Publications by authors named "Norimasa Iwasaki"

317 Publications

Risks vs. benefits of switching therapy in patients with postmenopausal osteoporosis.

Expert Rev Endocrinol Metab 2021 Jul 26:1-12. Epub 2021 Jul 26.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.

: Osteoporosis is characterized by the fragility of bones, leading to fractures and, consequently, the deterioration of functional capacity and quality of life. Postmenopausal women, in particular, are prone to osteoporosis and often require anti-osteoporosis treatment. In the last few decades, various anti-osteoporosis drugs have been approved for clinical use. In an aging society, osteoporosis cannot be treated using a single agent; therefore, switching therapy is an important treatment strategy.: This review covers switching therapy in patients with postmenopausal osteoporosis. It's extremely important to understand the characteristics of each drug including; limitations on the duration of use, side effects due to long-term use (such as atypical femur fracture and osteonecrosis of the jaw) or discontinuation (such as rebound phenomenon), compliance, and ability to prevent fractures. We review and summarize the risks and benefits of switching therapy.: When switching therapy, the order of drug administration is important. Routine monitoring should be continued after switching treatments. We recommend first using osteoanabolic agents in postmenopausal women with severe osteoporosis. In addition, identifying predictors of the efficacy and side effects of treatment may help prevent the inappropriate use of drugs for the treatment of osteoporosis.
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http://dx.doi.org/10.1080/17446651.2021.1956902DOI Listing
July 2021

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study.

Contemp Clin Trials Commun 2021 Sep 29;23:100805. Epub 2021 Jun 29.

Department of Orthopaedic Surgery, Hokkaido University Hospital, N14W5, Sapporo, Japan.

Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.
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http://dx.doi.org/10.1016/j.conctc.2021.100805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261539PMC
September 2021

Acellular Cartilage Repair Technique Based on Ultrapurified Alginate Gel Implantation for Advanced Capitellar Osteochondritis Dissecans.

Orthop J Sports Med 2021 Mar 11;9(3):2325967121989676. Epub 2021 Mar 11.

Faculty of Medicine and Graduate School of Medicine, Department of Orthopaedic Surgery, Hokkaido University, Sapporo, Japan.

Background: One of the most important limitations of osteochondral autograft transplant is the adverse effect on donor sites in the knee. Ultrapurified alginate (UPAL) gel is a novel biomaterial that enhances hyaline-like cartilage repair for articular defects. To avoid the need for knee cartilage autografting when treating osteochondritis dissecans (OCD) of the capitellum, we developed a surgical procedure involving a bone marrow stimulation technique (BMST) augmented by implantation of UPAL gel.

Hypothesis: BMST augmented by UPAL gel implantation improves the cartilage repair capacity and provides satisfactory clinical outcomes in OCD of the capitellum.

Study Design: Case series; Level of evidence, 4.

Methods: A total of 5 athletes with advanced capitellar OCD in the dominant elbow underwent BMST augmented by implantation of UPAL gel. The osteochondral defects were filled with UPAL gel after BMST. At a mean follow-up of 97 weeks, all patients were evaluated clinically and radiographically.

Results: At final follow-up, all 5 patients had returned to competitive-level sports, and 4 patients were free from elbow pain. The mean Timmerman-Andrews score significantly improved from 100 to 194 points. Radiographically, all patients exhibited graft incorporation and a normal contour of the subchondral cortex. Magnetic resonance imaging showed that the preoperative heterogeneity of the lesion had disappeared, and the signal intensity had returned to normal. Arthroscopic examinations consistently exhibited improvement in the International Cartilage Regeneration and Joint Preservation Society (ICRS) grade of lesions from 3 or 4 to 1 or 2 in 4 patients at 85 weeks postoperatively. Histologic analysis of biopsy specimens revealed an average total ICRS Visual Assessment Scale II histologic score of 1060.

Conclusion: The acellular cartilage repair technique using UPAL gel for advanced capitellar OCD provided satisfactory clinical and radiographic results. The present results suggest that this novel technique is a useful, minimally invasive approach for treating cartilaginous lesions in athletes.
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http://dx.doi.org/10.1177/2325967121989676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237226PMC
March 2021

Micro-computed tomography analysis of the lumbar pedicle wall.

PLoS One 2021 8;16(7):e0253019. Epub 2021 Jul 8.

Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America.

Background: Although the pedicle is routinely used as a surgical fixation site, the pedicle wall bone area fraction (bone area per unit area) and its distribution at the isthmus of the pedicle remain unknown. The bone area fraction at the pedicle isthmus is an important factor contributing to the strength of pedicle screw constructs. This study investigates the lumbar pedicle wall microstructure based on micro-computed tomography.

Methods: Six fresh-frozen cadaveric lumbar spines were analyzed. Left and right pedicles of each vertebra from L1 to L5 were resected for micro-computed tomography scanning. Data was analyzed with custom-written software to determine regional variation in pedicle wall bone area fraction. The pedicular cross-section was divided into four regions: lateral, medial, cranial, and caudal. The mean bone area fraction values for each region were calculated for all lumbar spine levels.

Results: The lateral region showed lower bone area fraction than the medial region at all spinal levels. Bone area fraction in the medial region was the highest at all levels except for L4, and the median values were 99.8% (95.9-100%). There were significant differences between the lateral region and the caudal region at L1, L2 and L3, but none at L4 and L5. The bone area fraction in the lateral region was less than 64% at all spinal levels and that in the caudal region was less than 67% at the L4 and L5 levels.

Conclusions: This study provides initial detailed data on the lumbar pedicle wall microstructure based on micro-computed tomography. These findings may explain why there is a higher incidence of pedicle screw breach in the pedicle lateral and caudal walls.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253019PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266093PMC
July 2021

Morphological analysis of Kambin's triangle using 3D CT/MRI fusion imaging of lumbar nerve root created automatically with artificial intelligence.

Eur Spine J 2021 Jul 3. Epub 2021 Jul 3.

Department of Orthopaedic Surgery, Hokkaido University Hospital, North-14, West-5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.

Purpose: We developed a software program that automatically extracts a three-dimensional (3D) lumbar nerve root image from magnetic resonance imaging (MRI) lumbar nerve volume data using artificial intelligence. The aim of this study is to evaluate the morphology of Kambin's triangle in three dimensions based on an actual endoscopic transforaminal surgical approach using three-dimensional (3D) computed tomography (CT)/ magnetic resonance imaging (MRI) fusion images of the lumbar spine and nerve tissue.

Methods: Three-dimensional lumbar spine/nerve images of 100 patients (31 males and 69 females; mean age, 66.8 years) were used to evaluate the relationship between the superior articular process (SAP), exiting nerve root (ENR), and dural canal at the L2/3, L3/4, and L4/5 levels at 45° and 60° approach angles.

Results: The SAP-ENR distance at 60° was the greatest at L4/5 and was significantly greater at L2/3 and L4/5 than at L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distance at 45° was the greatest at L2/3, and it was larger in L2/3 and L4/5 than in L3/4 (P < 0.01, P < 0.01, respectively). The SAP-ENR distances at L4/5 were significantly greater at 60° than at 45° (P < 0.01). The dural canal was located within Kambin's triangle on the plane of the upper endplate of the lower vertebra at L2/3 in 41.5% of the cases and at L3/4 in 14% of the cases at 60° but not at L4/5.

Conclusion: The 3D lumbar spine/nerve image enabled a combined assessment of the positional relationship between the SAP, ENR, and dural canal to quantify the safety zone of practical endoscopic spinal surgery using a transforaminal approach. Three-dimensional lumbar spine/nerve images could be useful for examining parameters, including bones and nerves, to ensure the safety of surgery.
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http://dx.doi.org/10.1007/s00586-021-06916-yDOI Listing
July 2021

Ulnar nerve morphology during elbow flexion in patients with and without cubital tunnel syndrome: a sonographic study.

J Hand Surg Eur Vol 2021 Jun 30:17531934211026108. Epub 2021 Jun 30.

Department of Orthopaedic Surgery, Hokkaido University, Sapporo, Japan.

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http://dx.doi.org/10.1177/17531934211026108DOI Listing
June 2021

Stress-Distribution Pattern Across the Glenohumeral Joint in Collegiate and Professional Baseball Players: A Computed Tomography Osteoabsorptiometry Study.

Orthop J Sports Med 2021 Jun 3;9(6):23259671211009185. Epub 2021 Jun 3.

Faculty of Medicine and Graduate School of Medicine, Department of Orthopaedic Surgery, Hokkaido University, Sapporo, Japan.

Background: The influence of long-term loading conditions on the articular surfaces of the glenohumeral joint can be determined by measuring stress-distribution patterns. Long-term pitching activity changes the stress distribution across the glenohumeral joint surface; however, the influence of competitive level on stress-distribution patterns remains unclear.

Purpose: To use computed tomography (CT) osteoabsorptiometry (CTOAM) to evaluate the distribution of subchondral bone density across the glenohumeral joint in collegiate and professional baseball players as well as to determine the effects of pitching activity on the articular surfaces.

Study Design: Descriptive laboratory study.

Methods: We evaluated 73 shoulders in 50 baseball players. CT imaging data were obtained from the dominant-side shoulder of 12 professional pitchers (PP group) and 15 professional fielders (PF group). CT imaging data were also obtained from both shoulders of 12 asymptomatic collegiate pitchers (CP group) and 11 collegiate fielders (CF group). The pattern of distribution of subchondral bone density across the articular surfaces of each glenohumeral joint was assessed by CTOAM. As a measure of bone density, the mean Hounsfield units (HU) were obtained for each joint surface, and the absolute values of the dominant shoulder were compared for each group.

Results: Stress-distribution patterns over the articular surfaces differed between the dominant and nondominant sides in the CP group as well as between both collegiate groups versus the PP group. In the CP group, the mean HU of the humeral head surface were greater on the nondominant versus dominant side ( = .035). On the dominant side, the mean HU of the humeral head surface and glenoid were greater in the CP versus the PP group ( = .001 and .027, respectively).

Conclusion: Stress distribution on the articular surface of the glenohumeral joint was affected by pitching ability and competitive level. Our analysis indicates that the traction force on the glenohumeral joint surface might be greater than compression force during pitching.

Clinical Relevance: The present findings suggest that pitching activity results in low stress to the articular surfaces of the glenohumeral joint. This supports the notion that mechanical conditions play a crucial role in the etiology of disorders specific to pitching activity.
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http://dx.doi.org/10.1177/23259671211009185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182204PMC
June 2021

Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis.

iScience 2021 Jun 24;24(6):102643. Epub 2021 May 24.

Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan.

Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.
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http://dx.doi.org/10.1016/j.isci.2021.102643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187833PMC
June 2021

Total shoulder arthroplasty with an anteriorly augmented glenoid component for glenohumeral osteoarthritis with anterior glenoid bone loss: a case report.

JSES Int 2021 May 18;5(3):365-370. Epub 2021 Feb 18.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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http://dx.doi.org/10.1016/j.jseint.2020.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178596PMC
May 2021

In vivo deformation of anatomically pre-bent rods in thoracic adolescent idiopathic scoliosis.

Sci Rep 2021 Jun 16;11(1):12622. Epub 2021 Jun 16.

Department of Orthopaedic Surgery, Hokkaido University Hospital, N15W7, Sapporo, Hokkaido, 060-8638, Japan.

Some surgical strategies can maintain or restore thoracic kyphosis (TK); however, next-generation surgical schemes for adolescent idiopathic scoliosis (AIS) should consider anatomical corrections. A four-dimensional correction could be actively achieved by curving the rod. Thus, anatomically designed rods have been developed as notch-free, pre-bent rods for easier anatomical reconstruction. This study aimed to compare the initial curve corrections obtained using notch-free rods and manually bent, notched rods for the anatomical reconstruction of thoracic AIS. Two consecutive series of 60 patients who underwent anatomical posterior correction for main thoracic AIS curves were prospectively followed up. After multilevel facetectomy, except for the lowest instrumented segment, either notch-free or notched rods were used. Patient demographic data, radiographic measurements, and sagittal rod angles were analyzed within 1 week after surgery. Patients with notch-free rods had significantly higher postoperative TK than patients with notched rods (P < .001), but both groups achieved three-dimensional spinal corrections and significantly increased postoperative rates of patients with T6-T8 TK apex (P = .006 for notch-free rods and P = .008 for notched rods). The rod deformation angle at the concave side was significantly lower in the notch-free rods than in the notched rods (P < .001). The notch-free, pre-bent rod can maintain its curvature, leading to better correction or maintenance of TK after anatomical spinal correction surgery than the conventional notched rod. These results suggest the potential benefits of anatomically designed notch-free, pre-bent rods over conventional, manually bent rods.
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http://dx.doi.org/10.1038/s41598-021-92187-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209019PMC
June 2021

Ultrapurified Alginate Gel Containing Bone Marrow Aspirate Concentrate Enhances Cartilage and Bone Regeneration on Osteochondral Defects in a Rabbit Model.

Am J Sports Med 2021 Jul 1;49(8):2199-2210. Epub 2021 Jun 1.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects.

Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects.

Study Design: Controlled laboratory study.

Methods: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks.

Results: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; < .05), the UPAL group (10.0 ± 3.3; < .05), and the UPAL-MSC group (12.2 ± 2.9; < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; < .05), the UPAL group (14.2 ± 3.9; < .05), and the UPAL-MSC group (16.3 ± 3.6; < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups.

Conclusion: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model.

Clinical Relevance: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.
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http://dx.doi.org/10.1177/03635465211014186DOI Listing
July 2021

Serum C-reactive protein is an early, simple and inexpensive prognostic marker for the progression of intramedullary lesion on magnetic resonance imaging from acute to subacute stage in patients with spinal cord injury.

Spinal Cord 2021 May 27. Epub 2021 May 27.

Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.

Study Design: Retrospective chart audit.

Objectives: This study aimed to identify conventional routine blood testing biomarkers associated with the progression of intramedullary injured area in patients with spinal cord injury (SCI).

Setting: A spinal cord injury center in Hokkaido, Japan.

Methods: We retrospectively reviewed 71 consecutive adults with acute SCI who were admitted within 24 h after injury and diagnosed as American Spinal Injury Association Impairment Scale Grade A or B at admission. Participants were divided into the progression (P group) and no progression group (NP group) based on the change of the hyperintense signal abnormality in the spinal cord on magnetic resonance imaging from the time of admission to 4 weeks after injury. Individual characteristics and blood testing data obtained in the first 4 weeks after injury were compared between groups.

Results: The P and NP groups were comprised of 16 and 55 participants, respectively. In univariate analyses, white blood cell (WBC) count on day 3 was significantly higher in group P than group NP (P = 0.021), as was serum C-reactive protein (CRP) level on day 3 (P = 0.015) and day 7 (P = 0.047). Multivariable analysis identified serum CRP level on day 3 as a significant independent prognostic factor for the progression of secondary SCI (OR, 1.138; 95% confidence interval, 1.01-1.28; P = 0.034).

Conclusions: Serum CRP level on day 3 after injury was a good predictor for the progression of intramedullary signal intensity change on MRI from acute to subacute stage in patients with SCI.
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http://dx.doi.org/10.1038/s41393-021-00640-6DOI Listing
May 2021

Changes in the Contact Stress Distribution Pattern of the Patellofemoral Joint After Medial Open-Wedge High Tibial Osteotomy: An Evaluation Using Computed Tomography Osteoabsorptiometry.

Orthop J Sports Med 2021 Apr 21;9(4):2325967121998050. Epub 2021 Apr 21.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Background: Medial open-wedge high tibial osteotomy (OWHTO) theoretically causes distalization and lateralization of the tibial tuberosity and the patella.

Purpose/hypothesis: The purpose of the study was to identify any changes in the stress distribution of subchondral bone density across the patellofemoral (PF) joint before and after OWHTO through the use of computed tomography (CT) osteoabsorptiometry. We hypothesized that OWHTO would alter the distribution of contact stress in the PF joint.

Study Design: Case series; Level of evidence, 4.

Methods: A total of 17 patients (17 knees) who underwent OWHTO were enrolled in this study between September 2013 and September 2015. All patients underwent radiologic examination preoperatively and at 1 year postoperatively, and the distribution patterns of subchondral bone density through the articular surface of the femoral trochlea and patella were assessed preoperatively and >1 year postoperatively using CT osteoabsorptiometry. The quantitative analysis of the obtained mapping data focused on location of the high-density area (HDA) through the articular surface of the PF joint. The percentage of HDA at each divided region of the articular surface of the femoral trochlea and the patella was calculated.

Results: In the radiologic evaluation, the Blackburne-Peel ratio was significantly reduced ( < .001) after surgery, and the tilting angle of the patella was significantly decreased ( < .001). On CT evaluation, the percentage of HDA in the lateral notch and lateral trochlea of the femur and in the medial portion of the lateral facet of the patella increased significantly after OWHTO surgery ( ≤ .038).

Conclusion: OWHTO significantly increased the stress distribution pattern of the lateral trochlea of the femur and the medial portion of the lateral facet of the patella. The procedure significantly lowered the patellar height and significantly decreased the patellar tilting angle after surgery.
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http://dx.doi.org/10.1177/2325967121998050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072873PMC
April 2021

Differential effects of anti-RANKL monoclonal antibody and zoledronic acid on necrotic bone in a murine model of Staphylococcus aureus-induced osteomyelitis.

J Orthop Res 2021 May 15. Epub 2021 May 15.

Department of Orthopaedic Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Osteomyelitis is characterized by progressive inflammatory bone destruction accompanied by severe pain and disability. However, with the exception of antibiotic therapies, there is no established therapy to protect the bone from infectious osteolysis. The anti-receptor activator of nuclear factor-kB ligand (RANKL) monoclonal antibody (anti-RANKL Ab) is a potential drug based on its proven effectiveness in preventing joint bone erosion in rheumatoid arthritis; however, the efficacy and adverse effects of anti-RANKL Ab in osteomyelitis remain to be investigated. In this study, we investigated the effects of anti-mouse RANKL Ab on acute osteomyelitis and compared them with those of zoledronic acid (ZA) using a murine model. Mice were inoculated with bioluminescent Staphylococcus aureus (Xen 29) on their left femur and then treated with ZA, anti-RANKL Ab, or phosphate-buffered saline as control. A 21-day longitudinal observational study using microcomputed tomography showed that both anti-RANKL Ab and ZA had an osteoprotective effect against infectious osteolysis. However, it was also demonstrated through bioluminescence imaging that ZA delayed the spontaneous reduction of bacterial load and through histology that it increased the amount of necrotic bone, while anti-RANKL Ab did not. Findings from histopathological and in vitro studies suggest that an intense inflammatory response around the necrotic bone could induce osteoclasts in a RANKL-independent manner, leading to the removal of necrotic bone, even after administration of the anti-RANKL Ab therapy. Collectively, anti-RANKL Ab may exert an osteoprotective effect without hampering the removal of the necrotic bone, which serves as a nidus for infection in osteomyelitis.
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http://dx.doi.org/10.1002/jor.25102DOI Listing
May 2021

Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review.

Int J Mol Sci 2021 Apr 24;22(9). Epub 2021 Apr 24.

Department of Orthopaedic Surgery, Hokkaido Spinal Cord Injury Center, Bibai 072-0015, Japan.

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.
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http://dx.doi.org/10.3390/ijms22094453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123121PMC
April 2021

Blood flow distribution after end-to-side anastomosis with wide arteriotomy in extremity free flap surgery.

J Plast Reconstr Aesthet Surg 2021 Mar 28. Epub 2021 Mar 28.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, JAPAN.

Purpose: Although many studies have investigated the optimal anastomotic procedure for the end-to-side (ETS) procedure with a free flap, no study has focused on the size of the arteriotomy. Some surgeons have recently described the effectiveness of ETS with wide arteriotomy, but the postoperative haemodynamics remains unclear for free flaps created using this technique. The aim of this study was to use ultrasonography to evaluate the postoperative blood flow distribution after ETS with a wide arteriotomy in extremity free flap surgery.

Methods: We evaluated 20 free flaps in 18 consecutive patients who received an ultrasonographic examination after free flap surgery using the ETS technique with wide arteriotomy for arterial anastomosis. All flaps were examined after surgery and blood flow was calculated for the flap and recipient vessels.

Results: All 20 flaps survived, but one flap developed asymptomatic arterial thrombosis and 19 flaps were analysed. For the ETS technique with wide arteriotomy, peripheral circulation was well preserved in all flaps. Comparison of flap types showed that blood flow was significantly higher in myocutaneous flaps than in fasciocutaneous flaps, but there was no significant difference according to the size of the arteriotomy.

Conclusions: Given the range of arteriotomy performed using the ETS with a wide arteriotomy technique, the blood flow volume in the flap depended on the type of flap but not on the size of the arteriotomy. A steal phenomenon related to the creation of a wide window in the receipt artery was not found in the analysed retrospective cohort.
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http://dx.doi.org/10.1016/j.bjps.2021.03.022DOI Listing
March 2021

Delayed lumbar plexus palsy due to giant psoas hematoma associated with vertebral compression fracture and direct oral anticoagulants: a case report.

BMC Musculoskelet Disord 2021 Apr 22;22(1):377. Epub 2021 Apr 22.

Department of Orthopaedic Surgery, Hokkaido Spinal Cord Injury Center, Higashi-4, Minami-1, 3-1, Bibai, Hokkaido, 072-0015, Japan.

Background: Osteoporotic vertebral compression fractures (VCFs) are commonly observed in elderly people and can be treated by conservatively with minimal risk of complications in most cases. However, utilization of direct oral anticoagulants (DOACs) increases the risks of secondary hematoma even after insignificant trauma. The use of DOACs increased over the past decade because of their approval and recommendation for both stroke prevention in non-valvular atrial fibrillation and treatment of venous thromboembolism. It is well known that DOACs are safer anticoagulants than warfarin in terms of major and nonmajor bleeding; however, we noted an increase in the number of bleeding events associated with DOACs that required medical intervention. This report describes the first case of delayed lumbar plexus palsy due to DOAC-associated psoas hematoma after VCF to draw attention to potential risk of severe complication associated with this type of common and stable trauma.

Case Presentation: An 83-year-old man presented with his left inguinal pain and inability to ambulate after falling from standing position and was prescribed DOACs for chronic atrial fibrillation. Computed tomography angiography revealed a giant psoas hematoma arising from the ruptured segmental artery running around fractured L4 vertebra. Because of motor weakness of his lower limbs and expansion of psoas hematoma revealed by contrast computed tomography on day 8 of his hospital stay, angiography aimed for transcatheter arterial embolization was tried, but could not demonstrate any major active extravasation; therefore spontaneous hemostasis was expected with heparin replacement. On day 23 of his stay, hematoma turned to decrease, but dysarthria and motor weakness due to left side cerebral infarction occurred. His pain improved and bone healing was achieved about 2 months later from his admission, however the paralysis of the left lower limb and aftereffects of cerebral infarction remained after 1 year.

Conclusion: In patients using DOACs with multiple risk factors, close attention must be taken in vertebral injury even if the fracture itself is a stable-type such as VCF, because segmental artery injury may cause massive psoas hematoma followed by lumbar plexus palsy and other complications.
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http://dx.doi.org/10.1186/s12891-021-04267-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063304PMC
April 2021

Bone Metabolism in the Healing Process of Lumbar Interbody Fusion-Temporal changes of bone turnover markers.

Spine (Phila Pa 1976) 2021 Apr 19. Epub 2021 Apr 19.

Spine Center, Hakodate Central General Hospital, Hakodate, Japan Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

Study Design: Prospective longitudinal study.

Objective: The aim of this study was to evaluate temporal changes of bone turnover markers (BTMs) after lumbar spinal fusion in patients without osteoporosis.

Summary Of Background Data: Radiological studies are the standard method to monitor bony fusion, but they do not allow a timely assessment of bone healing. BTMs react rapidly to changes in bone metabolism during fusion process and could be an additional tool to monitor this process.

Methods: A total of 78 non-osteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using CT sagittal and coronal images. Serum levels of bone specific alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin (OC) were measured to assess bone formation, and tartrate-resistant acid phosphatase 5b (TRACP-5b) was measured to assess bone resorption. Serum samples were obtained before surgery and at 1, 2, 4, 8, 13, 26, 39, and 52 weeks after surgery.

Results: A solid fusion was achieved in 71 of 78 patients (91%), and 7 patients resulted in pseudarthrosis. In the fusion group, the level of all BTMs once decreased at 1 postoperative week. Then, BAP and P1NP reached a peak at 4 weeks after surgery, and TRACP-5b and OC peaked at 8 weeks. Thereafter, the level of P1NP and TRACP-5b gradually got closer to the baseline over a year, and BAP kept high until 52 postoperative weeks. In the pseudarthrosis group, peak level of BTMs were significantly higher and the increased level of BAP and P1NP was kept until 52 weeks.

Conclusions: The current study demonstrated dynamics of BTMs after lumbar spinal fusion in patients without osteoporosis. These normal population data contribute as a baseline to evaluate the effect of osteogenic agents on bone metabolism after spinal fusion.Level of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000004075DOI Listing
April 2021

Effects after starting or switching from bisphosphonate to romosozumab or denosumab in Japanese postmenopausal patients.

J Bone Miner Metab 2021 Apr 13. Epub 2021 Apr 13.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Purpose: We aimed to investigate the longitudinal changes in bone metabolic markers and bone mineral density (BMD) after starting or switching from bisphosphonate (BP) to romosozumab (ROMO) or denosumab (DENO) therapies over 12 months and to determine predictors that establish associations with changes in BMD among the patients received the ROMO therapy.

Methods: Postmenopausal osteoporosis patients with a high risk of fracture-154 in total-were recruited; their therapies were switched to ROMO or DENO from BP/naïve or vitamin D (ND) (ND-ROMO: 43, BP-ROMO: 38, ND-DENO: 38, and BP-DENO: 35). Longitudinal changes in bone metabolic markers and BMD were evaluated.

Results: ROMO groups showed significant increases in BMD of the lumbar spine at 6 and 12 months and femoral neck at 12 months compared to the DENO groups. Although BP-ROMO showed significant increase in the lumbar spine BMD compared to BP-DENO, there were no significant differences in femoral neck and total hip BMDs between BP-ROMO and BP-DENO. Among the ROMO groups, % changes of BMD from baseline to 12 months were associated with bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months.

Conclusions: ROMO continuously increased BMD for 12 months and performed better than DENO. On the other hand, effects of ROMO switched from BP on BMD of femoral neck and total hip were almost same with DENO. Bone metabolic markers at baseline and changes in TRACP-5b from baseline to 3 months may predict the efficacy of ROMO after 12 months of administration.
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http://dx.doi.org/10.1007/s00774-021-01226-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042469PMC
April 2021

Hallux Valgus With Second Brachymetatarsia Discovered Accidentally: A Case Report.

J Foot Ankle Surg 2021 Mar 18. Epub 2021 Mar 18.

Professor, Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Hallux valgus deformity is one of the most common foot and ankle diseases, while brachymetatarsia is a rare foot anomaly with pathological shortening of a metatarsal bone. We present a case of hallux valgus deformity possibly due to second brachymetatarsia. As the hallux valgus was associated with dorsal dislocation of the second toe that made it difficult to evaluate the length of the second toe, the patient was unaware of the second metatarsal shortening until the lengths of the toes compared by manual reposition of the second MTP joint. In this case, proximal osteotomy of the first metatarsal on the hallux valgus and single-stage bone lengthening of the second metatarsal with iliac bone grafting on the second brachymetatarsia were performed. One year after the operation, the callosity of the third toe resolved and the clinical scores were improved. In the case of a hallux valgus deformity with second dorsal dislocation of the toes, surgeons should consider that there are rare cases with second metatarsal shortening. When hallux valgus associated with second brachymetatarsia is diagnosed, second metatarsal lengthening should be considered in addition to hallux valgus surgery.
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http://dx.doi.org/10.1053/j.jfas.2020.11.008DOI Listing
March 2021

Short-term efficacy and safety of zoledronate acid or denosumab in Japanese patients with postmenopausal osteoporosis.

J Bone Miner Metab 2021 Apr 5. Epub 2021 Apr 5.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

Introduction: We aimed to compare the efficacy after switching from either bisphosphonates (BPs) or non-BPs (NBPs) to combination therapies of denosumab (DMAb) or zoledronic acid (Zol) with eldecalcitol (ELD) in bone mineral density (BMD) and bone metabolism and investigate the prognostic and risk factors of side effects of this therapy.

Materials And Methods: One-hundred forty-eight patients with postmenopausal osteoporosis were recruited; their therapy was switched from BPs or NBPs to Zol or DMAb plus ELD (BP-Zol: 43, NBP-Zol: 32, BP-DMAb: 35, and NBP-DMAb: 38). Longitudinal changes in bone metabolic markers (P1NP and TRACP-5b) and BMD were evaluated.

Results: In the BP-Zol group, P1NP did not change after 6 months and increased by 38.9% after 12 months. TRACP-5b decreased 15.8% after 6 months, but came back to baseline values 12 months after administration. In the rest of the groups, the bone metabolic markers remained suppressed after 6 and 12 months. Compared with baseline, all groups showed increase in BMD after 6 and 12 months. Bone metabolic markers at baseline were correlated with %change in lumbar spine BMD from baseline to 12 months. P1NP and 25-hydroxy vitamin D levels at baseline were identified as potential predictors of development of acute-phase reactions.

Conclusions: The combination therapy of Zol or DMAb and ELD may increase BMD at 12 months after the first administration in Japanese patients with postmenopausal osteoporosis, regardless of BPs pretreatment. Bone metabolic markers at baseline may be useful predictors for reaction to the therapy and side effects caused by these combination therapies in postmenopausal osteoporosis.
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http://dx.doi.org/10.1007/s00774-021-01221-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021003PMC
April 2021

Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

Department of Orthopedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15, Nish-7, Kita-ku, Sapporo 060-8638, Japan.

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague-Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.
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http://dx.doi.org/10.3390/ijms22052552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962042PMC
March 2021

Effect of High Tibial Osteotomy on the Distribution of Subchondral Bone Density Across the Proximal Tibial Articular Surface of the Knee With Medial Compartment Osteoarthritis.

Am J Sports Med 2021 05 2;49(6):1561-1569. Epub 2021 Apr 2.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Background: The effect of high tibial osteotomy (HTO) on the stress distribution across the knee joint is not completely understood. Subchondral bone density is considered to reflect the pattern of stress distribution across a joint surface.

Purpose: To assess the distribution of subchondral bone density across the proximal tibia in nonarthritic knees and in the knees of patients with osteoarthritis (OA) before and after HTO.

Study Design: Cohort study; Level of evidence, 3.

Methods: We retrospectively collected radiological and computed tomography data from 16 patients without OA (control group) and 17 patients with OA. Data from the OA group were collected before and 1.5 years after HTO. Subchondral bone density of the proximal tibia was assessed with computed tomography-osteoabsorptiometry. The locations and percentages represented by high-density areas (HDAs) on the articular surface were quantitatively analyzed.

Results: The ratio of the HDA of the medial compartment to the total HDA (medial ratio) was significantly higher in the preoperative OA group (mean, 80.1%) than in the control group (61.3%) ( < .001). After HTO, the medial ratio decreased significantly to 75.1% ( = .035 in comparison with preoperative values) and was significantly correlated with the hip-knee-ankle angle in both groups: control ( = -0.551; = .033) and OA ( = -0.528; = .043). The change in medial ratio after HTO was significantly correlated with the change in hip-knee-ankle angle ( = 0.587; = .035). In the medial compartment, the HDA in the most lateral region of 4 subregions increased after HTO, but that in 3 medial subregions decreased.

Conclusion: In this exploratory study, HTO shifted the HDA of the medial compartment of the proximal tibial articular surface toward the lateral compartment. In contrast, the HDA of the most lateral region of the medial compartment increased after HTO. This change in subchondral bone density may result from the change in stress distribution.
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http://dx.doi.org/10.1177/03635465211002537DOI Listing
May 2021

Morphologic Changes in the Vertebral Artery Subsequent to Cervical Spine Degeneration and Aging: Analyses by Computed Tomography Angiography Using Multiplanar and 3-Dimensional Reconstructions.

World Neurosurg 2021 Jun 23;150:e686-e695. Epub 2021 Mar 23.

Department of Orthopedic Surgery, Hokkaido Spinal Cord Injury Center, Bibai, Hokkaido, Japan.

Objective: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion.

Methods: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated.

Results: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence.

Conclusions: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries.
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http://dx.doi.org/10.1016/j.wneu.2021.03.080DOI Listing
June 2021

Finite element analysis of double-plate fixation using reversed locking compression-distal femoral plates for Vancouver B1 periprosthetic femoral fractures.

BMC Musculoskelet Disord 2021 Mar 13;22(1):276. Epub 2021 Mar 13.

Department of Orthopaedic Surgery, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan.

Background: Internal fixation is recommended for treating Vancouver B1 periprosthetic femoral fractures. Although several fixation procedures have been developed with high fixation stability and union rates, long-term weight-bearing constructs are still lacking. Therefore, the aim of the present study was to evaluate the stability of a double-plate procedure using reversed contralateral locking compression-distal femoral plates for fixation of Vancouver B1 periprosthetic femoral fractures under full weight-bearing.

Methods: Single- and double-plate fixation procedures for locking compression-distal femoral plates were analysed under an axial load of 1,500 N by finite element analysis and biomechanical loading tests. A vertical loading test was performed to the prosthetic head, and the displacements and strains were calculated based on load-displacement and load-strain curves generated by the static compression tests.

Results: The finite element analysis revealed that double-plate fixation significantly reduced stress concentration at the lateral plate place on the fracture site. Under full weight-bearing, the maximum von Mises stress in the lateral plate was 268 MPa. On the other hand, the maximum stress in the single-plating method occurred at the defect level of the femur with a maximum stress value of 1,303 MPa. The principal strains of single- and double-plate fixation were 0.63 % and 0.058 %, respectively. Consistently, in the axial loading test, the strain values at a 1,500 N loading of the single- and double-plate fixation methods were 1,274.60 ± 11.53 and 317.33 ± 8.03 (× 10), respectively.

Conclusions: The present study suggests that dual-plate fixation with reversed locking compression-distal femoral plates may be an excellent treatment procedure for patients with Vancouver B1 fractures, allowing for full weight-bearing in the early postoperative period.
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http://dx.doi.org/10.1186/s12891-021-04152-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956136PMC
March 2021

Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis-a pilot study.

Arthritis Res Ther 2021 03 11;23(1):83. Epub 2021 Mar 11.

Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.

Background: This study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI.

Methods: Forty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery.

Results: The agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ < 0.40). Among the 152 joints with ON detected by WB-MRI, 92 joints (60.5%) were symptomatic, and 60 joints (39.5%) were asymptomatic. Twelve out of the 46 (26.0%) patients had multifocal (three or more distinct anatomical sites) ON. Nonetheless, while WB-BS detected symptomatic ON detected by WB-MRI as uptake lesions in 82.6% (76/92) of the joints, asymptomatic ON detected by WB-MRI was detected as uptake lesions in 21.7% (13/60) of the joints. All patients with multifocal ON had a history of steroid therapy, which was significantly higher than that in patients with oligofocal ON (P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015).

Conclusions: It might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.
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http://dx.doi.org/10.1186/s13075-021-02473-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947377PMC
March 2021

Impact of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis.

Clin Biomech (Bristol, Avon) 2021 Mar 20;83:105296. Epub 2021 Feb 20.

Department of Orthopaedic Surgery, Hokkaido University Hospital, N14W5, Sapporo, Hokkaido 060-8648, Japan. Electronic address:

Background: The aim of this study was to intraoperatively assess the effects of multilevel facetectomy on segmental spinal flexibility in patients with thoracic adolescent idiopathic scoliosis.

Methods: Twenty patients who underwent posterior thoracic adolescent idiopathic scoliosis curve correction were evaluated. Compressive or distractive loaded force of 50N was applied on the handle of a compressor or distractor connected to the necks of pedicle screws inserted at T7 to T11. Segmental spinal flexibility rates were calculated based on the distance between screw heads under the loaded and unloaded conditions. In addition, the flexibility rates were obtained before and after multilevel facetectomy.

Findings: Absolute flexibility rates of all segments significantly increased after multilevel facetectomy under both compressive and distractive forces (P < 0.01). The absolute change in the flexibility rate was significantly higher at the concave side than at the convex side under both compressive (P < 0.01) and distractive loaded forces (P = 0.046). No significant correlation was found between change in the flexibility rates and preoperative Cobb angle or preoperative curve flexibility.

Interpretation: From a biomechanical point of view, multilevel facetectomy provides proper spinal flexibility to improve the correction rate of posterior adolescent idiopathic scoliosis surgery. The effects are higher at the concave side than at the convex side.
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http://dx.doi.org/10.1016/j.clinbiomech.2021.105296DOI Listing
March 2021

An algorithm for using deep learning convolutional neural networks with three dimensional depth sensor imaging in scoliosis detection.

Spine J 2021 06 1;21(6):980-987. Epub 2021 Feb 1.

Department of Orthopedic Surgery, Hokkaido University Hospital, Nishi 5 Chome Kita 14 Jo, Kita Ward, Sapporo, Hokkaido 060-8648, Japan; Department of Advanced Medicine for Spine and Spinal Cord Disorders, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N15W7, Sapporo, Hokkaido 060-8638, Japan. Electronic address:

Background Context: Timely intervention in growing individuals, such as brace treatment, relies on early detection of adolescent idiopathic scoliosis (AIS). To this end, several screening methods have been implemented. However, these methods have limitations in predicting the Cobb angle.

Purpose: This study aimed to evaluate the performance of a three-dimensional depth sensor imaging system with a deep learning algorithm, in predicting the Cobb angle in AIS.

Study Design: Retrospective analysis of prospectively collected, consecutive, nonrandomized series of patients at five scoliosis centers in Japan.

Patient Sample: One hundred and-sixty human subjects suspected to have AIS were included.

Outcome Measures: Patient demographics, radiographic measurements, and predicted Cobb angle derived from the deep learning algorithm were the outcome measures for this study.

Methods: One hundred and sixty data files were shuffled into five datasets with 32 data files at random (dataset 1, 2, 3, 4, and 5) and five-fold cross validation was performed. The relationships between the actual and predicted Cobb angles were calculated using Pearson's correlation coefficient analyses. The prediction performances of the network models were evaluated using mean absolute error and root mean square error between the actual and predicted Cobb angles. The shuffling into five datasets and five-fold cross validation was conducted ten times. There were no study-specific biases related to conflicts of interest.

Results: The correlation between the actual and the mean predicted Cobb angles was 0.91. The mean absolute error and root mean square error were 4.0° and 5.4°, respectively. The accuracy of the mean predicted Cobb angle was 94% for identifying a Cobb angle of ≥10° and 89% for that of ≥20°.

Conclusions: The three-dimensional depth sensor imaging system with its newly innovated convolutional neural network for regression is objective and has significant ability to predict the Cobb angle in children and adolescents. This system is expected to be used for screening scoliosis in clinics or physical examination at schools.
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http://dx.doi.org/10.1016/j.spinee.2021.01.022DOI Listing
June 2021

Association Between Vitamin A Intake and Disease Severity in Early-Onset Heterotopic Ossification of the Posterior Longitudinal Ligament of the Spine.

Global Spine J 2021 Jan 25:2192568221989300. Epub 2021 Jan 25.

Department of Orthopedic Surgery, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Hokkaido, Japan.

Study Design: A sex- and age-matched case-control study and a cross-sectional study.

Objective: In our previous study, patients with early-onset (<50 years of age) ossification of the posterior longitudinal ligament (OPLL) had distinct features such as morbid obesity, a high prevalence of lifestyle-related diseases, and diffuse ossified lesions mainly affecting the thoracic spine. Our goals were to determine whether early-onset OPLL patients have unbalanced dietary habits and to identify nutritional factors associated with OPLL exacerbation.

Methods: In Study 1, the simple brief-type self-administered diet history questionnaire (BDHQ) was used to compare nutrient intake levels of early-onset OPLL patients (n = 13) with those of sex- and age-matched non-OPLL controls (n = 39) or with those of common OPLL (onset age ≥ 50 years, n = 62). In Study 2, serological validation was conducted for thoracic OPLL patients (n = 77) and non-OPLL controls (n = 101) in a nationwide multicenter study in Japan.

Results: The BDHQ showed that the early-onset OPLL patients had significantly lower intakes of vitamins A and B6 than non-OPLL controls. These results were validated by lower serum vitamins A and B6 levels in the early-onset thoracic OPLL patients. The severity of OPLL negatively correlated with serum vitamin A levels in male early-onset OPLL patients. The multiple regression analysis revealed that the severity of thoracic OPLL had an association with onset age and serum vitamin A level.

Conclusions: Vitamin A deficiency resulting from unbalanced dietary habits is associated with exacerbation of male early-onset OPLL.
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http://dx.doi.org/10.1177/2192568221989300DOI Listing
January 2021

Bone Marrow Aspirate Concentrate Combined with in Situ Forming Bioresorbable Gel Enhances Intervertebral Disc Regeneration in Rabbits.

J Bone Joint Surg Am 2021 Apr;103(8):e31

Departments of Orthopedic Surgery (D.U., K.Y., T.T., K.U., N.I., and H.S.) and Advanced Medicine for Spine and Spinal Cord Disorders (H.S.), Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Background: The current surgical procedure of choice for intervertebral disc (IVD) herniation is discectomy, which induces postoperative IVD degeneration. Thus, cell-based therapies, as a 1-step simple procedure, are desired because of the poor capacity of IVDs for self-repair. The aim of this study was to investigate the repair efficacy of ultra-purified alginate (UPAL) gels containing bone marrow aspirate concentrate (BMAC) for the treatment of discectomy-associated IVD degeneration in rabbits.

Methods: The mechanical properties of 3 types of gels-UPAL, UPAL containing bone marrow-derived mesenchymal stem cells (BMSCs), and UPAL containing BMAC-were evaluated. Forty rabbits were assigned to 5 groups: intact control, discectomy (to make the cavity), UPAL (implantation of the UPAL gel after discectomy), BMSCs-UPAL (implantation of a combination of autogenic BMSCs and UPAL gel after discectomy), and BMAC-UPAL (implantation of a combination of BMAC and UPAL gel after discectomy). The gels were implanted at 4 weeks after induction of IVD degeneration. At 4 and 12 weeks, magnetic resonance imaging (MRI) as well as histological and immunohistochemical analyses were performed to analyze IVD degeneration qualitatively and the viability of the implanted cells.

Results: There was no significant difference among the 3 types of gels in terms of the results of unconfined compression tests. The implanted cells survived for 12 weeks. The histological grades of the BMSCs-UPAL (mean and standard deviation, 2.50 ± 0.53; p < 0.001) and BMAC-UPAL (2.75 ± 0.64, p = 0.001) showed them to be more effective in preventing degeneration than UPAL gel alone (3.63 ± 0.52). The effectiveness of BMAC-UPAL was not significantly different from that of BMSCs-UPAL, except with respect to type-II collagen synthesis.

Conclusions: BMAC-UPAL significantly enhanced the repair of IVD defects created by discectomy. This approach could be an effective therapeutic strategy owing to its simplicity and cost-effectiveness compared with cell therapy using culture-expanded BMSCs.

Clinical Relevance: Local administration of the BMAC combined with UPAL gel could be an effective therapeutic strategy to enhance IVD repair after discectomy.
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http://dx.doi.org/10.2106/JBJS.20.00606DOI Listing
April 2021
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