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IntroductionPrevious studies on patients with symptoms of spinal ligament ossification, including ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF), have not clarified whether obesity is a cause or consequence of these diseases and were limited by selection bias. Thus, we investigated the association between obesity and the prevalence of spinal ligament ossification in randomly selected asymptomatic subjects.Materials and methodsBetween April 2020 and March 2021, 622 asymptomatic Japanese subjects who underwent computed tomography of neck to pelvis for medical check-up purposes were included. All subjects were divided into the following three groups: normal weight (body mass index [BMI] < 25 kg/m2), obese I (25 ≤ BMI < 30 kg/m2), and obese II (BMI ≥ 30 kg/m2). The relationship between factors affecting the presence of each spinal ligament ossification was evaluated using multivariate logistic regression analysis.ResultsThe proportion of subjects with thoracic OPLL was significantly higher in the obese II group than in the other two groups (vs. normal weight, P < 0.001; vs. obese I, P < 0.001). BMI was associated with the prevalence of OLF, cervical OPLL, thoracic OPLL, and ossification of the anterior longitudinal ligament (OALL). BMI was most significantly associated with the prevalence of thoracic OPLL (β, 0.28; 95% confidence interval, 0.17–0.39).ConclusionBMI was associated with the prevalence of OALL, cervical OPLL, thoracic OPLL, and OLF in asymptomatic subjects, suggesting that obesity is associated with the development of heterotopic ossification of the spinal ligaments.

Diffuse pulmonary ossification (DiPO) is characterised by widespread ectopic bone formation in the lungs. Idiopathic DiPO (I-DiPO) poses significant diagnostic challenges and its ossification mechanism remains unclear. Cicatricial organising pneumonia (CiOP) lesions form fibrous nodules without damaging lung structure. We investigated the histopathological features of I-DiPO, focusing on the surrounding fibrosis, and compared them with those of secondary DiPO (S-DiPO). An analysis was conducted using data from a nationwide DiPO survey in Japan. The dataset included clinical, radiological, and histopathological data of patients with suspected I-DiPO. The specific patterns of ossification and fibrotic findings such as CiOP, organising pneumonia (OP), and subpleural fibrosis were identified. Eighteen and seven patients were classified as having I-DiPO and S-DiPO, respectively. I-DiPO affects younger patients, progresses slowly, commonly occurs in the lower lungs, and has a lower mortality rate. S-DiPO affects older patients, presents with widespread lung lesions, and has a higher mortality rate. CiOP lesions were found in direct continuity with or near ossified lesions in 61.1% and 71.4% of patients with I-DiPO and S-DiPO, respectively. OP, CiOP, and ossified lesions often observed in the same locations in S-DiPO. DiPO has a unique pathogenesis, with an ossification transition occurring via the CiOP lesions. These findings provide valuable insights for future diagnostic approaches and management strategies for this condition.

IntroductionSystemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification.Materials and methodsClinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0–4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis.ResultsThe prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0–5.5 times higher in patients with OPLL (40–56%) than in the controls (10–11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34–2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament.ConclusionsThe strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Bones and Cartilage provides the most in-depth review ever assembled on the topic. It examines the function, development and evolution of bone and cartilage as tissues, organs and skeletal systems. It describes how bone and cartilage is developed in embryos and are maintained in adults, how bone reappears when we break a leg, or even regenerates when a newt grows a new limb, or a lizard a tail. This book also looks at the molecules and cells that make bones and cartilages and how they differ in various parts of the body and across species. It answers such questions as \"Is bone always bone?\" \"Do bones that develop indirectly by replacing other tissues, such as marrow, tendons or ligaments, differ from one another?\" \"Is fish bone the same as human bone?\" \"Can sharks even make bone?\" and many more. * Complete coverage of every aspect of bone and cartilage* Full of interesting and unusual facts* The only book available that integrates development and evolution of the skeleton* Treats all levels from molecular to clinical, embryos to evolution* Written in a lively, accessible style* Extensively illustrated and referenced* Integrates analysis of differentiation, growth and patterning* Covers all the vertebrates as well as invertebrate cartilages* Identifies the stem cells in embryos and adults that can make skeletal tissues

BackgroundThoracic ossification of ligamentum flavum (TOLF) can be asymptomatic and progress insidiously. But, long-term follow-up results of clinical progression of TOLF are still unknown.MethodsThe clinical progression of 81 patients with TOLF at our center, followed for 10 to 11 (mean, 10.3) years from May 2010 to November 2021, were analyzed. Among them, 51 patients with thoracic myelopathy were caused by single- or multi-segment TOLF, and received partial TOLF resection (30 patients) or total TOLF resection (21 patients). The remaining 30 patients showed TOLF on imaging examinations, but TOLF was not the responsible compressing factor causing myelopathy and with no TOLF resection. The mJOA score (total 11 scores) and spinal operation were used to evaluate the clinical progression at follow-up.ResultsDuring the 10- to 11-year follow-up of 81 TOLF patients, 71 (87.7%) had no deterioration of neurological function, and 10 (12.3%) patients had deterioration of neurological function and had another spinal operation, including only 4 (4.9%) suffered thoracic myelopathy caused by the progression of TOLF; 6 (7.4%) for other spinal diseases: 2 (2.5%) had fall damage and acute spinal cord injury at the TOLF level; 2 (2.5%) had thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL); 2 (2.5%) had cervical spondylosis and received cervical operation.ConclusionsMost TOLF (87.7%) patients had no clinical progression and received no reoperations for TOLF in the ten-year dimension (mean, 10.3 years). Narrow spinal canal for TOLF increases the risk of traumatic paraplegia.

Heterotopic ossification (HO) is pathological bone formation characterized by ossification within muscle, tendons, or other soft tissues. However, the cells of origin and mechanisms involved in the pathogenesis of HO remain elusive. Here we show that deletion of suppressor of fused (Sufu) in cathepsin K-Cre-expressing (Ctsk-Cre-expressing) cells resulted in spontaneous and progressive ligament, tendon, and periarticular ossification. Lineage tracing studies and cell functional analysis demonstrated that Ctsk-Cre could label a subpopulation of tendon-derived progenitor cells (TDPCs) marked by the tendon marker Scleraxis (Scx). Ctsk+Scx+ TDPCs are enriched for tendon stem cell markers and show the highest self-renewal capacity and differentiation potential. Sufu deficiency caused enhanced chondrogenic and osteogenic differentiation of Ctsk-Cre-expressing tendon-derived cells via upregulation of Hedgehog (Hh) signaling. Furthermore, pharmacological intervention in Hh signaling using JQ1 suppressed the development of HO. Thus, our results show that Ctsk-Cre labels a subpopulation of TDPCs contributing to HO and that their cell-fate changes are driven by activation of Hh signaling.

Introduction Heterotopic ossifications (HO) are common after total hip arthroplasty (THA). The invasiveness of surgical approaches plays a relevant role in HO development. The aims of this study were to assess the development of HO 6 months after THA through direct lateral approach (DLA) or direct anterior approach (DAA) without a dedicated orthopaedic table and to assess the clinical impact of HO. Methods This is a single-center IRB-approved, quasi-randomized prospective cohort, observational imaging study. Fifty patients underwent primary THA through DLA and 50 through DAA. Age, sex, BMI and side of the affected hip were collected. At the 6 post-operative month the Harris Hip Score (HHS) and the presence of HO (scored through the Brooker classification system) were assessed. Results There was no significant difference in the demographic data between groups. Operative time was significantly higher in the DAA group (72 ± 10 min vs. 58 ± 8 min: p  < 0.03). At 6 post-operative months the incidence of HO was 14% in the DAA group and 32% in the DLA group ( p  = 0.02). Severe HO (Brooker 3–4) were significantly more common in the DLA group ( p  = 0.04). There was no significant difference in the HHS of patients with HO between the DAA and DLA groups. There was no association between poorer clinical outcomes and the severity of HO. Conclusion The DAA without a dedicated orthopaedic table is associated with a significant lower incidence of HO than the DLA 6 months after elective THA. Except for the surgical approach, no other factors correlated with the occurrence of HO. Even though a lower HHS was found with severe HO, the correlation between severity of HO and clinical outcomes did not reach statistical significance.

Background Although posterior decompression with fusion (PDF) are effective for treating thoracic myelopathy, surgical treatment has a high risk of various complications. There is currently no information available on the perioperative complications in thoracic ossification of the longitudinal ligament (T-OPLL) and thoracic ossification of the ligamentum flavum (T-OLF). We evaluate the perioperative complication rate and cost between T-OPLL and T-OLF for patients underwent PDF. Methods Patients undergoing PDF for T-OPLL and T-OLF from 2012 to 2018 were detected in Japanese nationwide inpatient database. One-to-one propensity score matching between T-OPLL and T-OLF was performed based on patient characteristics and preoperative comorbidities. We examined systemic and local complication rate, reoperation rate, length of hospital stays, costs, discharge destination, and mortality after matching. Results In a total of 2,660 patients, 828 pairs of T-OPLL and T-OLF patients were included after matching. The incidence of systemic complications did not differ significantly between the T-OPLL and OLF groups. However, local complications were more frequently occurred in T-OPLL than in T-OLF groups (11.4% vs. 7.7% P  = 0.012). Transfusion rates was also significantly higher in the T-OPLL group (14.1% vs. 9.4%, P  = 0.003). T-OPLL group had longer hospital stay (42.2 days vs. 36.2 days, P  = 0.004) and higher medical costs (USD 32,805 vs. USD 25,134, P  < 0.001). In both T-OPLL and T-OLF, the occurrence of perioperative complications led to longer hospital stay and higher medical costs. While fewer patients in T-OPLL were discharged home (51.6% vs. 65.1%, P  < 0.001), patients were transferred to other hospitals more frequently (47.5% vs. 33.5%, P  = 0.001). Conclusion This research identified the perioperative complications of T-OPLL and T-OLF in PDF using a large national database, which revealed that the incidence of local complications was higher in the T-OPLL patients. Perioperative complications resulted in longer hospital stays and higher medical costs.

Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.

PurposeThoracic spinal stenosis (TSS) is a rare disease secondary to multiple pathological changes that differ in prevalence and clinical characteristics. The epidemiological characteristics of these pathologies are largely unknown due to the limited case samples and regional differences. Therefore, a systematic review was conducted to elucidate the prevalence and clinical characteristics of TSS.MethodsCase series and case reports on the ossification of the posterior longitudinal ligaments (OPLL), ossification of the ligamentum flavum (OLF) and thoracic disk herniation (TDH) were screened from PubMed, Embase and Web of Science databases and systematically reviewed. Epidemiological, demographic and segmental distribution data were extracted and analyzed.ResultsA total of 129 studies including 1935 subjects were selected, of which 361 (18.7%) were diagnosed with OPLL, 804 (41.5%) with OLF, 143 (7.4%) with OPLL + OLF and 627 (32.4%) with TDH. Most reports were from China, Japan and USA. Thoracic OPLL occurred mostly at the middle-thoracic spine (43.4%), while OLF predominately occurred at the lower-thoracic spine (63.1%). TDH was mainly localized in the middle (46.0%) and lower-thoracic (50.3%) spine. Thirty-two studies involving 524 patients described tandem spinal stenosis, of which 52.1% had accompanying cervical diseases and 35.9% lumbar diseases.ConclusionsThere are significant differences in the age, sex and segment distribution characteristics of different pathologies leading to TSS. Tandem spinal stenosis is not uncommon and should be considered when diagnosing TSS. Our findings provide new insights into the prevalence and clinical characteristics of TSS and can help reduce misdiagnosis.