Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft

BACKGROUND CONTEXT: Although autologous bone grafting is widely considered as an ideal source for interbody fusion, it still carries a risk of nonunion. The influence of the intervertebral device should not be overlooked. Requirements for artificial spinal devices are to join the vertebrae together and recover the original function of the spine rapidly. Ordered mineralization of apatite crystals on collagen accelerates bone functionalization during the healing process. Particularly, the stable spinal function requires the ingrowth of an ordered collagen and apatite matrix which mimics the intact intervertebral microstructure. This collagen and apatite ordering is imperative for functional bone regeneration, which has not been achieved using classical autologous grafting. PURPOSE: We developed an intervertebral body device to achieve high stability between the host bone and synthesized bone by controlling the ordered collagen and apatite microstructure. STUDY DESIGN: This was an in vivo animal study. METHODS: Intervertebral spacers with a through-pore grooved surface structure, referred to as a honeycomb tree structure, were produced using metal 3D printing. These spacers were implanted into normal sheep at the L2–L3 or L4–L5 disc levels. As a control group, grafting autologous bone was embedded. The mechanical integrity of the spacer/bone interface was evaluated through push-out tests. RESULTS: The spacer with honeycomb tree structure induced anisotropic trabecular bone growth with textured collagen and apatite orientation in the through-pore and groove directions. The push-out load of the spacer was significantly higher than that of the conventional autologous graft spacer. Moreover, the load was significantly correlated with the anisotropic texture of the newly formed bone matrix. CONCLUSIONS: The developed intervertebral spacer guided the regenerated bone matrix orientation of collagen and apatite, resulting in greater strength at the spacer/host bone interface than that obtained using a conventional gold-standard autologous bone graft. CLINICAL SIGNIFICANCE: Our results provide a foundation for designing future spacers for interbody fusion in human.Matsugaki A., Ito M., Kobayashi Y., et al. Innovative design of bone quality-targeted intervertebral spacer: accelerated functional fusion guiding oriented collagen and apatite microstructure without autologous bone graft. Spine Journal 23, 609 (2023); https://doi.org/10.1016/j.spinee.2022.12.011

A Functional SNP in BNC2 Is Associated with Adolescent Idiopathic Scoliosis

Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity. We previously conducted a genome-wide association study (GWAS) and detected two loci associated with AIS. To identify additional loci, we extended our GWAS by increasing the number of cohorts (2,109 affected subjects and 11,140 control subjects in total) and conducting a whole-genome imputation. Through the extended GWAS and replication studies using independent Japanese and Chinese populations, we identified a susceptibility locus on chromosome 9p22.2 (p = 2.46 × 10−13; odds ratio = 1.21). The most significantly associated SNPs were in intron 3 of BNC2, which encodes a zinc finger transcription factor, basonuclin-2. Expression quantitative trait loci data suggested that the associated SNPs have the potential to regulate the BNC2 transcriptional activity and that the susceptibility alleles increase BNC2 expression. We identified a functional SNP, rs10738445 in BNC2, whose susceptibility allele showed both higher binding to a transcription factor, YY1 (yin and yang 1), and higher BNC2 enhancer activity than the non-susceptibility allele. BNC2 overexpression produced body curvature in developing zebrafish in a gene-dosage-dependent manner. Our results suggest that increased BNC2 expression is implicated in the etiology of AIS

シンケイ センイショウ 1ガタ ノ セキチュウ ヘンケイ ニ トモナウ ロッコツ ズ ノ セキチュウカン ナイ ダッキュウ

2006 年4 月～2010 年3 月の神経線維腫症1 型に伴う脊柱変形手術例10 例中3 例に肋骨頭の脊柱管内脱臼がみられた.症例1 は6 歳の男児でT4-8:74°,T8-11:72° の側弯があり,左第4 と第5 肋骨頭の脊柱管内への陥入を認めた.症例2 は11 歳の男児でT3-7:100° の側弯とT3-T9:90° の後弯があり,左第6 肋骨頭が脊柱管内へ脱臼し,脊髄を圧排していた.症例3 は27 歳の女性でT6～9:73°,T9～12:68° の側弯とT6-10:91°の後弯を認め,右第7 肋骨頭の脊柱管内脱臼がみられた.本病態の報告例は少ないが,決して希な病態ではなくdystrophic change を伴う脊柱変形においては,肋骨頭の脊柱管内脱臼による潜在的リスクに注意する必要があると考える.Spinal deformities are common features in neurofibromatosistype-1( NF-1). Several types of deformities have been reported, however, intraspinal rib head dislocation (IRD)due to dystrophic change is very rare and not well understood. Between April 2006 and March 2010, we experienced3 patients with IRD out of 10 consecutive patients who underwent surgical treatment for dystrophic spinal deformities in NF-1. Case 1:A 6-year-old boy who had 74 ° short angular scoliosis at T4-8 and 72 ° at T8-11 underwent surgery in our institute. CT myelography demonstrated dystrophic changes with for aminal enlargement, vertebral body scalloping, rib penciling and mild IRD. He underwent the Growing Rod techniques and finally underwent posterior spinal fusion (PSF) from T1 to L2 combined with prophylactic rib head resection followed by anterior spinal fusion(ASF) with autologous fibular strut graft. No neurological complications were observed postoperatively and complete bony fusions were achieved. Case 2:Neurologically intact11-year-old boy presented with spinal deformity and caféau-lait spots. Radiography showed 100 ° scoliosis at T3-7and 72 ° at T3-9. CT myelography demonstrated dystrophic changes and IRD and impingement of spinal cord. He underwent PSF with removal of the T6 rib head followed by ASF. Case 3:A 27-year-old woman presented with back pain and spinal deformities. Radiography showed 73 °scoliosis at T6-9 and 91 ° at T9-12. CT myelography demonstrated dystrophic changes and IRD. She also underwentPSF with removal of T7 rib head followed by ASF. AllIRDs were observed at the apex of the convex side of scoliosis.It has a potential risk of spinal cord compression and may cause paraplegia or paraparesis. Therefore, high degree of suspicion is warranted for the treatments of scoliosis with intraspinal rib displacement in NF-1

カンイ ヨウツイ カドウイキ ソクテイキ ノ セイカクセイ ト シンライセイ ノ ケントウ

【目的】腰椎可動性の評価は腰痛性疾患の診断や治療効果判定に際し重要である.簡単な取り付け器具で体幹に装着し, X線撮影なしに腰椎可動域を評価できる簡易腰椎可動域測定器を開発し,測定データの正確性および信頼性を評価したので報告する.【方法】簡易腰椎可動域測定器は,金属製の固定板,その中央に垂直に取り付けられた計測バー,固定板を体幹に確実に固定するゴムバンドより構成されている.第12胸椎と仙骨上の体幹背面に装着した測定器による可動域と実際の腰椎可動域をX線およびCTを用いて計測し,正確性,測定者間および測定者内の一致度および再現性を検討した.【結果】前後屈および回旋可動域に関しては測定値とX線計測値はよく相関し,かつ,その平均値に有意差はないことから正確性は良好であった.一方,前後屈の各体位における測定値とX線計測値には有意差があること,各回旋位の計測値の相関関係にはばらつきが多かったことから,本測定器は腰椎の肢位をX線と同様に捉えていなかった.また,側屈可動域に関しては,測定値とX線計測値の相関は前後屈や回旋より劣り,かつ,その計測値にも有意差が見られたことから,側屈可動域に関する本測定器の正確性は不十分であった.さらに,測定者間および測定者内一致度はすべての項目で高く再現性も認められた.【結論】前後屈および回旋可動域は簡易腰椎可動域測定器により低コストで簡便に測定でき,その正確性や信頼性も優れていた.Purpose : It is important to evaluate mobility of the lumbar spine for assessment of lumbar spinal disorders and their therapeutic effects. We developed a simple measurement device for the lumbar range of motion (SMD-L-ROM) which can be installed on the trunk. SMD-L-ROM allows to evaluate mobility of the lumbar spine without x-ray exposure. Accuracy and reliability of the measurement device was assessed in this article. Method : SMD-L-ROM comprises two metallic immobilization plates (IPs) with a vertically installed bar and a rubber band for fixation of IP to the trunk. Two IPs were installed at the level of Th12 and the sacrum. Range of motion (ROM) of the lumbar spine was measured by using SMD-L-ROM and radiographic modalities (X-ray and CT). Consistency of the measured values by both of SMD-L-ROM and radiographic modalities was evaluated. Furthermore, inter- and intra-observer agreement of measured values by SMD-L-ROM was assessed. Results : Regarding measurement of ROM, there was a high correlation between SMD-L-ROM and X-ray/CT especially in the sagittal and axial plane. There was no significant difference in the average values of ROM between the two methods. On the other hand, SMD-L-ROM did not detect accurate position of the lumbar spine in all dimensions. There were no inter- and intra-observer errors of measured values by SMD-L-ROM. Conclusion : ROM of the lumbar spine was simply and economically measured with SMD-L-ROM. Accuracy and reliability of SMD-L-ROM was good enough for ROM measurement in the lumbar spine

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS