lab values, and bony fusion, based on dynamic radiographs and CT scans, were seen in all patients at latest follow-up. Staphylococcus aureus was the most frequently identified organism (8 patients). Four (29%) patients had positive blood cultures (all MRSA). Predisposing comorbidities were present in 12 patients. Six patients had epidural abscesses. Eight (57%) patients presented with neurologic deficits, ranging from paraparesis to quadriplegia. Complete recovery was seen in 7 (quadriplegia unchanged). At 1 year, mean VAS pain scores improved significantly (P < 0.05) from 7.9 (range, 3-10) to 2.8 (range, 0-6). Perioperative complications (non-BMP related) occurred in 2 patients. There were no surgically-related deaths. CONCLUSION: rhBMP-2 use, in combination with antibiotics and circumferential instrumented fusion, provides a safe and successful surgical treatment of medically nonresponsive PVO, with solid fusions obtained, good clinical results, and no adverse side effects from the BMP.

Analysis of cartilage tissue on a cellular level in fresh osteochondral allograft retrievals.

BACKGROUND: Fresh human osteochondral allografting is a biological cartilage replacement technique used to treat articular and osteoarticular defects in the knee. A small number of grafts fail, and we analyzed every retrieved graft during a 4-year period in order to learn more about the potential causes of failure. HYPOTHESIS: A large percentage of chondrocytes still remain viable many years after fresh osteochondral allografting. STUDY DESIGN: Descriptive laboratory study. METHODS: Retrieval specimens were obtained at the time of revision surgery and immediately analyzed. Chondrocyte viability and viable cell density were determined using a live/dead staining technique followed by confocal microscopy. Glycosaminoglycan content was a measure of the cartilage matrix. Radiolabeled sulfate uptake served as a biochemical marker of chondrocyte metabolic activity. Cartilage and subchondral bone were examined histologically. RESULTS: Fourteen patients yielded a total of 26 retrieval specimens that had been originally implanted as individual fresh osteochondral allografts. Average graft survival was 42 months. Chondrocyte viability was 82% +/- 17%, and chondrocyte viable cell density was 15 590 +/- 5900 viable cells/mm(3). Retrieved tissue demonstrated radiolabeled sulfate uptake of 437 +/- 270 counts per minute and 3.5% +/- 0.8% hexosamine per dry weight. Histologically, all specimens showed some degree of cartilage fibrillation. There was evidence of bone allograft incorporation in most specimens, as well as pannus formation in 4 specimens, but no evidence of immune rejection. CONCLUSION: A small percentage of fresh osteochondral allografts fail, but the precise cause is unknown. The main theories for failure investigated here include immunologic rejection, failure of bony incorporation, and chondrocyte death causing breakdown of the cartilage matrix. We show that chondrocytes remain viable many years after transplantation, allograft bone incorporates, and immune rejection does not seem to play a primary role in failure. CLINICAL RELEVANCE: Fresh osteochondral allografting is becoming more common in the treatment of articular cartilage defects in the knee. Our findings support the paradigm of fresh osteochondral allografting, the transplantation of hyaline cartilage with biological incorporation of the underlying bone scaffold. The reasons for failure of a small percentage of grafts remain unclear.

Chondrocyte viability after intra-articular calcaneal fractures in humans.

BACKGROUND: Chondral damage from the impact of injury may contribute to the high incidence of post-traumatic arthritis after calcaneal fractures, but this has yet to be proven. We sought to study the effect of intra-articular calcaneal fractures on chondrocyte viability and to correlate these effects with injury severity, time from injury to surgery, and patient age and co-morbidities. METHODS: Irreducible osteochondral fragments from 12 patients undergoing operative treatment for intra-articular calcaneal fractures were analyzed. Control cartilage was obtained from four tissue donors who died of unrelated causes. The cartilage was assessed for chondrocyte viability through the full thickness of tissue using a Live/Dead assay followed by laser scanning confocal microscopy. Patient demographics including injury classification and severity, time from injury to surgery, and patient age were recorded. RESULTS: Chondrocyte viability from fracture patients averaged 72.8% +/- 12.9% (range 53% to 95%), which was significantly lower than the 94.8% +/- 1.5% viability observed in the control specimens (p = 0.005). Chondrocyte viability declined with higher energy injuries (p = 0.13), time from injury to surgery (p = 0.07), and increasing patient age (p = 0.07). However, none of these factors reached a level of statistical significance. CONCLUSIONS: A significant decline in chondrocyte viability occurs after intra-articular fractures of the calcaneus. This may contribute to the development of post-traumatic arthritis.

Meniscal debridement with an arthroscopic radiofrequency wand versus an arthroscopic shaver: comparative effects on menisci and underlying articular cartilage.

PURPOSE: Meniscal debridement with an arthroscopic radiofrequency (RF) wand versus an arthroscopic shaver and their comparative effects on menisci and underlying articular cartilage were studied. METHODS: When repair is not feasible, degenerative or post-traumatic meniscal tears often need debridement. Six fresh bovine knees were harvested, the tibial plateau was dissected free from the femoral articulation and placed in a saline bath at 28 degrees C, with 10% to 15% of the posterior horn of menisci debrided arthroscopically, and the surfaces debrided using a basket punch plus shaver, punch plus RF wand, RF wand alone, and untreated control. Treatment time of each case was 24 seconds at wand power 7. We characterized an injury zone, as well as viability and metabolic activity of meniscal cells and tibial articular cartilage chondrocytes. RESULTS: Chondrocyte viability of the tibial articular surface was 96% to 98%. We saw no differences in viability or injury zone (0 to 150 microm) among debrided groups or versus the control for any experimental surface, with no significant difference in metabolic activity in menisci debrided surfaces versus control. Meniscal viability was variable with analyses showing substantial levels (150 to 500 microm) of cell death in debrided and control groups. Metabolic activity in treated meniscus was lower than in cartilage specimens. No significant differences were observed among treatment groups versus control. CONCLUSIONS: Focal areas of chondrocyte cell death were not seen. Meniscal samples showed cell death (150 to 500 mum) throughout the tissue. CLINICAL RELEVANCE: Debridement of menisci with a bipolar RF wand produces levels of cell injury and death similar to those of debridement with a basket punch mechanical shaver. The RF wand did not harm underlying articular surfaces and produced a precise cut to the meniscal surface.

Upregulation of apoptotic and matrix-related gene expression during fresh osteochondral allograft storage.

We identified changes in proapoptotic and extracellular matrix-related gene expression with prolonged storage of fresh osteochondral allografts using gene array analysis to better understand the process of graft degradation during storage. Six human distal femurs were obtained according to standard organ harvesting protocol and stored in serum-free allograft media. Each was examined at baseline (within 72 hours postmortem), 21 days (average time of implantation), and 35 days (maximum time to implantation) for proapoptotic and extracellular matrix-related gene expression using two 100-gene microarrays, cell viability using confocal microscopy, and proteoglycan synthesis via SO4 incorporation. We found numerous genes showing upregulation associated with increased storage time, including CD30, CD30 ligand, Fas, Fas ligand, tumor necrosis factor-alpha, and several caspases. Cell viability and proteoglycan synthesis also were significantly decreased with increased storage. Loss of chondrocytes via apoptosis is likely a key determinant of osteochondral allograft viability during storage, whereas extracellular matrix degeneration may occur at a later stage. These findings provide targets for future media modulation. Improved graft viability and the potential for lengthened storage periods through improved storage conditions may improve clinical outcomes and availability of fresh osteochondral allografts.

Analysis of stored osteochondral allografts at the time of surgical implantation.

BACKGROUND: To date, the morphological, biochemical, and biomechanical characteristics of articular cartilage in osteochondral allografts that have been stored have not been fully described. HYPOTHESIS: Osteochondral allografts procured and stored commercially for a standard period as determined by tissue banking protocol will have compromised chondrocyte viability but preserved extracellular matrix quality. STUDY DESIGN: Controlled laboratory study. METHODS: Unused cartilage from 16 consecutive osteochondral allografts was sampled during surgery after tissue bank processing and storage. Ten grafts were examined for cell viability and viable cell density using confocal microscopy, proteoglycan synthesis via 35SO4 uptake, and glycosaminoglycan content and compared with fresh cadaveric articular cartilage. Biomechanical assessment was performed on the 6 remaining grafts by measuring the indentation stiffness of the cartilage. RESULTS: The mean storage time for the transplanted specimens was 20.3 +/- 2.9 days. Chondrocyte viability, viable cell density, and 35SO4 uptake were significantly lower in allografts at implantation when compared to fresh, unstored controls, whereas matrix characteristics, specifically glycosaminoglycan content and biomechanical measures, were unchanged. In addition, chondrocyte viability in the stored allografts was preferentially decreased in the superficial zone of cartilage. CONCLUSION: Human osteochondral allografts stored for a standard period (approximately 3 weeks) before implantation undergo decreases in cell viability, especially in the critically important superficial zone, as well as in cell density and metabolic activity, whereas matrix and biomechanical characteristics appear conserved. The exact clinical significance of these findings, however, is unknown, as there are no prospective studies examining clinical outcomes using grafts stored for extended periods. CLINICAL RELEVANCE: Surgeons who perform this procedure should understand the cartilage characteristics of the graft after 21 days of commercial storage in serum-free media.