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Knee osteoarthritis (KOA) is one of the most common progressive, age-dependent chronic degenerative joint diseases. KOA often develops as a result of a gradual articular cartilage loss caused by its wear and tear. Numerous studies suggest that the degradation of the knee joint involves inflammatory components. This process is also associated with body composition, particularly being overweight and muscle mass loss. The present study aimed to search for novel circulating KOA inflammatory biomarkers, taking into account body composition characteristics. To this aim, we recruited 98 patients diagnosed and radiologically confirmed with KOA and 519 healthy controls from the Arab community in Israel. A panel of soluble molecules, related to inflammatory, metabolic, and musculoskeletal disorders, was measured by ELISA in plasma samples, while several body composition parameters were assessed with bioimpedance analysis. Statistical analysis, including multivariable logistic regression, revealed a number of the factors significantly associated with KOA, independently of age and sex. The most significant independent associations [OR (95% CI)] were fat body mass/body weight index—1.56 (1.20–2.02), systemic immune-inflammation index—4.03 (2.23–7.27), circulating vaspin levels—1.39 (1.15–1.68), follistatin/FSTL1 ratio—1.32 (1.02–1.70), and activin A/FSTL1 ratio—1.33 (1.01–1.75). Further clinical studies are warranted to confirm the relevance of these KOA-associated biological factors. Hereafter, they could serve as reliable biomarkers for KOA in the general human population. [ABSTRACT FROM AUTHOR]

Aim: In overweight/obese individuals, modest 5% weight loss and its maintenance promotes health; however, it is challenging and typically unachievable, especially in community settings. Established predictors of weight loss outcome in a community setting are lacking, hindering the development of practical interventions and prevention tools. Our aim was to identify predictors associated with 5% weight reduction (initial 6 months) and maintenance (1 year) in overweight and obese adults undergoing weight reduction treatment, free of charge, in a community setting. Methods: Computerised medical files of 11 842 adults aged 50.6 ± 16.3 years, attending 162 primary clinics, were analysed retrospectively. Thirty medical, biochemical and demographic independent variables were tested as potential predictors using multiple logistic regression models. Results: Significant predictors of high successful weight reduction were: not being treated with insulin (odds ratio (OR) = 0.53), higher baseline body mass index (OR = 1.05) and younger age (OR = 0.98). Weight maintenance predictors were: successful initial weight reduction (OR = 1.26), short time intervals between weighings (OR = 0.88) and frequent weighing (OR = 0.95). Visits to a dietitian were significantly associated with success during both periods: each visit raised the probability of success by 13.4 and 7.6%, respectively. Type 2 diabetes or use of hypoglycaemic drugs were not significant predictors. Conclusions: In a community‐based setting, number of visits to a dietitian is a strong predictor of successful weight reduction and maintenance. Initial success is a critical predictor of weight loss maintenance. Subgroup of older, diabetic patients treated with insulin has a dramatically lower probability of weight reduction success. [ABSTRACT FROM AUTHOR]

Declining estrogen levels during menopause are widely considered to be a major cause of age-dependent bone loss, which is primarily manifested by increased bone resorption by osteoclasts. We present accumulating evidence supporting another aspect of metabolic bone loss, suggesting that the combined interaction between age-dependent factors, namely, estrogen deficiency and reduced day-by-day activity/mechanical stimulation, directly leads to a reduction in anabolic processes. Such decreased bone formation results in diminished bone strength and failure to maintain the load-bearing competence of a healthy skeleton and to postmenopausal osteoporosis disorder. Estrogen receptors (ERs), as mediators of estrogenic actions, are essential components of bone osteocyte and osteoblast mechano-adaptive responses. ER expression appears to be upregulated by adequate circulating estrogen levels. ERα signaling pathways participate in the mechanotransduction response through obligatory 'non-genomic' actions that occur independently of estrogen binding to ER and by a potentially 'genomic', estrogen-dependent mode. The experimental data indicate that cross talk between the ERα-'non-genomic' and Wnt/β-catenin signaling pathways constitutes the major regulatory mechanism. This interaction uses mechanically and ER-induced prostaglandin E2 as a mediator for the downregulation of osteocyte production of sclerostin. Sclerostin suppression, in turn, is a central prerequisite for load-induced formation and mineralization of the bone matrix. It is therefore plausible that future strategies for preventing and treating postmenopausal osteoporosis may use estrogenic compounds (such as selective estrogen receptor modulators or phytoestrogens) with physical activity, to complement antiresorptive therapy, aimed at stopping further bone loss and possibly even reversing it by stimulation of bone gain. [ABSTRACT FROM AUTHOR]

Summary: There is a paucity of studies investigating association between ROR2 gene variants and osteoporosis and osteoarthritis-related phenotypes. The published literature suggests that osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are essential for bone metabolism and correlate with osteoarthritis manifestation and progression. The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma. The present results also suggest significant association between ROR2 polymorphisms and severity of radiographic hand osteoarthritis. Introduction: Despite the importance of the ROR-2 in skeletal physiology, there is a paucity of studies investigating the potential association of ROR2 gene variants with phenotypes relevant to osteoporosis and osteoarthritis. On the other hand, there is a considerable body of literature suggesting that OPG and RANKL and their ratio (OPG/RANKL) are essential for regulating bone resorption. This is also correlated with osteoarthritis manifestation and progression. The present study therefore examines whether ROR2 polymorphisms may be associated with the OPG/RANKL ratio and hand osteoarthritis (HOA). Methods: The study was conducted in a family-based sample of 1,515 Caucasian individuals, assessed for radiographic hand osteoarthritis, using the Kellgren/Lawrence score. Of these, 865 individuals were genotyped for 19 SNPs, relatively equally covering the ROR2 locus, and their plasma levels of OPG and RANKL were assayed. The association between the selected SNPs and OPG, along with the OPG/RANKL ratio and HOA, was explored using the pedigree disequilibrium test. Results: Of the total of 57 tests, 16 nominally significant results ( p < 0.05) were obtained, which is considerably more than the three normally expected for type I error. The significant association signals for all three phenotypes were mapped to the intron 1 region. The most significant results were detected between OPG/RANKL and rs7048756 ( p < 0.0005) and between adjacent rs4744107 and Kellgren/Lawrence score ( p = 0.006). Conclusions: The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma and also suggests ROR2 association with HOA. [ABSTRACT FROM AUTHOR]

The article highlights the workshop "Personalized Medicine Europe: Health, Genes and Society," cosponsored by the European Science Foundation and the Yoran Institute for Human Genome Research on June 19-21, 2005 at Tel-Aviv University in Tel Aviv, Israel. It consisted of 40 invited presentations, six oral poster presentations by graduate and post-graduate students and concluding panel discussion.

Presents a study on the testing of genetic influences on systolic blood pressure (SBP), body mass index (BMI), and segregation analysis in Israeli families, relating to human biology. Detailed information on methodologies and materials used in the study; Results of the study; Discussion on the study; Other detailed information.