Analysis of Risk Factors for Postoperative Deep Vein Thrombosis in Traumatic Spinal Fracture Complicated with Spinal Cord Injury.

The purpose of this study is to investigate the risk factors for postoperative deep vein thrombosis (DVT) in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed using ultrasound. Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bedrest, and MA values of TEG were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bedrest, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer > 5.065 mg/l, lower extremity < 3, duration of bedrest, and MA value of TEG are independent risk factors for postoperative DVT in SCI patients, D-dimer having the highest diagnostic value. When the above risk factors occur, clinicians need to be vigilant and take appropriate prevention and treatment measures.

[Changes and clinical significance of NLRP3 inflammasomes and related factors in patients with spinal fracture complicated with acute spinal cord injury].

OBJECTIVE: To investigate the changes and clinical significance of NOD like receptor protein 3 (NLRP3) inflammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury (SCI). METHODS: Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group, There were 48 males and 38 females, with an average age of (43.48±6.58) years old. And 100 healthy volunteers who underwent physical examination during the same time were selected as control group, including 56 males patients and 44 females patients, with an average age of (45.13±6.43) years old. Peripheral blood mononuclear cell (PBMC) were collected, and the mRNA expressions of NLRP3 and Caspase-1 were detected. Serum was collected and the levels of interleukin (IL)- 1ß, IL-18 were detected. According to Frankel's grade, the SCI group was divided into complete injury patients and incomplete injury patients, and according to the Japanese Orthopedic Society (JOA) grade, the SCI group was divided into good prognosis group and poor prognosis group. The difference of NLRP3, Caspase-1, IL-1ß, IL-18 among groups were compared, the influencing factors for poor prognosis in SCI patients was analyzed by Logistic regression. RESULTS: The mRNA expression levels of NLRP3 (1.41±0.33) and Caspase-1 (1.44±0.35) in PBMC and the levels of IL-1ß(45.34±13.22) pg·ml-1, IL-18(40.95±8.77) pg·ml-1 in serum of SCI group were higher than those of the control group[(1.00±0.19), (1.00±0.16), (16.58±4.24) pg·ml-1, (12.57±3.68) pg·ml-1] (P<0.05). The mRNA expression levels of NLRP3(1.63±0.34) and Caspase-1 (1.67±0.27) in PBMC and the levels of IL-1ß(51.09±11.10) pg·ml-1, IL-18 (47.65±7.93) pg·ml-1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury [(1.31±0.27), (1.34±0.33), (42.85±13.36) pg·ml-1, (38.05±7.48) pg·ml-1](P<0.05). The mRNA expression levels of NLRP3 (1.66±0.31) and Caspase-1 (1.72±0.31)in PBMC and the levels of IL-1ß(51.21±11.31) pg·ml-1, IL-18 (45.70±7.25) pg·ml-1 in serum, the proportion of complete injury(21 patients), and the proportion of spinal cord edema or bleeding of patients(15 patients) with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26), (1.37±0.36), (42.79±13.25) pg·ml-1、(38.90±8.63) pg·ml-1, 5、20 cases](P<0.05). Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing factors for poor prognosis in the SCI group (P<0.05). CONCLUSION: The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis, and NLRP3 expression can serve as a marker for evaluating prognosis.

Midregional Proatrial Natriuretic Peptide (MRproANP) is associated with vertebral fractures and low bone density in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Patients with COPD are often affected by loss of bone mineral density (BMD) and osteoporotic fractures. Natriuretic peptides (NP) are known as cardiac markers, but have also been linked to fragility-associated fractures in the elderly. As their functions include regulation of fluid and mineral balance, they also might affect bone metabolism, particularly in systemic disorders such as COPD. RESEARCH QUESTION: We investigated the association between NP serum levels, vertebral fractures and BMD assessed by chest computed tomography (CT) in patients with COPD. METHODS: Participants of the COSYCONET cohort with CT scans were included. Mean vertebral bone density on CT (BMD-CT) as a risk factor for osteoporosis was assessed at the level of TH12 (AI-Rad Companion), and vertebral compression fractures were visually quantified by two readers. Their relationship with N-terminal pro-B-type natriuretic peptide (NT-proBNP), Mid-regional pro-atrial natriuretic peptide (MRproANP) and Midregional pro-adrenomedullin (MRproADM) was determined using group comparisons and multivariable analyses. RESULTS: Among 418 participants (58% male, median age 64 years, FEV1 59.6% predicted), vertebral fractures in TH12 were found in 76 patients (18.1%). Compared to patients without fractures, these had elevated serum levels (p ≤ 0.005) of MRproANP and MRproADM. Using optimal cut-off values in multiple logistic regression analyses, MRproANP levels ≥ 65 nmol/l (OR 2.34; p = 0.011) and age (p = 0.009) were the only significant predictors of fractures after adjustment for sex, BMI, smoking status, FEV1% predicted, SGRQ Activity score, daily physical activity, oral corticosteroids, the diagnosis of cardiac disease, and renal impairment. Correspondingly, MRproANP (p < 0.001), age (p = 0.055), SGRQ Activity score (p = 0.061) and active smoking (p = 0.025) were associated with TH12 vertebral density. INTERPRETATION: MRproANP was a marker for osteoporotic vertebral fractures in our COPD patients from the COSYCONET cohort. Its association with reduced vertebral BMD on CT and its known modulating effects on fluid and ion balance are suggestive of direct effects on bone mineralization. TRIAL REGISTRATION: ClinicalTrials.gov NCT01245933, Date of registration: 18 November 2010.

Influence of serum uric acid on bone and fracture risk in postmenopausal women.

AIMS: Uric acid has been associated with several metabolic conditions, including bone diseases. Our objective here was to consider the relationship between serum uric acid levels and various bone parameters (bone mineral density, ultrasonographic parameters, vitamin D, PTH and serum calcium), as well as the prevalence and risk of fragility fracture. METHODS: An observational and cross-sectional study carried out on 679 postmenopausal women, classified into 3 groups according to their serum uric acid levels, in whom bone densitometry, calcaneus ultrasounds, PTH, vitamin D and serum calcium analysis were done. Bone fractures were collected through the clinical history and lateral spinal X-ray. RESULTS: Higher uric acid levels were found in women with older age, high BMI, diabetes, and high blood pressure. Higher levels of PTH and serum calcium were also observed, but did not effect on vitamin D. Serum uric acid was positively related to densitometric and ultrasonic parameters and negatively associated with vertebral fractures. CONCLUSIONS: In the population of postmenopausal women studied, sUA levels were correlated with BMD, BUA, and QUI-Stiffness, and this correlation was independent of age and BMI. In addition, sUA was associated with a decrease in vertebral fractures. These results imply a beneficial influence of sUA on bone metabolism, with both a quantitative and qualitative positive effect, reflected in the lower prevalence of vertebral fractures.

[Correlation between serum HDL/LDL and t-PINP /ß-CTX and osteoporotic vertebral fractures in elderly women].

OBJECTIVE: To explore high density lipoprotein (HDL)/low density lipoprotein (LDL) and total typeⅠcollagen amino terminal extender peptide (t-PINP)/ C-terminal peptide of typeⅠcollagen ß special sequence(ß-CTX)and risk of osteoporosis vertebral fractures (OPVFs) in elderly women. METHODS: The clinical data of 446 female OPVFs patients aged above 60 years old from January 2019 to December 2020 were retrospectively analyzed. According to whether or not fracture, patients were divided into non-fracture group (186 patients) and fracture group(260 patients). Univariate analysis was performed to analysis age, body mass index(BMI), N-terminal mioldle molecular fragment of osteocalcin, N-MID OC), t-PINP, ß-CTX, 25-hydroxyvitamin D[25-(OH) VitD], blood sugar (Glu), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), Ca, P, Mg, urea (UREA), creatinine (Cr) and Cystatin C(CysC), and correlation between OPVFs and the above indexes and lipid, bone metabolism indexes between two groups;Logistic regression was performed to analyze risk factors and stratification relationship between vertebral fracture and HDL/LDL, t-PINP/ß-CTX. Logistic regression was used to analyze risk factors and stratification relationship between OPVFs and HDL/LDL, t-PINP/ß-CTX. RESULTS: There were no significant difference in age and BMI between non-fracture group and fracture group (P>0.05). Compared with non-fracture group, contents of HDL, t-PINP/ß-CTX and HDL/LDL in fracture group were decreased, and contents of ß-CTX were increased (P<0.05). OPVFs was positively correlated with ß-CTX (r=0.110, P<0.05), and negatively correlated with HDL, HDL/LDL and t-PINP/ß-CTX (r=-0.157, -0.175, -0.181, P<0.05). HDL and HDL/LDL were negatively correlated with ß-CTX (r=-0.22, -0.12, P<0.05) and t-PINP (r=-0.13, -0.10, P<0.05). 25-(OH) VitD was positively correlated with TC and HDL (r=0.11, 0.18, P<0.05). HDL/LDL was positively correlated with t-PINP/ß-CTX(r=0.11, P=0.02). t-PINP/ß-CTX[OR=0.998, 95%CI(0.997, 1.000), P<0.05], HDL/LDL[OR=0.228, 95%CI(0.104, 0.499), P<0.01] were risk factors for vertebral fracture. The lower levels between two tristratified indicators, the higher the vertebral fracture rate. The risk of fracture was 2.5 and 2 times higher in the lowest stratum than in the highest stratum, with an adjusted OR was[2.112, 95%CI(1.310, 3.404)] and [2.331, 95%CI(1.453, 3.739)], respectively. CONCLUSION: Serum low HDL/LDL and t-PINP /ß-CTX are independent risk factors for OPVF in elderly women, and have good predictive value for OPVF risk.

Serum branched-chain amino acid levels are associated with fracture risk in Japanese women.

AIM: Branched-chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. METHODS: During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan-Meier analyses were conducted to examine time-dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. RESULTS: The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. CONCLUSIONS: Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; 24: 603-608.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

PURPOSE: Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. METHODS: We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9 years) with low serum IGF-1 (median value 52.4 ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. RESULTS: Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0 ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). CONCLUSION: Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0 ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

Risk factors for hip and vertebral fractures in chronic kidney disease: the CRIC study.

Fracture risk is high in chronic kidney disease (CKD) and underlying pathophysiology and risk factors may differ from the general population. In a cohort study of 3939 participants in the chronic renal insufficiency cohort (CRIC), we used Cox regression to test associations of putative risk factors with the composite of first hip or vertebral fracture assessed using hospital discharge codes. Mean age was 58 years, 45% were female, 42% were Black, and 13% were Hispanic. There were 82 hip and 24 vertebral fractures over a mean (SD) 11.1 (4.8) years (2.4 events per 1000 person-years [95% CI: 2.0, 2.9]). Measured at baseline, diabetes, lower body mass index (BMI), steroid use, proteinuria, and elevated parathyroid hormone (PTH) were each associated with fracture risk after adjusting for covariates. Lower time-updated estimated glomerular filtration rate (eGFR) was associated with fractures (HR 1.20 per 10 mL/min/1.73m2 lower eGFR; 95% CI: 1.04, 1.38) as were lower time-updated serum calcium and bicarbonate concentrations. Among time-updated categories of kidney function, hazard ratios (95% CI) for incident fracture were 4.53 (1.77, 11.60) for kidney failure treated with dialysis and 2.48 (0.86, 7.14) for post-kidney transplantation, compared with eGFR ≥60. Proton pump inhibitor use, dietary calcium intake, measures of vitamin D status, serum phosphate, urine calcium and phosphate, and plasma fibroblast growth factor-23 were not associated with fracture risk. In conclusion, lower eGFR in CKD is associated with higher fracture risk, which was highest in kidney failure. Diabetes, lower BMI, steroid use, proteinuria, higher serum concentrations of PTH, and lower calcium and bicarbonate concentrations were associated with fractures and may be modifiable risk factors.

People with chronic kidney disease are at high risk of fractures. Our research assessed the relationship between several patient characteristics and the risk of fractures in 3939 patients with chronic kidney disease. We found that the following characteristics were associated with a higher risk of a hip or spine fracture: having diabetes, lower body mass index, use of steroid-containing medications, lower kidney filtration rate ("eGFR"), higher amounts of protein spilled in the urine, lower calcium and bicarbonate levels, and higher parathyroid hormone levels. Future studies should assess if improving these characteristics decreases the risk of fractures in patients with chronic kidney disease.

Plasma D-Dimer Levels Can Provide Useful Diagnostic Information on Acute Vertebral Compression Fractures in Patients with Low Back Pain in the Emergency Room.

BACKGROUND: Patients with acute vertebral compression fractures (aVCFs) are frequently transferred to an emergency department by ambulance. The most useful imaging modality is magnetic resonance imaging (MRI); however, which patients should be prioritized for MRI evaluation may be unclear. The aim of this study was to evaluate plasma D-dimer levels as a biomarker for aVCFs. METHODS: This retrospective cohort study included patients with low back pain in the emergency department between November 2017 and October 2020. Patients with infections, patients with coagulation disorders, and patients without D-dimer level measurements were excluded. The presence of an aVCF was detected with MRI. Blood samples were collected for routine blood tests. The predictive factors for aVCFs were evaluated with univariate and multivariable logistic regression analyses. RESULTS: Overall, 191 consecutive MRI evaluations were ordered. After exclusions, 101 patients were reviewed. Based on MRI, 65 (64.4%) patients were diagnosed with aVCF. The presence of aVCF was significantly correlated with age (odds ratio [OR] = 1.052, 95% confidence interval [CI] 1.018-1.191), an old vertebral compression fracture (OR = 3.290, 95% CI 1.342-8.075), hemoglobin (OR = 0.699, 95% CI 0.535-0.912), and D-dimer levels (OR = 1.829, 95% CI 1.260-2.656). Results from a multivariable logistic regression analysis showed that D-dimer levels (OR = 1.642, 95% CI 1.188-2.228) remained a significant risk factor for the presence of aVCFs after adjustment for potential confounders. CONCLUSIONS: Plasma D-dimer levels can provide useful diagnostic information about whether an aVCF is present.

The Impact of D-Dimer on Postoperative Deep Vein Thrombosis in Patients with Thoracolumbar Fracture Caused by High-Energy Injuries.

OBJECTIVE: To investigate the dynamic variation of D-dimer and to evaluate the efficacy and accuracy of D-dimer level in patients with thoracolumbar fractures caused by high-energy injuries. METHODS: A total of 121 patients with thoracolumbar fractures caused by high-energy injuries were retrospectively identified and included in this study. There were 83 males and 38 females, with an average age of 48.6 ± 11.2 years. All patients were treated with either screw fixation surgery or decompression fixation surgery. The D-dimer levels were measured 1 day before surgery and on the first, third, and fifth days after surgery. The dynamic variation of D-dimer and the effects of risk factors on D-dimer levels were analysed. A receiver operating characteristic (ROC) curve analysis was performed and the appropriate D-dimer cut-off level was determined for deep vein thrombosis (DVT) screening. RESULTS: Due to a trough on the third day, D-dimer levels grew in an unsustainable manner following surgery (P < 0.001). Patients with the operation time >120 min (P = 0.009) and those with an American Spinal Injury Association (ASIA) score A-C (P < 0.001) had higher D-dimer levels. The area under the curve of D-dimer was the greatest on the third day. Applying stratified cut-off values did not change the sensitivity, specificity and negative predictive value in the group with an operation time >120 min, and ASIA score A-C group. CONCLUSIONS: D-dimer levels elevated with fluctuation in patients with thoracolumbar fractures caused by high-energy injuries after surgery. Both operation time and ASIA score had an impact on D-dimer levels. Regarding DVT diagnoses, the diagnostic value of D-dimer was highest on the third day postoperatively, and stratified cut-off values by these two factors did not show better diagnostic efficacy compared with a collective one.

Serum calcium-phosphorus product for predicting the risk of osteoporotic vertebral compression fractures in elderly patients: a retrospective observational study.

BACKGROUND: This study retrospectively analyzed and evaluated the potential correlations of serum calcium, serum phosphorus, and calcium-phosphorus product (Ca-P product) with the incidence of osteoporotic vertebral compression fractures (OVCFs), with the aim of exploring whether the Ca-P product can be used as a serological indicator to predict the risk of OVCFs. METHODS: This study randomly enrolled 400 elderly patients in our hospital with OVCFs and 400 patients with hip and knee arthroplasty due to femoral head necrosis or osteoarthritis from August 2013 to April 2021. Age, sex, past medical history, and admission biochemical indicators, including albumin, blood urea nitrogen, serum creatinine, serum calcium and serum phosphorus, were collected for statistical analysis. RESULTS: Albumin, serum calcium, serum phosphorus, Ca-P product, corrected serum calcium and corrected Ca-P product were lower in the OVCF group than in the non-OVCF group (P < 0.05). Multivariate logistic regression analysis showed that low values of serum calcium, serum phosphorus, Ca-P product, corrected blood calcium, and corrected Ca-P product can all be risk factors for OVCF. The ROC curve showed that the Ca-P product and corrected Ca-P product were effective in predicting the risk of OVCFs. The predictive value of the Ca-P product was the best; the cutoff point was 29.88, the sensitivity was 0.72 and the specificity was 0.62. The cutoff point of the corrected Ca-P product was 30.50, the sensitivity was 0.74, and the specificity was 0.62. CONCLUSION: The Ca-P product and corrected Ca-P product can be used as serological indicators to predict the risk of OVCFs in elderly individuals. Early clinical interventions targeting this risk factor can further reduce the risk of OVCFs. Also, timely and regular testing of the serum calcium and phosphorus level is recommended and encouraged for this group of people.

Diagnostic Performance of the Caprini Risk Assessment Model Combined With D-Dimer for Preoperative Deep Vein Thrombosis in Patients With Thoracolumbar Fractures Caused by High-Energy Injuries.

OBJECTIVE: To assess the validity of the Caprini risk assessment model (RAM) in risk stratification for deep vein thrombosis (DVT) and to investigate the diagnostic value of Caprini score combined with D-dimer in predicting DVT. METHODS: This study involved 429 patients with thoracolumbar fractures caused by high-energy injuries between October 2016 and November 2019. All patients were treated surgically and had a mean age of 45.3 ± 11.4 years. Patients were risk-stratified using the 2013 Caprini RAM. Mechanical and chemical prophylaxis were used for DVT. Duplex ultrasound of both lower extremities was performed before surgery. RESULTS: Of the 429 patients, 62 (14.45%) developed DVT. The incidence of preoperative DVT was correlated with Caprini score according to risk stratification(χ2 = 117.4, P < 0.001). Based on the original Caprini RAM, all the patients scored in the highest risk category (score ≥5). Further substratification showed that the majority (277 of 429, 64.57%) of the patients were in the Caprini score range 7-8 and the risk of preoperative DVT was significantly higher among patients with Caprini score >10. The area under the receiver operating characteristic curve of Caprini score and D-dimer was 0.816 and 0.769 when Caprini score >8 or D-dimer >1.81mg/L was considered the criterion of predicting the risk of DVT. When combining the 2 variables, the area under the ROC curve can increase to 0.846. CONCLUSIONS: The Caprini RAM is an effective and reliable DVT risk stratification tool in patients with thoracolumbar fractures caused by high-energy injuries. Caprini score >8 or D-dimer >1.81 mg/L may predict the occurrence of preoperative DVT and the Caprini score combined with D-dimer exhibit better diagnostic performance.

The Vessels-Bone Axis: Iliac Artery Calcifications, Vertebral Fractures and Vitamin K from VIKI Study.

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as >20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL; p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL; p < 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.

The fibrinogen levels on admission is a predictive marker of the contrast extravasation on enhanced computed tomography in sacral fracture.

ABSTRACT: Sacral fracture is the most frequent posterior injury among unstable pelvic ring fractures and is prone to massive hemorrhage and hemodynamic instability. Contrast extravasation (CE) on computed tomography (CT) is widely used as an indicator of significant arterial bleeding. However, while CE is effective to detect significant arterial bleeding but negative result cannot completely rule out massive bleeding. Therefore, additional factors help to compensate CE for the prediction of early hemodynamically unstable condition.We evaluated the risk factors that predict CE on enhanced computed CT in patients with sacral fractures. Patients were classified into 2 groups: CE positive on enhanced CT of the pelvis [CE(+)] and CE negative [CE(-)]. We compared age, sex, injury severity score (ISS), systolic blood pressure (sBP), type of sacral fracture based on Denis classification, platelet (PLT), base excess, lactate, prothrombin time-international normalized ratio, hemoglobin (Hb), activated partial thromboplastin time, D-dimer, and fibrinogen between the 2 groups.A total of 82 patients were treated for sacral fracture, of whom 69 patients were enrolled. There were 17 patients (10 men and 7 women) in CE(+) and 52 patients (28 men and 24 women) in CE(-). Age, ISS, and blood transfusion within 24 hours were significantly higher in the CE(+) group than in the CE(-) group (P = .023, P < .001, P < .001). sBP, Hb, PLT, fibrinogen were significantly lower in the CE(+) group than in the CE(-) group (P < .001, P < .001, P < .001, P < .001). D-dimer and lactate were higher in the CE(+) group than in the CE(-) group (P = .036, P < .001) with significant differences. On multivariate analysis, the level of fibrinogen was an independent predictor of CE(+). The area under the curve value for fibrinogen was 0.88, and the optimal cut-off value for prediction was 199 mg/dL.The fibrinogen levels on admission can predict contrast extravasation on enhanced CT in patients with sacral fractures. The optimal cut-off value of fibrinogen for CE(+) prediction in sacral fracture was 199 mg/dL. The use of fibrinogen to predict CE(+) could lead to prompt and effective treatment of active arterial hemorrhage in sacral fracture.

Efficacy of denosumab co-administered with vitamin D and Ca by baseline vitamin D status.

INTRODUCTION: In anti-osteoporosis drug trials, vitamin D and calcium (Ca) are common supplements; however, the optimal dose of each is unclear. Using data from the randomized, double-blind, placebo-controlled DIRECT trial, we assessed whether baseline serum 25-hydroxy vitamin D (25[OH]D) level influences the efficacy of denosumab co-administered with vitamin D and Ca. MATERIALS AND METHODS: In this prespecified sub-analysis, subjects with primary osteoporosis who received denosumab or placebo, plus vitamin D (≥ 400 IU/day) and Ca (≥ 600 mg/day), were classified as 25(OH)D deficient (< 20 ng/mL), insufficient (≥ 20 to < 30 ng/mL), and sufficient (≥ 30 ng/mL). Study endpoints included absolute serum 25(OH)D level at baseline, 12 months, and 24 months; change in serum 25(OH)D and bone mineral density (BMD) status from baseline; and incidence of new vertebral fractures at 24 months. RESULTS: In 475 denosumab-treated and 481 placebo-treated subjects, proportions with deficient/insufficient/sufficient 25(OH)D at baseline were 53.1%/37.1%/9.9% and 50.9%/42.0%/7.1%, respectively. Supplementation significantly increased mean serum 25(OH)D levels; at 24 months, mean levels were > 30 ng/mL (sufficient) in both treatment groups. Increase in BMD over time was higher in the denosumab group vs. placebo group in all three vitamin D status groups. At month 24, denosumab-treated subjects with deficient/insufficient baseline 25(OH)D had a significantly lower risk of new vertebral fracture vs. placebo-treated subjects. CONCLUSION: Among DIRECT trial subjects supplemented with ≥ 400 IU/day of vitamin D and ≥ 600 mg/day of Ca, baseline 25(OH)D sufficiency may not influence the efficacy of denosumab in increasing BMD or preventing vertebral fractures.

Effect of changes in serum levels of endogenous hydrogen sulfide on fracture healing: Study protocol clinical trial (SPIRIT compliant).

BACKGROUND: Fracture is a common disease; many factors affect fracture healing. Recent studies have confirmed that hydrogen sulfide (H2S) plays an essential role in bone formation, but most of these studies are drawing conclusions based on animal experiment; whether H2S could promote fracture healing in patients is still unclear. We aim to investigate the change of serum H2S in fracture patients, and analyze its effort on fracture healing. METHODS: This is a single-center, prospective cohort study. Patients with spinal or limb fracture will be recruited. Patient's serum and urine will be collected at baseline for examination (serum H2S, ß-CTX, OC, PINP, 25-OH-VitD3, S-CTX, urinary calcium, and urinary creatinine). All patients will be followed-up for 24 months in outpatients settings, the image of X-ray or CT will be reviewed and fracture healing will be judged by 2 experienced orthopedic physicians. The difference in serum parameters especially H2S will be compared between patients with fracture healed within 9 months and those with fracture unhealed at 9 months. DISCUSSION: Results of the trial could provide insight into influence of H2S on fracture healing. ETHICS AND DISSEMINATION: The study was approved by the ethics committee of School of Medicine UESTC & Sichuan Provincial People's Hospital Ethics Committee. All the participants will be asked to provide written informed consent before data collection. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conferences.

Vertebral Fractures in Type 2 Diabetes Patients: Utility of Trabecular Bone Score and Relationship With Serum Bone Turnover Biomarkers.

BACKGROUND: Patients with type 2 diabetes (T2D) have an increased risk for vertebral fracture (VF). The aim of this study is to determine the utility of trabecular bone score (TBS) in T2D patients with VF and the relationship of TBS with serum bone turnover biomarkers (SBTBs). METHODOLOGY: Postmenopausal T2D female patients were prospectively enrolled. All patients received: (1) dual-energy X-ray absorptiometry exam for bone mineral density (BMD), T-score, and TBS values; (2) lateral lumbar spine radiographs for VF assessment; and (3) SBTBs: bone specific alkaline phosphatase and Beta-C-Terminal telopeptides. BMD, T-score, TBS, and SBTBs were tested for association with VF. RESULTS: The study included 285 T2D patients (mean age = 61.1 years) and 32 patients had VF (11.2%). TBS had the strongest association with VF in T2D patients (area under curve 0.775). The TBS cutoff values for VF are 1.279 in T-score ≥1 and 1.236 in T-score <-1. In patients without VF, all sites of BMD and TBS are significantly associated with SBTBs, but in patients with VF, no associations are found between SBTBs and all sites of BMD and TBS. CONCLUSIONS: TBS can assess bone quality in the spine. The low TBS cutoff values for T2D patients with VF imply T2D does impair bone quality. Thus, TBS should be incorporated in VF risk assessment in T2D patients. In addition, a dissociated relationship between BMD and TBS with SBTBs represents imbalanced bone turnover rate and results in bone fragility and VF.

Higher Serum Uric Acid is a Risk Factor of Vertebral Fractures in Postmenopausal Women with Type 2 Diabetes Mellitus.

PURPOSE: Serum uric acid (UA) level may affect bone metabolism because it has an anti-oxidative effect. However, whether serum UA level is associated with a fracture risk in type 2 diabetes mellitus (T2DM) is unclear. We thus aimed to clarify the association between serum UA and bone parameters in T2DM. METHODS: We conducted a cross-sectional study to investigate the association of serum UA with bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), bone turnover markers such as osteocalcin and urine type I collagen cross-linked N-telopeptide (uNTX), and the prevalence of vertebral fractures (VF) in 356 postmenopausal women and 512 men with T2DM. RESULTS: Multiple regression analyses adjusted for age, duration of diabetes, hemoglobin A1c, body mass index and log (serum creatinine) showed that serum UA level was significantly and negatively associated with uNTX in postmenopausal women with T2DM, whereas it was not associated with osteocalcin or BMD at each site. In men, serum UA was not associated with BMD or bone turnover markers. Because postmenopausal women with VF were significantly older and had longer duration of diabetes, higher serum creatinine level and lower BMD than those without it, logistic regression analyses adjusted for these confounding factors were performed. Higher serum UA level was significantly associated with the presence of VF. CONCLUSIONS: The present study showed that higher serum UA is a risk factor for VF independently of BMD in postmenopausal women with T2DM.

Evaluating RANKL and OPG levels in patients with Duchenne muscular dystrophy.

RANKL-OPG should be explored in DMD patients to potentially provide targeted therapy. We quantified RANKL and OPG levels in DMD patients compared with controls. RANKL, OPG, and RANKL:OPG significantly declined with age in DMD patients suggesting some bone turnover markers are difficult to assess or use as therapeutic indicators. INTRODUCTION: Osteoporosis in Duchenne muscular dystrophy (DMD) is multi-factorial in nature with high prevalence of fractures. RANKL-OPG should be explored to potentially provide targeted therapy for these patients. We quantified RANKL, OPG, and RANKL:OPG levels in DMD patients compared with controls and analyzed the influence of age, glucocorticoid use, ambulatory status, bone density, and fracture history. METHODS: DMD patients were enrolled at CHLA. Controls were recruited from general pediatric clinic and in collaboration with samples from a previously completed study. Free soluble RANKL and OPG levels were quantified using a sandwich ELISA. RESULTS: Fifty DMD patients and 50 controls were enrolled. DMD patients had a significant decline in RANKL, OPG, and RANKL:OPG with age (p = < 0.0001, p = 0.026, and p = 0.002, respectively) while healthy controls showed no significant change. RANKL trended lower in patients on glucocorticoids (p = 0.05), attributed to the significantly older age in the treatment group. RANKL and RANKL:OPG levels were significantly lower in the non-ambulatory group compared with the ambulatory group (p = 0.010 and 0.036 respectively), again likely due to their older age. There was no correlation of RANKL, OPG, or RANKL:OPG with DXA Z-score or presence of vertebral fractures. CONCLUSION: There was significant decline in RANKL, OPG, and RANKL:OPG with age in DMD patients compared with controls, potentially due to disease severity or worsening osteoblastic function. This suggests some bone turnover markers may be difficult to assess or use as therapeutic indicators in DMD patients. Larger studies are needed to evaluate the role of RANKL-OPG in DMD patients to provide better targeted therapy.