Background: Heterotopic ossification of tendons and ligaments (HOTL) is a common clinical condition characterized by the absence of discernible features and a lack of effective treatment. In vitro experiments have demonstrated that mechanical stimulation can induce cell differentiation toward osteogenesis, thereby promoting heterotopic ossification. Currently, there are few experimental designs aimed at inducing ligament stretching in mice, and the mechanism of heterotopic ossification may not entirely mirror that observed in clinical cases. Therefore, there is an urgent imperative to develop a novel and feasible animal model. Methods: In this study, all the Enpp1 gene deficiency mice (a mouse model with heterotopic ossification of multiple ligaments) were divided into three groups: the control group, the spinal brake group, and the hyperactive group (treadmill training group). An external spinal fixation device was designed to restrict mice\'s spinal flexion and extension at 6 weeks of age. The brace was adjusted weekly according to the changes in the size of the mice. Additionally, treadmill training was used to increase activity in the spinal ligaments and Achilles tendons of the mice. Micro-CT scanning and HE staining were performed at 12, 20, and 28 W to evaluate the degree of ossification in the spinal ligament and Achilles tendon. What\'s more, As one of the mechanical stimulation transduction signals, YAP plays a crucial role in promoting osteogenic differentiation of cells. Immunofluorescence was utilized to assess YAP expression levels for the purpose of determining the extent of mechanical stimulation in tissues. Results: Our findings showed that a few ossification lesions were detected behind the vertebral space of mice at 8 weeks of age. Spinal immobilization effectively restricts the flexion and extension of cervical and thoracic vertebrae in mice, delaying spinal ligament ossification and reducing chronic secondary spinal cord injury. Running exercises not only enhance the ossification area of the posterior longitudinal ligament (PLL) and Achilles tendons but also exacerbate secondary spinal cord injury. Further immunofluorescence results revealed a notable increase in YAP expression levels in tissues with severe ossification, suggesting that these tissues may be subjected to higher mechanical stimulation. Conclusion: Mechanical stimulation plays a pivotal role in the process of heterotopic ossification in tissues. Our study provided valid animal models to further explore the pathological mechanism of mechanical stimulation in HOTL development.

Only a few studies have investigated the gap range of motion (gROM) in cervical myelopathy or deformity caused by ossification of the posterior longitudinal ligament (OPLL). The aim of this study is to investigate the correlation between the individual gROM and the postoperative clinical outcomes of patients with OPLL.
Consecutive patients of cervical myelopathy caused by OPLL were analyzed retrospectively. The clinical outcomes were evaluated using Visual Analogue Scale scores of the neck and arm pain and the Japanese Orthopaedic Association scores. Radiologic measurements included flexion ROM (fROM), which was defined as the difference of cervical lordosis in flexion and neutral positions, extension ROM (eROM), defined as the difference between neutral and extension positions, and gROM, defined as the difference between fROM and eROM. Patients were grouped by the values of gROM, and comparisons of all outcomes were made between the groups.
A total of 42 patients underwent surgery. The patients with greater gROM did not differ from those with smaller gROM by demographic characteristics. During follow-up (mean 45.8 months), both groups had similar improvements, but the C5 palsy rates were higher in the greater gROM group than in the smaller gROM group (71% and 22%, P < 0.05).
Simultaneous circumferential decompression and fixation is an effective surgical option for patients with cervical myelopathy caused by OPLL. A higher rate of postoperative C5 palsy was observed in the patients with greater gROMs after surgery, although all patients presented with similar clinical improvements.

Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear.
We aimed to determine the association between dyslipidemia and symptomatic OPLL.
Single institution cross-sectional study.
Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination.
Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia.
Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis.
The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus.
We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.

Ossification of the posterior longitudinal ligament (OPLL) is a heterotopic ossification that may cause spinal cord compression. With the recent development of computed tomography (CT) imaging, it is known that patients with OPLL often have complications related to ossification of other spinal ligaments, and OPLL is now considered part of ossification of the spinal ligaments (OSL). OSL is known to be a multifactorial disease with associated genetic and environmental factors, but its pathophysiology has not been clearly elucidated. To elucidate the pathophysiology of OSL and develop novel therapeutic strategies, clinically relevant and validated animal models are needed. In this review, we focus on animal models that have been reported to date and discuss their pathophysiology and clinical relevance. The purpose of this review is to summarize the usefulness and problems of existing animal models and to help further the development of basic research on OSL.

Some previous case reports have implied a relationship between acromegaly and ossification of the spinal ligaments. However, there have been no reports of a case series exploring the incidence of ossification of the spinal ligaments in patients with acromegaly. To this end, computed tomography (CT) of the spine in 10 consecutive patients with acromegaly was examined in this study. Five out of 10 patients had ossification of the spinal ligaments. Among them, two patients had ossification of the posterior longitudinal ligament (OPLL), which was noticeably higher than the prevalence of OPLL in the general adult population (1.9-4.3 %). Body mass index was significantly higher in the group with spinal ligament ossification (p = 0.03), but there were no significant differences in age, sex, serum phosphate, albumin-adjusted calcium, growth hormone (GH), standard deviation of insulin-like growth factor-1 (IGF-1), or the incidence of diabetes mellitus between the groups with or without ossification of the spinal ligaments. The ossification index (OS index) was used to determine the severity of spinal ligament ossification, and there were no significant correlations between the OS index and GH or IGF-1 (p = 0.51 and 0.75, respectively). This study was the first to report a high prevalence of spinal ossification in patients with acromegaly. In conclusion, this study suggested a possible association between acromegaly and ossification of the spinal ligaments, although the number of patients was insufficient to draw a conclusion. Acromegaly patients should be tested to confirm, or rule out, spinal ossification, and further studies to clarify the underlying mechanism of spinal ossification in acromegaly patients are warranted.

OBJECTIVE: The diagnosis and classification of ossification of the posterior longitudinal ligament (OPLL) can be difficult with radiography alone; therefore, computed tomography (CT) is also usually performed. There are many reports on the usefulness of digital tomosynthesis (DTS) for image analysis in orthopedics. This study aimed to compare the accuracy of DTS with radiography and CT for the diagnosis and classification of cervical OPLL (C-OPLL).
METHODS: We included 31 patients with OPLL and 30 with cervical spondylotic myelopathy. The patients\' cervical spine radiography, DTS, and CT images were each evaluated twice by three specialists and three residents.
RESULTS: In the intra-observer reliability study, there was one observer with a fair level of kappa values for radiography and DTS among three residents. The kappa values for CT were the best for all observers. In the inter-observer reliability study, the interclass correlation coefficient (ICC) values were high for both diagnosis and classification by specialists at the almost perfect level for all three imaging modalities. On the other hand, the ICC values for both diagnosis and classification for radiography by the residents were lower than those for DTS and CT.
CONCLUSIONS: This study revealed that DTS may be an alternative to CT for the diagnosis and classification of C-OPLL by specialists. Caution should be exercised in diagnosing and classifying C-OPLL using radiography and DTS by residents, and the use of CT is recommended.

UNASSIGNED: Postoperative C5 palsy is a common complication of laminoplasty for cervical ossification of the posterior longitudinal ligament (C-OPLL), although there are several hypotheses regarding its etiology, the exact pathomechanism for this undesirable event remain unclear. The aim of this study was to review clinical and imaging findings in patients with C5 palsy and to propose potential risk factors for this complication.
UNASSIGNED: A total of 220 consecutive patients who had undergone posterior spinal process-splitting laminoplasty (pSPSL) for C-OPLL between January 2018 and December 2019 were included in this study. Postoperative C5 palsy was defined as deltoid muscle weakness of a grade ≤3 in manual muscle test (MMT). These patients were divided into two groups based on the postoperative development of C5 palsy: patients with C5 palsy (group A) and those without C5 palsy (group B). The clinical and imaging covariates evaluated were age, sex, OPLL type, K-line, foraminal stenosis, gutter malposition, and preoperative spinal cord signal change. Logistic regression was used to analyze the independent risk factors for C5 palsy.
UNASSIGNED: In total, 211 patients (18 in group A and 193 in group B) were enrolled in this study, and the incidence of C5 palsy was 8.53%. Sixteen patients had a MMT of grade 3 and two had an MMT of grade ≤2. During the follow-up period (mean duration: 25.10±6.67 months), the MMT grade rose to 5 in 16 patients, 4 in one patient, and 3 in one patient. Multivariate analysis revealed that malposition of the bony gutter [odds ratio (OR) 11.073, 95% confidence interval (CI): 3.411, 35.948; P<0.001] and C4/5 intervertebral foramen stenosis (OR 8.455, 95% CI: 2.559, 27.936; P<0.001) were independent risk factors for C5 palsy.
UNASSIGNED: The incidence of C5 palsy was 8.53% among patients undergoing pSPSL for C-OPLL. Gutter malposition and C4/5 intervertebral foramen stenosis were identified as risk factors for this complication.

METHODS: Narrative review.
OBJECTIVE: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM).
METHODS: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM.
RESULTS: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals\' risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence of 24.2% in the healthy population, and 35.3% among individuals >60 years of age. Clinical radiculopathy and/or electrophysiological signs of cervical cord dysfunction appear to be risk factors for myelopathy development. Radiological progression of incidental Ossification of the Posterior Longitudinal Ligament (OPLL) is estimated at 18.3% over 81-months and development of myelopathy ranges between 0-61.5% (follow-up ranging from 40 to 124 months between studies) among studies. In patients with symptomatic DCM undergoing non-operative treatment, 20-62% will experience neurological deterioration within 3-6 years.
CONCLUSIONS: Current estimates surrounding the natural history of DCM, particularly those individuals with mild or minimal impairment, lack precision. Clear predictors of clinical deterioration for those treated with non-operative care are yet to be identified. Future studies are needed on this topic to help improve treatment counseling and clinical prognostication.

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is radiographically detectable in 3-6% of Asian individuals, although not all detectable OPLL cases lead to myelopathy. To date, it is unknown how many patients suffer from neurological symptoms due to OPLL. The purpose of this study was to investigate the epidemiology of symptomatic OPLL using Japan\'s national registry database.
METHODS: We examined the registry data of patients with OPLL who held a certificate of medical subsidy from the Japanese Ministry of Health, Labor and Welfare. The study period was from January 1, 2011 to December 31, 2012.
RESULTS: Registry data revealed that the incidence and the period prevalence of symptomatic OPLL were 0.005% (5 per 100,000 population) and 0.027% (27 per 100,000 population), respectively. OPLL occurred twice as often in men as in women. The peak age for onset of symptoms was 60-69 years. The mean Japanese Orthopedic Association (JOA) score was 9 points. Ninety percent of OPLL patients underwent surgery, and 90% of these surgeries were performed with a posterior approach. The most common indication for surgery was a JOA score of 11 points.
CONCLUSIONS: According to registry data, the prevalence of symptomatic OPLL was less than one-hundredth of that of radiographically detected OPLL. This indicates that most cases of radiographically detectable OPLL may be asymptomatic.

UNASSIGNED: The surgical outcomes of individual patient with ossification of the posterior longitudinal ligament (OPLL) can vary depending on various patient-related factors. Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) is a well-developed tool for outcome measurement and considers both disease-specific and general health aspects. This study aimed to investigate the reliability, validity, and responsiveness of the JOACMEQ in patients with OPLL in mainland China and to compare post-operative outcomes of OPLL patients between mainland China and Japan.
UNASSIGNED: This multicenter trial was performed between July 2009 and June 2019. The procedure for the JOACMEQ translation followed Beaton\'s guidelines. All patients enrolled were diagnosed with OPLL and had completed the JOACMEQ, the modified Japanese Orthopaedic Association (mJOA) scale, and the 36-Item Short Form Health Survey (SF-36) before and after surgery. The reliability (Cronbach\'s α and Pearson\'s correlation), construct validity (factor analysis), concurrent validity (Spearman\'s correlation with SF-36) and responsiveness (effect sizes) of JOACMEQ were evaluated. A mixed-model analytic approach was used to analyze differences in postoperative outcomes between the 2 countries.
UNASSIGNED: Ninety-one patients from mainland China and ninety-one patients from Japan were recruited. JOACMEQ showed satisfactory internal consistency (Cronbach\'s α=0.75). In test-retest reliability evaluation, except for the bladder function domain, the JOACMEQ domains had good test-retest reliability (0.89-0.96). In factor analysis, most of the items (19/24) were well clustered. Regarding clinical validity, all 5 domains were found to have moderate correlations with the physical component summary (PCS) of SF-36 (r=0.25-0.50), and the bladder function and quality of life domains also had moderate correlations (r=0.25-0.50) with the mental component summary (MCS) of SF-36. JOACMEQ showed a variable responsiveness in different domains (effect size =0.17-0.84; standardized response means =0.15-0.85). Regarding postoperative improvements in the JOACMEQ score, mixed-model analysis revealed a significant difference in the quality of life domain between Chinese and Japanese patients (16.0±18.7 vs. 7.8±17.7, P<0.05).
UNASSIGNED: JOACMEQ generally shows good reliability, good validity and mild responsiveness, and can identify the post-operative improvements in patients with OPLL in mainland China. Chinese OPLL patients showed a significantly larger improvement in postoperative quality of life compared to their Japanese counterparts.