Development and evaluation of nomograms for predicting osteoarthritis progression based on MRI cartilage parameters: data from the FNIH OA biomarkers Consortium.

BACKGROUND: Osteoarthritis (OA) is a leading cause of disability worldwide. However, the existing methods for evaluating OA patients do not provide enough comprehensive information to make reliable predictions of OA progression. This retrospective study aimed to develop prediction nomograms based on MRI cartilage that can predict disease progression of OA. METHODS: A total of 600 subjects with mild-to-moderate osteoarthritis from the Foundation for National Institute of Health (FNIH) project of osteoarthritis initiative (OAI). The MRI cartilage parameters of the knee at baseline were measured, and the changes in cartilage parameters at 12- and 24-month follow-up were calculated. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extract the valuable characteristic parameters at different time points including cartilage thickness, cartilage volume, subchondral bone exposure area and uniform cartilage thickness in different sub regions of the knee, and the MRI cartilage parameters score0, scoreΔ12, and scoreΔ24 at baseline, 12 months, and 24 months were constructed. ScoreΔ12, and scoreΔ24 represent changes between 12 M vs. baseline, and 24 M vs. baseline, respectively. Logistic regression analysis was used to construct the nomogram0, nomogramΔ12, and nomogramΔ24, including MRI-based score and risk factors. The area under curve (AUC) was used to evaluate the differentiation of nomograms in disease progression and subgroup analysis. The calibration curve and Hosmer-Lemeshow (H-L) test were used to verify the calibration of the nomograms. Clinical usefulness of each prediction nomogram was verified by decision curve analysis (DCA). The nomograms with predictive efficacy were analyzed by secondary analysis. Internal verification was assessed using bootstrapping validation. RESULTS: Each nomogram included cartilage score, KL grade, WOMAC pain score, WOMAC disability score, and minimum joint space width. The AUC of nomogram0, nomogramΔ12, and nomogramΔ24 in predicing the progression of radiology and pain were 0.69, 0.64, and 0.71, respectively. All three nomograms had good calibration. Analysis by DCA showed that the clinical effectiveness of nomogramΔ24 was higher than others. Secondary analysis showed that nomogram0 and nomogramΔ24 were more capable of predicting OA radiologic progression than pain progression. CONCLUSION: Nomograms based on MRI cartilage change were useful for predicting the progression of mild to moderate OA.

Novel nomogram for predicting the progression of osteoarthritis based on 3D-MRI bone shape: data from the FNIH OA biomarkers consortium.

BACKGROUND: Osteoarthritis(OA) is a major source of pain, disability, and socioeconomic cost in worldwide. However, there is no effective means for the early diagnosis of OA, nor can it accurately predict the progress of OA. To develop and validate a novel nomogram to predict the radiographic progression of mild to moderate OA based on three-dimensional(3D)-MRI bone shape and bone shape change during 24 months. METHOD: Analysis of publicly available data from the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium. Radiographic progression was defined as minimum radiographic narrowing of the medial tibiofemoral joint space of ≥ 0.7 mm from baseline at 24, 36, or 48 months. There were 297 knees with radiographic progression and 303 without. The bone shapes of the tibia, femur, and patella were evaluated by 3D-MRI at the baseline and at 24 months. Two nomograms were separately established by multivariate logistic regression analysis using clinical risk factors, bone shape at baseline (nomogram 0), or bone shape change at 24 months (nomogram Δ24). The discrimination, calibration, and usefulness were selected to evaluate the nomograms. RESULTS: There were significant differences between groups in baseline Kellgren-Lawrence (KL) grade, gender, age, and tibia, femur, and patella shape. The areas under the curve (AUC) of nomogram 0 and nomogram Δ24 were 0.66 and 0.75 (p < 0.05), with accuracy of 0.62 and 0.69, respectively. Both nomograms had good calibration. The decision curve analysis ( DCA) showed that nomogram Δ24 had greater clinical usefulness than nomogram 0 when the risk threshold ranged from 0.04 to 0.86. CONCLUSIONS: Nomograms based on 3D-MRI bone shape change were useful for predicting the radiographic progression of mild to moderate OA.

Defining matrix Gla protein expression in the Dunkin-Hartley guinea pig model of spontaneous osteoarthritis.

BACKGROUND: Matrix Gla (γ-carboxyglutamate) protein (MGP) is considered a strong inhibitor of ectopic calcification, and it has been associated with OA severity, although not conclusively. We utilized male Dunkin-Hartley (DH) guinea pigs to investigate the expression of MGP throughout aging and disease pathogenesis in a spontaneous model. METHOD: Twenty-five male DH guinea pigs were obtained and nurtured to several timepoints, and then randomly and equally divided by age into five subgroups (1-, 3-, 6-, 9-, and 12-months, with the 1-month group as the reference group). DH guinea pigs in each group were euthanized at the designated month-age and the left or right medial tibial plateaus cartilages were randomly excised. OA severity was described by modified Mankin Score (MMS) at microscopy (Safranin O/Fast Green stain). Proteomic evaluation using isobaric tags for relative and absolute quantification (iTRAQ) was performed to validate the age-related changes in the MGP profiles, and immunohistochemistry (IHC) methods were applied for semi-quantitative determination of MGP expression in articular cartilage. RESULTS: The histopathologic findings validated the increasing severity of cartilage degeneration with age in the DH guinea pigs. The MMS showed significant, stepwise (every adjacent comparison P < 0.05) disease progression with month-age. The iTRAQ indicated that MGP levels increased significantly with advancing age (P < 0.05), as supported by the IHC result (P < 0.05). CONCLUSION: Increased expression of MGP in male DH guinea pigs was present throughout aging and disease progression and may be link to increased OA severity. Further studies are needed to investigate and confirm the association between MGP levels and OA severity.

rs10865331 in 2p15 increases susceptibility to ankylosing spondylitis: a HuGE review and meta-analysis.

OBJECTIVES: 2p15 polymorphisms have been reported to increase ankylosing spondylitis (AS) susceptibility in several studies; however, when it comes to whether and how much of this risk exists, the results are inconclusive. The aim of this study is to investigate the correlation between rs10865331 in 2p15 and the risk of AS. METHODS: We conducted a HuGE review and meta-analysis of studies published through September 2019. Studies were identified in PubMed, Scopus, HuGE Navigator, Embase, and Web of Science databases. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk estimations were calculated. Sensitivity analysis, subgroup analysis and analysis for potential publication bias were also estimated. RESULTS: Eleven studies with 18555 AS patients and 43777 unrelated healthy individuals, each with a score greater than 6 on the Newcastle-Ottawa Scale (NOS), that investigated the association between rs10865331 in 2p15 and AS were included in our meta-analysis. Data were classified into the genotype analysis cohort, the OR-value cohort, and the pooled analysis cohort, and then a meta-analysis was performed. The OR value of the recessive model in the genotype analysis cohort was 1.376 (95% CI=1.204-1.572, p<0.001, I²=56.30%), and the OR value of the pooled analysis cohort was 1.295 (95% CI=1.228-1.365, p<0.001, I²=73.70%). These findings suggest that individual who carries this single nucleotide polymorphism (SNP) are about 30% more susceptible to developing AS. CONCLUSIONS: Our results suggest that rs10865331 is associated with a significantly higher risk of AS in all race and country subgroups that we have evaluated. Therefore, rs10865331 may be a useful genetic marker for predicting AS susceptibility. However, further studies are needed to confirm our findings.

Effects of ß2 Integrins on Osteoclasts, Macrophages, Chondrocytes, and Synovial Fibroblasts in Osteoarthritis.

ß2 integrins are transmembrane receptors that exist widely in human immune cells and participate in pathological processes such as chronic inflammation, thrombosis, and malignant tumor formation. They mainly mediate intercellular adhesion, coordinate the ingestion of extracellular matrix components, and regulate cytoskeleton formation, thereby regulating cell signaling. Osteoarthritis (OA) is a chronic joint disease that causes joint pain and increases disease burden; it has a high prevalence among populations worldwide. Previous studies have reported that ß2 integrins are overexpressed in OA and may play an essential role in the occurrence of OA. The important roles of ß2 integrins in the maturation and differentiation of osteoclasts, the regulation of bone homeostasis, and the polarization and migration of macrophages have also been reported. The present review aims to highlight the role of ß2 integrins in OA pathogenesis and outline their potential for serving as therapeutic targets.

The association between statin use and osteoarthritis-related outcomes: An updated systematic review and meta-analysis.

Objective: Findings among studies evaluating the effect of statin use and OA development in a 2020 meta-analysis of data from 11 observational studies of statin use and osteoarthritis (OA) revealed controversial results. We aimed to determine the associations between statin use and OA-related outcomes in an updated meta-analysis. Methods: The protocol was registered with PROSPERO (CRD42020163983). A systematic literature retrieval was performed in the online databases, including PubMed, Cochrane Library, Embase, Web of Science, and Scopus, from inception to 1 June 2022, for clinical studies that compared the effects of statin users vs. nonusers on OA-related outcomes risks. Systematic reviews and meta-analyses were performed to estimate the correlations between statin use and OA-related outcomes. Tendency analysis was also used to estimate dose-response effects. The risk of bias was evaluated with the Newcastle-Ottawa scale. Results: We included 23 studies involving more than 6,000,000 participants. Statin use was associated with increased OA risk (OR 1.099 [95%CI 1.002-1.206, p = 0.045]). Higher statin doses had higher OA risk (simvastatin equivalent daily of >40 mg). OA and related surgery risks were significantly reduced in statin users using antihypertensive drugs (AHDs). No significant differences were seen in other outcomes. Conclusion: This meta-analysis inferred that statin use might be associated with increased OA development, especially at higher doses. The present study highlights the importance of recognizing potential OA risk in the population with long-term and/or high-dose statin use, especially in older populations. In addition, AHDs are associated with lower OA risk and fewer surgeries in hypertensive statin users. Due to limitations of heterogeneity and confounders, more rigorous studies are needed to define the correlations between statin use and OA-related outcomes.

[Research on the extracorporeal cytocompatibility of a composite of HA, carbon fiber and polyetheretherket-one].

The present research was to study the biocompatibility of a composite of hydroxyapatite (HA), carbon fiber (CF) and polyetheretherket-one (PEEK) by co-culturing with the osteoblasts in vitro. Cell relative growth (RGR) was used as a quantitative assessment for cytotoxicity of the biomaterials by CCK-8. The proliferation index of the co-cultured cells and ALP activity was measured to study the effect of PEEK-HA-CF composites. Morphological properties of the osteoblast cells in vitro were observed by scanning electro-microscopy (SEM). The PEEK-HA-CF materials have no cytotoxicity to osteoblasts. The proliferation index of PEEK-HA-CF was higher than that of Ti alloy group, but these was no significant difference compared to that of control group. The ALP activity was the highest on PEEK-HA-CF composites surface after 7 days. The osteoblast cells co-cultured with the PEEK-HA-CF composite were adhered well to the biomaterial as observed under the SEM. The results suggested that the PEEK-HA-CF composites had good biocompatibility in vitro and might be a novel orthopedic implanted material.

Meta-analysis showing that ERCC1 polymorphism is predictive of osteosarcoma prognosis.

To investigate correlations between excision repair cross-complementation group 1 (ERCC1) and 2 (ERCC2) polymorphisms and osteosarcoma prognosis, we conducted a meta-analysis of studies published through October 2016. Studies were identified in the PubMed, ScienceDirect, Springer, and Web of Science databases using preferred reporting items for systematic reviews and meta-analyses (PRISMA). Odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), tumor response (TR), and event-free survival (EFS) were estimated. Our meta-analysis included eleven studies in which four SNPs (ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and rs1799793) reportedly associated with osteosarcoma prognosis were investigated. Each of these studies scored > 6 on the Newcastle-Ottawa Scale (NOS). We found that only one SNP, ERCC1 rs11615, correlated with improved OS and TR. The HR of T vs. C for OS was 1.455 (T/C, 95% CI = 1.151-1.839, P = 0.002, I2 = 37.80%). The OR of T vs. C for good TR was 0.554 (T/C, 95% CI = 0.437-0.702, P < 0.001, I2 = 0%). Few significant outcome was observed in subgroup analyses stratified based on study characteristics with adjustments for potential confounders. Our results suggest that ERCC1 rs11615 CC is associated with a better clinical outcome. This suggests rs11615 may be a useful genetic marker for predicting osteosarcoma prognosis.

Analysis of imaging characteristics of primary malignant bone tumors in children.

The present study aimed to investigate the imaging characteristics of primary malignant bone tumors in children. The imaging results of 34 children with primary malignant bone tumors confirmed by histopathological diagnosis between March 2008 and January 2014 were retrospectively analyzed. In total, 25 patients had osteosarcoma, with radiography and computed tomography (CT) showing osteolytic bone destruction or/and osteoblastic bone sclerosis, an aggressive periosteal reaction, a soft-tissue mass and cancerous bone. The tumors appeared as mixed magnetic resonance imaging (MRI) signals that were inhomogeneously enhanced. A total of 5 patients presented with Ewing sarcoma, with radiography and CT showing invasive bone destruction and a soft-tissue mass. Of the 5 cases, 2 showed a laminar periosteal reaction. The tumors were shown to have mixed low signal on T1-weighted images (T1WI) and high signal on T2-weighted images (T2WI); 1 case showed marked inhomogeneous enhancement. Another 3 patients exhibited chondrosarcoma. Of these cases, 1 was adjacent to the cortex of the proximal tibia, and presented with local cortical bone destruction and a soft-tissue mass containing scattered punctate and amorphous calcifications. MRI revealed mixed low T1 signal and high T2 signals. Another case was located in the medullary cavity of the distal femur, with radiography revealing a localized periosteal reaction. The tumor appeared with mixed MRI signals, and with involvement of the epiphysis and epiphyseal plates. Radiography and CT of the third case showed bone destruction in the right pubic ramus, with patchy punctate, cambered calcifications in the soft-tissue mass. MRI of the soft-tissue mass revealed isointensity on T1WI and heterogeneous hyperintensity on T2WI. Ossifications and the septum appeared as low T1WI and T2WI. Of the 34 patients, 1 patient presented with lymphoma involving the T12, L1 and L2 vertebrae. CT showed vertebral bone destruction, a soft-tissue mass and a compression fracture of L1. MRI showed a soft-tissue mass with low T1 signal and high T2 signal and marked inhomogeneous enhancement. Overall, osteosarcoma was the most common primary malignant bone tumor, followed by Ewing sarcoma, chondrosarcoma and lymphoma. Osteoblastic or osteolytic bone destruction, an invasive periosteal reaction, soft-tissue masses, a tumor matrix and inhomogeneous enhancement were important imaging features of malignant bone tumors.

Changes in energy metabolism in the quadriceps femoris after a single bout of acute exhaustive swimming in rats: a ³¹P-magnetic resonance spectroscopy study.

BACKGROUND: Little is known about the value of (31)P-magnetic resonance spectroscopy ((31)P-MRS) in in vivo assessment of exhaustive exercise-induced injury in skeletal muscle. We aimed to evaluate the value of a (31)P-MRS study using the quadriceps femoris after a single bout of acute exhaustive swimming in rats, and the correlation between (31)P-MRS and histological changes. METHODS: Sixty male Sprague-Dawley rats were randomly assigned to control, half-exhaustive, and exhaustive exercise groups. (31)P-MRS of the quadriceps femoris of the right lower limb was performed immediately after swimming exercise to detect Pi, PCr, and ß-ATP. The Pi/PCr, Pi/ß-ATP, PCr/ß-ATP, and PCr/(PCr+Pi) were calculated and pH measured. Areas under the receiver operating characteristic curve (AUCs) were calculated to evaluate the diagnostic potential of (31)P-MRS in identifying and distinguishing the three groups. HE staining, electron microscopy and desmin immunostaining after imaging of the muscle were used as a reference standard. The correlation between (31)P-MRS and the mean absorbance (A value) of desmin staining were analyzed with the Pearson correlation test. RESULTS: Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) showed statistically significant intergroup differences (P < 0.05). AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.905, 0.848, 0.930, and 0.930 for the control and half-exhaustive groups, while sensitivity and specificity were 90%/85%, 95%/55%, 95%/80%, and 90%/85%, respectively. The AUCs of Pi, PCr, Pi/PCr and PCr/(PCr+Pi) were 0.995, 0.980, 1.000, and 1.000 for the control and exhaustive groups, while sensitivity and specificity were 95%/90%, 100%/90%, 100%/95%, and 100%/95%, respectively. The AUCs of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were 0.735, 0.865, 0.903, and 0.903 for the half-exhaustive and exhaustive groups, while sensitivity and specificity were 80%/60%, 90%/75%, 95%/65%, and 95%/70%, respectively. In the half-exhaustive group, some muscle fibers exhibited edema in HE staining, and the unclear Z-discs and the mitochondria with vacuolar degeneration under electron microscopy. Compared with the half-exhaustive group, muscle fiber edema was increased in the exhaustive group, and the Z-discs were broken and the mitochondria exhibited marked vacuolar degeneration under electron microscopy. There were significant difference in A values of desmin staining in the right vastus lateralis among the control, half-exhaustive, and exhaustive groups with 0.58 ± 0.06, 0.30 ± 0.04, and 0.21 ± 0.02, respectively (P < 0.05). Histological examination also showed injury-induced changes in the vastus lateralis among the different intensities groups. Statistically a moderate correlation between (31)P-MRS and desmin was observed, the correlation coefficients of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) were -0.706, 0.709, -0.726, and 0.791, respectively (P < 0.01). CONCLUSIONS: (31)P-MRS can effectively reflect the changes in energy metabolism in the skeletal muscle after a single bout of acute exhaustive swimming in rats. Based on the significant correlation between (31)P-MRS parameters and histological changes, the changes of Pi, PCr, Pi/PCr, and PCr/(PCr+Pi) can indirectly reflect the degree of exercise-induced injury.