Thalassaemia Patients with Polymorphism of COL1A1 Sp1 are at Greater Risk of Spine Degenerative Changes.

OBJECTIVE: To explore the association of the COL1A1 Sp1 polymorphism with decreased bone density and spinal changes in ß-thalassaemia patients. STUDY DESIGN: Cross-sectional, comparative study. Place and Duration of the Study: University of Health Sciences, Lahore, from May 2020 to June 2021. METHODOLOGY: A total of 110 participants (55patients and 55 controls) of either gender, with ages ranging from 18-40 years were enrolled in the study. Bone density parameters including T-score, Z-score, bone-transmission time (BTT), and amplitude-dependent speed of sound (ADSOS) were assessed by ultrasound bone profiler. Lumbar spine radiographs were collected from patients and assessed for spine changes. Genotype analysis was done by HRM-PCR. Data were analysed using SPSS version 23. RESULTS: All bone density parameters were significantly lower in ß-thalassaemai patients (p<0.001). Spine degenerative changes were more obvious in patients with age <25 years (p=0.04). Loss of lumbar lordosis was seen in 74.5% of the patients. The frequency of mutant allele (ss) was 7.3% while heterozygous (Ss) frequency was found to be 33.6%. The polymorphism showed significant association with T-scores (p=0.03) and ADSOS (p=0.02) in patients. Radiographic grades were higher in osteopenic and osteoporotic patients (p=0.04). CONCLUSION: The association of polymorphism with decreased bone density in ß-thalassaemia patients revealed the potential role of genetics in bone changes and related disorders. KEY WORDS: Bone Density, COL1A1 Polymorphism, Osteoporosis, Thalassaemia.

MRI phenotypes of herniated discs associated with adjacent disc degeneration.

Adjacent segment degeneration is commonly observed in patients after fusion surgery. Among the associated risk factors is the preoperative presence of adjacent disc degeneration (ADD). The risk factors and other spine phenotypes associated with preoperative ADD is critical to understand the pathological process and better prognosis postsurgery. Current study aims to assess and compare the magnetic resonance imaging (MRI) spinal phenotype of herniated level with and without ADD. Preoperative T2W sagittal lumbar MRI images of 155 lumbar disc herniated patients were analyzed for the presence of ADD (Pfirrmann grade III and above). The herniated disc level was assessed for the presence and absence of vertebral endplate (VEP) defects, Modic changes, and high intensity zone (HIZ). Mean age of patients was 38 ± 2 years, almost 62% were males. ADD was found in 57%, VEP defects were seen in 62% of the herniated level, 24.5% showed Modic changes, 3.8% showed spondylolishthesis, and 15.5% revealed HIZ. Age and other demographic factors did not have any significant effect on the presence of ADD, the patients with extruded and sequestered discs had more ADD (p = 0.02). VEP defects were significantly higher in levels with ADD (p = 0.02). Patients with ADD had significantly VEP defect scores (p = 0.01), Modic score (p = 0.002), HIZ score (0.02), and posterior bulge score (p < 0.001). Findings suggest that affected levels with VEP defects and severe grade of disc herniation have the greater likelihood of having ADD. Once developed this ADD may also affect the other spinal levels, and also can affect postoperative prognosis.

Bullying, harassment, and discrimination of musculoskeletal researchers and the impact of the COVID-19 pandemic: an international study.

PURPOSE: Bullying, harassment, and discrimination (BHD) are prevalent in academic, scientific, and clinical departments, particularly orthopedic surgery, and can have lasting effects on victims. As it is unclear how BHD affects musculoskeletal (MSK) researchers, the following study assessed BHD in the MSK research community and whether the COVID-19 pandemic, which caused hardships in other industries, had an impact. METHODS: A web-based anonymous survey was developed in English by ORS Spine Section members to assess the impact of COVID-19 on MSK researchers in North America, Europe, and Asia, which included questions to evaluate the personal experience of researchers regarding BHD. RESULTS: 116 MSK researchers completed the survey. Of respondents, 34.5% (n = 40) focused on spine, 30.2% (n = 35) had multiple areas of interest, and 35.3% (n = 41) represented other areas of MSK research. BHD was observed by 26.7% (n = 31) of respondents and personally experienced by 11.2% (n = 13), with mid-career faculty both observing and experiencing the most BHD. Most who experienced BHD (53.8%, n = 7) experienced multiple forms. 32.8% (n = 38) of respondents were not able to speak out about BHD without fear of repercussions, with 13.8% (n = 16) being unsure about this. Of those who observed BHD, 54.8% (n = 17) noted that the COVID-19 pandemic had no impact on their observations. CONCLUSIONS: To our knowledge, this is the first study to address the prevalence and determinants of BHD among MSK researchers. MSK researchers experienced and observed BHD, while many were not comfortable reporting and discussing violations to their institution. The COVID-19 pandemic had mixed-effects on BHD. Awareness and proactive policy changes may be warranted to reduce/eliminate the occurrence of BHD in this community.

Mechanisms and clinical implications of intervertebral disc calcification.

Low back pain is a leading cause of disability worldwide. Intervertebral disc (IVD) degeneration is often associated with low back pain but is sometimes asymptomatic. IVD calcification is an often overlooked disc phenotype that might have considerable clinical impact. IVD calcification is not a rare finding in ageing or in degenerative and scoliotic spinal conditions, but is often ignored and under-reported. IVD calcification may lead to stiffer IVDs and altered segmental biomechanics, more severe IVD degeneration, inflammation and low back pain. Calcification is not restricted to the IVD but is also observed in the degeneration of other cartilaginous tissues, such as joint cartilage, and is involved in the tissue inflammatory process. Furthermore, IVD calcification may also affect the vertebral endplate, leading to Modic changes (non-neoplastic subchondral vertebral bone marrow lesions) and the generation of pain. Such effects in the spine might develop in similar ways to the development of subchondral marrow lesions of the knee, which are associated with osteoarthritis-related pain. We propose that IVD calcification is a phenotypic biomarker of clinically relevant disc degeneration and endplate changes. As IVD calcification has implications for the management and prognosis of degenerative spinal changes and could affect targeted therapeutics and regenerative approaches for the spine, awareness of IVD calcification should be raised in the spine community.

Management of Giant Cell Tumor of Talus With Extended Intralesional Curettage and Reconstruction Using Polymethylmethacrylate Cement.

An 18-year-old man presented with complaints of pain and swelling around the left ankle region. Local examination revealed diffuse, hard, mildly tender swelling with ill-defined margins over the medial aspect of the left ankle joint just below the medial malleolus. Radiographic and computed tomographic assessment revealed osteolytic lesion with moderately defined margins. Provisional diagnosis of Campanacci grade 2 giant cell tumor was made, which was later confirmed on histopathology. Extended intralesional curettage and reconstruction with polymethylmethacrylate cement was done under spinal anesthesia. Full weight bearing was allowed at 4 weeks when the below knee back slab was removed. Radiographic assessment was done every 3 months during the first year of follow-up and then every 6 months. No evidence of recurrence of tumor, collapse of talus, or avascular necrosis was found during follow-up. Managing such rare form of bone tumors with extended intralesional curettage and bone cement is an appropriate treatment and gives good functional results.Level of Evidence: Level V.

Lower urinary tract symptoms in patients with small prostates: Smooth muscle proliferation and calcification might be causative factors.

OBJECTIVES: The current study is designed to evaluate and compare the histological changes in the surgical samples of prostate taken from patients undergoing transurethral resection of prostate (TURP) for benign prostate hyperplasia (BPH) with different sizes. METHODS: Prostate surgical tissue samples were obtained from BPH patients undergoing TURP after taking informed consent. Ultrasound measure of prostatic weight and prostate-specific antigen (PSA) levels were obtained from the patients along with other clinical and demographic details. Tissue samples were fixed, processed, sectioned and stained with hematoxylin and eosin and Masson's trichrome to look for histological features, specifically smooth muscle proliferation. Immunohistochemical expression of bone morphogenetic protein (BMP)-2 was recorded to assess the calcification potential. RESULTS: Fifty-nine surgical samples were obtained from the patients of age range 50-90 years and body mass index (BMI) 15.6-33.3 kg/m2 . The range of ultrasound measures of prostate weight was 20-137 g with PSA ranged 1.03-93.3 ng/mL. Patients with small-sized prostate had significant severe smooth muscle proliferation (P < .001). Prostate size/weight had significant positive association with BMI (P < 0.001, r = 0.543) and negative association with BMP-2 (P < 0.001, r = -0.654). Samples with severe smooth muscle proliferation were with increased BMP-2 expression (P < .001) and higher levels of PSA levels (P = 0.004). BMP-2 expression revealed positive significant association with PSA (P < .001, r = 0.432). CONCLUSION: From this study we conclude that BPH patients with small-sized glands and high PSA levels have increased smooth muscle proliferation and calcification potential causing the symptoms of lower urinary tract symptoms in these patients.

Management of femoral shaft infected nonunion through customised Ilizarov external fixator assembly in a morbidly obese patient.

A 19-year-old morbidly obese man presented with infected nonunion of femoral shaft fracture. Patient had history of 13 failed fixation surgeries, assessment revealed 3-centimetre limb-length discrepancy with 3-centimetre gap nonunion. Wound debridement, primary compression and external fixation using a customised Ilizarov external fixation assembly were planned. A four-ring customised assembly was applied. Partial weight bearing was allowed from first postoperative day on walker. Patient was kept on a monthly follow-up. After complete union at 10 months after surgery, frame was dynamised. After 6 months of dynamisation, frame was removed, at that time patient was full weight bearing. Knee was still stiff with a range of motion of 0°-20°, and there was 6 cm of limb length discrepancy, which was managed with a shoe raise. At 9 months after frame removal, patient is mobile with fully united bone. Ilizarov external fixator can be a good managing option in such difficult and complicated cases.

Vertebral Endplate Changes Correlate with Presence of Cartilaginous Endplate in the Herniated Disc Tissue: Factor Predicting Failure of Conservative Treatment.

STUDY DESIGN: Cross-sectional comparative. PURPOSE: To characterize the scores of disc degeneration, inflammation, and nerve density in herniated disc samples and associate findings with the presence of vertebral endplate (VEP) changes on magnetic resonance imaging (MRI). OVERVIEW OF LITERATURE: Considering the role of disc composition in spontaneous regression and persistence of pain during conservative management, it is important to identify the influencing factors. VEP changes are highly associated with disc degeneration, but their correlation with herniated disc composition has not yet been reported. METHODS: Fifty-one discs were obtained from patients undergoing surgery for herniated disc. Their ages ranged from 19-65 years, and 31/51 were male. Pre-surgical T1 and T2 weighted lumbar-spine MRIs were analyzed to observe Pfirrmann grade, VEP defects, herniation type, Modic changes, and high-intensity zones (HIZ) at the affected level. Five-micron thick sections were stained with hematoxylin and eosin, Alcian blue periodic acid-Schiff stain; examined for histological degeneration scores (HDS; 0-15), inflammation (0 [absence]-3 [severe]), and presence of cartilaginous endplate (CEP). Three-micron thick sections were stained with protein-gene-product 9.5 and expression was counted/mm2. Data was analyzed, and p<0.05 was considered to indicate statistical significance. RESULTS: VEP defects, Modic changes, and HIZ were respectively observed in 30/51, 16/51, and 6/51 of the samples. CEP was observed in 26/51 samples and in 23/51 with endplate defects. Discs with adjacent VEP defects showed increased HDS (p<0.001) and inflammation (p<0.001). Discs with adjacent Modic changes also revealed increased HDS (p=0.01). Histological sections with CEP showed increased HDS (p<0.001) and inflammation (p<0.001), and nerve density was significantly positively correlated with HDS (r=0.27, p=0.02). CONCLUSIONS: VEP changes can modulate degeneration and inflammation of herniated discs. Presence of these changes is highly predictive of the occurrence of CEP in herniated discs, which leads to slow resorption and persistent clinical symptoms.

Preoperative management through modified halo-pelvic distraction assembly in a case of severe thoracic spine kyphosis.

BACKGROUND: Halo-traction device has been seen with favorable outcome in managing the patients with severe kyphotic deformities preoperatively, however, associated complications are inevitable. Slight modifications can improve the outcome and clinical efficacy. CASE DESCRIPTION: A 14-year-old boy was presented with severe kyphotic deformity of 141° from T1 to T10 thoracic vertebrae with diffuse paraspinal calcification in thoracic spine and complete loss of power of both lower limbs. A modified halo-pelvic distraction device was applied before the definitive surgery. The device comprised halo and pelvic assembly, the halo ring was connected to the head with 06 pins, while pelvic assembly had Ilizarov half pins connected to the arches. The assembly construct had four threaded rods, two of them were placed anterolateral and the other two were posterolateral. Distraction at the rate of 3 mm/day was started from 1st postoperative day for 35 days. The neurology improved in both lower limbs and kyphotic angle reduced to 56° from 141°. Surgery at this stage was done and a standalone solid titanium cage was placed from T1 to T10 vertebral body after debridement. No peri- or post-operative complications were observed. CONCLUSION: The application of halo-pelvic distraction before corrective surgeries can not only reduce the severity of the kyphotic deformity making the definitive surgery easy but neurology can also be improved. The high-risk complications associated with acute correction of deformities can be minimized using our modified halo-pelvic distraction device.

Malunited and malrotated Salter-Harris type I fracture of distal femur managed with circular ring external Ilizarov fixator.

A 9-year-old girl presented with malunited Salter-Harris type I fracture of distal femur treated by bone-setter (unreliable-practitioner). Assessment revealed 3 cm limb-length-discrepancy and affected leg was unable to bear weight, knee was stiff with no active-range of motion; radiographs showed displaced sagittally malunited femoral condyle with 163° posterior distal femoral angle (PDFA). Correction planned with circular-ring-external Ilizarov fixator using distraction-osteogenesis through supracondylar osteotomy and gradual anterior opening. Partial weight bearing allowed from first postoperative day on walker. Eight weeks follow-up showed restored anatomical position of femoral condyle and PDFA. During anterior-distraction and angulation correction, tibia subluxated posteriorly, for that assembly extended to tibia which gradually translated tibia anteriorly and reduced knee. Twenty weeks after removal of assembly patient was advised knee-ankle-foot-orthosis. At 40 weeks of frame removal, patient was walking without support and pain. Managing such rare injuries with distraction-osteogenesis technique allows gradual correction and monitoring, till desirable degree of correction is achieved.

Spinopelvic alignment predicts disc calcification, displacement, and Modic changes: Evidence of an evolutionary etiology for clinically-relevant spinal phenotypes.

Lumbar disc-displacement, Modic changes (MCs), and UTE Disc Sign (UDS) on MRI are clinically relevant spinal phenotypes that can lead to sciatica/LBP. Not all degenerated discs result in disc-displacement, MCs and UDS, suggesting varied etiologies. Spinopelvic parameters have been implicated in various spinal disorders. Pelvic incidence (PI) is "fixed parameter" since skeletal maturity. No study has addressed disc-displacement, MCs and UDS in context of spinopelvic parameters. Therefore, the aim of study was to determine if spinopelvic parameters are associated and predict clinically-relevant MRI-phenotypes. One hundred and eight population-based subjects (mean age: 52.3 years) were recruited. Spondylolisthesis and scoliosis individuals were excluded. Lumbar lordosis (LL), PI, sacral slope (SS), and pelvic tilt (PT) were assessed on lateral plain radiographs. Disc degeneration was assessed and summated, and presence or not of disc-displacement and MCs were noted on T2W MRI. UDS was detected on UTE. Following exclusion criteria, 95 subjects were assessed. Disc-displacement (82.1%), MCs (52.6%), and UDS (37.9%) were associated with lower PI, SS, LL, and LL/PI index. On multivariate analyses, lower PI was significantly related to development of these MRI phenotypes (adjusted OR range:0.95-0.92; P < .05), with critical PI value of 42° or lower exhibiting fourfold increase risk of combined phenotypes (P = .020). Of UDS discs, 39.3% had adjacent MCs and 83.6% had disc-displacement. 87.5% of MC had directly adjacent UDS. The first study to note that PI may "predict" the development of disc-displacement, MCs and UDS, suggesting potential sub-variants and mechanistic susceptibility that may be grounded in spinopelvic evolution. An "evolutionary etiological pathway" of spinal phenotype development is proposed.

Associations Between Intervertebral Disc Degeneration Grading Schemes and Measures of Disc Function.

Disc degeneration is a major cause of spinal dysfunction and pain, but grading schemes concentrate on tissue changes rather than altered function. The aim of this study was to compare disc degeneration grading systems with each other, and with biomechanical measures of disc function. Sixty-six motion segments (T8-9 to L5-S1) were dissected from cadavers aged 48-98 years. Disc function was assessed by measuring nucleus pressure (IDP) and maximum stresses in the annulus under 1 kN of compression. Detailed "scores" of disc degeneration were based on independent radiographic, macroscopic, and microscopic evaluations. For each evaluation, scores were used to assign a degeneration "grade" (I-IV), and functional measures were then correlated with degeneration scores and grades. Results showed that all measures were reliable (intraclass correlation coefficients: 0.82-0.99). Macroscopic and microscopic assessments were highly correlated with each other (r: 0.57-0.89, p < 0.001) but only weakly correlated with radiographic features. The overall macroscopic and microscopic scores of degeneration increased significantly with age and at lower spinal levels, although the influence of age was less marked in the case of the microscopic scores. IDP decreased with age and at lower spinal levels, but annulus stresses were more variable. Importantly, IDP and annulus stresses decreased consistently with all measures of disc degeneration, and these associations remained strong after controlling for age, gender, and spinal level. We conclude that radiographic and tissue-based assessments of disc degeneration are consistent with each other, and are more closely related to mechanical (dys)function than to age or spinal level. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1946-1955, 2019.

Multidimensional vertebral endplate defects are associated with disc degeneration, modic changes, facet joint abnormalities, and pain.

The aim of the current study was to investigate the multi-dimensional characteristics of lumbar endplate defects in humans in relation to disc degeneration and other MRI phenotypes as well as their role with pain and disability. A total of 108 subjects were recruited and underwent 3T MRI of the lumbar spine. Structural endplate defects were identified and their dimensions were measured in terms of maximum width and depth, and were then standardized to the actual width of the endplate and depth of the vertebral body, respectively. Both width and depth of all endplate defects in each subject were added separately and scores were assigned on the basis of size from 1 to 3. Combining both scores provided "cumulative endplate defect scores." Disc degeneration scores, Modic changes, disc displacement, HIZ, and facet joint changes were assessed. Subject demographics, pain profile, and Oswestry Disability Index (ODI) were also obtained. Endplate defects were observed in 67.5% of the subjects and in 13.5% of the endplates. All dimensions of endplate defects showed significance with disc degenerative scores, Modic changes, and posterior disc displacement (p < 0.05). Maximum width (p = 0.009) and its standardized value (p = 0.02), and cumulative endplate defect scores (p = 0.004) increased with narrow facet joints. Cumulative endplate defect scores showed a strong positive association with ODI (p < 0.05) compared to disc degenerative scores. Large size endplate defects were strongly associated with degenerative spine changes and more back-related disability. Findings from this study stress the need to assess endplate findings from a multi-dimensional perspective, whose role may have clinical utility. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Structural vertebral endplate nomenclature and etiology: a study by the ISSLS Spinal Phenotype Focus Group.

PURPOSE: Vertebral endplate abnormalities may be associated with disc degeneration and, perhaps, pain generation. However, consensus definitions for endplate findings on spine MRI do not exist, posing a challenge to compare findings between studies and ethnic groups. The following survey was created to characterize the variability among the global spine community regarding endplate structural findings with respect to nomenclature and etiology. METHODS: A working group within the International Society for the Study of the Lumbar Spine (ISSLS) Spinal Phenotype Focus Group was established to assess the endplate phenotype. A survey which consisted of 13 T2-weighted sagittal MRIs of the human lumbar spine illustrating the superior and inferior endplates was constructed based on discussion and agreement by the working group. A list of nomenclature and etiological terms with historical precedence was generated. Participants were asked to describe the endplates of each image and select from 14 possible nomenclatures and 10 etiological terms along with the option of free text response. The survey was entered into RedCap and was circulated throughout the ISSLS membership for data capture. Participants' demographics were also noted. RESULTS: The survey was completed by 55 participants (87% males; 85% above 45 years of age, 39 clinicians, and 16 researchers). Sixty-eight percent of researchers and seventy-four percent of clinicians reported more than 16 and 20 years of research and clinical experience. Considerable variation existed in selection of nomenclature, etiology, and degree of severity of the endplate structural findings (reliability coefficients for single measures in each case were 0.3, 0.08, and 0.2, respectively). Sixty-seven percent regarded Modic changes as being a structural endplate finding. Approximately 84 and 80% of clinicians and researchers, respectively, agreed that a standardized endplate nomenclature and understanding the etiology is clinically important and needed. CONCLUSIONS: This study found that variations exist with respect to endplate nomenclature and etiology between clinicians and basic scientists, and paves the way for a consensus process to formalize the definitions.

The association of lumbar intervertebral disc calcification on plain radiographs with the UTE Disc Sign on MRI.

PURPOSE: The pathogenesis and the clinical impact of disc calcification are not well known. Utilizing ultra-short time-to-echo (UTE) magnetic resonance imaging, the UTE Disc Sign (UDS) (i.e., hypo/hyper-intense disc band) was developed and found to be more significantly related to pain and disability than the conventional T2-weighted (T2W) MRI. It has been hypothesized that the UDS may represent mineralized deposits in the disc. The following study addressed the relationship between disc calcification on plain radiographs to that of the UDS on MRI. METHODS: A cross-sectional study was performed on 106 Southern Chinese subjects (50% male; mean age 52.3 years). Standing lateral plain radiographs as well as T2W and UTE MRI of L1-S1 (n = 530 discs) were performed of all subjects. Lateral radiographs were used to localize disc calcification of the lumbar spine, T2W MRI was utilized to assess disc degeneration based on a defined grading scheme, and the UTE MRI was implemented to detect the UDS (hyper- or hypo-intense band across a disc). Disc degeneration and UDS scores were summed to represent cumulative scores. Subject demographics and disability profiles (Oswestry Disability Index: ODI) were obtained. RESULTS: Disc calcification on plain radiographs was observed in 33.9% of subjects (55.5% males; mean age 54.3 years), whereas UDS was noted in 40.5% of subjects (51.1% males; mean age 55.0 years). Of these subjects, 66.6% calcification and 74.4% UDS occurred at the three lowest lumbar levels, while multilevel calcification and UDS involved 19.4 and 39.5%, respectively. 72.2% of subjects with plain radiographic disc calcification had corresponding UDS on UTE MRI (p < 0.001). Multilevel disc calcification on plain radiographs was associated with multilevel UDS (71.4%, p < 0.001). Both the number of calcified disc levels on plain radiographs and the number of UDS levels were also significantly and positively correlated with each other (r = 0.58, p < 0.001). Subjects with disc calcification and positive UDS as well as individuals with increased disc degeneration scores on T2 W MRI were significantly older (p < 0.05). The cumulative UDS score on UTE MRI significantly correlated with worse ODI scores (r = 0.31; p = 0.001), whereas cumulative disc calcification scores on plain radiographs did not (r = 0.15; p = 0.19). CONCLUSIONS: This is the first study to compare the UDS on UTE MRI with disc calcification on plain radiographs. Disc calcification was correlated with the UDS on UTE, suggesting that the UDS may represent disc calcification. However, UTE MRI appears to be a more sensitive imaging modality in identifying subtle and unique disc changes that may not be revealed on plain radiographs or conventional MRI. This disconnect may rationalize the significant correlation of UTE with disability in comparison with the conventional imaging, further stressing its potential clinical importance.

The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability.

STUDY DESIGN: Cross-sectional. OBJECTIVE: To assess the distribution of the ultra-short time-to-echo (UTE) disc sign (UDS) and its association with disc degeneration, other magnetic resonance imaging (MRI) phenotypes, pain, and disability profiles. SUMMARY OF BACKGROUND DATA: Disc degeneration has been conventionally assessed by T2-weighted (T2W) signal intensity on MRI; however, its clinical utility has been questionable. UTE MRI assesses short T2 components. The authors have identified a new imaging biomarker on UTE-the UDS. METHODS: One hundred eight subjects were recruited. T2W MRI assessed disc degeneration and other phenotypes, and T1-rho MRI values represented quantitative proteoglycan disc profiles of L1-S1. UDS was detected on UTE (i.e., hyper-/hypointense disc band). A UDS score (cumulative number of UDS levels) and T2W summated lumbar degenerated scores (cumulative disc degeneration score) were assessed. Subject demographics, chronic low back pain (LBP), and disability profiles (Oswestry Disability Index: ODI) were obtained. RESULTS: UDS was noted in 39.8% subjects, 61.4% occurred at the lower lumbar spine and 39.5% had multilevel UDS. UDS subjects had significantly greater severity and extent of disc degeneration, and Modic changes (P < 0.05). By disc levels, a higher prevalence of disc degeneration/displacement, Modic changes, and spondylolisthesis were noted in UDS discs than non-UDS discs (P < 0.05). T1-rho values were also lower in UDS discs (P = 0.022). The majority of UDS could not be detected on T2W. The UDS score significantly correlated with worse ODI scores (r = 0.311; P = 0.001), whereas T2W cumulative disc degeneration score did not (r = 0.13; P = 0.19). LBP subjects exhibited more multilevel UDS (P < 0.015) but not on T2W MRI (P = 0.53). The UDS score was significantly related to LBP (P = 0.009), whereas T2W cumulative disc degeneration score was not (P = 0.127). CONCLUSION: This is the first study to report "UDS" in humans. UDS is a novel imaging biomarker that is highly associated with degenerative spine changes, chronic LBP, and disability than conventional T2W MRI. LEVEL OF EVIDENCE: 2.

Defects of the vertebral end plate: implications for disc degeneration depend on size.

BACKGROUND CONTEXT: Bony vertebral end plates must be porous to allow metabolite transport into the disc, and yet strong to resist high intradiscal pressure (IDP). End plate defects may therefore have nutritional and mechanical consequences for the disc, depending on their size and type. We hypothesize that broad, diffuse defects are more closely associated with disc decompression and degeneration than are focal Schmorl's node-type defects. PURPOSE: This study aimed to determine how the size and type of end plate defects are related to decompression and degeneration in the adjacent intervertebral disc. STUDY DESIGN: Mechanical, histologic, and micro-computed tomographic investigations were carried out in cadaver spines. METHODS: The study involved 40 motion segments (T8-T9 to L4-L5) dissected from 23 cadavers aged 48-98 years. Intradiscal stresses were measured, under 1 kN compression, by pulling a pressure transducer along the disc's midsagittal diameter. The resulting "stress profiles" revealed nucleus pressure (IDP) and maximum stresses in the anterior and posterior annulus. Micro-computed tomography was then used to examine all 40 discs, with 5 mm of adjacent bone on either side, so that end plate defects could be characterized at a resolution of 35 µm. Cross-sectional area (in the transverse plane), volume, location, and morphologic type were determined for all bony defects in the 80 end plates. Finally, discs from each motion segment (with hyaline cartilage and bone attached) were sectioned (undecalcified) at 7 µm for histology to allow degeneration to be assessed. RESULTS: Substantial defects were identified in 24 of 40 specimens (35 of 80 end plates). Of these, 83% was centrally located, and 17% was laterally located. Defects occurred more frequently in male than female specimens (p=.043), and were more common in thoracic than lumbar end plates (p=.002), although lumbar defects were greater in volume (p=.05). Defect area and volume increased with decreasing IDP, with decreasing peak stress in the annulus, and with increasing tissue degeneration. Stepwise multiple regression showed that average defect area depended most strongly on IDP, whereas maximum defect area and volume depended most strongly on peak stress in the anterior annulus. Multiple end plate defects were associated with lower values of IDP and higher degeneration scores when compared with erosions and Schmorl's nodes. CONCLUSIONS: Disc degeneration has a stronger association with large or multiple end plate defects than with small or single defects (of any type). Large end plate defects probably allow greater volume changes within the disc, leading to greater nucleus decompression.

Porosity and Thickness of the Vertebral Endplate Depend on Local Mechanical Loading.

STUDY DESIGN: Mechanical and microcomputed tomography (micro-CT) study of cadaver spines. OBJECTIVE: To compare porosity and thickness of vertebral endplates with (1) compressive stresses measured in adjacent intervertebral discs and (2) grade of disc degeneration. SUMMARY OF BACKGROUND DATA: Endplate porosity is important for disc metabolite transport, and yet porosity increases with age and disc degeneration. We hypothesize that porosity is largely determined by mechanical loading from adjacent discs. METHODS: Forty motion segments (T8-9 to L4-5) were dissected from 23 cadavers aged 48 to 98 years. Each was subjected to 1 kN compression during which time intradiscal stresses were measured by pulling a pressure transducer along the disc's midsagittal diameter. "Stress profiles" revealed the average pressure in the nucleus, and the maximum stress in the anterior and posterior annulus. Specimens were further dissected to obtain discs with endplates (and 5 mm of bone) on either side. Microcomputed tomography scans (resolution 35 µm) were analyzed to calculate thickness and porosity in the midsagittal regions of all 80 endplates. Average values for the anterior, central, and posterior regions of each endplate were obtained. Disc degeneration was assessed macroscopically and microscopically. RESULTS: Endplate porosity was inversely related to its thickness, being greatest in the central region opposite the nucleus, and least near the periphery. Superior endplates (relative to the disc) were 14% thicker (P < 0.001) and 4% less porous (P = 0.008) than inferior. In each of the 3 endplate regions (anterior, central, and posterior), porosity was inversely and significantly related to mechanical loading (pressure or maximum stress) in the adjacent disc region (P < 0.01 in all cases). Disc degeneration was best predicted by (reduced) nucleus pressure (R = 0.46, P < 0.001) and (reduced) maximum stress in the anterior annulus (R = 0.31, P < 0.001). CONCLUSION: Mechanical loading is a major determinant of endplate thickness and porosity. Disc degeneration is more closely related to reduced disc stresses than to endplate thickness or porosity. LEVEL OF EVIDENCE: N/A.

Why do some intervertebral discs degenerate, when others (in the same spine) do not?

This review suggests why some discs degenerate rather than age normally. Intervertebral discs are avascular pads of fibrocartilage that allow movement between vertebral bodies. Human discs have a low cell density and a limited ability to adapt to mechanical demands. With increasing age, the matrix becomes yellowed, fibrous, and brittle, but if disc structure remains intact, there is little impairment in function, and minimal ingrowth of blood vessels or nerves. Approximately half of old lumbar discs degenerate in the sense of becoming physically disrupted. The posterior annulus and lower lumbar discs are most affected, presumably because they are most heavily loaded. Age and genetic inheritance can weaken discs to such an extent that they are physically disrupted during everyday activities. Damage to the endplate or annulus typically decompresses the nucleus, concentrates stress within the annulus, and allows ingrowth of nerves and blood vessels. Matrix disruption progresses by mechanical and biological means. The site of initial damage leads to two disc degeneration "phenotypes": endplate-driven degeneration is common in the upper lumbar and thoracic spine, and annulus-driven degeneration is common at L4-S1. Discogenic back pain can be initiated by tissue disruption, and amplified by inflammation and infection. Healing is possible in the outer annulus only, where cell density is highest. We conclude that some discs degenerate because they are disrupted by excessive mechanical loading. This can occur without trauma if tissues are weakened by age and genetic inheritance. Moderate mechanical loading, in contrast, strengthens all spinal tissues, including discs.

Significance of cartilage endplate within herniated disc tissue.

PURPOSE: Disc herniations sometimes contain hyaline cartilage fragments, but their origins and significance are uncertain. METHODS: Herniations were removed surgically from 21 patients (aged 35-74 years) whose main symptom was sciatica (10 patients) or back pain (11 patients). Frozen sections, 5 µm thick, were examined histologically, and antibodies were used to label the matrix-degrading enzyme MMP 1, pro-inflammatory mediator TNFα, and cell proliferation marker Ki-67. Proportions of each tissue type were quantified by image analysis. Cartilage and bone components of the endplate were examined in 7-µm frozen sections from 16 cadaveric spines, aged 61-98 years. RESULTS: Cartilage fragments were found in 10/21 herniations. They averaged 5.0 mm in length, comprised 25 % of the herniation area, and two had some bone attached. Hyaline cartilage was more common in herniations from patients with sciatica (7/10) than with back pain (3/11, P = 0.050), and the area (%) of the herniation occupied by the cartilage was greater in sciatica patients (P < 0.05). Cartilage fragments showed little evidence of swelling, proteoglycan loss or inflammatory cell invasion, although cell clustering was common, and TNFα was sometimes expressed. Each cartilage fragment showed at least one straight edge, as if it had been peeled off the bony endplate, and this mechanism of failure was demonstrated in preliminary mechanical experiments. CONCLUSION: Disc herniations often include hyaline cartilage pulled from the vertebral endplates. Cartilage fragments show little swelling or proteoglycan loss, and may be slow to resorb, increasing the risk of persisting sciatica. Loss of cartilage will increase endplate permeability, facilitating endplate inflammation and disc infection.