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Purpose: To investigate the age-specific normative values of whole-body sagittal alignment (WBSA) including global balance parameters in healthy adults and to clarify the correlations among parameters based on the data from three international multicenter. Methods: Three hundred and seventeen healthy subjects (range: 20–84 y.o., mean: 43.8 ± 14.7 y.o.) were included and underwent whole-body biplanar X-ray imaging system. Spinopelvic parameters and knee flexion (KF), the center of acoustic meatus (CAM)-hip axis (HA), and C2 dentiform apophyse (OD)-HA, the cranial center (Cr)-HA were evaluated radiologically. Sub-analysis for correlation analysis between age and parameters and among parameters was performed to investigate age-specific change and compensatory mechanisms. Results: For age-related change, C2-7 angle (r = .326 for male/.355 for female), KF (r = .427/.429), and SVA (r = .234/.507) increased with age in both male and female group. For global parameters related to the center of the gravity, correlations with age were not significant (r = .120/.161 for OD-HA, r = .163/.275 for Cr-HA, r = .149/.262 for CAM-HA). Knee flexion (KF) has correlation with global parameters (i.e., SVA, OD-HA, Cr-HA, CAM-HA) and does not have correlations with local spinopelvic alignment. Conclusion: While several local alignment changes with age were found, changes in global parameters related to the center of gravity were kept relatively mild by the chain of compensation mechanisms including the lower limbs. We showed the normative values for a comprehensive WBSA in standing posture from large international healthy subjects’ database.

Aging and spinal disease impair standing whole body sagittal alignment (WBS alignment), which leads to stooping. When WBS alignment deteriorates, compensatory mechanisms are activated to maintain standing posture. Increase of the compensation impairs health-related quality of life (HRQOL). The purpose of this research was to determine whether postural factors, age, and sex affect HRQOL.This cross-sectional study evaluated the influence of WBS alignment, standing body sway (balance), skeletal muscle mass (SMM), aging, and sex on HRQOL in healthy volunteers (n = 150; mean age 40.9 years [20-76], 96 women). Age, sex, weight, height, and body mass index (BMI) were obtained. HRQOL was assessed with Scoliosis Research Society-22 (SRS-22r). WBS alignment and balance were measured by EOS imaging with simultaneous force plate measurement. SMM was measured using a medical body composition analyzer. Based on the bivariate analysis between the SRS-22r subtotal and all parameters, selected ten parameters were used for multivariate logistic regression analysis to identify affecting factors to SRS-22r.Men had significantly higher weight, height, BMI, and SRS-22r score in all domains. The L4-S1 lumbar lordosis angle was greater in men, and pelvic tilt and knee hyperextension were greater in women. Women had a more stable standing posture, whereas men had significantly higher SMM values. Multivariate logistic regression analysis revealed that age, sex, and TPA were identified as significant factors affecting SRS-22r.In healthy volunteers, SRS-22r is affected by aging, sex (woman had a lower score), and sagittal malalignment. Neither Standing balance nor SMM, however, affect SRS-22r.4.

Background Proper identification of lumbosacral transitional vertebrae (LSTV) is important to characterize the relationship between the transitional segment and adjacent levels. Classical classification schemes are inaccurate with respect to the whole spine. We propose a precise vertebral numbering method and investigated the relationship between LSTV and whole-body sagittal alignment. Methods A total of 291 healthy adult volunteers with no history of spinal disease were evaluated with biplanar slot scanning full body stereoradiography to determine the prevalence of LSTV. Vertebrae were counted from the first cervical vertebra using both coronal and sagittal plane images. We then investigated the influence of LSTV on whole-body sagittal alignment in 279 participants. Whole-body key parameters descriptive statistics were compared among groups according to the number of vertebrae (L4, L5, and L6). Statistical analysis was performed between normal and LSTV cases using the Steel-Dwass analysis. Results Of the 291 subjects, 14 (4.8%) had 23 vertebrae and 16 (5.5%) had 25 vertebrae. Eleven (3.8%) had Th11, 3 (1.0%) had L4, and 1 (0.3%) had Th11 + L6, 16 (5.5%) had L6. Compared with the normal group, the sacral base in relation to the pelvis was higher in the L4 group and lower in the L6 group. The C2–C7 angle and lumbar lordosis (LL) were increased in both the L4 and L6 groups. All remaining parameters were decreased in the L4 group and increased in the L6 group. The relationship between LL and PI was similar in the normal and LSTV groups, despite the difference in the sacral base location. Conclusions We propose a precise method for numbering the vertebrae using coronal and sagittal full body images. The spinopelvic parameters of the LSTV population significantly differed from those in the normal spine population due to differences in the sacral base location.

OBJECTIVE Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

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.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.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.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.

We aimed to investigate the impact of long corrective fusion to the ilium on the physical function in elderly patients with adult spinal deformity and its correlation with spinopelvic parameters and health-related quality of life outcomes.We included 60 female patients who underwent long corrective fusion from T9 or T10 to the pelvis for adult spinal deformities (mean age of 69.8 years, range 55-78 years). The radiographic parameters, health-related quality of life outcomes using the Scoliosis Research Society Outcome Instrument-22 and physical function assessments were reviewed preoperatively and at 1-year postoperatively.All spinopelvic parameters, except for thoracolumbar kyphosis, and all domains of the Scoliosis Research Society Outcome Instrument-22 significantly improved at 1-year postoperatively (p 0.0001). Physical function results, including those for one-leg standing time, timed up-and-go test, and 6-min walk tests, significantly improved at 1-year postoperatively (p 0.005). Based on forward stepwise multivariate logistic regression, the predicted timed up-and-go test and 6-min walk test outcomes at 1-year postoperatively were as follows: timed up-and-go test, 7.8 + 0.47 × preoperative timed up-and-go test - 0.21 × 1-year postoperative grasping power +0.015 × 1-year postoperative C1 sagittal vertical axis (R2 = 0.6209, p 0.0001); 6-min walk test, 309.2-9.1 × body mass index + 11.6 × 1-year postoperative grasping power + 3.3 × 1-year postoperative thoracolumbar kyphosis - 0.59 × 1-year postoperative C1 sagittal vertical axis (R2 = 0.4409, p 0.0001).Corrective long fusion surgery for adult spinal deformity in normalizing sagittal alignment improves trunk balance and gait performance. Postoperative physical function depends on the preoperative physical performance status and skeletal muscle status; thus, preoperative interventions for improved physical function are recommended.

To evaluate the impact of the flexibility of thoracolumbar or lumbar (TL/L) curves on low back pain (LBP) and disc degeneration in adult patients nonoperatively treated for adolescent idiopathic scoliosis (AIS). Forty-seven adult patients (46 women; mean age, 40.5 years) nonoperatively treated for AIS with TL/L curves were included. The patients completed radiological examinations, magnetic resonance imaging, and a questionnaire survey for LBP evaluation. The flexibility of the spinal deformity was evaluated using supine side-bending radiographs. Radiographic measurements were correlated with scores for LBP and disc degeneration. The average magnitude and flexibility of the TL/L curve were 49.0° and 56%, respectively. The magnitudes of the TL/L curve and disc wedging were significantly correlated with LBP (|r|= 0.3–0.4). The flexibility of the TL/L curve and disc wedging, and the lumbar lateral range of motion (ROM) were significantly correlated with LBP and disc degeneration (|r|= 0.3–0.5). After controlling for the magnitudes of the TL/L curve and disc wedging, the flexibility of L4/5 disc wedging and the lumbar lateral ROM remained significantly correlated with the Scoliosis Research Society-22 pain score (partial correlation coefficient [r′] = 0.5 and 0.3), Oswestry Disability Index (− 0.3 and − 0.3), and disc degeneration (− 0.4 and 0.3). In AIS patients with TL/L curves, the flexibility of L4/5 disc wedging and the lumbar lateral ROM were significantly correlated with LBP and disc degeneration, independent of the magnitudes of the coronal deformities. Our findings indicate that maintaining or improving lumbar flexibility may be beneficial for preventing or treating LBP.

A retrospective cohort study using prospectively collected data.To investigate the incidence and impact of fusion to the upper thoracic spine on neck-shoulder symptoms after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS).Axial neck-shoulder pain is established as a sequela of posterior cervical spine surgery and is mainly caused by the dissection of extensor muscles in the cervical and upper thoracic spine.Sixty-three female patients with AIS who underwent PSF using segmental pedicle screw constructs for structural main thoracic curve with a minimum 2-year follow-up were included. Axial neck-shoulder pain was assessed using the visual analog scale and cervical spine function domain score of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire. The patients were divided into 2 groups, a higher group (underwent fusion up to T3 or above, n=27) and a lower group (underwent fusion up to T4 or below, n=36), and radiologic and clinical outcomes were compared.The incidence of axial neck-shoulder pain (visual analog scale ≥30) preoperatively and at the 2-year follow-up was 29 and 40%, respectively. The pain and mental health domains of the Scoliosis Research Society-22 and cervical spine function domain of the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire were correlated with the severity of axial neck pain. In the comparison of clinical outcomes between the 2 groups, the pain domain score of the Scoliosis Research Society-22 in the lower group was significantly better than that in the higher group at the 2-year follow-up (P0.05). Other parameters showed no significant differences preoperatively or at the 2-year follow-up.Female patients with AIS had a relatively high incidence of axial neck-shoulder pain after PSF, which affected their health-related quality of life. Both groups showed similar clinical outcomes, and the cranial fusion level did not affect axial neck-shoulder pain and cervical spine function.Level 3.

In a population of asymptomatic volunteers across 5 countries, we sought to: (a) establish normative values of the Odontoid-Central Sacral Vertical Line (OD-CSVL) across patient factors, and (b) assess correlations of OD-CSVL with other radiographic parameters. A prospective, cross-sectional study of asymptomatic adult volunteers, ages 18–80 years, were enrolled across 5 countries (France, Japan, Singapore, Tunisia, United States) forming the Multi-Ethnic Alignment Normative Study (MEANS) cohort. Included volunteers had no known spinal disorder(s), no significant neck/back pain (VAS ≤ 2; ODI ≤ 20), and no significant scoliosis (Cobb ≤ 20°). Radiographic measurements included commonly used coronal alignment parameters (mm) and angles (°). OD-CSVL was defined as the difference between the odontoid plumb line (line from the tip of the odontoid vertically down) and the CSVL (vertical line from the center of the sacrum). Chi-square, student’s t tests, Kruskal–Wallis, Wilcoxon rank-sum, linear regression, and Pearson’s correlation were used with significance at p

Study Design: A finite element analysis study. Objective: Of proximal junctional failure, upper instrumented vertebra (UIV) fracture can causes severe spinal cord injury. Previously, we reported that higher occupancy rate of pedicle screw (ORPS) at UIV prevented UIV fracture in adult spinal deformity surgery; we had not yet tested this finding using a biomechanical study. The purpose of present study was to measure the differences in loads on the UIV according to the length of PS and ORPS. Methods: We designed an FE model of a lumbar spine (L1-S1) using FE software. The PS was set from L2 to S1 and connected the rod. The FE model simulated flexion (8 Nm) to investigate the loads at UIV (L2) according to the length of the PS. There were 5 screw lengths examined: 40 (ORPS 36.4%), 45 (48.5%), 50 (66.7%), 55 (81.8%), and 60 mm (93.9%). Results: Stress with bending motion was likely to occur at the upper front edge of the vertebral body, the pedicles, and the screw insertion point. The maximum equivalent stress according to screw lengths of 40, 45, 50, 55, and 60 mm were 45.6, 37.2, 21.6, 13.3, and 14.8 MPa, respectively. The longer screw, the less stress was applied to UIV. No remarkable change was observed between the screw lengths of 55 and 60 mm. Conclusions: Increasing ORPS to 81.8% or more reduced the load on the UIV. To prevent UIV fracture, the PS length in the UIV should be more than ORPS 81.8%.

Background It is well known that correction surgery for adult spinal deformity (ASD) improves sagittal and coronal spinopelvic alignment, but the surgery effect on lower extremities (LE) is not well clarified. The aim of this study was to test the hypothesis that LE alignment also improves following spinopelvic correction surgery for ASD as a function of compensatory mechanism, and to clarify an effect of the severity of knee osteoarthritis (OA) on the improvement. Methods We retrospectively evaluated spinopelvic alignment, hip knee ankle angle (HKA), knee flexion angle (KF), and severity of the knee OA in thirty-nine patients with ASD before, two weeks and three months after the surgery. The grade of knee OA was evaluated by Kellgren Lawrence grading, and classified grade 0 to 2 into mild, and 3, 4 into severe OA. All the values were compared by paired t test or Wilcoxon signed rank test with significant p value of Results Following the surgery, not only spinopelvic, but also bilateral HKA and KF were significantly improved. HKA in mild OA side was more normalized compared to that in severe side. Although KF of both bilateral mild and bilateral severe OA groups improved, the improvement of mild group was more significant. Conclusion The 3D alignment of LE improved following spinopelvic correction surgery. The improvement was inadequate in cases with severe knee OA.

Background The differences in etiology, clinical manifestation, and whole body standing alignment between single-level LDS (sLDS) and double-level LDS (dLDS) have not been sufficiently clarified. We hypothesized that the etiology and manifestations of dLDS differ from those of sLDS. This study aimed to test this hypothesis. Methods A total of 112 cases with sLDS, 25 cases with dLDS, and 50 healthy volunteers as a normal control were enrolled in the study. Following the data collection on demographic and Health-related quality of life (HRQOL) by ODI and SRS-22, radiologic measurement by EOS system and MRI examination including lumbar spinal stenosis (LSS), facet angle, and segmental instability defined by facet opening were performed. All the parameters were compared among the groups. Correlations among radiologic parameters and HRQOL were analyzed. Risk factors for sLDS and dLDS were investigated respectively using multivariate logistic analysis. Results Age is the most important etiologic factor of sLDS; whereas high PI, age, and sagittally oriented facet joints are the important factors for dLDS. HRQOL significantly correlates with sagittal alignment. HRQOL does not, however, significantly differ between patients with sLDS and dLDS. Although the mean value of %slip was higher in the dLDS group than in the sLDS group, the difference was not statistically significant. %slip positively correlated with the PI. The number of spinal stenoses (LSS) per patient is significantly higher in patients with dLDS than in patients with sLDS. The HRQOL does not, however, correlate with the number of LSS. Conclusions Age is the most important etiologic factor of sLDS; whereas high PI, age, and sagittally oriented facet joints are the important factors for dLDS. HRQOL does not significantly differ between patients with sLDS and dLDS. Number of LSS is significantly higher in dLDS than in sLDS without statistical difference in terms of HRQOL outcome.

Background Although several radiographic predictors for pulmonary function in adolescent patients have been reported, those in adult patients remain unclear. Therefore, we aimed to investigate the associations between spinal deformity and pulmonary function in nonoperatively treated adult patients with adolescent idiopathic scoliosis (AIS). Methods Of 319 patients treated nonoperatively for AIS, 90 (average age, 40.0 ± 6.5 years) underwent both full-length standing radiographs and pulmonary function test. Standard two-dimensional (2-D) radiographic measurements were performed. Three-dimensional thoracic kyphosis (3-D TK) was calculated from 2-D standing radiograph data using a validated formula: 3-D TK (°) = 18.1 + 0.81 × (2-D TK) + 0.54 × (Cobb angle of thoracic curve). 3-D TK was defined as the sum of segmental kyphosis between T5 and T12, which eliminates the overestimation of TK in 2-D measurements due to rotational deformity. Bivariable correlation analysis, followed by a stepwise multiple linear regression analysis, was performed. Results The average Cobb angle of the thoracic curve at the time of survey was 49.4° ± 14.6° with flexibility of 37.5% ± 18.2%. Thoracic curve magnitude, flexibility, apical vertebral rotation and translation, and 3-D TK were significantly correlated with percent-predicted forced vital capacity (%FVC) and expiratory volume in 1 s (%FEV1.0). Stepwise multiple regression analysis showed that curve flexibility and 3-D TK were significant, independent predictors of %FVC (R2 = 0.358) and %FEV1.0 (R2 = 0.335), curve flexibility having a greater impact (standardized coefficient > 0.45) than 3-D TK ( Conclusions Our results indicate that nonoperatively treated patients with AIS should be recommended to maintain flexibility of the thoracic curve to prevent future pulmonary impairment. Moreover, 3-D TK is another independent predictor of pulmonary function, which suggests that segmental sagittal alignment is a component of deformity correction to focus on.

A retrospective long-term follow-up study.To investigate the health-related quality of life (HRQOL) status in middle-aged patients with adolescent idiopathic scoliosis (AIS) treated non-surgically.The HRQOL status using various established questionnaires for non-operated AIS patients has not been fully investigated in long-term follow-up surveys.Inclusion criteria were non-surgical treatment for AIS, more than or equl to 30° major scoliosis at skeletal maturity (Risser grade ≥4), and age more than or equl to 30 years at the time of the survey. A total of 107 AIS patients were included and divided into three groups (single main thoracic [MT] curve group; n = 50, single thoracolumbar/lumbar [TL/L] curve group; n = 19, and double-major [DM] curve group; n = 38) based on curve location at skeletal maturity. Age- and sex-matched volunteers were selected as the control group.There were no significant differences in age at survey, body mass index, bone mineral density of the femoral neck, and skeletal muscle mass index among the groups. In all groups, major scoliosis progressed by approximately 0.5°/yr from the time of skeletal maturity to the survey. The thoracolumbar (TL/L) and double-major (DM) groups showed significantly worse visual analog scale scores for low back pain compared with the main thoracice (MT) group (P 0.05). The all-scoliosis groups showed significantly worse scores for self-image domain of the Scoliosis Research Society Outcome Instrument-22 (SRS-22) than the control group (P 0.0001). The TL/L group showed significantly worse scores for walking ability and social function domains of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) (P 0.05). There were no significant differences in Oswestory Disability Index and Short-Form-12 among the four groups.AIS patients with single MT curve maintain equal HRQOL status compared with healthy controls. Patients with structural TL/L curves are likely to experience greater annual TL/L curve progression and have substantial low back pain or worse low back pain-specific HRQOL status during middle age.4.

Multicenter Cohort.Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers stratified by age and gender.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.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.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 ( P0.0001). Sagittal vertical axis increased across age groups from -14.2 mm in young adults to 17.0 mm in patients64. 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.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).3.

This is a cross-sectional cohort.The aim was to describe sagittal plane alignment and balance in a multinational cohort of nondegenerated, asymptomatic adults.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.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.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).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.

Fulcrum-bending (FB) correction is considered to provide the best estimation of main thoracic (MT) curve flexibility and postoperative correction in surgical treatment for adolescent idiopathic scoliosis (AIS). However, few studies evaluated the usefulness of FB radiographs for proximal thoracic (PT) curve. We aimed to perform flexibility assessments using both active side-bending (SB) and FB radiographs and evaluate surgical outcomes after posterior spinal fusion (PSF) for Lenke type 2 AIS.This study included 38 consecutive patients with Lenke type 2 AIS who underwent PSF using a pedicle screw construct with a minimum 2-year follow-up. Radiographic parameters, including correction rate, SB and FB flexibility, and FB correction index (FBCI: [correction rate/FB flexibility] × 100), were evaluated preoperatively, immediately after surgery, and at the 2-year follow-up. The clinical outcomes were preoperatively evaluated using the Scoliosis Research Outcomes Instrument-22 and at the follow-up.All scoliosis curves significantly improved and shoulder balance shifted toward left shoulder elevation (all comparisons, p 0.0001). There were significant differences between the SB and FB corrections in the PT and MT curves (p 0.0001). The magnitudes of the discrepancies between the SB and FB corrections in the PT and MT curves were 11.2° ± 5.2° and 11.6° ± 7.2°, respectively. FB correction did not differ from postoperative Cobb angles correction immediately after surgery or at the 2-year follow-up; the mean FBCIs in the PT and MT curves were 98.8% and 105.5%, respectively. The self-image domain SRS-22 scores had significantly increased at the 2-year follow-up (p 0.0001).There were significant differences between the SB and FB corrections, and FB correction tended to approximate the postoperative curve correction (FBCI = 100%) for PT and MT curves in patients with Lenke type 2 AIS. FB flexibility is more reliable than SB flexibility in evaluating actual curve flexibility even for the PT curve.

Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.

Context Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. Objective Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. Methods Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). Results The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10–5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10–5, OR 5.21, 95% CI 2.76-9.86). Conclusion AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

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.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.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°.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.

A retrospective, long-term follow-up study.We aimed to investigate the long-term impacts of brace treatment for adolescent idiopathic scoliosis (AIS) on the musculoskeletal system.Although full-time brace treatment is the mainstay of conservative treatment for AIS, the restrictive nature of brace treatment for lumbosacral motion might negatively affect the musculoskeletal system.Of 319 patients treated nonoperatively for AIS, 80 patients completed clinical and imaging examinations. Body composition, including body fat mass, lean mass, fat percent, and muscle mass, was estimated via bioelectrical impedance analysis. Bone mineral density (BMD) was measured at the lumbar spine and left hip. In 73 patients, the measurement of cross-sectional area and fatty degeneration of paraspinal muscles at the superior endplate of L4 were performed using axial T2-weighted magnetic resonance imaging. Patients were divided into the full-time brace (FB;13 hours per day) and nonfull-time brace (NFB; observation, part-time bracing, or drop out from FB within a year) groups.There were 44 patients in the FB group and 36 in the NFB group. Patients in the FB group were significantly younger at the initial visit (12.7 ± 1.3 years) and older at the final follow-up (41.5 ± 5.6 years) than those in the NFB group (14.2 ± 3.2 and 37.4 ± 7.1 years, respectively; P 0.01). The rate of patients engaging in mild or moderate sports activity in adulthood tended to be higher in the FB group (47.7%) than in the NFB group (25%) (P = 0.11). However, there were no significant differences in body composition, paraspinal muscle morphology, and BMD between the two groups both before and after adjusting for age.Full-time brace wearing during adolescence did not have any negative impacts on the musculoskeletal system in adulthood. This information will be helpful for improving the compliance of full-time bracing.4.