Increased matrix metalloproteinase-2 in ligamentum flavum hypertrophy and the regulation of MMP-2/TIMPs by elastin-derived peptides.

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

Characteristics of Spinal Morphology According to the "Current" and "Theoretical" Roussouly Classification Systems in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study (MEANS).

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVE: To classify spinal morphology using the "current" and "theoretical" Roussouly systems and assess sagittal alignment in an asymptomatic cohort. METHODS: 467 asymptomatic volunteers were recruited from 5 countries. Radiographic parameters were measured via the EOS imaging system. "Current" and "theoretical" Roussouly classification was assigned with sagittal whole spine imaging using sacral slope (SS), pelvic incidence (PI), and the lumbar apex. One-way analysis of variance (ANOVA) was performed to compare subject characteristics across Roussouly types, followed by post hoc Bonferroni correction. RESULTS: Volunteers were categorized into 4 groups (Types 1-4) and 1 subgroup (Type 3 AP) using the "current" and "theoretical" Roussouly systems. The mean PI in "current" Roussouly groups was 40.8° (Type 1), 43.6° (Type 2), 52.4° (Type 3), 62.4° (Type 4), and 43.7° (Type 3AP). The mean PI in "theoretical" Roussouly groups was 36.5° (Type 1), 39.1°(Type 2), 52.5° (Type 3), 67.3° (Type 4), and 51.0° (Type 3AP). The difference in PI between "current" and "theoretical" Roussouly types was significant for Type 1 (P = .02), Type 2 (P < .001), Type 4 (P < .001), and Type 3AP (P < .001). 34.7% of subjects had a "current" Roussouly type different from the "theoretical" type. Type 3 theoretical shape had the most frequent mismatch, constituting 61.1% of the mismatched subjects. 51.5% of mismatched Type 3 become "current" Type 4. CONCLUSION: The distribution of Roussouly types differs depending on whether the "current" or "theoretical" classification are employed. A sizeable proportion of volunteers exhibited current and theoretical type mismatch, highlighting the need to interpret sagittal alignment cautiously when utilizing the Roussouly system.

Characteristics of Spinal Morphology according to the Global Alignment and Proportion (GAP) Score in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study.

STUDY DESIGN: Multi-Ethnic Alignment Normative Study (MEANS) cohort: prospective, cross-sectional, multi-center. OBJECTIVE: To analyze the distribution of GAP scores in the MEANS cohort and compare the spinal shape via stratification by GAP alignment category, age, and country. SUMMARY OF BACKGROUND DATA: The GAP score has been used to categorize spinal morphology and prognosticate adult spinal deformity surgical outcomes and mechanical complications. We analyzed a large, multiethnic, asymptomatic cohort to assess the distribution of GAP scores. METHODS: 467 healthy volunteers without spinal disorders were recruited in 5 countries. Sagittal radiographic parameters were measured via the EOS imaging system. The GAP total and constituent factor scores were calculated for each patient. Kruskal-Wallis rank sum test was performed to compare variables across groups, followed by post hoc Games Howell test. Fisher's exact test was used to compare categorical variables. The significance level was set to P<0.05. RESULTS: In the MEANS cohort, 13.7% (64/467) of volunteers were≥60 years old, and 86.3% (403/467) were<60 years old. 76.9% (359/467) was proportioned, 19.5% (91/467) was moderately disproportioned, and 3.6% (17/467) was severely disproportioned. There was no significant difference in the frequency of proportioned, moderately, or severely disproportioned GAP between subjects from different countries (P=0.060). Those with severely disproportioned GAP alignment were on average 14.5 years older (P=0.016), had 23.1° lower magnitude lumbar lordosis (LL) (P<0.001), 14.2° higher pelvic tilt (P<0.001), 13.3° lower sacral slope (P<0.001), 24.1° higher pelvic-incidence (PI)-LL mismatch (P<0.001), 18.2° higher global tilt (P<0.001) than those with proportioned GAP; thoracic kyphosis and PI were not significantly different (P>0.05). CONCLUSION: The GAP system applies to a large, multi-ethnic, asymptomatic cohort. Spinal alignment should be considered on a spectrum, as 19.5% of the asymptomatic volunteers were classified as moderately disproportioned and 3.6% severely disproportioned. Radiographic malalignment does not always indicate symptoms or pathology. LEVEL OF EVIDENCE: 3.

The Importance of Pelvic Obliquity in Assessing Spinal Coronal Alignment: Normative Values, Demographic, and Radiographic Correlations.

STUDY DESIGN: Prospective, cross-sectional study. OBJECTIVE: In a geographically diverse population of asymptomatic volunteers, we sought to report the incidence of pelvic obliquity (PO), establish normative values of PO across patient factors, and assess the correlation of PO with radiographic parameters. SUMMARY OF BACKGROUND DATA: PO is defined as the misalignment of the pelvis and can be assessed through several anatomic landmarks. Significant PO, whether caused by leg-length discrepancy or not, can lead to coronal malalignment which causes severe pain and disability. Significant emphasis has been placed on achieving appropriate sagittal alignment in recent decades; however, a greater understanding of coronal alignment is needed, and PO is a crucial aspect of evaluating the coronal plane in adult spinal deformity patients. METHODS: Asymptomatic adult volunteers, ages 18-80 years, enrolled patients from 5 countries (France, Japan, Singapore, Tunisia, and the United States) in the "multiethnic alignment normative study" cohort (IRB 201812144). The included volunteers had no known spinal disorder(s), no significant neck or back pain (Visual Analog Scale: ≤2; Oswestry Disability Index: ≤20), and no abnormal alignment (Cobb ≤20°). PO was measured in the frontal plane as the distance between the highest points of each acetabulum, calculated along the vertical axis in millimeters (mm). The incidence of PO was defined as PO ≥10 mm. Kruskal-Wallis, Wilcoxon rank-sum, Pearson correlation, and linear regression were used. RESULTS: A total of 467 patients were included, and PO values by age, sex, body mass index, and country were provided. The overall incidence of PO ≥10 mm was 4.3%, and a nonsignificant trend toward increased PO with age was seen ( P = 0.077). No significant differences were seen in PO between sex, ethnicity, or body mass index groups. No significant correlation existed between PO and other commonly used coronal radiographic measurements. CONCLUSION: PO ≥10 mm occurred in 4.3% of asymptomatic volunteers. Despite the importance of recognizing PO in preventing coronal malalignment, PO did not seem to be associated with other radiographic and demographic information, which underscores the importance of intentionally assessing for any PO before surgery. These results in an asymptomatic population provide a foundation for studying PO in patients with spinal pathology.

Trends in surgical management of spinal metastases in a Singaporean tertiary referral center: a 17-year retrospective review.

Introduction: Surgical treatment is increasingly the treatment of choice in cancer patients with epidural spinal cord compression and spinal instability. There has also been an evolution in surgical treatment with the advent of minimally invasive surgical (MIS) techniques and separation surgery. This paper aims to investigate the changes in epidemiology, surgical technique, outcomes and complications in the last 17 years in a tertiary referral center in Singapore. Methods: This is a retrospective study of 383 patients with surgically treated spinal metastases treated between January 2005 to January 2022. Patients were divided into 3 groups, patients treated between 2005 - 2010, 2011-2016, and 2017- 2021. Demographic, oncological, surgical, patient outcome and survival data were collected. Statistical analysis with univariate analysis was performed to compare the groups. Results: There was an increase in surgical treatment (87 vs 105 vs 191). Lung, Breast and prostate cancer were the most common tumor types respectively. There was a significant increase in MIS(p<0.001) and Separation surgery (p<0.001). There was also a significant decrease in mean blood loss (1061ml vs 664 ml vs 594ml) (p<0.001) and total transfusion (562ml vs 349ml vs 239ml) (p<0.001). Group 3 patients were more likely to have improved or normal neurology (p=<0.001) and independent ambulatory status(p=0.012). There was no significant change in overall survival. Conclusion: There has been a significant change in our surgical practice with decreased blood loss, transfusion and improved neurological and functional outcomes. Patients should be managed in a multidisciplinary manner and surgical treatment should be recommended when indicated.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment.

OBJECTIVE: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. METHODS: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20-79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). RESULTS: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7-S1 sagittal vertical axis (SVA) (p < 0.001), C2-7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). CONCLUSION: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2-7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

The Thoracolumbar Inflection Point in a Population of Asymptomatic Volunteers: A Multi-Ethnic Alignment Normative Study Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To show population variance in the Inflection Point (IP) and its role in defining maximum Thoracic Kyphosis (TK) and Lumbar Lordosis (LL). METHODS: 468 asymptomatic adult volunteers were included in the Multi-Ethnic Normative Alignment Study (MEANS). To find parameters correlating with IP, the vertebrae and discs were numbered such that C7 was 0, T1 was 1, with T1-T2 disc being 1.5, etc. Statistical analysis was performed by a correlation matrix for IP and the 9 other selected parameters along with linear regressions. RESULTS: The overall mean IP was 12.44 approximately corresponding to T12-L1 disc with the median being 12.50, range was T8-L4. The cohort was then stratified by sex and ethnicity, but there was no significant difference in IP between groups. IP in younger subjects was 13 (L1), compared to 12.5 (T12-L1 disc) in older subjects (P < .05). IP was moderately correlated with the TK apex (r = .66). No strong correlation was found between IP and LL magnitude or apex, TK magnitude, sacral slope, or Pelvic Incidence (PI). In terms of other sagittal parameters, PI and LL demonstrated a significant positive correlation. PI and TK did not have a strong association. CONCLUSIONS: The mean IP was at the T12-L1 disc, however IP ranged from T8 to L4. Older subjects tended to have a relatively more cephalad IP. No radiographic variable was found to be a strong predictor of the IP. TK apex was found to have a moderate correlation.

Morphological description of sagittal lumbar spinal alignment using curve magnitude, span, and apex-the multiethnic alignment normative study (MEANS).

BACKGROUND CONTEXT: Current definition of lumbar lordosis uses the L1-S1 angle. Prevailing classification of sagittal spinal morphology, derived from a young adult population, classifies the spine into four subtypes defined by their sacral slope (SS) and curve morphology. PURPOSE: To describe physiological sagittal alignment of the lumbar spine across age groups using three main parameters that dictate the lumbar curve: angular magnitude, span, and apex. STUDY DESIGN: A large, multicenter, cross-sectional radiographic comparison study. PATIENT SAMPLE: Four hundred sixty-eight healthy, asymptomatic subjects aged 18 to 80 years from five countries (184 males, 284 females; 98 France, 119 Japan, 79 Singapore, 80 Tunisia, 92 USA, mean age 40.61±14.99 years). OUTCOME MEASURES: Sagittal lumbar profile subtypes clustered based on lumbar curve angular magnitude (ie, Cobb angle of the lumbar lordosis), span, and apex, and described by sagittal radiographic parameters. METHODS: Subjects underwent whole-body low-dose EOS stereoradiographs. Comparisons between conventional L1-S1 lumbar lordosis (cLL) and true lumbar lordosis (tLL, defined by the inflection-S1 angle) were conducted. Using the K-means clustering algorithm, lumbar curve angular magnitude, span and apex were used to classify sagittal spinal morphology into subtypes, stratified across age groups. Further univariate and multivariate analyses were conducted to compare radiographic parameters across subtypes, and identify predictors for the lumbar curve's angular magnitude, span and apex. RESULTS: Mean cLL was -57.27±11.37°, and tLL was -62.62±10.76°. Using tLL, instead of cLL, to describe sagittal spinal morphology, we found significant differences in terms of angular magnitude of the lumbar curve, the median thoracolumbar inflection vertebral level and pelvic incidence-lumbar lordosis mismatch Multivariate analysis found a larger SS, more positive T9 tilt, and more kyphotic T4-T12 predictive for a more lordotic tLL, while a larger overhang distance predicted for a less lordotic tLL (p-values<.001). In addition, a larger T9 tilt, less lordotic L1-L5 and smaller PT were predictors of a more caudal thoracolumbar inflection and lumbar apical vertebral levels (p-values<.001). Sagittal lumbar profiles of subjects age<30 years, 30≤age<60 years and age≥60 years, could be classified into 4, 6, and 3 subtypes, respectively. CONCLUSIONS: Sagittal lumbar profile subtypes vary across age groups, with more homogenous morphologies at the extremes of ages. Improved understanding of the morphological evolution of sagittal spinal profiles with age in asymptomatic individuals will help guide future individualized surgical treatment.

Sagittal spinal alignment varies with an individual's race: results of the multi-ethnic alignment normative study (MEANS).

PURPOSE: Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers of three difference races. METHODS: Asymptomatic volunteers between the ages of 18-80 years were enrolled prospectively and then analyzed retrospectively from six different centers. Volunteers included reported no significant neck or back pain, nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low dose stereoradiograph. Volunteers were grouped into three main races; Asian (A), Arabo-Bèrbère (B), and Caucasian (C). The Asian volunteers included in this study were from Japan and Singapore. RESULTS: There were statistical differences in the Age, ODI, and BMI of the volunteers from the three different races. Asian volunteers had the lowest age (A: 36.7, B: 45.5, C: 42.0) and BMI (A: 22.1, B: 27.1, C: 27.3). Pelvic morphology including pelvic incidence (A: 51.0, B: 52.0, C: 52.5, p = 0.37), pelvic tilt (A: 11.9, B: 12.3, C: 12.9, p = 0.44), and sacral slope (A: 39.1, B: 39.7, C: 39.6, p = 0.77) were similar amongst the 3 races. Regional spinal alignment was different between the groups. Thoracic Kyphosis (A: 32.9, B: 43.3, C: 40.0, p < 0.0001) and Lumbar lordosis (A: - 54.2, B: - 60.4, C: - 59.6, p < 0.0001) were lower in Asians compared to Caucasian and Arabo-Bèrbère volunteers despite having similar pelvic incidence. CONCLUSION: Volunteers in the Asian group had lower lumbar lordosis and thoracic kyphosis when compared to the Arabo-Bèrbère and Caucasian groups while all groups had similar pelvic morphology. Thoracic Kyphosis had no correlation with Pelvic Incidence, while Lumbar Lordosis correlated well with both Thoracic Kyphosis and Pelvic Incidence. Thoracic kyphosis may be an independent variable in establishing adequate lumbar lordosis and varies based on an individual's race.

Systemic Diclofenac Sodium Reduces Postoperative rhBMP-2 Induced Neuroinflammation: A Rodent Model Study.

STUDY DESIGN: This is a basic science, animal research study. OBJECTIVE: This study aims to explore, in rodent models, the effectiveness of systemic nonsteroidal anti-inflammatory drugs in reducing recombinant human bone morphogenetic protein-2 (rhBMP-2) induced neuroinflammation. SUMMARY OF BACKGROUND DATA: rhBMP-2 is increasingly used to augment fusion in lumbar interbody fusion surgeries, although it can cause complications including postoperative radiculitis. MATERIALS AND METHODS: Eighteen 8-week-old Sprague-Dawley rats underwent Hargreaves testing to measure the baseline thermal withdrawal threshold before undergoing surgical intervention. The L5 nerve root was exposed and wrapped with an Absorbable Collagen Sponge containing rhBMP-2. Rats were randomized into 3 groups: (1) Low dose (LD), (2) high dose (HD) diclofenac sodium, and (3) saline, receiving daily injection treatment. Hargreaves testing was performed postoperatively on days 5 and 7. Seroma volumes were measured by aspiration and the nerve root was then harvested for hematoxylin and eosin, immunohistochemistry, Luxol Fast Blue staining, and real-time quantitative polymerase chain reaction. The Student t test was used to evaluate the statistical significance among groups. RESULTS: The intervention groups showed reduced seroma volume, and a general reduction of inflammatory markers (MMP12, MAPK6, GFAP, CD68, and IL18) compared with controls, with the reduction in MMP12 being statistically significant ( P = 0.02). Hematoxylin and eosin and immunohistochemistry of the nerve roots showed the highest macrophage density in the saline controls and the lowest in the HD group. Luxol Fast Blue staining showed the greatest extent of demyelination in the LD and saline groups. Lastly, Hargreaves testing, a functional measure of neuroinflammation, of the HD group demonstrated a minimal change in thermal withdrawal latency. In contrast, the thermal withdrawal latency of the LD and saline groups showed a statistically significant decrease of 35.2% and 28.0%, respectively ( P < 0.05). CONCLUSION: This is the first proof-of-concept study indicating that diclofenac sodium is effective in alleviating rhBMP-2-induced neuroinflammation. This can potentially impact the clinical management of rhBMP-2-induced radiculitis. It also presents a viable rodent model for evaluating the effectiveness of analgesics in reducing rhBMP-2-induced inflammation.

Variation in Lumbar Shape and Lordosis in a Large Asymptomatic Population: A MEANS Study.

STUDY DESIGN: Prospective, cross-sectional cohort study. OBJECTIVE: To determine the relationship between lumbar shape and sagittal parameters. SUMMARY OF BACKGROUND DATA: Understanding the lumbar shape is vital for deformity surgery. Normative sagittal parameters and spine shape remain unstudied in large, multiethnic, asymptomatic cohorts. MATERIALS AND METHODS: A prospective, cross-sectional cohort of 468 asymptomatic volunteers between 18 and 80 years was enrolled across 5 countries. Demographic data and radiographic parameters such as pelvic incidence (PI) were collected. Pearson correlation test and linear regression were used to find the relationship between lumbar lordosis (LL) and other parameters. One-way analysis of variance and Welch 2-sample t test were performed to compare lumbar shape across such categories as PI and lumbar apex followed by post hoc Bonferroni correction if needed. RESULTS: PI was moderately correlated with proximal lumbar lordosis (pLL) ( r = -0.54) and weakly correlated with distal lumbar lordosis (dLL) ( r = -0.16). Thoracic kyphosis (T1-T12) was moderately correlated with pLL ( r = -0.35) and dLL ( r = -0.29). dLL was moderately correlated with LL ( r = 0.64). 2.6% (12/468) of subjects had lumbar apex at L2, 40.2% (188/468) at L3, 56.6% at L4 (265/468), and 0.6% (3/468) at other levels. Mean PI was different between volunteers with the apex at L3 and L4. A lower mean PI was associated with the apex at L4 (49.0°), whereas a higher mean PI was associated with the apex at L3 (55.8°). The mean PI-LL mismatch for volunteers was -5.4° with a range from -35° to 39.7°. PI-LL mismatch increased from a mean of -10.1° in volunteers with low PI to a mean of 2.2° in volunteers with high PI. Age was not correlated with LL ( P = 0.84). CONCLUSIONS: In asymptomatic adult volunteers, pLL showed a moderate correlation with PI and increased with PI, whereas dLL showed a weak correlation. The lumbar apex migrated proximally with increasing PI. Segmental lordosis and apex position instead of solely global lordosis should be emphasized. LEVEL OF EVIDENCE: Level III.

Prevalence and Risk Factors of Degenerative Spondylolisthesis and Retrolisthesis in the Thoracolumbar and Lumbar Spine - An EOS Study Using Updated Radiographic Parameters.

STUDY DESIGN: Single centre, cross-sectional study. OBJECTIVES: The objective is to report the prevalence of spondylolisthesis and retrolisthesis, analyse both conditions in terms of the affected levels and severity, as well as identify their risk factors. METHODS: A review of clinical data and radiographic images of consecutive spine patients seen in outpatient clinics over a 1-month period is performed. Images are obtained using the EOS® technology under standardised protocol, and radiographic measurements were performed by 2 independent, blinded spine surgeons. The prevalence of both conditions were shown and categorised based on the spinal level involvement and severity. Associated risk factors were identified. RESULTS: A total of 256 subjects (46.1% males) with 2304 discs from T9/10 to L5/S1 were studied. Their mean age was 52.2(± 18.7) years. The overall prevalence of spondylolisthesis and retrolisthesis was 25.9% and 17.1% respectively. Spondylolisthesis occurs frequently at L4/5(16.3%), and retrolisthesis at L3/4(6.8%). Majority of the patients with spondylolisthesis had a Grade I slip (84.3%), while those with retrolisthesis had a Grade I slip. The presence of spondylolisthesis was found associated with increased age (P < .001), female gender (OR: 2.310; P = .005), predominantly sitting occupations (OR:2.421; P = .008), higher American Society of Anaesthesiology grades (P = .001), and lower limb radiculopathy (OR: 2.175; P = .007). Patients with spondylolisthesis had larger Pelvic Incidence (P < .001), Pelvic Tilt (P < .001) and Knee alignment angle (P = .011), but smaller Thoracolumbar junctional angle (P = .008), Spinocoxa angle (P = .007). Retrolisthesis was associated with a larger Thoracolumbar junctional angle (P =.039). CONCLUSION: This is the first study that details the prevalence of spondylolisthesis and retrolisthesis simultaneously, using the EOS technology and updated sagittal radiographic parameters. It allows better understanding of both conditions, their mutual relationship, and associated clinical and radiographic risk factors.

A Risk Quantification Reference Table for Progressed Adolescent Idiopathic Scoliosis Surgery: An Exact Case Matched Outcomes Analysis.

STUDY DESIGN: Retrospective Exact Matched case-control study. OBJECTIVES: Surgical treatment delay in AIS due to family preferences is common. This study aims to quantify the increase in risks as the Cobb angle increases and provide a Quantifiable Risk Reference Table that can be utilized for counseling. METHODOLOGY: AIS patients were divided into 3 groups: Group A: Cobb angle 50-60°, Group 61-70°, and Group CFinal ≥80°. Each patient in Group CFinal who had curve progression were then traced-back-in-time (TBIT) to review the clinical data at earlier presentations at 50-60° (C1), and 61-70° (C2). Patient demographics, radiological, operative, and outcomes data were compared between Group A vs C1 and Group B vs Group C2. RESULTS: A total of 614 AIS surgeries were reviewed. Utilizing the EM technique, a total of 302 AIS patients were recruited. There were 147, 111, 31, and 32 patients matched in Groups A, B, C1, and C2, respectively. C2 Final patients had 34% curve pattern change, 23.2% higher incidence of requiring two surgeries, and 17.3% increase in complications. There was a statistically significant increase of 2.4 spinal levels fused, 12% increase in implant density, 35% increase in operative time, 97% increase in intra-operative blood loss, 10% loss of scoliosis correction, 40% longer hospitalization stay, and 36% increase in costs for patients who had curve progression. CONCLUSION: This study is the first to use a homogenously matched AIS cohort to provide a Quantifiable Risk Reference Table. The Risk Table provides essential knowledge for treating physicians when counseling AIS patients.

Fluoxetine improves bone microarchitecture and mechanical properties in rodents undergoing chronic mild stress - an animal model of depression.

Depression is one of the most prevalent mental disorders associated with reductions in bone mineral density and increased fracture risk. Fluoxetine is a highly prescribed selective serotonin reuptake inhibitor (SSRI) in the treatment of depression and is reported to be a risk factor for fractures. The present study examined the effect of fluoxetine on bone microarchitecture and the mechanical properties under chronic mild stress (CMS), a rodent model of depression. Thirty-one 6-9 week-old rats were allocated to 4 groups: 1) CMS + fluoxetine group (n = 10), 2) fluoxetine-only group (n = 5), 3) CMS + placebo group (n = 10) and 4) control group (no CMS and treatment) (n = 6). After 16 weeks, bone microarchitecture of the distal femur was analyzed by µCT. Mechanical properties were assessed by the three-point bending test, and antidepressant efficacy was determined by sucrose preference and forced swimming tests. Significant correlations were found between volume of sucrose intake and bone volume/tissue volume (BV/TV) (p = 0.019) and elastic absorption energy (p = 0.001) in the fluoxetine only group. The fluoxetine-only group showed significantly higher in the second moment of area in y-direction (p = 0.0298), horizontal outer diameter (mm) (p = 0.0488) and average midshaft thickness (mm) (p = 0.00047) than control group. Comparing with the control group, there was a significant reduction in trabecular number (Tb.N) in the CMS + fluoxetine group (p = 0.026) but not the fluoxetine-only group (p > 0.05). Significant increases in trabecular separation were observed in the metaphysis of CMS + placebo (p = 0.003) and CMS + fluoxetine (p = 0.004) groups when compared to the control group but not in the fluoxetine-only group (p > 0.05). During the three-point bending test, the fluoxetine-only group demonstrated significantly higher structural strength than controls (p = 0.04). Micro computed tomography (µCT) slices showed loss of trabecular bone in the metaphysis region of the CMS + fluoxetine and CMS + placebo groups but not the fluoxetine-only and control groups. In an animal model of depression, the adverse effect on the bone microarchitecture was caused by CMS but not by fluoxetine. Without exposure to CMS, fluoxetine significantly increased the cross-sectional area, trabecular bone area, structural strength and osteoblasts / bone area as compared to control condition.

Age and Gender Based Spinopelvic and Regional Spinal Alignment in Asymptomatic Adult Volunteers: Results of the Multi-Ethnic Alignment Normative Study (MEANS).

BACKGROUND: Spinal alignment can have a significant impact on a patient's overall quality of life. Predicting the ideal sagittal spinal alignment of a specific individual is still a difficult task. The Multi-Ethnic Alignment Normative Study (MEANS) investigated skeletal alignment, including the spine and lower extremities, of the largest multi-ethnic cohort of asymptomatic adult volunteers. In this analysis, the authors aim to assess normative values of spinopelvic parameters and the regional cervical, thoracic, and lumbar spinal alignment in asymptomatic volunteers stratified by age and sex. MATERIALS AND METHODS: Asymptomatic volunteers between ages 18 and 80 years were enrolled prospectively from centers in France, Japan, Singapore, Tunisia, and the United States. Volunteers included reported no significant neck or back pain (Visual Analog Scale ≤2), nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph. RESULTS: MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Mean cervical lordosis from C2 to C7 was -0.4±12.7°. The T1-slope averaged 23.0±7.9° and showed strong correlation ( r =0.87) with the C7-slope mean of 19.8±8.6°. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. Average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. The mean pelvic incidence (PI) measured 52.0±10.7° and pelvic tilt was 12.5±7.3°. Sacral slope averaged 39.5±8.2°. The average PI-LL was -5.4±10.7°. Approximately 60% of volunteers met the PI-LL criteria within ±10°, 8.3% were ≥10°, while 32.1% were ≤-10°. LL showed moderate correlation with PI ( r =0.53) and TK ( r =0.50), while there was no correlation between TK and PI. Multiple linear regression including PI, TK, and age resulted in the following equation LL=14.6+0.57 (PI)+0.57 (TK)-0.2 (age) ( r =0.75). CONCLUSIONS: LL did not change with increasing age in asymptomatic volunteers. However, TK did increase with age leading to an increase in T1-slope and a compensatory increase in cervical lordosis. TK did not correlate with PI and was an independent variable in the prediction of LL. LEVEL OF EVIDENCE: Level II-prospective cohort study.

Age- and Gender-based Global Sagittal Spinal Alignment in Asymptomatic Adult Volunteers: Results of the Multiethnic Alignment Normative Study (MEANS).

STUDY DESIGN: Multicenter Cohort. OBJECTIVE: Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender. SUMMARY OF BACKGROUND DATA: Our understanding of ideal sagittal alignment is still evolving. The Multiethnic Alignment Normative Study (MEANS) investigated skeletal alignment of the largest multiethnic cohort of asymptomatic adult volunteers. We aim to assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender. MATERIALS AND METHODS: Asymptomatic volunteers between the ages of 18-80 years were enrolled prospectively and then analyzed retrospectively from six different centers. Volunteers included reported no significant neck or back pain, nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low-dose stereoradiograph. RESULTS: MEANS consisted of 468 volunteers with a mean age of 40.4±14.8 years. Thoracic kyphosis (TK) from T4 to T12 showed a mean of 37.4±10.9°. The average L1-S1 lumbar lordosis (LL) was -57.4±11.3°. LL did not show significant differences across the five age groups. TK showed a significant difference based on age ( P <0.0001). Sagittal vertical axis increased across age groups from -14.2 mm in young adults to 17.0 mm in patients >64. Similar trend was seen for T1 pelvic angle with a mean of 5.0° in young adults and 13.7° in those older than age 64. Knee flexion increased across age groups without a significant change in odontoid-knee distance which is a surrogate for the center of the head aligned over the knees. CONCLUSIONS: In asymptomatic volunteers, sagittal alignment parameters showed a slow and steady change across age groups exemplified by an increase in TK. However, LL did not show a significant decrease across age groups. Volunteers used compensatory mechanisms such as slight pelvis retroversion, knee flexion, and neck extension to maintain an aligned sagittal posture with their head centered over their knees (odontoid-knee). LEVEL OF EVIDENCE: 3.

The T4-L1-Hip Axis: Defining a Normal Sagittal Spinal Alignment.

STUDY DESIGN: This is a cross-sectional cohort. OBJECTIVE: The aim was to describe sagittal plane alignment and balance in a multinational cohort of nondegenerated, asymptomatic adults. SUMMARY OF BACKGROUND DATA: Current sagittal alignment targets were developed using correlations between radiographic and quality-of-life measures in spinal deformity patients, rather than disease-free samples leading to relatively poor accounting for variance within a population. MATERIALS AND METHODS: Sagittal balance was defined using vertebral body tilt and spinopelvic alignment was defined as the vertebral pelvic angles from C2 to L5 (vertebral pelvic angle=vertebral tilt+pelvic tilt). Associations with pelvic incidence (PI) were assessed using linear regression. Multivariable linear regression was used to estimate a normal L1-S1 lordosis, adjusting for PI and the L1 pelvic angle (L1PA). Correlation between the L1 and T4 pelvic angles was assessed to define a normal thoracic alignment conditioned on lumbar alignment. RESULTS: Among 320 volunteers from 4 continents, median age was 37% and 60% were female. C2 tilt was independent of PI with minimal variation. PI was inadequate for estimating a normal lumbar lordosis (L1-S1, r2 =0.3), but was strongly associated with the lumbar pelvic angles (L1PA, r2 =0.58). Defining lumbar lordosis as a function of PI and L1PA resulted in high explained variance ( R2 =0.74) and the T4 pelvic angle had near perfect correlation with the L1PA ( r =0.9). CONCLUSIONS: We defined normal sagittal balance and spinopelvic alignment in a disease-free international volunteer cohort. Four parameters are either fixed or directly modifiable in surgery and can define a normal thoracic and lumbar alignment: the L1-S1 lordosis defined as a function of PI and the L1PA; and the T4 pelvic angle is nearly equivalent to the L1PA, aligning the T4-L1-hip axis.

ProDisc-C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study.

PURPOSE: Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment disease (ASD) at 24-months post-surgery in Asian patients with symptomatic cervical disc disease (SCDD). METHODS: This multicentre, prospective, randomized controlled trial was initiated after ethics committee approval at nine centres (China/Hong Kong/Korea/Singapore/Taiwan). Patients with single-level SCDD involving C3-C7-vertebral segments were randomized (2:1) into: group-A treated with ProDisc-C and group-B with ACDF. Assessments were conducted at baseline, 6-weeks, 3/6/12/18/24-months post-surgery and annually thereafter till 84-months. Primary endpoint was overall success at 24-months, defined as composite of: (1) ≥ 20% improvement in neck disability index (NDI); (2) maintained/improved neurologic parameters; (3) no implant removal/revision/re-operation at index level; and (4) no adverse/severe/life-threatening events. RESULTS: Of 120 patients (80ProDisc-C,40ACDF), 76 and 37 were treated as per protocol (PP). Overall success (PP) was 76.5% in group-A and 81.8% in group-B at 24-months (p = 0.12), indicating no clear non-inferiority of ProDisc-C to ACDF. Secondary outcomes improved for both groups with no significant inter-group differences. Occurrence of ASD was higher in group-B with no significant between-group differences. Range of motion (ROM) was sustained with ProDisc-C but lost with ACDF at 24-months. CONCLUSION: Cervical TDR with ProDisc-C is feasible, safe, and effective for treatment of SCDD in Asians. No clear non-inferiority was demonstrated between ProDisc-C and ACDF. However, patients treated with ProDisc-C demonstrated significant improvement in NDI, neurologic success, pain scores, and 36-item-short-form survey, along with ROM preservation at 24-months. Enrolment difficulties resulted in inability to achieve pre-planned sample size to prove non-inferiority. Future Asian-focused, large-scale studies are needed to establish unbiased efficacy of ProDisc-C to ACDF.

Correlation analysis of the PI-LL mismatch according to the pelvic incidence from a database of 468 asymptomatic volunteers.

PURPOSE: Previous studies on adults with degenerative scoliosis (ADS) have been fixed the threshold of PI-LL mismatch less than 10° for achieving good clinical outcomes. Recent studies discussed that PI-LL mismatch should consider individual pelvic incidence (PI) and should be set first in a normal population. The purpose of this study is to assess the variability of PI-LL mismatch according to PI in an asymptomatic population. METHODS: Full-body low dose stereoradiographic evaluation was done in a multi-ethnic cohort of 468 asymptomatic adult volunteers. Patients were clustered in three groups depending on individual PI values: PI < 45°, 45° < PI < 60° and PI > 60°. 3D measurements were performed using a commercially available 2D/3D modeling software to establish a correlation of PI with other spinopelvic parameters. ANOVA and Tukey's HSD for post-hoc analysis were used to determine the differences between the three groups. RESULTS: In our asymptomatic population, the mean value of PI-LL mismatch is - 5.4° ± 10.7°. Clusterization of the population reveals significant differences in the distribution of L1S1 lordosis, pelvic tilt and PI-LL with positive linear correlation according to PI values. As an interestingly result, PI-LL mismatch is equal to 0° when PI is around 64°. CONCLUSIONS: The present study demonstrated that PI-LL mismatch is negative in an asymptomatic population (- 5.4° ± 10.7°) and the value should be customized to each patient to be able to restore the appropriate lordosis in ADS. The PI-LL mismatch is given by the formula PI-LL = - 28.5 + 0.44 × PI.

Pelvic thickness, sex, ethnicity, and age affect pelvic incidence in healthy volunteers of Multi-Ethnic Alignment Normative Study (MEANS) database.

BACKGROUND: The purpose of this study was to investigate the affecting factors on pelvic incidence (PI) and to test the hypothesis that PI changes even after skeletal maturity probably due to hypermobility of the sacroiliac joint using a large international multi-center database. METHODS: A prospective and cross-sectional healthy adult volunteers, ages 18-80 years, across 5 countries were used. Radiographic measurements included standard whole body alignment parameters. Bivariate regression analyses between PI versus demographics and spino-pelvic anatomical parameters were performed. An effect of sex on pelvic anatomical parameters was also investigated. Multivariate logistic regression with a forward stepwise procedure was performed to identify the contributing factors to PI, and an appropriate model was obtained. RESULTS: PI showed a significant positive correlation with age in pooled data. Divided by sex, however, there was no correlation in men, but women showed a significant higher correlation coefficient. Pelvic thickness (PTh) had a significant negative correlation with age in pooled data. Divided by sex, no correlation was found in men, but there was a significant correlation in women with higher correlation coefficient. The stepwise multivariate analysis for the factors on PI identified four significant factors: age, sex, ethnicity, and PTh. CONCLUSIONS: PTh, sex, ethnicity, and age affected PI. There was a positive correlation between PI and age. The tendency was more significant in woman than in man. The results support the hypothesis that PI increases with aging, but the change seems to be small and needs to be verified in a longitudinal evaluation.