Publications by authors named "Hasibullah Habibi"

11 Publications

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Gender-specific analysis for the association between trunk muscle mass and spinal pathologies.

Sci Rep 2021 Apr 9;11(1):7816. Epub 2021 Apr 9.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

We investigated the relationship between trunk muscle mass and spinal pathologies by gender. This multicenter cross-sectional study included patients aged ≥ 30 years who visited a spinal outpatient clinic. Trunk and appendicular muscle mass were measured using bioelectrical impedance analysis. The Oswestry Disability Index (ODI), visual analog scale (VAS) score for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated to evaluate spinal pathology. The association between trunk muscle mass and these parameters was analyzed by gender using a non-linear regression model adjusted for patients' demographics. We investigated the association between age and trunk muscle mass. We included 781 men and 957 women. Trunk muscle mass differed significantly between men and women, although it decreased with age after age 70 in both genders. Lower trunk muscle mass was significantly associated with ODI, SVA, and EQ5D score deterioration in both genders; its association with VAS was significant only in men. Most parameters deteriorated when trunk muscle mass was < 26 kg in men and < 19 kg in women. Lower trunk muscle mass was associated with lumbar disability, spinal imbalance, and poor quality of life in both genders, with significant difference in muscle mass.
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http://dx.doi.org/10.1038/s41598-021-87334-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035169PMC
April 2021

Trunk Muscle Mass Measured by Bioelectrical Impedance Analysis Reflecting the Cross-Sectional Area of the Paravertebral Muscles and Back Muscle Strength: A Cross-Sectional Analysis of a Prospective Cohort Study of Elderly Population.

J Clin Med 2021 Mar 12;10(6). Epub 2021 Mar 12.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.

Trunk muscles play an important role in supporting the spinal column. A decline in trunk muscle mass, as measured by bioelectrical impedance analysis (TMM-BIA), is associated with low back pain and poor quality of life. The purpose of this study was to determine whether TMM-BIA correlates with quantitative and functional assessments traditionally used for the trunk muscles. We included 380 participants (aged ≥ 65 years; 152 males, 228 females) from the Shiraniwa Elderly Cohort (Shiraniwa) study, for whom the following data were available: TMM-BIA, lumbar magnetic resonance imaging (MRI), and back muscle strength (BMS). We measured the cross-sectional area (CSA) and fat-free CSA of the paravertebral muscles (PVM), including the erector spinae (ES), multifidus (MF), and psoas major (PM), on an axial lumbar MRI at L3/4. The correlation between TMM-BIA and the CSA of PVM, fat-free CSA of PVM, and BMS was investigated. TMM-BIA correlated with the CSA of total PVM and each individual PVM. A stronger correlation between TMM-BIA and fat-free CSA of PVM was observed. The TMM-BIA also strongly correlated with BMS. TMM-BIA is an easy and reliable way to evaluate the trunk muscle mass in a clinical setting.
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http://dx.doi.org/10.3390/jcm10061187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001452PMC
March 2021

Biglycan expression and its function in human ligamentum flavum.

Sci Rep 2021 Mar 1;11(1):4867. Epub 2021 Mar 1.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi Machi, Abeno-Ku, Osaka, 545-8585, Japan.

Hypertrophy of the ligamentum flavum (LF) is a major cause of lumbar spinal stenosis (LSS), and the pathology involves disruption of elastic fibers, fibrosis with increased cellularity and collagens, and/or calcification. Previous studies have implicated the increased expression of the proteoglycan family in hypertrophied LF. Furthermore, the gene expression profile in a rabbit experimental model of LF hypertrophy revealed that biglycan (BGN) is upregulated in hypertrophied LF by mechanical stress. However, the expression and function of BGN in human LF has not been well elucidated. To investigate the involvement of BGN in the pathomechanism of human ligamentum hypertrophy, first we confirmed increased expression of BGN by immunohistochemistry in the extracellular matrix of hypertrophied LF of LSS patients compared to LF without hypertrophy. Experiments using primary cell cultures revealed that BGN promoted cell proliferation. Furthermore, BGN induces changes in cell morphology and promotes myofibroblastic differentiation and cell migration. These effects are observed for both cells from hypertrophied and non-hypertrophied LF. The present study revealed hyper-expression of BGN in hypertrophied LF and function of increased proteoglycan in LF cells. BGN may play a crucial role in the pathophysiology of LF hypertrophy through cell proliferation, myofibroblastic differentiation, and cell migration.
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http://dx.doi.org/10.1038/s41598-021-84363-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921587PMC
March 2021

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

J Orthop Sci 2021 Feb 23. Epub 2021 Feb 23.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures.

Methods: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-β1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-β1-induced myofibroblast differentiation and fibrosis.

Results: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-β1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-β1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells.

Conclusion: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-β1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.
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http://dx.doi.org/10.1016/j.jos.2021.01.004DOI Listing
February 2021

Expression and function of FGF9 in the hypertrophied ligamentum flavum of lumbar spinal stenosis patients.

Spine J 2021 Feb 10. Epub 2021 Feb 10.

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Background Context: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). A previous study found that fibroblast growth factor 9 (FGF9) was upregulated with mechanical stress in rabbit LF. However, the expression and function of FGF9 are not well understood in human LF.

Purpose: To evaluate FGF9 expression and function in human LF with and without hypertrophy.

Study Design: This study employed a basic research study design utilizing human LF tissue for histological analyses.

Patient Samples: Hypertrophied LF tissue sample from patients with LSS, and nonhypertrophied (control) LFs from patients with lumbar disc herniation or other diseases were obtained during surgery.

Methods: LF specimens were histologically analyzed for FGF9 and vascular endothelial growth factor A (VEGF-A) by immunohistochemistry. The number of total and FGF9 immuno-positive cells and blood vessels were counted and compared between LF with and without hypertrophy. For functional analysis, the effect of FGF9 on cell proliferation and migration was examined using a primary cell culture of human LF.

Results: Histological studies revealed that the total cell number was significantly higher in the LF of patients with LSS than in the LF of control patients. Immunohistochemistry showed that the percentage of FGF9-positive cells was significantly higher in the LF of patients with LSS than in the controls, and it positively correlated with patients' age, regardless of disease. Double immune-positive cells for FGF9 and VEGF-A were often observed in vascular endothelial cells and fibroblasts in the fibrotic area of hypertrophied LF, and the number of double positive vessels was significantly higher in LF of LSS patients than in the LF of controls. Primary cell culture of human LF revealed that FGF9 promoted the proliferation and migration of LF cells.

Conclusion: The present study demonstrated that FGF9 expression is highly upregulated in hypertrophied human LF. FGF9 potentially plays a pivotal role in the process of hypertrophy of LF, which is associated with mechanical stress, through cell proliferation and migration.

Clinical Significance: The results from this study partially reveal the molecular mechanisms of LF hypertrophy and suggest that FGF9 may be involved in the process of LF degeneration in elderly patients.
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http://dx.doi.org/10.1016/j.spinee.2021.02.004DOI Listing
February 2021

Impact of paravertebral muscle in thoracolumbar and lower lumbar regions on outcomes following osteoporotic vertebral fracture: a multicenter cohort study.

Arch Osteoporos 2021 01 3;16(1). Epub 2021 Jan 3.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

We investigated the effect of paravertebral muscle (PVM) on poor prognosis in osteoporotic vertebral fracture (OVF) and remaining lower back pain (LBP) in the thoracolumbar and lower lumbar regions. Additional OVF occurrence in the thoracolumbar and remaining LBP in the lumbar region was significantly related to PVM fat infiltration percentage.

Purpose: Paravertebral muscle (PVM) is an important component of the spinal column. However, its role in the healing process after osteoporotic vertebral fracture (OVF) is unclear. This study aimed to clarify the effect of PVM in thoracolumbar and lower lumbar regions on OVF clinical and radiological outcomes.

Methods: This was a multicenter prospective cohort study from 2012 to 2015. Patients ≥ 65 years old who presented within 2 weeks after fracture onset were followed up for 6 months. PVM was measured at the upper edge of the L1 and L5 vertebral body in the magnetic resonance imaging (MRI) T2-axial position at registration. The cross-sectional area (CSA), relative CSA (rCSA), and fat infiltration percentage (FI%) were measured. Severe vertebral compression, delayed union, new OVF, and remaining low back pain (LBP) were analyzed.

Results: Among 153 patients who were followed up for 6 months, 117 with measurable PVM were analyzed. Their average age was 79.1 ± 7.2 years, and 94 were women (80.3%). There were 48 cases of severe vertebral compression, 21 delayed unions, 11 new OVF, and 27 remaining LBP. Among all poor prognoses, only the FI% of the PVM was significantly associated with new OVF (p = 0.047) in the thoracolumbar region and remaining LBP (p = 0.042) in the lumbar region.

Conclusion: The occurrence of additional OVF in the thoracolumbar region and remaining LBP in the lumbar region was significantly related to the FI% of the PVM. Physicians should be aware that patients with such fatty degeneration shown in acute MRI may require stronger treatment.
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http://dx.doi.org/10.1007/s11657-020-00866-6DOI Listing
January 2021

Long-term, Time-course Evaluation of Ligamentum Flavum Hypertrophy Induced by Mechanical Stress: An Experimental Animal Study.

Spine (Phila Pa 1976) 2021 May;46(9):E520-E527

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Experimental animal study.

Objective: The aim of this study was to clarify chronological effects of mechanical stress on ligamentum flavum (LF) using a long-term fusion rabbit model.

Summary Of Background Data: LF hypertrophy is a major pathology of lumbar spinal stenosis (LSS), but its mechanism remains unclear. We previously demonstrated mechanical-stress-induced LF hypertrophy with a rabbit model. However, we only investigated LFs at a single time point in the short-term; the effects of long-term mechanical stress have not been elucidated.

Methods: Eighteen-week-old male New Zealand White rabbits were randomly divided into two groups: the mechanical stress group underwent L2-3 and L4-5 posterolateral fusion and resection of the L3-4 supraspinal muscle, whereas the control group underwent only surgical exposure. Rabbits were sacrificed 16 and 52 weeks after the procedure. Axial specimens of LFs at L3-4 were evaluated histologically. Immunohistochemistry for alpha-smooth muscle actin (α-SMA) was performed to assess the numbers of vessels and myofibroblasts.

Results: In the mechanical stress group, LFs at the L3-4 level exhibited hypertrophy with elastic fiber disruption and cartilage matrix production at 16 and 52 weeks. A trend test indicated that mechanical stress induced LF hypertrophy, elastic fiber disruption, and cartilage matrix production in a time-dependent manner, with the lowest levels before treatment and the highest at 52 weeks. Immunostaining for α-SMA showed similar numbers of vessels in both groups, whereas the percentage of myofibroblasts was significantly larger at 16 and 52 weeks in the mechanical stress group than in the control group.

Conclusion: We demonstrated that long-term mechanical stress caused LF hypertrophy with progressive elastic fiber disruption and cartilage matrix production accompanied by enhanced myofibroblasts. In addition, the reported rabbit model could be extended to elucidate the mechanism of LF hypertrophy and to develop new therapeutic strategies for LSS by preventing LF hypertrophy.Level of Evidence: SSSSS.
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http://dx.doi.org/10.1097/BRS.0000000000003832DOI Listing
May 2021

The Severity of Cervical Disc Degeneration Does Not Impact 2-year Postoperative Outcomes in Patients With Cervical Spondylotic Myelopathy Who Underwent Laminoplasty.

Spine (Phila Pa 1976) 2020 Sep;45(18):E1142-E1149

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Retrospective cohort study.

Objective: The aim of this study was to evaluate the impact of cervical disc degeneration (CDD) severity on 2-year postoperative outcomes following laminoplasty.

Summary Of Background Data: The impact of CDD on postoperative outcomes of cervical laminoplasty has not been well established.

Methods: A total of 144 patients who underwent open-door laminoplasty for cervical spondylotic myelopathy (CSM) were enrolled. Six cervical discs were independently analyzed for degeneration severity using a previously reported grading system (grade 0: none, grade 3: severest). The relationship between the segmental range of motion (ROM) and the severity of CDD was evaluated. Subsequently, after dividing overall patients into mild and severe CDD groups by the average of CDD scores, the mixed-effect model was applied to assess 2-year postoperative outcomes, including physician-assessed myelopathy scores, patient-reported outcomes, and preoperative radiographic parameters. Finally, as additional analysis, the severe CDD group was further divided into two groups: group 1 included patients with a grade 3 CDD change in their most stenotic level and group 2 included the others. The 2-year postoperative myelopathy score was compared between groups 1 and 2.

Results: The cervical segments with grade 3 CDD showed significantly smaller ROM compared with those with grade 0, 1, or 2 CDD (P < 0.01). There were no significant differences in postoperative improvements in myelopathy, pain, patient-reported physical and mental status, and radiographic parameters, except for quality of life (QOL) scores between CDD groups. A significant (P = 0.02) postoperative improvement in QOL scores was noted in the severe CDD group. In an additional analysis, myelopathy score at 2 years postoperatively was significantly higher in group 1 than group 2 (P = 0.041).

Conclusion: The severity of CDD did not negatively impact 2-year postoperative laminoplasty outcomes. The postulated reason is that the decreased segmental instability in the level with severe CDD may affect surgical outcomes positively.

Level Of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003528DOI Listing
September 2020

Increased advanced glycation end products in hypertrophied ligamentum flavum of diabetes mellitus patients.

Spine J 2019 10 10;19(10):1739-1745. Epub 2019 Jun 10.

Department of Orthopaedic Surgery, Osaka City University, 1-4-3 Asahi Machi, Abeno-Ku, Osaka 545-8585, Japan.

Background Context: Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). Although LSS prevalence is known to be higher in patients with diabetes mellitus (DM), the underlying pathomechanisms are not well understood. Abnormal advanced glycation end products (AGEs) formation occurs in DM and promotes tissue damage in various organs through degeneration and inflammation.

Purpose: To analyze and compare LF histology focused on AGE status between control patients, LSS patients with DM, and LSS patients without DM.

Study Design/setting: Basic research study design utilizing human LF tissue for histologic analyses.

Patient Sample: LF tissue samples were collected from patients who underwent lumber decompression surgery for LSS in the author's institution.

Outcome Measures: Quantitative visualization of Masson's Trichrome (MT) stains, and AGE immunohistochemistry (IHC) for the three groups.

Methods: Ten LF specimens from LSS patients with DM (DM group, mean age 71.4 years), 10 from LSS patients without DM (non-DM group, mean age 71.2 years), and 9 from patients with lumbar disc herniation or cauda equina tumor (control group, mean age 49.0 years) were harvested during surgery and histologically analyzed. Percentage of elastic fiber areas (%EF) was measured with MT staining, and the percentage of AGE immuno-positive areas (%AGEs) was measured with IHC.

Results: The average %EFs were 12.8 in the DM group, 17.1 in the non-DM group, and 24.9 in the control group. The decrease in the elastic fibers was significantly more in the DM group than in the non-DM (p<.01) and control groups (p<.001). Accumulation of AGEs was found mainly in the extracellular matrix in areas of elastic fiber disruption. The %AGEs were 18.3 in the DM group, 12.1 in the non-DM group, and 4.6 in the control group. These were significantly larger in the DM group than in the non-DM (p<.01) and control (p<.01) groups. The %AGEs also positively correlated with patient age (p<.01, R=0.47).

Conclusions: Accumulation of AGEs is significantly greater in the LF of DM patients and correlates with patient age. AGEs may accelerate degeneration and hypertrophy of LF with age and may lead to higher prevalence of LSS in patients with DM.

Clinical Significance: The present results partly reveal the molecular mechanism of LF hypertrophy, suggesting that AGEs may be involved in the process of LF degeneration in the elderly and patients with DM.
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http://dx.doi.org/10.1016/j.spinee.2019.06.001DOI Listing
October 2019

Fibroblast Growth Factor 9 Is Upregulated Upon Intervertebral Mechanical Stress-Induced Ligamentum Flavum Hypertrophy in a Rabbit Model.

Spine (Phila Pa 1976) 2019 Oct;44(20):E1172-E1180

Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.

Study Design: Case-control study of an animal model.

Objective: To investigate the factors that are upregulated and potentially related to degenerative changes in the ligamentum flavum (LF) upon mechanical stress concentration.

Summary Of Background Data: LF hypertrophy is reported to be associated with mechanical stress. However, few studies, using exhaustive analysis with control subjects, on the molecular mechanisms of LF hypertrophy have been published.

Methods: Fourteen rabbits were used for this study. The first group underwent L2-3 and L4-5 posterolateral fusion with instrumentation and resection of the L3-4 supraspinal muscle to concentrate the mechanical stress on L3-4, whereas the other group underwent a sham operation. The deep layer of the LF from L2-3 to L4-5 in both groups was harvested after 16 weeks. Gene expression was evaluated exhaustively using DNA microarray and real-time polymerase chain reaction (RT-PCR). Fibroblast growth factor 9 (FGF9) protein expression was subsequently examined by immunohistological staining.

Results: A total of 680 genes were found to be upregulated upon mechanical stress concentration and downregulated upon mechanical shielding compared with those in the sham group. Functional annotation analysis revealed that these genes not only included those related to the extracellular matrix but also those related to certain FGF families. On RT-PCR validation and immunohistological analysis, we identified that the FGF9 protein increases in the LF upon mechanical stress, especially in the area wherein degenerative changes were frequently identified in the previous literature.

Conclusion: FGF9 and its pathway are suggested to contribute to the degenerative changes in the LF following mechanical stress. This finding will be helpful in further understanding the molecular mechanism of human LF degeneration.

Level Of Evidence: N/A.
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http://dx.doi.org/10.1097/BRS.0000000000003089DOI Listing
October 2019

ISSLS PRIZE IN CLINICAL SCIENCE 2019: clinical importance of trunk muscle mass for low back pain, spinal balance, and quality of life-a multicenter cross-sectional study.

Eur Spine J 2019 05 6;28(5):914-921. Epub 2019 Feb 6.

Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Study Design: A multicenter cross-sectional study.

Objectives: To clarify the relationship of trunk muscle mass with low back pain, spinal sagittal balance, and quality of life. Few reports have investigated the relationship of trunk muscle mass with lumbar spine function and spinal balance, and the clinical significance of trunk muscle mass remains unclear.

Methods: Patients attending spinal outpatient clinics at 10 different medical institutions were enrolled in this study. Patient demographics, trunk muscle mass and appendicular skeletal muscle mass (ASM) measured by bioelectrical impedance analysis (BIA), body mass index (BMI), Charlson Comorbidity Index (CCI), the Oswestry Disability Index (ODI), visual analog scale (VAS) for low back pain, sagittal vertical axis (SVA), and EuroQol 5 Dimension (EQ5D) score were investigated. Multivariate nonlinear regression analysis was used to investigate the association of trunk muscle mass with the ODI, VAS score, SVA, and EQ5D score.

Results: Of 2551 eligible patients, 1738 (mean age 70.2 ± 11.0 years; 781 men and 957 women) were enrolled. Trunk muscle mass was significantly correlated with the ODI, VAS score, SVA, and EQ5D score (P < 0.001) when adjusted for age, sex, BMI, ASM, CCI, and history of lumbar surgery. Patient deterioration was associated with a decrease in trunk muscle mass, and the deterioration accelerated from approximately 23 kg.

Conclusions: Trunk muscle mass was significantly associated with the ODI, VAS score, SVA, and EQ5D score. Trunk muscle mass may assume an important role to elucidate and treat lumbar spinal dysfunction and spinal imbalance. These slides can be retrieved under Electronic Supplementary Material.
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http://dx.doi.org/10.1007/s00586-019-05904-7DOI Listing
May 2019