BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells.

The use of BMP-2 in orthopedic surgery is limited by uncertainty surrounding its effects on the differentiation of mesenchymal stem cells (MSCs) and how this is affected by cellular aging. This study compared the effects of recombinant human BMP-2 (rhBMP-2) on osteogenic and adipogenic differentiation between senescent and non-senescent MSCs. Senescent and non-senescent MSCs were cultured in osteogenic and adipogenic differentiation medium containing various concentrations of rhBMP-2. The phenotypes of these cells were compared by performing a calcium assay, adipogenesis assay, staining, real-time PCR, western blotting, and microarray analysis. rhBMP-2 induced osteogenic differentiation to a lesser extent (P < 0.001 and P = 0.005 for alkaline phosphatase activity and Ca2+ release) in senescent MSCs regardless of dose-dependent increase in both cells. However, the induction of adipogenic differentiation by rhBMP-2 was comparable between them. There was no difference between these two groups of cells in the adipogenesis assay (P = 0.279) and their expression levels of PPARγ were similar. Several genes such as CHRDL1, NOG, SMAD1, SMAD7, and FST encoding transcription factors were proposed to underlie the different responses of senescent and non-senescent MSCs to rhBMP-2 in microarray analyses. Furthermore, inflammatory, adipogenic, or cell death-related signaling pathways such as NF-kB or p38-MAPK pathways were upregulated by BMP-2 in senescent MSCs, whereas bone forming signaling pathways involving BMP, SMAD, and TGF- ß were upregulated in non-senescent MSCs as expected. This phenomenon explains bone forming dominance by non-senescent MSCs and possible frequent complications such as seroma, osteolysis, or neuritis in senescent MSCs during BMP-2 use in orthopedic surgery.

Analysis of pelvic compensation for dynamic sagittal imbalance using motion analysis.

PURPOSE: To analyze pelvic compensation during walking in patients with severe sagittal plane deformity by using motion analysis. METHODS: A total of 44 patients with sagittal plane deformity who were scheduled to undergo surgery were included. Motion analysis was performed 3 consecutive times during walking to estimate the anterior pelvic tilt (Ant-PT) angle, trunk kyphosis (TK) angle, and distance of the center of gravity (CoG) from the center of mass (CoM) of the pelvic segment, and hip and knee joint angles during gait. The patients were classified into Ant-PT+/Ant-PT-, TK+/TK-, and CoG+/CoG- groups according to the changes in Ant-PT angle, TK angle, and distance of the CoG from the CoM of the pelvic segment. Increases and decreases in the values of the variables from the first trial to the third trial were indicated with "+" and "-" signs, respectively. RESULTS: The mean Ant-PT angle, TK angle, and distance of the CoG from the CoM of the pelvic segment increased progressively, and the differences in the values of these variables from the first to the third trials were statistically significant (P = 0.046, P = 0.004, and P = 0.007 for the Ant-PT angle, TK angle, and distance of the CoG from the CoM of pelvic segment, respectively). Among the 44 patients, 27 and 34 were classified into the Ant-PT+ and CoG+ groups, respectively. Older age and higher body mass index (BMI) were significantly associated with the Ant-PT+ group. The CoG+ group demonstrated a significantly higher height and weight than the CoG- group. CONCLUSIONS: Higher BMI, height, and weight are risk factors for progressive worsening of dynamic sagittal imbalance. These slides can be retrieved under Electronic Supplementary Material.

Definitions of unfavorable surgical outcomes and their risk factors based on disability score after spine surgery for lumbar spinal stenosis.

BACKGROUND: Risk factors for unfavorable surgical outcomes are dependent on the definitions of the unfavorable surgical outcomes. The aims of this study were to compare risk factors for each unfavorable surgical outcome according to two different definitions of "unfavorable" surgical outcomes after surgery for lumbar spinal stenosis (LSS) as well as compare the clinical course from the preoperative period to 3 years postoperatively between cases with favorable and unfavorable outcomes according to the two different definitions. METHODS: Overall, 295 patients who underwent spine surgery for LSS and a follow-up evaluation at 3 years postoperatively were enrolled and divided into favorable and unfavorable groups, based on two different definitions for unfavorable surgical outcomes, as evaluated at 12 months postoperatively: the patient-reported outcome (PRO) and minimal clinically important difference (MCID) methods. In the PRO method, patients with a postoperative Oswestry Disability Index (ODI) score > 22 were considered as having an "unfavorable" outcome, whereas in the MCID method, those with a postoperative ODI score that changed < 12.8 points from the preoperative value were classified as having an "unfavorable" outcome. As a primary outcome, risk factors for unfavorable surgical outcomes according to each definition were investigated at 12 months postoperatively. RESULTS: In the PRO method, female sex (P = 0.011; odds ratio (OR): 2.340), elementary school attainment (vs. university attainment; P = 0.035; OR: 2.875), and higher preoperative ODI score (P = 0.028; OR: 2.340) were associated with higher odds for an unfavorable surgical outcome. In the MCID method, a higher preoperative ODI score was associated with higher odds (P <  0.001; OR: 0.920) of a favorable surgical outcome. In the PRO method, the favorable outcome group demonstrated significantly lower visual analog scale for back and leg pain and lower ODI scores than the unfavorable outcome group at 3 years postoperatively, whereas in the MCID method, clinical outcomes were not different between the two groups at 3 years postoperatively. CONCLUSION: A higher preoperative ODI score may be a risk factor for postoperative ODI > 22 after surgery for LSS. It may also be associated with higher odds for improvements in the ODI score of > 12.8.

The impact of COVID-19 pandemic on orthopaedic resident education: a nationwide survey study in South Korea.

PURPOSE: There have not been well-designed survey studies investigating the impact of the coronavirus disease 2019 (COVID-19) pandemic on orthopaedic resident education. METHODS: A 58-question, web-based survey was administered to orthopaedic residents in South Korea. A total of 229 orthopaedic residents from 43 hospitals completed the survey questionnaire. RESULTS: The average working time of 72.7 hours/week before the pandemic was decreased to 65.6 hours/week during the pandemic (p < 0.001). The time working in the operating room was significantly decreased during the pandemic, but not in the emergency centre and outpatient clinic. The education times for lecture and clinical case discussion were decreased during the pandemic (both, p < 0.001), respectively. While the use of traditional teaching methods was decreased, the use of online-based teaching methods was increased (p < 0.001). However, satisfaction level with online-based teaching methods was significantly lower compared with that of traditional teaching methods. The average working time exposed to the patients with COVID-19 was 9.7 hours/week. About 47.6% of orthopaedic residents experienced isolation or quarantine. The average score for quality of life, which was 68.9 out of 100 scores before the pandemic, decreased to 61.7 during the pandemic (p < 0.001). The most stressful factor for orthopaedic residents during the pandemic was family/relative health, followed by their own health and residency program. CONCLUSION: The COVID-19 pandemic had a significant impact on orthopaedic resident education in South Korea. Therefore, flexible and sustainable strategies are necessary to prepare for the future as well as the current pandemic situation.

The prevalence and impact of frailty in patients with symptomatic lumbar spinal stenosis.

PURPOSE: To investigate the prevalence of frailty in patients with symptomatic lumbar spinal stenosis (LSS) and a propensity score-matched control group, and to analyze the association between symptomatic LSS and frailty. METHODS: This study included 2 groups: 1 consisting of patients with symptomatic LSS (LSS group) and the other including healthy elderly subjects without degenerative spinal disease (control group). Baseline sociodemographic data, variables regarding frailty assessment, and clinical outcomes were collected. The frailty was assessed with Fried criteria. Between the LSS and control groups, the prevalence of frailty was compared. Among all participants, risk factors for frailty were identified using multivariate logistic regression. RESULTS: Totally, 843 subjects participated (142 in LSS group and 701 in control group) in this study. After the propensity score matching (142 in each group), the LSS group had significantly higher prevalence of frail than the control group (P < 0.001): 59 (41.5%) participants in the LSS group were frail, whereas 10 (7.0%) participants in the control group were frail. Within LSS group analysis showed that participants with frailty had significantly higher disability and lower quality of life compared to those in a robust state. Among all participants, LSS and age were found to be significant risk factors for frail in multivariate logistic regression model. CONCLUSIONS: The present study highlights a strong association between symptomatic LSS and frailty. Furthermore, symptom severity and disability caused by LSS are significantly related to frailty. Therefore, early detection and appropriate treatment for frailty in patients with LSS is important. These slides can be retrieved under Electronic Supplementary Material.

Validation and cross-cultural adaptation of the Korean version of the Core Outcome Measures Index in patients with degenerative lumbar disease.

PURPOSE: To translate and cross-culturally adapt the Core Outcome Measures Index (COMI) into the Korean language and to test the psychometric properties of the Korean COMI in patients with degenerative lumbar spine diseases. METHODS: A cross-cultural adaptation of the COMI into Korean was carried out using established guidelines. A total of 117 patients with lumbar spinal diseases were recruited from the spinal center of a tertiary care teaching institution and completed a baseline questionnaire including the newly translated COMI, the visual analog scale for back pain and for leg pain, the Oswestry Disability Index (ODI), and the EuroQOL-5 dimensions (EQ-5D). Within 2 weeks after the first assessment, 83 (71%) completed a second COMI questionnaire and a transition question (no change, slight change, moderate change, a lot of change) by phone to assess reproducibility. RESULTS: COMI summary scores displayed 1.7% floor effects and no ceiling effect. For construct validity, each COMI item and COMI summary score well correlated with its corresponding reference questionnaire. Therefore, the predefined hypotheses for the construct validities of each COMI item (ρ > 0.4 with the corresponding questionnaire) and the COMI summary score (ρ > 0.6 with both ODI and EQ-5D) were confirmed. Intraclass correlation coefficients of each COMI item and summary score ranged from 0.93 to 0.98. Therefore, the hypothesis for reliability (ICC > 0.8) was confirmed. CONCLUSIONS: The present study highlights that the Korean version of the COMI is a reliable and valid outcome tool for use in Korean-speaking patients with degenerative lumbar spinal disease. These slides can be retrieved under Electronic Supplementary Material.

Morphological changes of vertebral compression fracture with intra-vertebral cleft treated with percutaneous vertebroplasty.

BACKGROUND: Vertebroplasty represents an established treatment option for osteoporotic vertebral compression fracture (OVCF), but its radiographic and clinical outcomes have not been clearly described in patients with intra-vertebral cleft (IVC). The aim of this study was to assess vertebral height restoration, recollapse and change of back pain in OVCF patients with or without IVC. METHODS: The records of 108 patients with IVC (group I) and 233 patients without IVC (group II) were included in our analysis between March 2001 and February 2014. The heights of the anterior, middle, and posterior columns, as well as the wedge angle (WA) of the fractured vertebral body were measured. For each vertebral column, the mean height of the superior and inferior vertebral body served as reference. Pre-operative, postoperative, and final compression rates (CR), as well as restoration and recollapse rates were calculated for each column. Subjective back pain was assessed as the numeric rating scale (NRS) score. RESULTS: The overall incidence of IVC in OVCF patients who underwent vertebroplasty was 20.8% (127/611 patients). Group I showed significantly higher CR over the entire follow-up period, with the exception of CR for the anterior column at final follow-up, and CR for the posterior column throughout the follow-up. The mean restoration rates at the anterior and middle column immediately after vertebroplasty were also significantly larger in group I. Recollapse rate in all columns was similar for groups I and II. The mean wedge angle was significantly larger in group I over the entire follow-up period. The groups did not differ in terms of NRS score at final follow-up. CONCLUSIONS: Vertebroplasty restores vertebral body heights and WA more effectively in OVCF patients with IVC, and provides satisfactory radiographic and clinical outcomes regardless of the presence of IVC.

The significance of frailty in the relationship between socioeconomic status and health-related quality of life in the Korean community-dwelling elderly population: mediation analysis with bootstrapping.

PURPOSE: Firstly, to investigate the prevalence of frailty and impact on health-related quality of life (HRQOL) in a Korean community-dwelling elderly population using the Fried frailty criteria; secondly, to investigate the associations among frailty, socioeconomic status (SES), and HRQOL of the Korean community-based population; and thirdly, to analyze the relationship between education, income, and frailty. METHODS: Nine hundred and sixty-four apparently heathy subjects from the Korean community-based population were enrolled in this prospective cross-sectional study. Using self-reported questionnaires, demographic data, SES, and HRQOL were evaluated. Frailty status was determined according to the Fried frailty criteria. After adjustment of covariates including age, sex, and BMI, multivariate linear regression analyses were conducted to assess each component of the proposed mediation models, and mediation was also verified by the bootstrapping technique. RESULTS: Among the 964 participants, 530 (55.0%), 399 (41.4%), and 35 (3.6%) participants were classified into the robust, pre-frailty, and frailty group, respectively. The frail group demonstrated significantly lower HRQOL. Participants with lower income or education level had significantly higher chances of being frail. Frailty acted as a mediator in this association between low SES (education and income) and low HRQOL. Furthermore, income contributed most to the explanation of educational differences in frailty, suggesting full mediation. CONCLUSION: Frailty has a significant negative influence on HRQOL in the community-based elderly population, and acts as a mediator between SES and HRQOL. As a mediator, income can explain educational difference related with the frailty.

Comparative study of the efficacy of transdermal buprenorphine patches and prolonged-release tramadol tablets for postoperative pain control after spinal fusion surgery: a prospective, randomized controlled non-inferiority trial.

PURPOSE: To compare the efficacy of a transdermal buprenorphine patch (5, 10, 15, and 20 µg/h) with that of oral tramadol (150, 200, 250, and 300 mg) for postoperative pain control after single level spinal fusion surgery. METHODS: The present study (ClinicalTrials.gov, number NCT02416804) was a prospective, randomized controlled non-inferiority trial designed to determine the efficacy of buprenorphine TDS for alleviating postoperative pain following patient controlled analgesia (PCA) in persons underwent a single level posterior lumbar interbody fusion surgery through 1:1 allocation. The primary outcome was the Visual Analog Pain Scale (VAS) score for postoperative back pain at 7 days after surgery. The non-inferior margin of the VAS was set at δ = 1.5 points. RESULTS: The VAS score (primary outcome) for postoperative back pain at 7 days after surgery in the Buprenorphine group was not inferior compared to the Tramadol group. The overall changes in VAS scores for postoperative pain during follow-up assessments over a 2-week period did not differ between both groups. However, the VAS scores for postoperative pain significantly improved with time after surgery in both groups. The patterns of changes in the VAS scores for postoperative pain during the follow-up period were not significantly different between the both groups. CONCLUSIONS: The efficacy of buprenorphine TDS was not inferior to that of oral tramadol medication for alleviating postoperative pain in the subacute period from 72 h after surgery, following PCA administration. In addition, adverse events were similar between both groups.

Contribution of catastrophizing to disability and pain intensity after osteoporotic vertebral compression fracture.

BACKGROUND: Pain catastrophizing is a key variable that contributes to disability not only in chronic pain disorders but also after trauma. However, there is little evidence concerning the effect of catastrophizing on pain intensity and disability after osteoporotic vertebral compression fracture. Therefore, the purpose of this study was to evaluate the contribution of catastrophizing to disability and pain intensity after osteoporotic vertebral compression fracture. METHOD: We analyzed 35 patients with acute single-level osteoporotic vertebral compression fractures within 3 days of trauma. Data on demographics, education level, Charlson comorbidity index, pain catastrophizing scale (PCS) score, visual analog scale (VAS) score for back pain, and Oswestry Disability Index (ODI) were collected. VAS score for back pain and ODI were assessed at enrollment as well as at 2, 6, and 12 weeks after fracture. RESULTS: Each VAS score for back pain and ODI significantly improved compared to the initial values (P < 0.001). Among the independent variables, age and/or PCS score significantly correlated with VAS score for back pain and/or ODI over follow-up assessments. Hierarchical regression analysis finally showed that PCS score was a significant predictor for disability only in the acute period such as immediately and 2 weeks after fracture, whereas age was significantly associated with ODI at 6 and 12 weeks after fracture. CONCLUSIONS: The present study shows that catastrophizing can contribute to disability only in the acute period after osteoporotic vertebral compression fracture. As the compression fracture heals, however, age is the critical determinant of disability.

Skeletal overgrowth syndrome caused by overexpression of C-type natriuretic peptide in a girl with balanced chromosomal translocation, t(1;2)(q41;q37.1).

Chromosomal translocation of 2q37.1 just distal to the NPPC gene coding for C-type natriuretic peptide (CNP) and subsequent overproduction of CNP have been reported to cause a skeletal overgrowth syndrome. Loeys-Dietz syndrome (LDS) is one of marfanoid overgrowth syndromes, of which subtype IV is caused by haploinsufficiency of transforming growth factor beta 2 (TGFB2). We report on a girl with clinical phenotypes of overgrowth syndrome, including long and slim body habitus, macrodactyly of the big toe, scoliosis, ankle valgus deformity, coxa valga, slipped capital femoral epiphysis, and aortic root dilatation. Karyotyping revealed a balanced chromosomal translocation between 1q41 and 2q37.1, and the breakpoints could be mapped by targeted resequencing analysis. On chromosome 2q37.1, the translocation took place 200,365 bp downstream of NPPC, and serum level of the amino terminal of CNP was elevated. The contralateral site of translocation on chromosome 1q41 disrupted TGFB2 gene, presumed to cause its haploinsufficiency. This case supports the concept that NPPC is overexpressed because of the loss of a specific negative regulatory control in the normal chromosomal location, and demonstrates the effectiveness of targeted resequencing in the mapping of breakpoints.

Comparative observational study of surgical outcomes of lumbar foraminal stenosis using minimally invasive microsurgical extraforaminal decompression alone versus posterior lumbar interbody fusion: a prospective cohort study.

INTRODUCTION: There is no comparative study regarding surgical outcomes between microsurgical extraforaminal decompression (MeFD) and posterior lumbar interbody fusion (PLIF) for the treatment of lumbar foraminal stenosis (LFS). Therefore, the purpose of this study was to compare the surgical outcomes of LFS using two different techniques: MeFD alone or PLIF. METHODS: For the purposes of this study, a prospectively collected observational cohort study was conducted. Fifty-five patients diagnosed with LFS who were scheduled to undergo spinal surgery were included in this study. According to the chosen surgical technique, patients were assigned to either the MeFD group (n = 25) or the PLIF group (n = 30). The primary outcome was Oswestry Disability Index (ODI) score at 1 year after surgery. RESULTS: The baseline patient characteristics and preoperative ODI score, visual analog scale (VAS) scores for back and leg pain, and Short Form-36 score were not significantly different between the two groups. At 12 months postoperative, the mean ODI score in the MeFD and PLIF groups was 25.68 ± 14.49 and 27.20 ± 12.56, respectively, and the 95% confidence interval (-9.76-6.73) was within the predetermined margin of equivalence. The overall ODI score and VAS scores for back and leg pain did not differ significantly over the follow-up assessment time between the two groups. However, the ODI score and VAS scores for back and leg pain improved significantly over time after surgery in both groups. In the MeFD group, revision surgery was required in three patients (12%). CONCLUSIONS: This study demonstrated that MeFD alone and PLIF have equivalent outcomes regarding improvement in disability at 1 year after surgery. However, the higher rate of revision surgery in the MeFD group should emphasize the technically optimal amount of decompression.

The influence of intrinsic disc degeneration of the adjacent segments on its stress distribution after one-level lumbar fusion.

INTRODUCTION: The presence of degeneration alters the stress within that particular degenerated disc. Therefore, the state of degeneration of the disc at the level adjacent to a single level fusion would influence the rate of subsequent further degeneration of that same adjacent disc. Therefore, the purpose of this study was to investigate the biomechanical effect of the disc degeneration at the adjacent segment on the stress of the corresponding segment after one segment lumbar fusion using validated finite element (FE) models. METHOD: Three validated L2-L5 FE models with different grades of disc degeneration (normal, mild, moderate) at the L2-L5 were simulated. Based on the intact models that represented each grade of disc degeneration, the matched L3-L4 instrumented fusion models were developed. Therefore, three intact models and three matched fusion models were simulated. Under the 400-N pre-compressive follower loading, 7.5 Nm moments simulating flexion, extension, lateral bending, and torsion in five steps were imposed on the L2 superior endplate of three intact models. The hybrid loading protocol was utilized for the fusion models. The intradiscal pressure and the maximal von Mises stress of the annulus fibrosus in the L2-L3 and L4-L5 segments were analyzed and compared between fusion and intact models with each grade of disc degeneration. RESULTS: Disc degeneration led to an increase of maximal von Mises stress of annulus fibrosus at this degenerated disc, related to disc degeneration under flexion, extension, lateral bending and torsion moments. Furthermore, the fusion also increased a maximal von Mises stress of annulus fibrous at both proximal and distal adjacent segments under hybrid protocol. The increases of annular stress were greater at the proximal adjacent segment than those at distal adjacent segment. However, the contribution of the fusion surgery to the increment rate of annulus fibrosus stress at the adjacent segment did not increase in relation with disc degeneration states at the adjacent segment. CONCLUSION: The present study demonstrates disc degeneration per se and fusion can cause the increase of disc stress at the adjacent segment. However, they seem not to act synergistically. Therefore, the proper decision of fusion extent needs comprehensive individual considerations about the degree of facet degeneration, canal stenosis and patient's activity.

Factors influencing the surgical decision for the treatment of degenerative lumbar stenosis in a preference-based shared decision-making process.

INTRODUCTION: In a preference-based shared decision-making system, several subjective and/or objective factors such as pain severity, degree of disability, and the radiological severity of canal stenosis may influence the final surgical decision for the treatment of lumbar spinal stenosis (LSS). However, our understanding of the shared decision-making process and the significance of each factor remain primitive. In the present study, we aimed to investigate which factors influence the surgical decision for the treatment of LSS when using a preference-based, shared decision-making process. METHODS: We included 555 patients, aged 45-80 years, who used a preference-based shared decision-making process and were treated conservatively or surgically for chronic leg and/or back pain caused by LSS from April 2012 to December 2012. Univariate and multivariable-adjusted logistic regression analyses were used to assess the association of surgical decision making with age, sex, body mass index, symptom duration, radiologic stenotic grade, Oswestry Disability Index (ODI), visual analog scale (VAS) scores for back and leg pain, Short Form-36 (SF-36) subscales, and motor weakness. RESULTS: In univariate analysis, the following variables were associated with a higher odds of a surgical decision for LSS: male sex; the VAS score for leg pain; ODI; morphological stenotic grades B, C, and D; motor weakness; and the physical function, physical role, bodily pain, social function, and emotional role of the SF-36 subscales. Multivariate analysis revealed that male sex, ODI, morphological stenotic grades C and D, and motor weakness were significantly associated with a higher possibility of a surgical decision. CONCLUSION: Motor weakness, male sex, morphological stenotic grade, and the amount of disability are critical factors leading to a surgical decision for LSS when using a preference-based shared decision-making process.

Prediction of postoperative pain intensity after lumbar spinal surgery using pain sensitivity and preoperative back pain severity.

OBJECTIVES: To investigate the role of preoperative pain sensitivity and preoperative symptom severity for prediction of postoperative pain intensity after lumbar spine surgery. METHODS: This study consisted of two groups who underwent decompression surgery alone (62 patients) or decompression with fusion surgery (37 patients) for lumbar spinal stenosis (LSS). Pain Sensitivity Questionnaire (PSQ) and visual analog pain scale (VAS) for back pain and leg pain were collected preoperatively with detailed medical history. The assessment was performed immediately after surgery when the patients had completely recovered and regained their complete consciousness from general anesthesia (H0) and subsequently 4, 8, 18, 30, 48, and 72 hours (H4, H8, H18, H30, H48, and H72) thereafter as they recovered. RESULTS: Both groups showed a decrease in back pain and leg pain with the time postoperatively. In fusion group, preoperative VAS for back pain was significantly correlated with postoperative VAS for back pain at H0, H4, H8, and H18, and PSQ minor/total PSQ also showed a significant correlation with postoperative back pain at H48 and H72. In contrast, only total PSQ and PSQ minors were significantly correlated with postoperative back pain at H18 and H30 in decompression group. Hierarchical regression analysis finally showed that each preoperative back pain and PSQ minor was predictive of immediate postoperative back pain (from H0 to H18) in fusion group and delayed postoperative back pain (H18, H30) in decompression group. CONCLUSIONS: The study highlights that each preoperative back pain and individual pain sensitivity could predict the different aspects of postoperative pain after lumbar surgery.

The effects of recombinant human bone morphogenetic protein-2-loaded tricalcium phosphate microsphere-hydrogel composite on the osseointegration of dental implants in minipigs.

Bone formation in tooth defect areas and the osseointegration of dental implants are very important for successful dental implant surgery. The aim of the present study was to assess the strengthening effect of a ß-TCP microsphere-hydrogel composite containing recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone healing and implant osseointegration. The molars and premolars on the left and right sides of the maxilla were extracted from six male minipigs, and dental implants were placed using either the ß-TCP microsphere-hydrogel carrier alone or the carrier loaded with rhBMP-2 (500 µg). The animals were kept alive for a further 8 weeks. The molars and premolars from the left and the right sides of the mandibles of another six minipigs were extracted, and the animals were kept alive for 4 weeks. Two 5-mm-diameter bone defects were then made on both sides of the mandible. The defects were filled with saline, ß-TCP microsphere-hydrogel carrier, or the carrier loaded with rhBMP-2 (300 µg), and dental implant fixtures were inserted. The animals were kept alive for a further 4 weeks. Bone formation was examined using plane radiographs, micro-CT, and the histology of undecalcified specimens. The group treated with the rhBMP-2-loaded carrier composite showed a significantly higher percentage bone volume and a greater trabecular thickness for the newly formed bone in the tooth defect areas when compared to the group treated with the carrier alone. The rhBMP-2 group had a significantly higher osseointegration, a larger percentage bone volume, greater trabecular thickness in the newly formed bone in tooth defect areas, a larger newly formed bone fraction in the fixture pitch, and a greater number of newly formed trabecular bones when compared to the other groups. We confirmed that the rhBMP-2-loaded carrier composite promotes new bone formation after tooth extraction and strengthens osseointegration of dental fixtures by improving the degree of osseointegration around the dental implant fixture.

Fabrication of an rhBMP-2 loaded porous ß-TCP microsphere-hyaluronic acid-based powder gel composite and evaluation of implant osseointegration.

Methods to improve osseointegration that include implantation of rhBMP-2 with various kinds of carriers are currently of considerable interest. The present study was conducted to evaluate if the rhBMP-2 loaded ß-TCP microsphere-hyaluronic acid-based powder-like hydrogel composite (powder gel) can act as an effective rhBMP-2 carrier for implantation in host bone with a bone defect or poor bone quality. The release pattern for rhBMP-2 was then evaluated against an rhBMP-2-loaded collagen sponge as a control group. Dental implants were also inserted into the tibias of three groups of rabbits: an rhBMP-2 (200 µg) loaded powder gel composite implanted group, an implant only group, and a powder gel implanted group. Micro-CT and histology of the implanted areas were carried out four weeks later. The rhBMP-2 powder gel released less rhBMP-2 than the collagen sponge, but it continued a slow release for more than 7 days. The rhBMP-2 powder gel composite improved osseointegration of the dental implant by increasing the amount of new bone formation in the implant pitch and it improved the bone quality and bone quantity of new bone. The histology results indicated that the rhBMP-2 powder gel composite improved the osseointegration in the cortical bone as well as the marrow space along the fixture. The bone-to-implant contact ratio of the rhBMP-2 (200 µg) loaded powder gel composite implanted group was significantly higher than those of the implant only group and the powder gel implanted group. The powder gel appeared to be a good carrier and could release rhBMP-2 slowly to promote the formation of new bone following implantation in a bone defect, thereby improving implant osseointegration.

The influence of pain sensitivity on the treatment outcome of transforaminal epidural steroid injection in patients with lumbar spinal stenosis.

The aim of this study was to investigate the effect of individual pain sensitivity on the results of transforaminal epidural steroid injection (TFESI) for the patients with lumbar spinal stenosis (LSS). Seventy-seven patients with LSS were included in this study. Prospectively planned evaluations were performed twice consecutively before and 2 months after TFESI. These included a detailed medical history, a physical examination, and completion of a series of questionnaires, including pain sensitivity questionnaire (PSQ), Oswestry disability index (ODI), and visual analog scale (VAS) for back and leg pain. The correlations were analyzed among variables between total PSQ/PSQ-moderate/PSQ-minor and pain and disability level measured by VAS for back/leg pain and ODI both before and 2 months after TFESI. Two months after TFESI, there were significant decreases in VAS for back/leg pain and ODI compared with those before injection. Before injection, VAS for back pain and leg pain was highly associated with the PSQ scores including total PSQ and PSQ subscores after adjustment for age, BMI, and grade of canal stenosis. However, any subscores of PSQ and total PSQ scores were not correlated with either VAS for back pain/leg pain or ODI 2 months after TFESI with adjustment made to age, BMI, gender, and grade of canal stenosis. This study highlights that individual pain sensitivity does not influence the outcomes of TFESI treatment in patients with LSS, even though pain sensitivity has a significant negative correlation with symptom severity of LSS.

Translation, cross-cultural adaptation, and validity of the Korean version of the pain sensitivity questionnaire in chronic pain patients.

The purpose of this study was to translate pain sensitivity questionnaires (PSQ) into the Korean language, perform a cross-cultural adaption of the PSQ, and validate the Korean version of PSQ in patients with degenerative spinal disease. The PSQ was translated forward and backward, cross-culturally adapted by 2 independent translators, and approved by an expert committee. The final Korean version of the PSQ was tested on 72 patients with degenerative spinal disease. Test-retest reliability was evaluated for 60 patients (83%) who completed the second assessment in an interval of 4 weeks. The mean PSQ-minor, PSQ-moderate, and PSQ-total (standard deviation [SD]) were 5.40 (2.02), 6.46 (1.98), and 5.93 (1.93), respectively. The PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version showed very good internal consistencies determined by the Cronbach's α of 0.926, 0.869, and 0.877, respectively. For convergent validity, the PSQ scores of the Korean version showed significant correlations with pain catastrophizing scale (PCS) (r = 0.377, P = 0.002; r = 0.365, P = 0.003; r = 0.362, P = 0.003 for PSQ-total, PSQ-minor, and PSQ-moderate of the Korean version, respectively). For test-retest reliability, the intraclass correlation coefficients were 0.782 for PSQ-total, 0.752 for PSQ-minor, and 0.793 for PSQ-moderate. In conclusion, the validated Korean version of PSQ is a transculturally equivalent, reliable, and valid tool to assess individual pain sensitivity.

Finite element modeling of stress distribution in intervertebral spacers of different surface geometries.

Intervertebral disc spacers using bioactive ceramics have been used to treat degenerative spinal disease. Tooth-shaped spacers are commonly used to prevent migration, but there is a possibility of fracture when inserted or after insertion. Intervertebral disc spacers with either an isosceles triangle-shaped tooth (T1) or a right triangle-shaped tooth (T2) were used as a control group. The design factors for the experimental group were modified to prevent fractures induced by stress concentration, and the surfaces of the spacers were designed as either an isosceles triangle-shaped valley (V1) or a right triangle-shaped valley (V2). Linear analysis using finite element model (FEM) was performed, and Von Mises stress distribution was calculated by applying 1000 N of uniformly distributed load. Samples of the V2 design were made with bioactive glass-ceramics (BGS-7) and evaluated for compressive strength, fatigue degree, and impact strength. Von Mises stress was highest at the first tooth from the posterior side for the control group and at the center for the experimental group. Compared with the control group, the experimental group showed 18.4% and 82.5% reduction (V1 vs. T1 and V2 vs. T2, respectively) in the maximum stress at the bottom of the valleys. The FEM analysis revealed that the V2 design had the most even load distribution. The V2 samples with bioactive glass-ceramics were evaluated for compressive strength, and all six samples were not fractured up to 24 000 N. However, the average impact strength was 19.42 kN, suggesting that momentary force caused damage at a lower load than compression with a steady speed. The BGS-7 intervertebral disc spacer with V2 design was not fractured during the fatigue test at maximum pressure of 8000 N, R ≥10, 5 Hz, and 5 million cycles. These data confirm that the BGS-7 spacer with the V2 design may be clinically applicable. Collectively, the modified surface geometry of the experimental group significantly lowered Von Mises stress values at the bottom of the valleys, and thus the possibility of fracture by compressive load was greatly reduced. Also, impact during insertion was confirmed to cause fracture more easily, as the impact strength was lower than the compressive strength in the experimental group.