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Purpose: To determine the efficacy and poor prognostic factors of posterolateral full-endoscopic debridement and irrigation (PEDI) surgery for thoraco-lumbar pyogenic spondylodiscitis. Methods: We included 64 patients (46 men, 18 women; average age: 63.7 years) with thoracic/lumbar pyogenic spondylodiscitis who had undergone PEDI treatment and were followed up for more than 2 years. Clinical outcomes after PEDI surgery were retrospectively investigated to analyze the incidence and risk factors for prolonged and recurrent infection. Results: Of 64 patients, 53 (82.8%) were cured of infection after PEDI surgery, and nine (17.2%) had prolonged or recurrent infection. Multivariate analysis demonstrated that significant risk factors for poor prognosis included a large intervertebral abscess cavity (P = 0.02) and multilevel intervertebral infections (P < 0.05). Conclusion: PEDI treatment is an effective, minimally invasive procedure for pyogenic spondylodiscitis. However, a large intervertebral abscess space could cause instability at the infected spinal column, leading to prolonged or recurrent infection after PEDI. In cases with a large abscess cavity with or without vertebral bone destruction, endoscopic drainage alone may have a poor prognosis, and spinal fixation surgery could be considered. [ABSTRACT FROM AUTHOR]

Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[−], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6–2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(−) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF. [ABSTRACT FROM AUTHOR]

Introduction: Systemic 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.Clinical 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.The 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.The 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.Materials and methods: Systemic 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.Clinical 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.The 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.The 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.Results: Systemic 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.Clinical 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.The 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.The 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.Conclusions: Systemic 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.Clinical 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.The 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.The 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. [ABSTRACT FROM AUTHOR]

Introduction: Bisphosphonates (BPs) have been shown to reduce the incidence of vertebral fractures during the first year or two of glucocorticoid (GC) treatments and are therefore recommended as a first-line treatment for GC-induced osteoporosis (GIO). However, there are theoretical concerns about the long-term use of BPs in low-turnover osteoporosis caused by chronic GC therapy. Materials and methods: We analyzed the trabecular microarchitecture, bone metabolism, and material strength of iliac crest bone biopsy samples from 10 female patients with rheumatoid arthritis who received an average of 6.7 years of BP therapy for GIO (GIOBP group), compared with those of 10 age- and bone mineral density (BMD)-matched non-rheumatoid arthritis postmenopausal women (reference group). Results: Patients in the GIOBP group had a significantly greater fracture severity index, as calculated from the number and the extent of vertebral fractures compared with the reference patients. Micro-computed tomography analysis showed that the degree of mineralization and trabecular microarchitecture were significantly lower in the GIOBP group than in the reference patients. Patients in the GIOBP group exhibited lower bone contact stiffness, determined by micro-indentation testing, than in the reference group. The contact stiffness of the bone was negatively correlated with the fracture severity index and the daily prednisolone dosage. Immunohistochemistry and serum bone turnover markers showed decreased osteoclastic activity, impaired mineralization, and an increased fraction of empty lacunae in the GIOBP group. Conclusion: Our findings indicate that patients receiving long-term BP for GIO are still at high risk for fragility fractures because of poor bone quality. [ABSTRACT FROM AUTHOR]

Introduction: Previous 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 methods: Between 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. Results: The 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). Conclusion: BMI 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. [ABSTRACT FROM AUTHOR]

Background: The number of spinal infections has been increasing in developed countries due to the increase of aged or immunosuppressed patients. Spondylitis caused by multidrug-resistant (MDR) bacterial infection often become intractable and require long-term antibiotic therapy and multiple surgeries. Therefore, it is of great importance to understand risk factors for MDR spinal infections. The aim of this study was to elucidate the risk factors for MDR bacterial spondylitis.Methods: A total of 122 patients (82 men, 40 women; average age: 63.8 y) with thoracic/lumbar spondylitis who underwent posterolateral full-endoscopic debridement and irrigation were included. The organisms detected by this endoscopic procedure were investigated, and the incidence and risk factors for MDR bacterial infection were retrospectively analyzed.Results: Cultures of specimens obtained by endoscopic procedures were positive in 78 patients (63.9%). Among 68 isolated bacteria, MDR bacteria accounted for 47.1%. Multivariate analysis showed that significant risk factors for MDR bacterial infection included autoimmune connective tissue disease (P = 0.03) and central venous catheter (P = 0.02). The incidence of MDR bacteria in patients who were administered a broad-spectrum antibiotic for more than 1 month preoperatively was 64.0%, which was significantly higher than in patients who were administered a broad-spectrum antibiotic for less than 1 month and patients who were administered a narrow-spectrum antibiotic (P < 0.01, P < 0.01, respectively).Conclusions: The significant risk factors for MDR bacterial spondylitis included immunosuppressed conditions, such as autoimmune connective tissue disease, presence of central venous catheter, and longer administration periods of a broad-spectrum antibiotic. In patients with pyogenic spondylitis who could not be controlled with previous antibiotics and whose result of culture was negative, administration of anti-MRSA antibiotics would be considered when they have the risk factors identified in this study. [ABSTRACT FROM AUTHOR]

Although ossification of the posterior longitudinal ligament (OPLL) commonly develops in the cervical spine, it also occurs, albeit less commonly, in the thoracic spine. However, data are scarce regarding the characteristics of patients with thoracic OPLL. In the current study, we performed a cross-sectional study on a total of 133 patients with OPLL to clarify the clinical characteristics of patients with thoracic OPLL compared with those of patients with cervical OPLL. The subjects were divided into four groups according to the main region of OPLL and treatment type: C-OPLL-C, cervical OPLL treated conservatively; C-OPLL-S, cervical OPLL treated via surgery; T-OPLL-C, thoracic OPLL treated conservatively; and T-OPLL-S, thoracic OPLL treated via surgery. Symptoms developed at an earlier age in the T-OPLL-S group than in the C-OPLL groups. Current body mass index (BMI), maximum lifetime BMI, and BMI at the age of 20 years were significantly higher in the T-OPLL-S group than in the C-OPLL groups. Yearly weight gain from the age of 20 years to the age at which maximum body weight was attained was significantly greater in the T-OPLL-S group than in the C-OPLL groups. The T-OPLL group showed a higher rate of co-existence of OPLL at other regions or ossification of the ligamentum flavum compared to the C-OPLL groups. Our findings demonstrate that severe obesity, early-onset of symptoms, and diffuse ossification of spinal ligaments are distinct features of patients with myelopathy caused by thoracic OPLL. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the incidence and causes of a second rise in C-reactive protein (CRP) levels following spinal instrumentation surgery and to help determine how an abnormal CRP response should be interpreted and managed during postoperative care.Methods: The medical records of 948 patients who underwent instrumented spine fusion surgery and met the inclusion criteria were retrospectively reviewed to assess the frequency and causes of a second rise (SR) of CRP. A SR of CRP was defined when the CRP level after postoperative day 7 increased by more than 0.5 mg/dl from that at the previous time-point. The diagnostic cut-off value of CRP elevation for detection of surgical site infection (SSI) was determined. Cut-off values were analyzed using receiver operating characteristic (ROC) curves. Bayes' theorem was used to determine blood test posterior probabilities for SSI-positive cases using cutoff values of re-evaluated CRP levels.Results: SR of CRP occurred in 107 of the 948 patients. Of the patients with SR of CRP, 38 (35%) patients had developed SSI, 33 (31%) patients had causes other than SSI, and the remaining 36 patients had unidentified causes. Among the patients with SR, excluding those with causes other than SSI, the best diagnostic cut-off value of SR for detection of SSI was 3.04 mg/dl (area under the curve was 0.74). The posterior test probability was 84.4%.Conclusions: For patients with SR of CRP, who had no causes other than SSI, an SR value of 3.04 mg/dl correlated with a high probability of developing SSI. [ABSTRACT FROM AUTHOR]

Since bone mass is not the only determinant of bone strength, there has been increasing interest in incorporating the bone quality into fracture risk assessments. We aimed to examine whether the magnetic resonance imaging (MRI) T1 or T2 mapping value could provide information that is complementary to bone mineral density for more accurate prediction of cancellous bone strength. Four postmenopausal women with hip osteoarthritis underwent 3.0-T MRI to acquire the T1 and T2 values of the cancellous bone of the femoral head before total hip arthroplasty. After the surgery, the excised femoral head was portioned into multiple cubic cancellous bone specimens with side of 5 mm, and the specimens were then subjected to microcomputed tomography followed by biomechanical testing. The T1 value positively correlated with the yield stress (σ y) and collapsed stress (σ c). The T2 value did not correlate with the yield stress, but it correlated with the collapsed stress and strength reduction ratio (σ c / σ y), which reflects the progressive re-fracture risk. Partial correlation coefficient analyses, after adjusting for the bone mineral density, showed a statistically significant correlation between T1 value and yield stress. The use of multiple coefficients of determination by least squares analysis emphasizes the superiority of combining the bone mineral density and the MRI mapping values in predicting the cancellous bone strength compared with the bone mineral density-based prediction alone. The MRI T1 and T2 values predict cancellous bone strength including the change in bone quality. • There are few non-invasive methods for assessing bone volume and quality. • Magnetic resonance imaging T1 map value reflects underlying fracture risk. • Magnetic resonance imaging T2 map value helps predict progressive re-fracture risk. • Magnetic resonance imaging complements bone mineral density to predict bone strength. [ABSTRACT FROM AUTHOR]

Despite preclinical studies demonstrating the effectiveness of teriparatide for skeletal repair in small animals, inconclusive data from clinical trials have raised questions regarding the optimal teriparatide dosing regimen for bone repair. To address this, we assessed the effect of teriparatide frequency and dose on long-bone healing using a mouse femur osteotomy/fracture model. Eight-week-old male ICR mice were subjected to open femur osteotomies, then randomized into following five groups (n = 8 per group): vehicle; low dose/high frequency: 3 μg/kg/dose, 3 times/day; low dose/low frequency: 9 μg/kg/dose, 1 time/day; high dose/high frequency: 9 μg/kg/dose, 3 times/day; high dose/low frequency: 27 μg/kg/dose, 1 time/day. Skeletal repair was assessed by microcomputed tomography, mechanical testing, and histology 4 weeks after surgery. High-dose and/or high-frequency teriparatide treatment increased callus bone volume but failed to have a significant impact on the biomechanical recovery of fractured femurs, possibly because of impaired cortical shell formation in fracture calluses. Meanwhile, low-dose/low-frequency teriparatide therapy enhanced callus bone formation without interfering with cortical shell formation despite a lesser increase in callus bone volume, leading to significant two and fourfold increases in ultimate load and stiffness, respectively. Our findings demonstrate that administering teriparatide at higher doses and/or higher frequencies raises fracture callus volume but does not always accelerate the biomechanical recovery of fractured bone, which points to the importance of finding the optimal teriparatide dosing regimen for accelerating skeletal repair. [ABSTRACT FROM AUTHOR]

Background: Lumbar decompression surgery is a commonly used treatment for degenerative lumbar spinal stenosis; however, some patients develop symptomatic spinal instability following decompression surgery. The objective of this study was to reveal risk factors for delayed instability following decompression surgery for lumbar spinal stenosis.Methods: One hundred ten patients who underwent single-level lumbar decompression between 2008 and 2014 were retrospectively reviewed. Surgical indication for decompression surgery was symptomatic lumbar canal stenosis without spondylolisthesis or with minimum spondylolisthesis (less than 4 mm translation). Patients with gross segmental motion (>10° in disc angle, >2 mm translation) on flexion-extension lumbar radiographs were excluded. Age, sex, body mass index, smoking history, diabetes mellitus, autoimmune connective tissue diseases including rheumatoid arthritis, and the use of glucocorticoids were investigated. Radiographic measurements included disc angle, disc height, slippage, facet angle, segmental motion (flexion-extension), lumbar alignment, facet effusion, and disc degeneration. Data were analyzed using multivariate forward selection stepwise logistic regression, chi-square tests, and Student t-test.Results: Six of 110 patients (5.5%) developed symptomatic spinal instability at the operative level and underwent spinal fusion surgery at an average of 2.1 years postoperatively. Autoimmune connective tissue disorders and chronic use of glucocorticoids were associated with the occurrence of symptomatic spinal instability requiring spine fusion surgery, while there was no significant difference in radiographic parameters and demographic factors excluding autoimmune connective tissue diseases between reoperation and non-reoperation groups.Conclusions: Patients with autoimmune connective tissue disorders receiving chronic glucocorticoid therapy are more likely to develop symptomatic spinal instability following decompression surgery for lumbar canal stenosis without or with minimal spondylolisthesis. [ABSTRACT FROM AUTHOR]

Abstract The treatment of juvenile osteoporosis has not been established due to a lack of data regarding the efficacy and adverse effects of therapeutic agents. The possible adverse effects of the long-term use of antiresorptive therapies on skeletal growth in children is of particular concern. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption, and its deficiency suppresses bone remodeling in the secondary spongiosa, but not in the primary spongiosa, due to a compensatory mechanism of osteoclastogenesis. This prompted us to develop an anti-Siglec-15 therapy for juvenile osteoporosis because most anti-resorptive drugs have potential adverse effects on skeletal growth. Using growing rats, we investigated the effects of an anti-Siglec-15 neutralizing antibody (Ab) on systemic bone metabolism and skeletal growth, comparing this drug to bisphosphonate, a first-line treatment for osteoporosis. Male 6-week-old F344/Jcl rats were randomized into six groups: control (PBS twice per week), anti-Siglec-15 Ab (0.25, 1, or 4 mg/kg every 3 weeks), and alendronate (ALN) (0.028 or 0.14 mg/kg twice per week). Treatment commenced at 6 weeks of age and continued for the next 6 weeks. Changes in bone mass, bone metabolism, bone strength, and skeletal growth during treatment were analyzed. Both anti-Siglec-15 therapy and ALN increased bone mass and the mechanical strength of both the femora and lumbar spines in a dose-dependent manner. Anti-Siglec-15 therapy did not have a significant effect on skeletal growth as evidenced by micro-CT-based measurements of femoral length and histology, whereas high-dose ALN resulted in growth retardation with histological abnormalities in the growth plates of femurs. This unique property of the anti-Siglec-15 Ab can probably be attributed to compensatory signaling for Siglec-15 inhibition in the primary spongiosa, but not in the secondary spongiosa. Thus, anti-Siglec-15 therapy could be a safe and effective for juvenile osteoporosis. Highlights • Anti-Siglec-15 Ab does not result in adverse effects on skeletal growth in growing rats. • Anti-Siglec-15 Ab increases bone mass and mechanical properties of long bones and lumbar vertebral bodies in growing rats. • Anti-Siglec-15 Ab could be safe and effective for juvenile osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: The cervical pedicle screw (CPS) requires careful and accurate placement because of the critical risk for neurovascular injury. This study aimed to introduce and evaluate the safety and efficacy of a new CPS placement technique using intraoperative C-arm cone-beam CT (CBCT) and a pilot screw without navigation system.Methods: This was a case-control study to compare the accuracy and safety of intraoperative C-arm CBCT-guided CPS placement with freehand CPS placement under lateral fluoroscopy using control data from a previous multicenter study. A total of 166 CPSs were inserted under intraoperative C-arm CBCT guidance in 48 consecutive patients (20 rheumatoid arthritis, 16 degenerative spinal disorders, 6 spinal tumor, 2 congenital deformity, 2 ossification of posterior longitudinal ligament, and 2 fracture dislocation). Accuracy and safety of CPS placement were assessed.Results: The overall malposition rate was 2.4% (4 screws in grade 1: malposition by less than half-screw diameter, 0 in grade 2: malposition by more than half-screw diameter), which was significantly lower than the reported malposition rate of 14.8% in lateral fluoroscopy-guided freehand placement. There were no complications directly related to CPS insertion. The average estimated effective radiation dose per surgery was 14.7 mSv.Conclusions: The novel technique enables intraoperative adjustment of the trajectory of the CPS as well as confirmation of the CPS path before penetrating the isthmus of the pedicle, resulting in accurate and safe CPS placement, which outweighs the demerits of radiation exposure. These slides can be retrieved under Electronic Supplementary Material. [ABSTRACT FROM AUTHOR]

ABSTRACT: The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification; however, exogenous PPi is rapidly hydrolyzed by tissue non‐specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1ttw/ttw (twy) mouse model. Twenty male twy mice were randomized into four groups: (i) vehicle (Control); (ii) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously); (iii) levamisole + exogenous PPi (160 µmol/kg/day sc continuously); and (iv) nuclear retinoic acid receptor‐γ (RARγ) agonist (6 µg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro‐computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle‐treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist‐treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1256–1261, 2018. [ABSTRACT FROM AUTHOR]

Fourier transform infrared (FTIR) imaging is a powerful tool for the assessment of bone quality; however, it requires the preparation of thin bone sections. Conventional poly(methyl methacrylate) (PMMA) embedding for the preparation of sections takes more than two weeks and causes denaturation of the bone. Development of a quick and easy sample preparation technique without denaturation is needed for accurate clinical evaluation of fresh calcified bone using FTIR imaging. Frozen sectioning allows the quick and easy preparation of thin sections without denaturation, but it requires a substrate with good chemical resistance and improved heat shock resistance. Polypropylene (PP) film afforded both good chemical resistance and greater heat shock resistance, and the 4-μm-thick PP film coated with glue was thin enough for the IR beam to pass through it, while the optical anisotropy of infrared bands overlapping with PO43- band was negligible. The bone quality of femoral thin sections prepared by the conventional PMMA embedding and sectioning procedure (RESIN-S) or the newly developed frozen sectioning procedure (FROZEN-S) was evaluated by FTIR imaging. The mineral-to-matrix ratio and crystallinity in the RESIN-S sections were higher than those in the FROZEN-S sections, whereas the carbonate-to-phosphate ratio in the RESIN-S sections was lower than that in the FROZEN-S sections. In RESIN-S, the increased mineral-to-matrix ratio could be caused by dehydration, and the increased crystallinity and decreased carbonate-to-phosphate ratio might be consequence of dissolution of bone mineral during PMMA embedding. Therefore, the combined use of PP film coated with glue and the frozen sectioning procedure without denaturation appears well suited to the assessment of the bone quality of fresh calcified bone using FTIR imaging. [ABSTRACT FROM AUTHOR]

Background: Hematogenous vertebral osteomyelitis (HVO) has a generally favorable prognosis if appropriate treatment is initiated in its early phase; however, some intractable cases with HVO can develop neurological impairment as well as spinal deformity during the course of treatment and these sequelae may lead to impaired quality of life (QOL). In this study, we aimed to evaluate the long-term relapse rate, mortality, and QOL of patients with HVO.Methods: In this retrospective case series study, medical records of 60 patients with HVO with a mean follow-up period of 8 years (5-23 years) were reviewed to assess demographic data, details of infection, and clinical course. Mortality rate was assessed using a Kaplan-Meier plot. QOL was measured using the EuroQol 5 Dimension (EQ-5D) questionnaire and residual pain using a numeric rating scale (NRS).Results: HVO relapsed in 4 of 60 patients (7%). Overall 5-year survival rate in 60 patients with HVO was 85%. The factors associated with increased mortality were malignant tumor, diabetes mellitus, chronic use of glucocorticoids, and drug-resistant strains of staphylococcus. Female-to-male ratio, NRS, prevalence of neurological impairment were significantly higher in patients with low EQ-5D score (poor health) compared to those with high EQ-5D score (good health).Conclusions: Patients with HVO have shorter life expectancy if they have malignancy, diabetes mellitus, chronic use of glucocorticoids, and a history of drug-resistant strains of staphylococcus infection. Female gender, residual neurological defects and persistent back pain are associated with impaired QOL in patients with HVO. [ABSTRACT FROM AUTHOR]

• Patients with OPLL exhibit higher whole-body BMD in both men and women. • OPLL patients had a lower rate of history of vertebral fractures and osteoporosis. • Among women, diffuse-type OPLL was associated with BMD of femoral neck and skull. Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. We investigated whether patients with OPLL develop increased whole-body BMD. Single institution cross-sectional study. Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 69-year-old woman with rheumatoid arthritis (RA), chronic and low back pain. She was treated with anti-interleukin (IL)-6 antibody tocilizumab and methylprednisolone for her RA. A diagnosis of pyogenic spondylodiscitis was made as revealed in computed tomography scanning and magnetic resonance imaging (MRI). The patient undergone spinal decompression and fusion with an iliac bone graft.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common skeletal disorder in the elderly, which can develop into periosteal hyperostosis and paradoxically into immobilization-associated trabecular osteoporosis. The bone anabolic agent, teriparatide (TPD), seems to be a rational treatment for the immobilization-associated osteoporosis. However, it can lead to development of hyperostosis lesions in DISH patients. Here, we demonstrate TPD effectively treats trabecular osteoporosis while simultaneously promoting ankylosis of the spine in DISH model tiptoe-walking Yoshimura (twy) mice, compared with the ICR mice. Eighteen male twy mice were divided into three groups, and ICR mice were used as a normal control. Subcutaneous injections of TPD or phosphate-buffered saline (PBS) were performed according to three dosing regimens; 40 µg/kg once daily (TPD × 1 group), 40 µg/kg three times daily (TPD × 3 group), and PBS (control; Ctl group). Treatment was commenced at the age of 7 weeks and continued for 5 weeks. Micro-computed tomography (µCT) and histological analysis were performed. Longitudinal µCT study revealed that trabecular bone volume in both the vertebral body and distal femur decreased with time in the Ctl group, but increased dramatically in the TPD × 3 group. The twy mice developed ankylosis of the spine, the progression of which was accelerated with TPD therapy. We also confirmed that TPD therapy promoted ossification of spinal ligaments. Histomorphometrical study revealed that TPD treatment increased bone formation at the vertebrae enthesis region and in the trabecular bone. TPD therapy effectively treats trabecular osteoporosis, but potentially promotes ankylosis of the spine in patients with DISH. [ABSTRACT FROM AUTHOR]

Osteoclastogenesis requires immunoreceptor tyrosine-based activation motif signaling. Multiple immunoreceptors associated with immunoreceptor tyrosine-based activation motif adaptor proteins, including DNAX-activating protein 12 kDa (DAP12) and Fc receptor common γ (FcRγ), have been identified in osteoclast lineage cells, and some are involved in arthritis-induced bone destruction. Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with DAP12. Whether Siglec-15 is involved in arthritis-induced bone lesions, however, remains unknown. Here we used a murine antigen-induced arthritis model to examine the role of Siglec-15 in the development of bone lesions induced by joint inflammation. Arthritis was unilaterally induced in the knee joints of 8-week-old female wild-type (WT) and Siglec-15 −/− mice, and the contralateral knees were used as a control. The degree of joint inflammation, and cartilage and subchondral bone destruction in Siglec-15 −/− mice was comparable to that in WT mice, indicating that Siglec-15 is not involved in the development of arthritis and concomitant cartilage and subchondral bone destruction. On the other hand, the degree of periarticular bone loss in the proximal tibia of the arthritic knee was significantly lower in Siglec-15 −/− mice compared to WT mice. Although osteoclast formation in the metaphysis was enhanced in both WT and Siglec-15 −/− mice after arthritis induction, mature multinucleated osteoclast formation was impaired in Siglec-15 −/− mice, indicating impaired osteoclast bone resorptive function in the periarticular regions of the arthritic joint in Siglec-15 −/− mice. Confirming this result, Siglec-15 −/− primary unfractionated bone marrow cells harvested from arthritic femurs and tibiae failed to develop into mature multinuclear osteoclasts. Our findings suggest that Siglec-15 is a therapeutic target for periarticular bone loss, but not for joint destruction, in inflammatory arthritis, such as rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is an immunoreceptor that regulates osteoclast development and bone resorption in association with an immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein, DNAX-activating protein 12 kDa (DAP12). Although Siglec-15 has an important role in physiologic bone remodeling by modulating RANKL signaling, it is unclear whether it is involved in pathologic bone loss in which multiple osteoclastogenic factors participate in excessive osteoclastogenesis. Here we demonstrated that Siglec-15 is involved in estrogen deficiency-induced bone loss. WT and Siglec-15 −/− mice were ovariectomized (Ovx) or sham-operated at 14 wk of age and their skeletal phenotype was evaluated at 18 and 22 wk of age. Siglec-15 −/− mice showed resistance to estrogen deficiency-induced bone loss compared to WT mice. Although the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts increased after ovariectomy in both WT and Siglec-15 −/− mice, the increase was lower in Siglec-15 −/− mice than in WT mice. Importantly, osteoclasts in Siglec-15 −/− mice were small and failed to spread on the bone surface, indicating impaired osteoclast differentiation. Because upregulated production of TNF-α as well as RANKL is mainly responsible for estrogen deficiency-induced development of osteoclasts, we examined whether Siglec-15 deficiency affects TNF-α-induced osteoclastogenesis in vitro . The TNF-α mediated induction of TRAP-positive multinucleated cells was impaired in Siglec-15 −/− cells, suggesting that Siglec-15 is involved in TNF-α induced osteoclastogenesis. We also confirmed that signaling through osteoclast-associated receptor/Fc receptor common γ chain, which is an alternative ITAM adaptor to DAP12, rescues multinucleation but not cytoskeletal organization of TNF-α and RANKL-induced Siglec-15 − / − osteoclasts, indicating that the Siglec-15/DAP12 pathway is especially important for cytoskeletal organization of osteoclasts in both RANKL and TNF-α induced osteoclastogenesis. The present findings indicate that Siglec-15 is involved in estrogen deficiency-induced differentiation of osteoclasts and is thus a potential therapeutic target for postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Abstract: Teriparatide (PTH1–34) promotes skeletal repair and increases bone mass. Vitamin K is involved in bone mineralization as a coenzyme of γ-carboxylase for Gla proteins, and therefore vitamin K insufficiency caused by malnutrition or therapeutic intake of the vitamin K antagonist warfarin could affect the efficacy of PTH1–34 therapy for bone repair. In the present study, we investigated whether vitamin K influences the efficacy of PTH1–34 therapy for bone repair in a rat osteotomy model. Female 12-week-old Sprague–Dawley rats were subjected to a closed midshaft osteotomy of the femur and randomized into four groups (n=10 per group): vehicle, PTH1–34 (daily 30μg/kg/day subcutaneous injection)+solvent (orally, three times a week), PTH1–34 +warfarin (0.4mg/kg/day orally, three times a week), and PTH1–34 +vitamin K2 (menatetrenone, 30mg/kg/day orally, three times a week). Serum γ-carboxylated and uncarboxylated osteocalcin (Gla-OC and Glu-OC) levels and radiographic healing were monitored every 2weeks. Skeletal repair was assessed by micro-computed tomography, mechanical testing, and histology at 8weeks after surgery. PTH1–34 amplified the osteotomy-induced increase in Gla-OC and improved the mechanical properties as well as the volumetric bone mineral tissue density of the fracture callus. Concurrent use of warfarin decreased the response to PTH1–34 therapy in terms of mechanical recovery, probably by impairing mineralization due to the lack of Gla-OC. Although the effects of combination therapy with PTH1–34 and vitamin K2 on bone repair did not significantly exceed those of PTH1–34 monotherapy in rats fed sufficient dietary vitamin K, postoperative Gla-OC levels were correlated with the mechanical properties of the osteotomized femur in PTH1–34-treated rats regardless of the use of warfarin or vitamin K2. These findings suggest the importance of vitamin K dependent γ-carboxylation of OC for realizing the full effects of PTH1–34 on skeletal repair. [Copyright &y& Elsevier]

Objective Glucocorticoid (GC) therapy is associated with increased risk of fracture in patients with rheumatoid arthritis (RA). To elucidate the cause of this increased risk, we examined the effects of chronic erosive inflammatory arthritis and GC treatment on bone quality, structure, and biomechanical properties in a murine model. Methods Mice with established arthritis and expressing human tumor necrosis factor α (TNFα) transgene (Tg) and their wild-type (WT) littermates were continually treated with GC (prednisolone 5 mg/kg/day via subcutaneous controlled-release pellet) or placebo for 14, 28, or 42 days. Microstructure, biomechanical properties, chemical composition, and morphology of the tibiae and lumbar vertebral bodies were assessed by micro-computed tomography, biomechanical testing, Raman spectroscopy, and histology, respectively. Serum markers of bone turnover were also determined. Results TNF-Tg and GC treatment additively decreased mechanical strength and stiffness in both the tibiae and the vertebral bodies. GC treatment in the TNF-Tg mice increased the ductility of tibiae under torsional loading. These changes were associated with significant alterations in the biochemical and structural composition of the mineral and organic components of the bone matrix, a decrease in osteoblast activity and bone formation, and an increase in osteoclast activity. Conclusion Our findings indicate that the concomitant decrease in bone strength and increase in bone ductility associated with chronic inflammation and GC therapy, coupled with the significant changes in the bone quality and structure, may increase the susceptibility of the bone to failure under low-energy loading. This may explain the mechanism of symptomatic insufficiency fractures in patients with RA receiving GC therapy who do not have radiographic manifestations of fracture. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Based on its proven anabolic effects on bone in osteoporosis patients, recombinant parathyroid hormone (PTH) has been evaluated as a potential therapy for skeletal repair. In animals, the effect of PTH has been investigated in various skeletal repair models such as fractures, allografting, spinal arthrodesis and distraction osteogenesis. These studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms, which include effects on mesenchymal stem cells, angiogenesis, chondrogenesis, bone formation and resorption. Furthermore, PTH has been shown to enhance bone repair in challenged animal models of aging, inflammatory arthritis and glucocorticoid-induced bone loss. This pre-clinical success has led to off-label clinical use and a number of case reports documenting PTH treatment of delayed-unions and non-unions have been published. Although a recently completed phase 2 clinical trial of PTH treatment of patients with radius fracture has failed to achieve its primary outcome, largely because of effective healing in the placebo group, several secondary outcomes are statistically significant, highlighting important issues concerning the appropriate patient population for PTH therapy in skeletal repair. Here, we review our current knowledge of the effects of PTH therapy for bone healing, enumerate several critical unresolved issues (e.g., appropriate dosing regimen and indications) and discuss the long-term potential of this drug as an adjuvant for endogenous tissue engineering. [ABSTRACT FROM AUTHOR]

Structural allografts used for critical bone defects have limited osteogenic properties for biointegration. Although ex vivo tissue-engineered constructs expressing bone morphogenetic protein-2 (BMP2) have demonstrated efficacy in critical defect models, similar success has not been achieved with off-the-shelf acellular approaches, including allografts coated with freeze-dried single-stranded adeno-associated virus (ssAAV-BMP2). To see whether the self-complementary AAV serotype 2.5 vector (scAAV2.5-BMP2) could overcome this, we performed side-by-side comparisons in vitro and in the murine femoral allograft model. Although ssAAV-BMP2 was unable to induce BMP2 expression and differentiation of C3H10T1/2 cells in culture, scAAV2.5-BMP2 transduction led to dose-dependent BMP2 expression and alkaline phosphatase activity, and displayed a 25-fold increased transduction efficiency in vivo. After 6 weeks, the ssAAV-BMP2 coating failed to demonstrate any significant effects. However, all allografts coated with 1010 scAAV2.5-BMP2 formed a new cortical shell that was indistinguishable to that formed by live autografts. Additionally, coated allografts experienced reduced resorption resulting in a threefold increase in graft bone volume versus autograft. This led to biomechanical superiority versus both allografts and autografts, and equivalent torsional rigidity to unfractured femur. Collectively, these results demonstrate that scAAV2.5-BMP2 coating overcomes the major limitations of structural allografts, which can be used to heal critical defects of any size. [ABSTRACT FROM AUTHOR]

Abstract: Despite the remarkable healing potential of long bone fractures, traumatic injuries that result in critical defects require challenging reconstructive limb sparing surgery. While devitalized allografts are the gold standard for these procedures, they are prone to failure due to their limited osseointegration with the host. Thus, the quest for adjuvants to enhance allograft healing remains a priority for this unmet clinical need. To address this, we investigated the effects of daily systemic injections of 40μg/kg teriparatide (recombinant human parathyroid hormone) on the healing of devitalized allografts used to reconstruct critical femoral defects (4mm) in C57Bl/6 mice. The femurs were evaluated at 4 and 6weeks using micro CT, histology, and torsion testing. Our findings demonstrated that teriparatide induced prolonged cartilage formation at the graft-host junction at 4weeks, which led to enhanced trabeculated bone callus formation and remarkable graft-host integration at 6-weeks. Moreover, we observed a significant 2-fold increase in normalized callus volume (1.04±0.3 vs. 0.54±0.14mm3/mm; p<0.005), and Union Ratio (0.28±0.07 vs. 0.13±0.09; p<0.005), compared to saline treated controls at 6-weeks. Teriparatide treatment significantly increased the torsional rigidity (1175±311 versus 585±408N.mm2) and yield torque (10.5±4.2 versus 6.8±5.5N.mm) compared to controls. Interestingly, the Union Ratio correlated significantly with the yield torque and torsional rigidity (R2 =0.59 and R2 =0.77, p<0.001, respectively). These results illustrate the remarkable potential of teriparatide as an adjuvant therapy for allograft repair in a mouse model of massive femoral defect reconstruction, and warrant further investigation in a larger animal model at longer time intervals to justify future clinical trials for PTH therapy in limb sparing reconstructive procedures. [Copyright &y& Elsevier]

Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA) infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection. The penetration efficacy of linezolid into the annulus fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was lower than that of vancomycin (27, 11, and 14%, respectively). The penetration efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%, respectively), however, was higher than that of vancomycin (67 and 9%, respectively). These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection. [ABSTRACT FROM AUTHOR]

The selective estrogen receptor modulator raloxifene is therapeutically beneficial for postmenopausal connective tissue degradation, such as osteoporosis, vascular sclerosis, and dermal degradation; however, the effects of raloxifene on postmenopausal tendon metabolism have not been clarified. In this study, we investigated the effects of raloxifene analogue (LY117018) on cell proliferation and collagen metabolism using cultured rat Achilles tendon fibroblasts. 17β-Estradiol (E2; 10−11-10−9 M) and LY117018 (10−9-10−7 M) had no significant effects on tendon fibroblast proliferation, based on a BrdU (5-bromo-2′-deoxyuridine) incorporation assay (24 hr) and a WST-8 colorimetric assay (2 or 6 days). Neither E2 nor LY117018 significantly altered the expression of type I collagen, which is a main component of the tendon extracellular matrix (ECM), whereas both E2 and LY117018 significantly increased the expression of matrix metalloproteinase (MMP)-13, which is responsible for tendon collagen degradation in rat. Also, both E2 and LY117018 increased the expression of type III collagen and elastin, which are minor components of tendon ECM, but are considered to govern the elastic properties of tendons. These changes in collagen and MMP induced by either E2 or LY117018 were attenuated by the estrogen receptor alpha blocker ICI 182,780. The results of this study suggest that postmenopausal estrogen deficiency might downregulate tendon collagen turnover and decrease tendon elasticity. Further, raloxifene treatment might restore these changes to premenopausal levels. [ABSTRACT FROM AUTHOR]

Abstract: Bone grafting is commonly used to treat skeletal disorders associated with a large bone defect or unstable joint. Spinal arthrodesis surgery, which is the most common application of bone graft, is performed in the elderly and anti-resorptive therapy is sometimes started postoperatively in patients with bone fragility due to osteoporosis, despite insufficient knowledge about the effects of these drugs on bone graft healing. Therefore, we studied the effect of bisphosphonates (BP) and selective estrogen receptor modulators (SERM) on bone graft healing in an ovariectomized rat spinal arthrodesis model. Female Sprague–Dawley rats (n =100) were ovariectomized or sham-operated, and randomized into four groups: Sham (sham-operated+vehicle), Ovx (ovariectomy+vehicle), Ovx-Rlx (ovariectomy+raloxifene, 1 mg/kg/day), and Ovx-Aln (ovariectomy+alendronate, 0.01 mg/kg/day). Four weeks after ovariectomy, lumbar spinal arthrodesis surgery was performed using an autologous bone graft. Animals were killed 2, 4, and 8 weeks after surgery, and fusion assessment, three-dimensional micro-computed tomography, histomorphometry, mRNA expression analysis, and serum bone metabolic marker analysis were performed. The results indicated that neither BP nor SERM significantly altered the fusion rate, but the bone graft healing process was differentially affected. BP inhibited endochondral ossification and graft bone resorption, but induced the growth of a larger, denser fusion mass compared to Ovx by strongly suppressing osteoclastic activity. SERM mildly suppressed bone remodeling, but did not significantly inhibit the ossification process, leading to a fusion mass comparable with that of Sham animals. These findings suggested that spinal fusion surgery outcome is not likely to be altered by BP or SERM treatment started immediately after spinal arthrodesis surgery; however, to avoid adverse effects of BP on bone graft healing, BP treatment should be delayed during the immediate postoperative period. [Copyright &y& Elsevier]

The article presents a retrospective review of the clinical results and complications of circumferential spinal cord decompression through posterior approach for thoracic ossification of posterior longitudinal ligament. This study examined the outcomes and efficiency of the procedure reporting the incidence of complications.

Abstract: Bone grafting is commonly used to treat skeletal disorders associated with large bone defect or unstable joint. It can take several months, however, to achieve a solid union and bony fusion sometimes delays or fails especially in osteoporosis patients. Therefore, we used a rat spinal arthrodesis model to examine whether intermittent administration of human PTH(1–34) accelerates bone graft healing. Eighty-two male Sprague–Dawley rats underwent posterolateral spinal arthrodesis surgery using autologous bone grafts. Animals were given daily subcutaneous injections of hPTH(1–34) (40 μg/kg/day PTH group) or 0.9% saline vehicle (control group) from immediately after surgery till death. Five rats each were killed 2, 4, 7, and 14 days after the surgery, and mRNA expression analysis was performed on harvested grafted bone. Seven rats each were killed 14, 28, and 42 days after the surgery, and the lumbar spine, which contained the grafted spinal segment, was subjected to fusion assessment, microstructural analysis using three-dimensional micro-computed tomography, and histologic examination. Serum bone metabolism markers were analyzed. The results indicated that PTH administration decreased the time required for graft bone healing and provided a structurally superior fusion mass in the rat spinal arthrodesis model. PTH administration increased the fusion rate on day 14 (14% in the control group and 57% in the PTH group), accelerated grafted bone resorption, and produced a larger and denser fusion mass compared to control. mRNA expression of both osteoblast- and osteoclast-related genes was upregulated by PTH treatment, and serum bone formation and resorption marker levels were higher in the PTH group than in the control group. Histologically calculated mineral apposition rate, mineralized surface and osteoclast surface were also higher in the PTH group than in the control group. These findings suggest that intermittent administration of PTH(1–34) enhanced bone turn over dominantly on bone formation at the graft site, leading to the acceleration of the spinal fusion. Based on the results of this study, intermittent injection of hPTH(1–34) might be an efficient adjuvant intervention in spinal arthrodesis surgery and all other skeletal reconstruction surgeries requiring bone grafts. [Copyright &y& Elsevier]

Abstract: Sialic acid, which is located at the end of the carbohydrate moiety of cell surface glycoconjugates, is involved in many biologic responses, such as intercellular reactions and virus–cell fusion, especially in hematopoietic cells. Here we provide experimental evidence that the sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation. Lectin histochemical study demonstrated the existence of both alpha (2,3)-linked-sialic acid and alpha (2,6)-linked-sialic acid in mouse bone marrow-derived macrophages and in the RAW264.7 macrophage cell line, which are osteoclast precursors. Flow cytometric analysis of surface lectin staining revealed the kinetics of these sialic acids during osteoclastogenesis: alpha (2,3)-linked-sialic acid was abundantly expressed throughout osteoclastogenesis, whereas alpha (2,6)-linked-sialic acid levels declined at the terminal stage of osteoclast differentiation. To investigate the role of sialic acid in osteoclast differentiation, we performed an osteoclastogenesis assay with or without exogenous sialidase treatment. Desialylated cells formed TRAP-positive mononuclear cells, but did not become multinuclear cells despite the normal expression of osteoclast markers such as cathepsin K, integrin β3, and nuclear factor-ATc1. Flow cytometric analysis also demonstrated that exogenous sialidase effectively removed alpha (2,6)-linked-sialic acid, but only slightly changed the alpha (2,3)-linked-sialic acid content, suggesting that alpha (2,6)-linked-sialic acid might be involved in osteoclast differentiation. Findings from knockdown analysis using small interfering RNA oligonucleotides against alpha 2,6-sialyltransferase support this idea: alpha (2,6)-linked-sialic acid-deficient cells markedly inhibit the formation of multinuclear osteoclasts. Our findings suggest that alpha (2,6)-linked-sialic acid of cell surface glycoconjugates has a role in osteoclast differentiation, possibly via its role in the cell–cell fusion process. [Copyright &y& Elsevier]

Background Context: Therapeutic devices for spinal disorders, such as spinal fusion cages, must be able to facilitate the maintenance and rapid recovery of spinal function. Therefore, it would be advantageous that future spinal fusion cages facilitate rapid recovery of spinal function without secondary surgery to harvest autologous bone.Purpose: This study investigated a novel spinal cage configuration that achieves in vivo mechanical integrity as a devise/bone complex by inducing bone that mimicked the sound trabecular bone, hierarchically and anisotropically structured trabeculae strengthened with a preferentially oriented extracellular matrix.Study Design/settings: In vivo animal study.Methods: A cage possessing an anisotropic through-pore with a grooved substrate, that we termed "honeycomb tree structure," was designed for guiding bone matrix orientation; it was manufactured using a laser beam powder bed fusion method through an additive manufacturing processes. The newly designed cages were implanted into sheep vertebral bodies for 8 and 16 weeks. An autologous bone was not installed in the newly designed cage. A pull-out test was performed to evaluate the mechanical integrity of the cage/bone interface. Additionally, the preferential orientation of bone matrix consisting of collagen and apatite was determined.Results: The cage/host bone interface strength assessed by the maximum pull-out load for the novel cage without an autologous bone graft (3360±411 N) was significantly higher than that for the conventional cage using autologous bone (903±188 N) after only 8 weeks post-implantation.Conclusions: These results highlight the potential of this novel cage to achieve functional fusion between the cage and host bone. Our study provides insight into the design of highly functional spinal devices based on the anisotropic nature of bone.Clinical Significance: The sheep spine is similar to the human spine in its stress condition and trabecular bone architecture and is widely recognized as a useful model for the human spine. The present design may be useful as a new spinal device for humans. [ABSTRACT FROM AUTHOR]

Introduction: A 28.2 μg twice-weekly formulation of teriparatide (2/W-TPD) was developed to provide comparably high efficacy for osteoporosis to a 56.5 μg once-weekly formulation while improving the safety and persistence rate. In the current study, we aimed to elucidate the real-world persistence of 2/W-TPD and to identify the factors associated with the discontinuation of 2/W-TPD in patients with severe osteoporosis. Materials and methods: This retrospective study included 90 patients who were treated with 2/W-TPD at three hospitals in Japan. Patient information was collected, including age, sex, distance to the hospital, family structure, comorbidities, previous treatment for osteoporosis, timing of the injection, side effects and duration of 2/W-TPD treatment, barthel index (BI), and bone mineral density (BMD) of the lumbar spine and femoral neck. We examined the factors influencing 2/W-TPD discontinuation using the Cox proportional hazards model. Results: The 12 month completion rate of 2/W-TPD therapy was 47.5%. The Cox hazard analysis identified side effects [Hazard Ratio (HR) = 14.59, P < 0.001], low BMD of the femoral neck (HR = 0.04, P = 0.002), and morning injection (HR = 3.29, P = 0.006) as risk factors influencing the discontinuation of 2/W-TPD. Other variables, including age, did not contribute to the continuation of 2/W-TPD. Conclusion: One year continuation rate of 2/W-TPD was higher than the previously reported value of the once-weekly formulation in real-world setting, probably due to the lower incidence of side effects. Introducing injection of 2/W-TPD may further improve the persistence of TPD therapy for osteoporosis. [ABSTRACT FROM AUTHOR]

Effective treatment of juvenile osteoporosis, which is frequently caused by glucocorticoid (GC) therapy, has not been established due to limited data regarding the efficacy and adverse effects of antiresorptive therapies on the growing skeleton. We previously demonstrated that sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) targeting therapy, which interferes with osteoclast terminal differentiation in the secondary, but not primary, spongiosa, increased bone mass without adverse effects on skeletal growth, whereas bisphosphonate, a first-line treatment for osteoporosis, increased bone mass but impaired long bone growth in healthy growing rats. In the present study, we investigated the efficacy of anti-Siglec-15 neutralizing antibody (Ab) therapy against GC-induced osteoporosis in a growing rat model. GC decreased bone mass and deteriorated mechanical properties of bone, due to a disproportionate increase in bone resorption. Both anti-Siglec-15 Ab and alendronate (ALN) showed protective effects against GC-induced bone loss by suppressing bone resorption, which was more pronounced with anti-Siglec-15 Ab treatment, possibly due to a reduced negative impact on bone formation. ALN induced histological abnormalities in the growth plate and morphological abnormalities in the long bone metaphysis but did not cause significant growth retardation. Conversely, anti-Siglec-15 Ab did not show any negative impact on the growth plate and preserved normal osteoclast and chondroclast function at the primary spongiosa. Taken together, these results suggest that anti-Siglec-15 targeting therapy could be a safe and efficacious prophylactic therapy for GC-induced osteoporosis in juvenile patients. • Anti-Siglec-15 Ab increases trabecular bone mass over a range of distal metaphysis. • Anti-Siglec-15 Ab did not show any negative impacts on the growth plate. • It preserved osteoclast and chondroclast function at the primary spongiosa. • Anti-Siglec-15 Ab may be a safe prophylactic therapy for juvenile osteoporosis. [ABSTRACT FROM AUTHOR]

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 nonosteoporosis patients who had undergone one- or two-level transforaminal lumbar interbody fusion were included. Fusion status was assessed using computed tomography 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 seven 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 was significantly higher and the increased level of BAP and P1NP was kept until 52 weeks.Conclusion: The present 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. [ABSTRACT FROM AUTHOR]

Background: Although the prognosis of incomplete cervical spinal cord injury (SCI) diagnosed as American Spinal Injury Association Impairment Scale grade C (AIS C) is generally favorable, some patients remain non-ambulatory. The present study explored the clinical factors associated with the non-ambulatory state of AIS C patients.Methods: This study was a single-center retrospective observational study. Seventy-three participants with AIS C on admission were enrolled and divided into two groups according to ambulatory ability after one year. Prognostic factors of SCI were compared in ambulatory (A-group) and non-ambulatory participants (NA-group). Univariable and multivariable logistic regression analyses were performed on demographic information, medical history, mechanism of injury, presence of fracture, ASIA motor scores (MS) of the extremities, neurological findings, including an anorectal examination on admission, and imaging findings.Results: Forty-one patients were included in the A-group and 32 in the NA-group. Univariable analysis revealed that the following factors were related to poor outcomes (p < 0.05): older age, history of cerebrovascular disorder, impairment/absence of S4-5 sensory score, deep anal pressure (DAP) (-), voluntary anal contraction (VAC) (-), anorectal tone (-), anal wink reflex (-), and low MS of the upper and lower extremities. In the multivariable analysis using age, presence or absence of sacral abnormality, and history of cerebrovascular disorders (adjusted for these three factors), older age and presence of sacral abnormality on admission were independent risk factors for a non-ambulatory state at the 1-year follow-up.Conclusions: Incomplete AIS C SCI individuals with older age and/or impairment of anorectal examination could remain non-ambulatory at 1-year follow-up. [ABSTRACT FROM AUTHOR]

Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to investigate the characteristics of patients with cervical spinal cord injuries (CSCI) with diffuse idiopathic skeletal hyperostosis (DISH). We included 153 consecutive patients with CSCI who underwent posterior decompression and fusion surgery. The patients were divided into two groups based on the presence of DISH. Patient characteristics, neurological status on admission, nutritional status, perioperative laboratory variables, complications, neurological outcomes at discharge, and medical costs were compared between the groups. The DISH group (n = 24) had significantly older patients (72.1 vs. 65.9, p = 0.036), more patients with low-impact trauma (62.5% vs. 34.1%, p = 0.009), and a lower preoperative prognostic nutritional index on admission (39.8 vs. 42.5, p = 0.014) than the non-DISH group (n =129). Patients with DISH had significantly higher rates of ventilator management (16.7% vs. 3.1%, p = 0.022) and pneumonia (29.2% vs. 8.5%, p = 0.010). There was no significant difference in medical costs and neurological outcomes on discharge. Patients with CSCI and DISH were older, had poor nutritional status, and were prone to postoperative respiratory complications, while no differences were found between the neurological outcomes of patients with CSCI with and without DISH. [ABSTRACT FROM AUTHOR]

Background: Preventive management to reduce the risk of coronavirus disease-2019 (COVID-19) spread led to delays in active rehabilitation, which may have negatively impacted the outcomes of patients with traumatic spinal cord injury (SCI). Therefore, the aim of this study was to clarify the influence of preventive management on the rate of perioperative complications after surgical treatment for SCI. Methods: This single-center retrospective study examined the cases of 175 patients who had SCI surgery between 2017 and 2021. We could not continue early rehabilitation interventions starting on April 30, 2020, because of our preventive management to reduce the risk of COVID-19 spread. Using a propensity score-matched model, we adjusted for age, sex, American Spinal Injury Association impairment scale score at admission, and risk factors for perioperative complications described in previous studies. Perioperative complication rates were compared between the COVID-19 pandemic and prepandemic groups. Results: Of the 175 patients, 48 (the pandemic group) received preventive management. The preliminary analysis revealed significant differences between the unmatched pandemic and prepandemic groups with respect to age (75.0 versus 71.2 years, respectively; p = 0.024) and intraoperative estimated blood loss (152 versus 227 mL; p = 0.013). The pandemic group showed significant delays in visiting the rehabilitation room compared with the prepandemic group (10 versus 4 days from hospital admission; p < 0.001). There were significant differences between the pandemic and prepandemic groups with respect to the rates of pneumonia (31% versus 16%; p = 0.022), cardiopulmonary dysfunction (38% versus 18%; p = 0.007), and delirium (33% versus 13%; p = 0.003). With a propensity score-matched analysis (C-statistic = 0.90), 30 patients in the pandemic group and 60 patients in the prepandemic group were automatically selected. There were significant differences between the matched pandemic and prepandemic groups with respect to the rates of cardiopulmonary dysfunction (47% versus 23%; p = 0.024) and deep venous thrombosis (60% versus 35%; p = 0.028). Conclusions: Even with early surgical intervention, late mobilization and delays in active rehabilitation during the COVID-19 pandemic increased perioperative complications after SCI surgery. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Although severe cervical compressive-extension (CE) injuries are usually repaired using a combined anterior-posterior approach, the repair is possible using a posterior approach alone with reliable anchors. This study aimed to present the outcomes and imaging analysis results of posterior cervical decompression and fusion (PCDF) for severe CE injuries. We retrospectively reviewed 16 patients who underwent PCDF surgery for severe CE injuries (>50% subluxation) between January 2012 and December 2018. All patients completed 1-year follow-up, and their mean age at the time of surgery was 63.5 years. American Spinal Injury Association Impairment Scale (AIS) grade, kyphotic angle of lower vertebra (KALV), and anterior defect area of lower vertebra (ADLV) were assessed preoperatively. Of 16 patients, nine patients improved at the final follow-up, and eight patients could walk with or without assistance. All patients achieved bone union postoperatively, but four patients showed progression of correction loss of ≥10°. Therefore, patients were divided into two groups: NL group with correction loss of <10°; L group with correction loss of ≥10°. All patients in L group showed KALV of ≥15°, while 10 of 12 patients in NL group showed KALV of <15°. Furthermore, all patients in L group showed ADLV of ≥50%, whereas all patients in NL group showed ADLV of <50%. PCDF is feasible and a favorable procedure for severe CE injuries that require early reduction and cervical spinal stabilization. However, in the cases of advanced destruction of the anterior vertebra, loss of correction after PCDF might occur postoperatively. [ABSTRACT FROM AUTHOR]

Symptomatic postoperative lumbar epidural hematoma (PLEH) may lead to poor outcomes even after evacuation. This study aimed to verify the short-term clinical outcomes after the evacuation of PLEH and to clarify the characteristics of the patients with poor postoperative outcomes. Twenty-five patients (average age; 70.4 years) underwent PLEH evacuation after lumbar spine surgery. The mean follow-up period was 12.0 (range 3–37) months. Pre and postoperative Japanese Orthopedic Association scores and visual analog scale (VAS) of low back pain (LBP), leg pain, and leg numbness were retrospectively collected. The dural sac cross-sectional area at the most compressed level was measured on magnetic resonance imaging. The patients were classified into 2 groups: poor outcome group (P group) had less than 50% of Japanese Orthopedic Associationrecovery rate and good group (G group) with 50% or more recovery rate. The rate of delayed evacuation (over 24 hours of onset) was significantly higher in P group than in G group (P = 0.027). There was no significant difference in dural sac cross-sectional areabetween the 2 groups (P = 0.438). VAS of LBP, leg pain, and leg numbness in G group significantly improved postoperatively. Although VAS of LBP and leg pain in P group significantly improved postoperatively, there was no significant difference between the pre and postoperative VAS of leg numbness. Delayed evacuation of PLEH can lead to poor postoperative outcomes after lumbar spine surgery. Moreover, patients with poor outcomes remained with postoperative leg numbness. Early evacuation of symptomatic PLEH is key to avoid poor outcomes and persistent leg numbness. [ABSTRACT FROM AUTHOR]

Background Context: Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have closely investigated the factors contributing to the quality of life (QOL) in the chronic phase after thoracolumbar OVFs using detailed radiographic evaluation.Purpose: This study aimed to identify factors associated with the QOL in the chronic phase after thoracolumbar OVF.Design: Post-hoc analysis of a prospective randomized study.Patient Sample: Participants included 195 patients with fresh thoracolumbar OVF managed conservatively with a brace who were available for radiographic analysis 48 weeks after injury.Outcome Measures: The degree of QOL impairment at 48 weeks after thoracolumbar OVF was assessed using the Japanese three-level version of the EuroQol five-dimensional questionnaire (EQ-5D) score.Methods: Univariate and multivariate regression analyses were used to evaluate the relationships between the QOL and radiographic factors.Results: The univariate analysis showed that age, analgesic use, T10/L5 Cobb angle on magnetic resonance imaging (MRI), subsequent vertebral fracture, and nonunion were significantly associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. The multiple regression analysis showed that nonunion, analgesic use, subsequent vertebral fracture, and sacral slope on MRI were independently associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. Receiver operating characteristic analysis for the deterioration of QOL showed that the cutoff value for sacral slope on MRI was 35 degrees.Conclusions: This study demonstrated that nonunion, subsequent vertebral fracture, and lower sacral slope were independently associated with poorer QOL in the chronic phase of thoracolumbar OVF managed conservatively with a brace. Therefore, improving or preventing these factors in patients with thoracolumbar OVF in the chronic phase may improve the QOL of the affected patients. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T. [ABSTRACT FROM AUTHOR]

Abstract: Background context: In the cervical spine, the combination of ossification of the ligamentum flavum (OLF) and ossification of the posterior longitudinal ligament (OPLL) is rarely seen. There have been only four cases reported in the English literature. Purpose: We describe two more cases that exhibited cervical myelopathy resulting from the combination of cervical OLF and OPLL and required surgery. A literature review with a comparative analysis between previous reports and present cases was also performed. Study design: Case report and literature review. Patient sample: Two patients with combined OLF and OPLL. Outcome measures: Preoperative computed tomography, magnetic resonance imaging, and pathological findings from operative specimens were used to confirm the diagnoses. Methods: A 76-year-old man (Case 1) presented with disturbance of gait and fine finger movement. Magnetic resonance imaging showed severe spinal canal stenosis and cord compression at the C3–C4 level. Computed tomography showed OPLL at the C2–C6 levels (segmental type) and OLF at the left C3–C4 level. The patient underwent posterior decompression and OLF resection. A 75-year-old man (Case 2) presented with sensory disturbance and muscle weakness in his bilateral upper extremities and disturbance in fine finger movements. Magnetic resonance imaging showed severe spinal canal stenosis and cord compression at the C2–C3 and C3 levels. Computed tomography showed OPLL at the C3–C7 levels (mixed type) and OLF at the left C2–C3 and C3 levels. The patient also underwent posterior decompression and OLF resection. Results: In both cases, histological examination of the surgical specimens showed osseous tissue and enchondral ossification within the ligamentum flavum, and the diagnosis in each case was OLF. After surgery, both patients'' symptoms immediately improved, and no recurrence was observed at 2 years after surgery. Conclusions: We experienced two cases of cervical myelopathy resulting from the combination of OLF and OPLL in the cervical spine. The symptoms of myelopathy were treated successfully by laminectomy and laminoplasty with OLF resection in both cases. The literature review including the present two cases revealed that cervical OLF tended to occur adjacent or close to the margin of cervical OPLL, suggesting that the increased mechanical stress at the junction of OPLL may be a causative factor. [Copyright &y& Elsevier]