Skin autofluorescence, a non-invasive biomarker of advanced glycation end products, and its relation to radiographic and MRI based osteoarthritis.

OBJECTIVES: Accumulation of advanced glycation end products (AGEs) in articular cartilage during aging has been proposed as a mechanism involved in the development of osteoarthritis (OA). Therefore, we investigated a cross-sectional relationship between skin AGEs, a biomarker for systemic AGEs accumulation, and OA. METHODS: Skin AGEs were estimated with the AGE Reader™ as skin autofluorescence (SAF). Knee and hip X-rays were scored according to Kellgren and Lawrence (KL) system. KL-sum score of all four joints was calculated per participant to assess severity of overall radiographic OA (ROA) including or excluding those with prosthesis. Knee MRI of tibiofemoral joint (TFMRI) was assessed for cartilage loss. Sex-stratified regression models were performed after testing interaction with SAF. RESULTS: 2,153 participants were included for this cross-sectional analysis. In women (n = 1,206) for one unit increase in SAF, the KL-sum score increased by 1.15 (95% confidence interval = 1.00-1.33) but excluding women with prosthesis, there was no KL-sum score increase [0.96 (0.83-1.11)]. SAF was associated with higher prevalence of prosthesis [Odds ratio, OR = 1.67 (1.10-2.54)] but not with ROA [OR = 0.83 (0.61-1.14)] when compared to women with no ROA. In men (n = 947), there was inconclusive association between SAF and KL sum score or prosthesis. For TFMRI (n = 103 women), SAF was associated with higher prevalence of cartilage loss, full-thickness [OR = 5.44 (1.27-23.38)] and partial-thickness [OR = 1.45 (0.38-5.54)], when compared to participants with no cartilage loss. CONCLUSION: Higher SAF in women was associated with higher prosthesis prevalence and a trend towards higher cartilage loss on MRI. Our data presents inconclusive results between SAF and ROA in both sexes.

The Gut Microbiome: a New Frontier in Musculoskeletal Research.

PURPOSE OF THE REVIEW: The human gut harbors a complex community of microbes that influence many processes regulating musculoskeletal development and homeostasis. This review gives an update on the current knowledge surrounding the impact of the gut microbiota on musculoskeletal health, with an emphasis on research conducted over the last three years. RECENT FINDINGS: The gut microbiota and their metabolites are associated with sarcopenia, osteoporosis, osteoarthritis, and rheumatoid arthritis. The field is moving fast from describing simple correlations to pursue establishing causation through clinical trials. The gut microbiota and their microbial-synthesized metabolites hold promise for offering new potential alternatives for the prevention and treatment of musculoskeletal diseases given its malleability and response to environmental stimuli.

Development of a prediction model for future risk of radiographic hip osteoarthritis.

OBJECTIVE: To develop and validate a prognostic model for incident radiologic hip osteoarthritis (HOA) and determine the value of previously identified predictive factors. DESIGN: We first validated previously reported predictive factors for HOA by performing univariate and multivariate analyses for all predictors in three large prospective cohorts (total sample size of 4548 with 653 incident cases). The prognostic model was developed in 2327 individuals followed for 10 years from the Rotterdam Study-I (RS-I) cohort. External validation of the model was tested on discrimination in two other cohorts: RS-II (n = 1435) and the Cohort Hip and Cohort Knee (CHECK) study (n = 786). RESULTS: From the total number of 28 previously reported predictive factors, we were able to replicate 13 factors, while 15 factors were not significantly predictive in a meta-analysis of the three cohorts. The basic model including the demographic, questionnaire, and clinical examination variables (area under the receiver-operating characteristic curve (AUC) = 0.67) or genetic markers (AUC = 0.55) or urinary C-terminal cross-linked telopeptide of type II collagen (uCTX-II) levels (AUC = 0.67) alone were poor predictors of HOA in all cohorts. Imaging factors showed the highest predictive value for the development of HOA (AUC = 0.74). Addition of imaging variables to the basic model led to substantial improvement in the discriminative ability of the model (AUC = 0.78) compared with uCTX-II (AUC = 0.74) or genetic markers (AUC = 0.68). Applying external validation, similar results were observed in the RS-II and the CHECK cohort. CONCLUSIONS: The developed prediction model included demographic, a limited number of questionnaire, and imaging risk factors seems promising for prediction of HOA.

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.