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.

A new serum biochemical marker of synovium turnover predicts radiographic progression in patients with early arthritis.

OBJECTIVE: To investigate whether serum Col 3-4, a new biochemical marker of synovial tissue turnover, was associated with progression of joint damage in patients with early arthritis. METHODS: A total of 788 early arthritis patients (<6 months of symptoms, 82% diagnosis of RA, 18% undifferentiated arthritis) from the prospective ESPOIR study were investigated. Progression was defined as an increase of 1 or 5 unit(s) in radiographic van der Heijde modified Sharp score between baseline and 1 or 5 years, respectively. Associations between baseline Col 3-4 and progression were assessed by logistic regression. RESULTS: Each standard deviation increase of baseline Col 3-4 levels was associated with an increased 5-yr total damage progression with an odds ratio (OR, 95% CI) of 1.51 (1.21, 1.88), which remained significant when DAS28, C-reactive protein and anti-citrullinated protein antibodies positivity were included in the model [OR (95% CI): 1.34 (1.01, 1.76)]. Further adjustment for bone erosion did not modify the association. Patients with both Col 3-4 in the highest quintile and bone erosion had a >2-fold higher risk of progression [OR (95% CI): 7.16 (2.31, 22)] than patients with either high Col 3-4 [2.91 (1.79, 4.73)] or bone erosion [2.36 (2.38, 3.70)] alone. Similar associations were observed for prediction of 12 months progression. CONCLUSIONS: Increased serum Col 3-4 is associated with a higher risk of structural progression, independently of major risk factors. Col 3-4 may be useful in association with bone erosion to identify patients with early arthritis at higher risk.

The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

A meta-analysis of previous falls and subsequent fracture risk in cohort studies.

The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. INTRODUCTION: Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). METHODS: The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. RESULTS: Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33-1.51) and men (HR 1.53, 95% CI 1.41-1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27-1.84) in men vs. HR 1.32 (95% CI 1.20-1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men. CONCLUSIONS: A previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.

Plasma Cartilage Acidic Protein 1 Measured by ELISA Is Associated With the Progression to Total Joint Replacement in Postmenopausal Women.

OBJECTIVE: To investigate the association of plasma cartilage acidic protein 1 (CRTAC1), a novel biochemical marker of osteoarthritis (OA), and total joint replacement (TJR) in postmenopausal women. METHODS: The association of plasma CRTAC1 with the incidence of TJR was investigated in a prospective cohort including 478 postmenopausal women. A total of 38 women underwent a TJR for OA during a median follow-up of 18 years. Every one of the TJR cases were age- and BMI (kg/m2)-matched with 2 controls with no TJR from the same cohort. Plasma CRTAC1 was measured before TJR. The association between CRTAC1 and TJR incidence was investigated by conditional logistic regression. RESULTS: Increased CRTAC1 was associated with a higher risk of TJR with an odds ratio (OR) of 1.80 (95% CI 1.11-2.92) for 1 SD increase, which remained significant after adjusting for Western Ontario and McMaster Universities Osteoarthritis Index, knee OA baseline severity (Kellgren-Lawrence grade), hip OA, and hip bone mineral density. Urinary crosslinked C-telopeptide of type II collagen (CTX-II) was also associated with a higher risk of TJR with an adjusted OR of 1.83 (95% CI 1.11-3.00). When CRTAC1 and CTX-II were included in the same model, both markers were significantly associated with TJR with similar ORs. CONCLUSION: CRTAC1 is a new risk indicator of TJR for OA in postmenopausal women. Combined with knee and hip OA and CTX-II, it may help to identify subjects at risk for TJR.

Association of circulating hsa-miRNAs with sarcopenia: the SarcoPhAge study.

OBJECTIVE: To identify a microRNA signature associated to sarcopenia in community-dwelling older adults form the SarcoPhAge cohort. METHODS: In a screening phase by next generation sequencing (NGS), we compared the hsa-miRome expression of 18 subjects with sarcopenia (79.6 ± 6.8 years, 9 men) and 19 healthy subjects without sarcopenia (77.1 ± 6 years, 9 men) at baseline. Thereafter, we have selected eight candidate hsa-miRNAs according to the NGS results and after a critical assessment of previous literature. In a validation phase and by real-time qPCR, we then analyzed the expression levels of these 8 hsa-miRNAs at baseline selecting 92 healthy subjects (74.2 ± 10 years) and 92 subjects with sarcopenia (75.3 ± 6.8 years). For both steps, the groups were matched for age and sex. RESULTS: In the validation phase, serum has-miRNA-133a-3p and has-miRNA-200a-3p were significantly decreased in the group with sarcopenia vs controls [RQ: relative quantification; median (interquartile range)]: -0.16 (-1.26/+0.90) vs +0.34 (-0.73/+1.33) (p < 0.01) and -0.26 (-1.07/+0.68) vs +0.27 (-0.55/+1.10) (p < 0.01) respectively. Has-miRNA-744-5p was decreased and has-miRNA-151a-3p was increased in the group with sarcopenia vs controls, but this barely reached significance: +0.16 (-1.34/+0.79) vs +0.44 (-0.31/+1.00) (p = 0.050) and +0.35 (-0.22/+0.90) vs +0.03 (-0.68/+0.75) (p = 0.054). CONCLUSION: In subjects with sarcopenia, serum hsa-miRNA-133a-3p and hsa-miRNA-200a-3p expression were downregulated, consistent with their potential targets inhibiting muscle cells proliferation and differentiation.

C-reactive protein predicts endocortical expansion but not fracture in older men: the prospective STRAMBO study.

In older men, higher high-sensitivity C-reactive protein (hsCRP) concentrations were associated with faster prospectively assessed endocortical expansion (distal radius, distal tibia) and slightly higher cortical bone loss at distal tibia, but not with the fracture risk. High hsCRP level has a limited impact on bone decline in older men. PURPOSE: Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant. We studied the association of the hsCRP with the prospectively assessed decrease in areal bone mineral density (aBMD), bone microarchitecture decline, and fracture risk in older men. METHODS: At baseline, hsCRP was measured in 823 men aged 60-88. Areal BMD and bone microarchitecture (distal radius, distal tibia) were assessed by dual-energy X-ray absorptiometry and high-resolution peripheral QCT, respectively, at baseline and after 4 and 8 years. Data on incident fractures were collected for 8 years. RESULTS: Higher hsCRP concentration was associated with faster increase in aBMD at the whole body and lumbar spine, but not other sites. Higher hsCRP levels were associated with faster decrease in cortical area and more rapid increase in trabecular area at the distal radius (0.048 mm2/year/SD, p < 0.05) and distal tibia (0.123 mm2/year/SD, p < 0.001). At the distal tibia, high hsCRP level was associated with greater decrease in total and cortical volumetric BMD (vBMD) and in failure load. The hsCRP levels were not associated with the fracture risk, even after accounting for competing risk of death. CONCLUSION: Higher hsCRP levels were associated with greater endocortical expansion at the distal radius and tibia. Higher hsCRP was associated with slightly faster decrease in total and cortical vBMD and failure load at distal tibia, but not with the fracture risk. Thus, high hsCRP levels are associated with faster cortical bone loss, but not with fracture risk in older men.

Spondyloarthritis and Sarcopenia: Prevalence of Probable Sarcopenia and its Impact on Disease Burden: The Saspar Study.

To evaluate the prevalence of probable, confirmed, and severe sarcopenia in spondyloarthritis (SpA), according to the European Working Group on Sarcopenia in Older People 2019 (EWGSOP2) definition. A total of 103 patients (51% women) with SpA, mean age 47.1 ± 13.7 years, were included and compared to 103 age- and sex-matched controls. Grip strength was measured by dynamometry. Body composition was assessed by whole-body densitometry. In SpA patients gait speed was measured by the 4-m-distance walk test and quality of life was evaluated with a specific health-related questionnaire for sarcopenia (SaRQoL®). Twenty-two SpA patients (21%) versus 7 controls (7%) had a low grip strength, i.e., probable sarcopenia (p < 0.01), 15 SpA (15%) patients and 7 controls (7%) had low Skeletal Muscle mass Index (SMI) (ns), respectively, and 5 and 2% of SpA patients and controls had low grip strength and low SMI, i.e., confirmed sarcopenia (ns). All the sarcopenic SpA patients had a low gait speed, i.e., severe sarcopenia. Finally, probable sarcopenic SpA patients had significantly higher C-Reactive Protein (CRP, p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI score, p < 0.01), lower gait speed (p < 0.001), and SarQoL® score (p < 0.001) than SpA patients with normal grip strength. According to EWGSOP2 definition, the prevalence of probable sarcopenia was significantly higher in SpA patients compared to controls. Probable sarcopenia was associated with higher inflammation and disease activity, impaired muscle performance, and quality of life. These results suggest that muscle strength may be a salient hallmark in SpA.

Elevated lipoprotein(a) as a predictor for coronary events in older men.

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5-6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30-50 mg/dl) levels of Lp(a) over 8 years (Gray's test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0-4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.

Costs of patient management over 18 months following a hip, clinical vertebral, distal forearm, or proximal humerus fragility fracture in France-results from the ICUROS study.

This observational study prospectively assessed direct and indirect costs related to patient management over 18 months following hip, clinical vertebral, humeral, or distal forearm fracture events in France. It appears that their levels were much higher than the previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures. INTRODUCTION: This prospective observational study assessed the costs related to patient management over the 18-month period following the event of a hip, clinical vertebral, humeral, or distal forearm fracture in France. METHODS: Individuals aged ≥ 50 years old with the diagnosis of a fragility fracture in six French University Hospitals were enrolled in the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS). All resources used over the defined period and related to fracture and the underlying osteoporosis management were collected by questionnaires at baseline, 4 months, 12 months, and 18 months. Information was collected by direct or phone contact completed by patients' records and interviews of partner, family, and general practitioners. Costs were estimated from a societal perspective, including direct and indirect costs. We implemented recursive partitioning analysis (RPA), a statistical learning algorithm to identify predictors of costs. RESULTS: Four hundred thirty-one patients (mean age 72.5 years; 84.6% women) were evaluated. Among them, 17.6% had a prior fracture in the last 5 years. Approximately half of the whole group lived alone in the community, and 56.8% were from a low- or middle-income category. Over the 18-month period of evaluation, total costs (including initial fracture-related and follow-up ones) were 23 926 €, 14 561 €, and 6 905 € for the hip, clinical vertebral, and distal forearm fracture, respectively. Over a year, costs related to a humeral fracture were 10 319 €. The RPA identified mobility impairment prior to fracture as a predictor of increase in costs related to fracture. CONCLUSIONS: Our study for the first time prospectively assessed total costs related to the four main osteoporotic fractures in France. It appears that their levels were much higher than previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures.

Dual-energy CT hybridation and kernel processing effects on the estimation of bone mineral mass and density: a calcination study on ex vivo human femur.

INTRODUCTION: Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS: DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS: QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION: BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Risk Factors for the Incident Decline of Physical Performance in Older Men: The Prospective Strambo Study.

Risk factors of physical performance decline in older men remain uncertain. We assessed risk factors of incident physical performance deterioration in older men followed up prospectively. In a cohort of 821 men aged 60-87, physical performance was assessed by four tests (five chair stands, standing with closed eyes, forward and backward tandem walk) at baseline, 4 and 8 years. Various predictive biological measurements were performed at baseline. Serum creatinine/ cystatin C (Cr/CysC) ratio was used as an index of muscle mass. In multivariate models, higher age, higher fat mass index (FMI = fat mass/height2), low physical activity, prior stroke and fracture were associated with poor physical performance at baseline. Higher age, low physical activity, low calcium intake, prior non-vertebral fractures, low apparent free testosterone concentration and poor health status were associated with higher risk of loss to follow-up. Low grip strength, Parkinson's disease and stroke were associated with higher risk of incident inability to do five chair stands. Low Cr/CysC ratio and high FMI were associated with high risk of incident inability to perform forward and backward tandem walk. Sarcopenic obesity (co-occurrence of lower tertile of Cr/CysC and upper tertile of FMI) was associated with higher risk of incident inability to perform forward (OR = 3.31, 95% CI 1.88-5.84, p < 0.001) and backward tandem walk and of incident inability to perform more than one test (OR = 5.82, 95% CI 1.29-26.27, p < 0.001). In conclusion, sarcopenic obesity and poor health are associated with higher risk of incident severe decline of physical performance.

High Cardiovascular Risk in Older Men With Severe Peripheral Artery Calcification on High-Resolution Peripheral QCT Scans: The STRAMBO Study.

[Figure: see text].

Relationship between diffuse idiopathic skeletal hyperostosis and fragility vertebral fracture: a prospective study in older men.

OBJECTIVE: To analyse the risk of incident vertebral and non-vertebral fracture in men with DISH. METHODS: In 782 men ages 50-85 years, DISH was diagnosed using Resnick's criteria. In men followed prospectively for 7.5 years, a radiographic incident vertebral fracture was defined by a decrease of ≥20% or ≥4mm in any vertebral height vs baseline. Self-reported incident non-vertebral fractures were confirmed by medical records. RESULTS: Men with DISH had higher BMD at the lumbar spine (P < 0.05), but not at other skeletal sites. After adjustment for confounders including disc space narrowing (DSN) and endplate irregularity, the risk of vertebral fracture was higher in men with DISH vs men without DISH [10/164 (6.1%) vs 16/597 (2.7%), P < 0.05; odds ratio (OR) 2.89 (95% CI 1.15, 7.28), P < 0.05]. DISH and low spine BMD were each associated with a higher vertebral fracture risk. The vertebral fracture risk was higher in men who had both DISH and severe DSN. DISH and endplate irregularities (EIs) were each associated with higher vertebral fracture risk. DISH, DSN and EIs define the intervertebral space dysfunction, which was associated with higher vertebral fracture risk [OR 3.99 (95% CI 1.45, 10.98), P < 0.01]. Intervertebral space dysfunction improved the vertebral fracture prediction (ΔAUC = +0.111, P < 0.05), mainly in men with higher spine BMD (>0.9 g/cm2; ΔAUC = +0.189, P < 0.001). DISH was not associated with the risk of non-vertebral fracture. CONCLUSION: DISH is associated with higher vertebral fracture risk, independently of other risk factors. Assessment of the intervertebral space dysfunction components may improve the vertebral fracture prediction in older men.

Distal phalangeal bone erosions observed by HR-pQCT in patients with psoriatic onycholysis.

OBJECTIVES: PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. METHODS: We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. RESULTS: Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P < 0.001). CONCLUSION: Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis. TRIAL REGISTRATION: ClinicalTrails.gov, https://clinicaltrials.gov, NCT02813720.

The role of biochemical markers of joint tissue remodelling to predict progression and treatment efficacy in inflammatory rheumatic diseases.

Structural damage is a hallmark in RA, spondyloarthropy (SpA) and psoriatric arthritis (PsA). Its progression is difficult to predict and current radiological or inflammatory biological markers lack sensitivity. Biochemical markers of bone, cartilage and synovial tissues provide a dynamic indication of the anabolism and catabolism of joint tissues and can be easily measured by immunoassays. Novel biochemical markers including post-translational modifications of matrix proteins and enzyme-generated neoepitopes with increased tissue and/or biological pathway specificity have been developed. Their evaluation in clinical trials of novel biologic therapies and epidemiological studies indicated that their measurements could be useful to predict progression of structural damage and treatment efficacy, independently of current clinical, radiological and biological indices of disease activity. In this paper we briefly describe the latest developments in biochemical markers and critically analyse the clinical data assessing the utility of established and novel biochemical markers in RA, SpA and PsA.

Where Two Common Conditions of Aging Meet: Osteoarthritis and Sarcopenia.

Osteoarthritis and sarcopenia are the most frequently described musculoskeletal disorders in older persons but the intertwining of these conditions and of their functional and cellular causes is complex. This narrative review aims to identify the links between osteoarthritis and sarcopenia described 1-in clinical studies, 2-in in vitro studies, and 3-the available treatment strategies for both conditions. Electronic databases were used for the literature search of all studies investigating the relationship between sarcopenia and the presence of concomitant osteoarthritis. This review identified a limited number of clinical and morphometric studies on the complex relationship between osteoarthritis and sarcopenia. Studies present a number of methodological limitations due to definition and assessment of both entities. Low lean mass is one of the main actors of this cross-talk between muscle and bone, and adipose tissue plays a major role that had been underestimated. Bone Morphogenetic Proteins and myostatin pathways are key mediators and play an important role in both muscle and bone homeostasis. Common therapeutic recommendations are still missing. There is a need for good quality prospective studies on concomitant sarcopenia and osteoarthritis, more translational research, and pharmacological and non-pharmacological therapies in order to identify common denominators for the management of sarcopenia, osteoarthritis, and their comorbidities.

Correction to: Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review.

The original version of this article unfortunately contained a mistake in one of the co-author's name. The co-author Cyrus Cooper's degree "FMedSci" was incorrectly tagged as family name. This has been corrected with this erratum.

Is There Enough Evidence for Osteosarcopenic Obesity as a Distinct Entity? A Critical Literature Review.

The co-existence of impaired bone health (osteopenia/osteoporosis), reduced muscle mass and strength (sarcopenia), and increased adiposity (obesity) in middle-aged and older people has been identified in recent studies, leading to a proposal for the existence of "osteosarcopenic obesity" as a distinct entity. Evidence for the pathophysiological overlap of these conditions is mounting, although a causal relationship is yet to be established. Each component condition occurs frequently with increasing age, and with shared risk factors in many instances, thus, an overlap of these three conditions is not surprising. However, whether the concurrent existence of sarcopenia, osteoporosis and obesity leads to an increased risk of adverse musculoskeletal outcomes and mortality above and beyond the risks associated with the sum of the component parts remains to be proven and is a question of research interest. In this article, we review evidence for the existence of osteosarcopenic obesity including the current operational definition of osteosarcopenic obesity, prevalence, pathophysiology, outcomes and exploratory approaches to the management of components. We conclude that, there is insufficient evidence to support a discrete clinical entity of osteosarcopenic obesity at this time. To expand knowledge and understanding in this area, there is a need for consensus on a definition of osteosarcopenic obesity which will allow for identification, further epidemiological studies and comparisons between studies. Additionally, studies should assess whether the clinical outcomes associated with osteosarcopenic obesity are worse than the mere addition of those linked with its components. This will help to determine whether defining a person as having this triad will eventually result in a more effective treatment than addressing each of the three conditions separately.

Spatial Distribution of Microcracks in Osteoarthritic Femoral Neck: Influence of Osteophytes on Microcrack Formation.

Osteophytes have been suggested to influence the bone mechanical properties. The aim of this study was to compare the microcrack density in osteophytes with that in the other parts of the osteoarthritic femoral neck (FN). The presence of microcracks was investigated in the ultra-distal FN and in the osteophytes in samples obtained during hip arthroplasty in 24 postmenopausal women aged 67 ± 10 years. Furthermore, the 3D microarchitecture and the collagen crosslinks contents were assessed by high-resolution peripheral quantitative computed tomography and high-performance liquid chromatography, respectively. Osteophytes were present in the 24 FN, mainly at the level of the inferior quadrant. Microcracks were present in all FN with an average of 2.8 per sample. All observed microcracks were linear. The microcrack density (Cr.N/BV; #/mm2) was significantly higher in cancellous than in cortical bone (p = 0.004), whereas the microcrack length (Cr.Le, µm) was significantly greater in cortical bone (p = 0.04). The collagen crosslinks ratio pyridinoline/deoxypyridinoline was significantly and negatively correlated with Cr.N/BV in the posterior (r' = - 0.68, p = 0.01) and inferior (r' = - 0.53, p = 0.05) quadrants. Microcracks were observed in seven osteophytes in seven patients. When microcracks were present in the osteophyte area, Cr.N/BV was also significantly higher in the whole FN and in the quadrant of the osteophyte compared to the cases without microcrack in the osteophyte (p < 0.03). In conclusion, in FN from hip osteoarthritis microcracks are present in all FNs but in only 23% of the osteophytes. The microcrack formation was greater and their progression was smaller in the cancellous bone than in the cortex. The spatial distribution of microcracks varied according to the proximity of the osteophyte, and suggests that osteophyte may influence microcrack formation related to changes in local bone quality.