Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study.

OBJECTIVES: To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA. METHODS: In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI). RESULTS: In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA. After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis. CONCLUSIONS: We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.

Effect of nutritional supplementation on bone mineral density in children with sickle cell disease: protocol for an open-label, randomised controlled clinical trial.

INTRODUCTION: Children with sickle cell disease show a significant decrease in bone mineral density, an increase in resting energy expenditure of more than 15%, a decrease in fat and lean mass as well as a significant increase in protein turnover, particularly in bone tissue. This study aims to evaluate the effectiveness of an increase in food intake on bone mineral density and the clinical and biological complications of paediatric sickle cell disease. METHODS AND ANALYSIS: The study is designed as an open-label randomised controlled clinical trial conducted in the Paediatrics Unit of the Orléans University Hospital Centre. Participants aged 3-16 years will be randomly divided into two groups: the intervention group will receive oral nutritional supplements (pharmacological nutritional hypercaloric products) while the control group will receive age-appropriate and gender-appropriate nutritional intake during 12 months. Total body less head bone mineral density will be measured at the beginning and the end of the trial. A rigorous nutritional follow-up by weekly 24 hours recall dietary assessment and planned contacts every 6 weeks will be carried out throughout the study. A school absenteeism questionnaire, intended to reflect the patient's school productivity, will be completed by participants and parents every 3 months. Blood samples of each patient of both groups will be stocked at the beginning and at the end of the trial, for future biological trial. Clinical and biological complications will be regularly monitored. ETHICS AND DISSEMINATION: The protocol has been approved by the French ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-Mer 2, Toulouse; approval no: 2-20-092 id9534). Children and their parents will give informed consent to participate in the study before taking part. Results will be disseminated through peer-reviewed journals or international academic conferences. TRIAL REGISTRATION NUMBER: NCT04754711.

Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study.

Fracture risk increases with lower areal bone mineral density (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) dual energy X-ray absorptiometry (DXA) which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8 years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3 months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

Performance of Radiological and Biochemical Biomarkers in Predicting Radio-Symptomatic Knee Osteoarthritis Progression.

Imaging biomarkers permit improved approaches to identify the most at-risk patients encountering knee osteoarthritis (KOA) progression. This study aimed to investigate the utility of trabecular bone texture (TBT) extracted from plain radiographs, associated with a set of clinical, biochemical, and radiographic data, as a predictor of long-term radiographic KOA progression. We used data from the Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium dataset. The reference model made use of baseline TBT parameters adjusted for clinical covariates and radiological scores. Several models based on a combination of baseline and 24-month TBT variations (TBT∆TBT) were developed using logistic regression and compared to those based on baseline-only TBT parameters. All models were adjusted for baseline clinical covariates, radiological scores, and biochemical descriptors. The best overall performances for the prediction of radio-symptomatic, radiographic, and symptomatic progression were achieved using TBT∆TBT parameters solely, with area under the ROC curve values of 0.658 (95% CI: 0.612-0.705), 0.752 (95% CI: 0.700-0.804), and 0.698 (95% CI: 0.641-0.756), respectively. Adding biochemical markers did not significantly improve the performance of the TBT∆TBT-based model. Additionally, when TBT values were taken from the entire subchondral bone rather than just the medial, lateral, or central compartments, better results were obtained.

Short-term variations in trabecular bone texture parameters associated to radio-clinical biomarkers improve the prediction of radiographic knee osteoarthritis progression.

The present study aims to examine whether the short-term variations in trabecular bone texture (TBT) parameters, combined with a targeted set of clinical and radiographic data, would improve the prediction of long-term radiographic knee osteoarthritis (KOA) progression. Longitudinal (baseline, 24 and 48-month) data, obtained from the Osteoarthritis Initiative cohort, were available for 1352 individuals, with preexisting OA (1 < Kellgren-Lawrence < 4) at baseline. KOA progression was defined as an increase in the medial joint space narrowing score from the 24-months to the 48-months control point. 16 regions of interest were automatically selected from each radiographic knee and analyzed using fractal dimension. Variations from baseline to 24 months in TBT descriptors as well as selected radiographic and clinical readings were calculated. Different logistic regression models were developed to evaluate the progression prediction performance when associating TBT variations with the selected clinical and radiographic readings. The most predictive model was mainly determined using the area under the receiver operating characteristic curve (AUC). The proposed prediction model including short-term variations in TBT parameters, associated with clinical covariates and radiographic scores, improved the capacity of predicting long-term radiographic KOA progression (AUC of 0.739), compared to models based solely on baseline values (AUC of 0.676, p-value < 0.008).

A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography.

Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using high-resolution peripheral quantitative compute tomography (HR-pQCT), to provide an alternative approach for patient-specific assessment of fracture risk. Using an international prospective cohort of older adults (n = 6802) we developed a tool to predict osteoporotic fracture risk, called µFRAC. The model was constructed using random survival forests, and input predictors included HR-pQCT parameters summarizing BMD and microarchitecture alongside clinical risk factors (sex, age, height, weight, and prior adulthood fracture) and femoral neck areal BMD (FN aBMD). The performance of µFRAC was compared to the Fracture Risk Assessment Tool (FRAX) and a reference model built using FN aBMD and clinical covariates. µFRAC was predictive of osteoporotic fracture (c-index = 0.673, p < 0.001), modestly outperforming FRAX and FN aBMD models (c-index = 0.617 and 0.636, respectively). Removal of FN aBMD and all clinical risk factors, except age, from µFRAC did not significantly impact its performance when estimating 5-year and 10-year fracture risk. The performance of µFRAC improved when only major osteoporotic fractures were considered (c-index = 0.733, p < 0.001). We developed a personalized fracture risk assessment tool based on HR-pQCT that may provide an alternative approach to current clinical methods by leveraging direct measures of bone density and structure. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Novel insights into the anatomy and histopathology of the sacroiliac joint and correlations with imaging signs of sacroiliitis in case of axial spondyloarthritis.

For a better understanding of the pathophysiology of spondyloarthropathy (SpA), a detailed anatomical description of the sacroiliac joint is required because sacroiliitis is the earliest and most common sign of SpA and an essential feature for the diagnosis of ankylosing spondylitis. Beyond the anatomy, the histopathology of sacroiliac entheses and immunological mechanisms involved in sacroiliitis are crucial for a better understanding of disease causation. In this narrative review, we discuss the core anatomical, histological, and immunohistological observations involved in the development of sacroiliitis, focusing particularly on imaging-based information associated with sacroiliitis. Finally, we try to answer the question of whether at the sacroiliac joint, enthesitis precedes synovitis and subchondral bone changes in SpA.

Effectiveness of Shiatsu on Fatigue in Patients with Axial Spondyloarthritis: Protocol for a Randomized Cross-Over Pilot Study.

INTRODUCTION: Spondyloarthritis (SpA) is a serious chronic inflammatory rheumatism implying different painful and crippling symptoms that require a multidisciplinary approach for the patient. Fatigue is one of the less well treated symptoms, even if its repercussion on everyday life is noticeable. Shiatsu is a Japanese preventive and well-being therapy that aims to promote better health. However, the effectiveness of shiatsu in SpA-associated fatigue has never been studied yet in a randomized study. METHODS AND ANALYSIS: We describe the design of SFASPA (Etude pilote randomisée en cross-over évaluant l'efficacité du Shiatsu sur la FAtigue des patients atteints de SPondyloarthrite Axiale), a single-center, randomized controlled cross-over trial with allocation of patients according to a ratio (1:1) evaluating the effectiveness of shiatsu in SpA-associated fatigue. The sponsor is the Regional Hospital of Orleans, France. The two groups of 60 patients each will receive three "active" shiatsu and three sham shiatsu treatments (120 patients, 720 shiatsu). The wash-out period between the active and the sham shiatsu treatments is 4 months. PLANNED OUTCOMES: The primary outcome is the percentage of patients responding to the FACIT-fatigue score. A response to fatigue is defined as an improvement, i.e., an increase of ≥ 4 points in the FACIT-fatigue score, which corresponds to the "minimum clinically important difference" (MCID). Differences in the evolution of activity and impact of the SpA will be assessed on several secondary outcomes. An important aim of this study is also to gather material for further trials with higher proof of evidence. TRIAL REGISTRATION: NCT05433168, date of registration, June 21st, 2022 (clinicaltrials.gov).

Radiographic Biomarkers for Knee Osteoarthritis: A Narrative Review.

Conventional radiography remains the most widely available imaging modality in clinical practice in knee osteoarthritis. Recent research has been carried out to develop novel radiographic biomarkers to establish the diagnosis and to monitor the progression of the disease. The growing number of publications on this topic over time highlights the necessity of a renewed review. Herein, we propose a narrative review of a selection of original full-text articles describing human studies on radiographic imaging biomarkers used for the prediction of knee osteoarthritis-related outcomes. To achieve this, a PubMed database search was used. A total of 24 studies were obtained and then classified based on three outcomes: (1) prediction of radiographic knee osteoarthritis incidence, (2) knee osteoarthritis progression and (3) knee arthroplasty risk. Results showed that numerous studies have reported the relevance of joint space narrowing score, Kellgren-Lawrence score and trabecular bone texture features as potential bioimaging markers in the prediction of the three outcomes. Performance results of reviewed prediction models were presented in terms of the area under the receiver operating characteristic curves. However, fair and valid comparisons of the models' performance were not possible due to the lack of a unique definition of each of the three outcomes.

Comparative performance of composite measures from two phase III clinical trials of ixekizumab in psoriatic arthritis.

BACKGROUND/OBJECTIVE: The aim of this study was to evaluate relative performance of composite measures in psoriatic arthritis and assess the impact of structural damage and functional disability on outcomes during ixekizumab treatment. METHODS: Data from SPIRIT-P1 and SPIRIT-P2 were analysed to evaluate the effect of ixekizumab on achievement of low disease activity (LDA) and remission with the minimal disease activity (MDA) and very low disease activity (VLDA) composite, Disease Activity index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score, GRAppa Composite ScorE and modified Composite Psoriatic Disease Activity Index (mCPDAI). Performance was compared by quantifying residual symptom burden and the impact of structural damage and functional disability. RESULTS: Significantly more ixekizumab-treated patients achieved treatment targets at week 24 versus placebo assessed with all composites. More patients achieved targets assessed by mCPDAI and DAPSA than other composites. Residual disease activity was similar between composites, but residual high patient-reported outcomes (PROs) and functional disability were more frequent when assessed with mCPDAI and DAPSA. Achievement of treatment targets was reduced by high baseline levels of structural damage and functional disability. CONCLUSION: Residual disease activity was similar in patients achieving treatment targets assessed with all composites, but residual high PROs and functional disability were more common when assessed with mCPDAI and DAPSA, most likely due to the absence/attenuated functional assessment in these composites. High baseline levels of structural damage and functional disability attenuated response rates with all composites, affecting MDA/VLDA most prominently; LDA may be the most appropriate target in these patients. TRIAL REGISTRATION NUMBER: NCT01695239.

Gene Expression and Chondrogenic Potential of Cartilage Cells: Osteoarthritis Grade Differences.

Recent data suggest that cells isolated from osteoarthritic (OA) cartilage express mesenchymal progenitor cell (MPC) markers that have the capacity to form hyaline-like cartilage tissue. Whether or not these cells are influenced by the severity of OA remains unexplored. Therefore, we analyzed MPC marker expression and chondrogenetic potential of cells from mild, moderate and severe OA tissue. Human osteoarthritic tibial plateaus were obtained from 25 patients undergoing total knee replacement. Each sample was classified as mild, moderate or severe OA according to OARSI scoring. mRNA expression levels of MPC markers-CD105, CD166, Notch 1, Sox9; mature chondrocyte markers-Aggrecan (Acan), Col II A1, hypertrophic chondrocyte and osteoarthritis-related markers-Col I A1, MMP-13 and ALPL were measured at the tissue level (day 0), after 2 weeks of in vitro expansion (day 14) and following chondrogenic in vitro re-differentiation (day 35). Pellet matrix composition after in vitro chondrogenesis of different OA-derived cells was tested for proteoglycans, collagen II and I by safranin O and immunofluorescence staining. Multiple MPC markers were found in OA cartilage resident tissue within a single OA joint with no significant difference between grades except for Notch1, which was higher in severe OA tissues. Expression levels of CD105 and Notch 1 were comparable between OA cartilage-derived cells of different disease grades and bone marrow mesenchymal stem cell (BM-MSC) line (healthy control). However, the MPC marker Sox 9 was conserved after in vitro expansion and significantly higher in OA cartilage-derived cells compared to its levels in the BM-MSC. The in vitro expansion of cartilage-derived cells resulted in enrichment while re-differentiation in reduction of MPC markers for all three analyzed grades. However, only moderate OA-derived cells after the in vitro chondrogenesis resulted in the formation of hyaline cartilage-like tissue. The latter tissue samples were also highly positive for collagen II and proteoglycans with no expression of osteoarthritis-related markers (collagen I, ALPL and MMP13). MPC marker expression did not differ between OA grades at the tissue level. Interestingly after in vitro re-differentiation, only moderate OA-derived cells showed the capacity to form hyaline cartilage-like tissue. These findings may have implications for clinical practice to understand the intrinsic repair capacity of articular cartilage in OA tissues and raises the possibility of these progenitor cells as a candidate for articular cartilage repair.

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

Proton pump inhibitors (PPIs) are an antacid drug often used in acid-related disorders. They decrease acid secretion in the stomach by blocking an enzyme called H+/K+ ATPase which controls acid production. Introduced to the market in 1989, their use has increased rapidly worldwide and they are now among the top 10 most prescribed drugs in the United States. As of 2015, the FDA has already approved six drugs of this class (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole and rabeprazole). Recently, the risks and benefits of long-term PPI use were questioned and many studies indicated that their use should be carefully considered, especially in young patients, whose treatment with these drugs could last many years. Even greater concerns have been raised about a potential positive association between PPIs and osteoporotic fracture risk including the hip, spine and wrist. Although based on observational studies, there is substantial evidence associating the long-term use of PPIs and fracture. This relationship is only partially admitted due to the lack of consistent effects of PPIs on bone mineral density loss. Therefore, this narrative review aimed to discuss the recent findings pertaining to the risk of osteoporotic fracture associated with PPIs, in particular prolonged use, and to call for further research to elucidate the mechanisms associated with this bone fragility.

French recommendations on the prevention and treatment of osteoporosis secondary to bariatric surgery.

INTRODUCTION: This article presents the initial recommendations of the Groupe de Recherche et d'Information sur les Ostéoporoses (Osteoporosis Research and Information Group [GRIO]) and the Société Française de Rhumatologie (French Rheumatology Society [SFR]) on the prevention and treatment of osteoporosis secondary to bariatric surgery. METHODS: The recommendations were produced by a working group comprising 4 expert rheumatologists, 3 medically qualified nutritionists, 2 obesity surgeons, 1 physical activity specialist, and 1 patient-association representative. RESULTS: The following generally recommended measures apply to all patients with an indication for bariatric surgery or who have already undergone bariatric surgery: normalize calcium and protein intake, attain a 25(OH) vitamin D concentration of between 30 and 60ng/mL; prevent the risk of falls, and introduce a suitable regimen of physical activity. An initial assessment of fracture risk should be routinely performed - ideally before the first bariatric surgery procedure - (i) in the case of RYGB and biliopancreatic diversion, regardless of age, (ii) in patients at high risk of fracture, regardless of age, and (iii) in all menopausal women and all men ≥ 50 years old, regardless of the type of bariatric surgical procedure. The fracture risk assessment is based on a determination of osteoporosis risk factors and bone mineral density measurements. Anti-osteoporosis treatment - zoledronic acid as the first line of treatment - is indicated for menopausal women and men ≥ 50 years old with (i) a history of severe fracture, regardless of T-score, (ii) a history of non-severe fracture and a T-score ≤ -1, and (iii) no history of fracture and a T-score ≤ -2. CONCLUSIONS: There is an increased risk of fracture after bariatric surgery. Clinicians should focus their attention on patients at high fracture risk such as postmenopausal women and men older than 50 years. More research is necessary to direct and support guidelines.

Interim 2-Year Analysis from SERENA: A Real-World Study in Patients with Psoriatic Arthritis or Ankylosing Spondylitis Treated with Secukinumab.

INTRODUCTION: Sustained improvement of high degree in clinical outcomes have been demonstrated in phase 3 trials with secukinumab in both psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The objective of the SERENA study was to evaluate the effectiveness, retention rates, and safety of secukinumab in patients with PsA and AS. METHODS: SERENA is an ongoing, longitudinal, real-world observational study involving patients with moderate-to-severe psoriasis, PsA, or AS. Patients had received at least 16 weeks of secukinumab treatment before recruitment to the study. Retention rate was defined as percentage of patients who continued secukinumab treatment over the course of study. Effectiveness of secukinumab in AS and PsA cohorts was assessed using descriptive statistics. RESULTS: The current interim analysis included 1004 patients with PsA or AS. Overall secukinumab retention rates at 2 years after enrolment were 74.9 and 78.9% in patients with PsA and AS, respectively. At baseline and at 2 years, swollen joint count [3.3 (5.8) vs. 2.9 (5.8)], tender joint count [6.3 (9.4) vs. 5.6 (7.2)] in patients with PsA and BASDAI scores [3.2 (2.3) vs. 2.9 (2.3)] in patients with AS, suggest sustained effectiveness for patients remaining on secukinumab for at least 2 years after enrolment. A total of 73 patients had treatment interruption; 78% of these patients reinitiated secukinumab without a loading dose. No new or unexpected safety signals were reported. CONCLUSIONS: After more than 2 years since initiation, secukinumab demonstrated high retention rates and favorable safety profile as well as sustained effectiveness in patients who continued secukinumab treatment.

Subchondral tibial bone texture of conventional X-rays predicts total knee arthroplasty.

Lacking disease-modifying osteoarthritis drugs (DMOADs) for knee osteoarthritis (KOA), Total Knee Arthroplasty (TKA) is often considered an important clinical outcome. Thus, it is important to determine the most relevant factors that are associated with the risk of TKA. The present study aims to develop a model based on a combination of X-ray trabecular bone texture (TBT) analysis, and clinical and radiological information to predict TKA risk in patients with or at risk of developing KOA. This study involved 4382 radiographs, obtained from the OsteoArthritis Initiative (OAI) cohort. Cases were defined as patients with TKA on at least one knee prior to the 108-month follow-up time point and controls were defined as patients who had never undergone TKA. The proposed TKA-risk prediction model, combining TBT parameters and Kellgren-Lawrence (KL) grades, was performed using logistic regression. The proposed model achieved an AUC of 0.92 (95% Confidence Interval [CI] 0.90, 0.93), while the KL model achieved an AUC of 0.86 (95% CI 0.84, 0.86; p < 0.001). This study presents a new TKA prediction model with a good performance permitting the identification of at risk patient with a good sensitivy and specificity, with a 60% increase in TKA case prediction as reflected by the recall values.

Is there still a place for methotrexate in severe psoriatic arthritis?

The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient's decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.

Prediction of knee osteoarthritis progression using radiological descriptors obtained from bone texture analysis and Siamese neural networks: data from OAI and MOST cohorts.

BACKGROUND: Trabecular bone texture (TBT) analysis has been identified as an imaging biomarker that provides information on trabecular bone changes due to knee osteoarthritis (KOA). In parallel with the improvement in medical imaging technologies, machine learning methods have received growing interest in the scientific osteoarthritis community to potentially provide clinicians with prognostic data from conventional knee X-ray datasets, in particular from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST) cohorts. PATIENTS AND METHODS: This study included 1888 patients from OAI and 683 patients from MOST cohorts. Radiographs were automatically segmented to determine 16 regions of interest. Patients with an early stage of OA risk, with Kellgren and Lawrence (KL) grade of 1 < KL < 4, were selected. The definition of OA progression was an increase in the OARSI medial joint space narrowing (mJSN) grades over 48 months in OAI and 60 months in MOST. The performance of the TBT-CNN model was evaluated and compared to well-known prediction models using logistic regression. RESULTS: The TBT-CNN model was predictive of the JSN progression with an area under the curve (AUC) up to 0.75 in OAI and 0.81 in MOST. The predictive ability of the TBT-CNN model was invariant with respect to the acquisition modality or image quality. The prediction models performed significantly better with estimated KL (KLprob) grades than those provided by radiologists. TBT-based models significantly outperformed KLprob-based models in MOST and provided similar performances in OAI. In addition, the combined model, when trained in one cohort, was able to predict OA progression in the other cohort. CONCLUSION: The proposed combined model provides a good performance in the prediction of mJSN over 4 to 6 years in patients with relevant KOA. Furthermore, the current study presents an important contribution in showing that TBT-based OA prediction models can work with different databases.

Effect of Denosumab Compared With Risedronate on Bone Strength in Patients Initiating or Continuing Glucocorticoid Treatment.

In a randomized clinical trial in patients initiating glucocorticoid therapy (GC-I) or on long-term therapy (GC-C), denosumab every 6 months increased spine and hip bone mineral density at 12 and 24 months significantly more than daily risedronate. The aim of this study was to evaluate the effects of denosumab compared with risedronate on bone strength and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in GC-I and GC-C. A subset of 110 patients had high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and tibia at baseline and at 12 and 24 months. Cortical and trabecular microarchitecture were assessed with standard analyses and failure load (FL) with micro-finite element analysis. At the radius at 24 months, FL remained unchanged with denosumab and significantly decreased with risedronate in GC-I (-4.1%, 95% confidence interval [CI] -6.4, -1.8) and, in GC-C, it significantly increased with denosumab (4.3%, 95% CI 2.1, 6.4) and remained unchanged with risedronate. Consequently, FL was significantly higher with denosumab than with risedronate in GC-I (5.6%, 95% CI 2.4, 8.7, p < 0.001) and in GC-C (4.1%, 95% CI 1.1, 7.2, p = 0.011). We also found significant differences between denosumab and risedronate in percentage changes in cortical and trabecular microarchitectural parameters in GC-I and GC-C. Similar results were found at the tibia. To conclude, this HR-pQCT study shows that denosumab is superior to risedronate in terms of preventing FL loss at the distal radius and tibia in GC-I and in increasing FL at the radius in GC-C, based on significant differences in changes in the cortical and trabecular bone compartments between treatment groups in GC-I and GC-C. These results suggest that denosumab could be a useful therapeutic option in patients initiating GC therapy or on long-term GC therapy and may contribute to treatment decisions in this patient population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Wearable transcutaneous electrical nerve stimulation (actiTENS®) is effective and safe for the treatment of knee osteoarthritis pain: a randomized controlled trial versus weak opioids.

INTRODUCTION: Despite their poor tolerance, especially in the elderly, weak opioids (WO) remain commonly prescribed for patients with knee osteoarthritis (KOA). We compared the efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) device with WO for the treatment of moderate-to-severe, nociceptive KOA chronic pain. METHODS: The study was a non-inferiority, multicentric, prospective, randomized, single-blind, controlled, 2-parallel groups Trial. A total of 110 patients with KOA were included (Kellgren-Lawrence radiographic grade ⩾2; American College of Rheumatology criteria), with chronic moderate-to-severe nociceptive pain (mean 8-day pain intensity (PI) ⩾ 4 on an 11-point numerical rating scale), in failure to non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with neuropathic pain were excluded. The co-primary endpoints were mean PI at 3 months (M3) and number of potentially treatment-related adverse events (TRAEs). Secondary outcomes included Western Ontario MAC Master University function subscale (range, 0-68), additional pain and quality of life measures, and responder rates. RESULTS: The non-inferiority of W-TENS was demonstrated in both the per protocol (PP) and intent-to-treat (ITT) populations. At M3, PI in PP population was 3.87 (2.12) compared with 4.66 (2.37) [delta: -0.79 (0.44); 95% CI (-1.65, 0.08)] in W-TENS and WO groups, respectively. A planned superiority analysis showed a significant superiority of W-TENS over WO on PI at M3 (p = 0.0124). The number of TRAEs was significantly lower in the W-TENS group (n = 7) than in the WO group (n = 36) (p < 0.001). Other secondary outcomes also favored W-TENS. CONCLUSION: W-TENS was more effective and better tolerated than WO in the treatment of chronic nociceptive KOA pain and offers an interesting non-pharmacological analgesic alternative in the management of KOA.Trial Registration: ClinicalTrials.gov: NCT03902340.

Bariatric Surgery and Osteoporosis.

It has been increasingly acknowledged that bariatric surgery adversely affects skeletal health. After bariatric surgery, the extent of high-turnover bone loss is much greater than what would be expected in the absence of a severe skeletal insult. Patients also experience a significant deterioration in bone microarchitecture and strength. There is now a growing body of evidence that suggests an association between bariatric surgery and higher fracture risk. Although the mechanisms underlying the high-turnover bone loss and increase in fracture risk after bariatric surgery are not fully understood, many factors seem to be involved. The usual suspects are nutritional factors and mechanical unloading, and the roles of gut hormones, adipokines, and bone marrow adiposity should be investigated further. Roux-en-Y gastric bypass (RYGB) was once the most commonly performed bariatric procedure worldwide, but sleeve gastrectomy (SG) has now become the predominant bariatric procedure. Accumulating evidence suggests that RYGB is associated with a greater reduction in BMD, a greater increase in markers of bone turnover, and a higher risk of fracture than SG. These findings should be taken into consideration in determining the most appropriate bariatric procedure for patients, especially those at higher fracture risk. Before and after all bariatric procedures, sufficient calcium, vitamin D and protein intake, and adequate physical activity, are needed to counteract negative impacts on bone. There are no studies to date that have evaluated the effect of osteoporosis treatment on high-turnover bone loss after bariatric surgery. However, in patients with a diagnosis of osteoporosis, anti-resorptive agents may be considered.