Low vitamin D and the risk of developing chronic widespread pain: results from the European male ageing study.

BACKGROUND: The association between low levels of vitamin D and the occurrence of chronic widespread pain (CWP) remains unclear. The aim of our analysis was to determine the relationship between low vitamin D levels and the risk of developing CWP in a population sample of middle age and elderly men. METHODS: Three thousand three hundred sixty nine men aged 40-79 were recruited from 8 European centres for a longitudinal study of male ageing, the European Male Ageing Study. At baseline participants underwent assessment of lifestyle, health factors, physical characteristics and gave a fasting blood sample. The occurrence of pain was assessed at baseline and follow up (a mean of 4.3 years later) by shading painful sites on a body manikin. The presence of CWP was determined using the ACR criteria for fibromyalgia. Serum 25-hydroxyvitamin D (25-(OH) D) was assessed by radioimmunoassay. Logistic regression was used to determine the relationship between baseline vitamin D levels and the new occurrence of CWP. RESULTS: Two thousand three hundred thirteen men, mean age 58.8 years (SD = 10.6), had complete pain and vitamin data available and contributed to this analysis. 151 (6.5%) developed new CWP at follow up and 577 (24.9%) were pain free at both time points, the comparator group. After adjustment for age and centre, physical performance and number of comorbidities, compared to those in upper quintile of 25-(OH) D ( ≥36.3 ng/mL), those in the lowest quintile (<15.6 ng/mL) were more likely to develop CWP (Odds Ratio [OR] = 1.93; 95% CI = 1.0-3.6). Further adjustment for BMI (OR = 1.67; 95% CI = 0.93-3.02) or depression (OR = 1.77; 95% CI = 0.98-3.21), however rendered the association non-significant. CONCLUSIONS: Low vitamin D is linked with the new occurrence of CWP, although this may be explained by underlying adverse health factors, particularly obesity and depression.

Functional interaction between sequestosome-1/p62 and autophagy-linked FYVE-containing protein WDFY3 in human osteoclasts.

Paget's disease of bone (PDB) is a late-onset disorder characterised by focal areas of increased bone resorption, with osteoclasts that are increased in size, multinuclearity, number and activity. PDB-causing missense and nonsense variants in the gene encoding Sequestosome-1/p62 (SQSTM1) have been identified, all of which cluster in and around the ubiquitin-associated (UBA) domain of the protein. SQSTM1 is ubiquitously expressed and there is, as yet, no clear reason why these mutations only appear to cause an osteoclast-related phenotype. Using co-immunoprecipitation and tandem mass spectrometry, we identified a novel interaction in human osteoclast-like cells between SQSTM1 and Autophagy-Linked FYVE domain-containing protein (ALFY/WDFY3). Endogenous ALFY and SQSTM1 both localised within the nuclei of osteoclasts and their mononuclear precursors. When osteoclasts were starved to induce autophagy, SQSTM1 and ALFY relocated to the cytoplasm where they formed large aggregates, with cytoplasmic relocalisation appearing more rapid in mature osteoclasts than in precursors in the same culture. Overexpression of wild-type SQSTM1 in HEK293 cells also resulted in the formation of cytoplasmic aggregates containing SQSTM1 and endogenous ALFY, as did overexpression of a PDB-causing missense mutant form of SQSTM1, indicating that this mutation does not impair the formation of SQSTM1- and ALFY-containing aggregates. Expression of ALFY in bone cells has not previously been reported, and the process of autophagy has not been studied with respect to osteoclast activity. We have identified a functional interaction between SQSTM1 and ALFY in osteoclasts under conditions of cell stress. The difference in response to starvation between mature osteoclasts and their precursors may begin to explain the cell-specific functional effects of SQSTM1 mutations in PDB.

Update on the epidemiology, risk factors and disease outcomes of osteoarthritis.

Osteoarthritis (OA) is the most frequent form of arthritis and a leading cause of pain and disability worldwide. OA can affect any synovial joint, although the hip, knee, hand, foot and spine are the most commonly affected sites. Knowledge about the occurrence and risk factors for OA is important to define the clinical and public health burden of the disease to understand mechanisms of disease occurrence and may also help to inform the development of population-wide prevention strategies. In this article, we review the occurrence and risk factors for OA and also consider patient-reported outcome measures that have been used for the assessment of the disease.

Brief Report: Synovial Fluid White Blood Cell Count in Knee Osteoarthritis: Association With Structural Findings and Treatment Response.

OBJECTIVE: Osteoarthritis (OA) is a disease with a significant inflammatory component. The aim of this analysis was to determine the relationship between synovial fluid (SF) white blood cell (WBC) count and 2 parameters: disease severity and the reduction in knee pain after intraarticular (IA) steroid injection. METHODS: Subjects with painful knee OA were recruited for participation in an open-label study of IA steroid therapy. Information was obtained about knee pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, and a proportion of subjects underwent magnetic resonance imaging (MRI). Prior to injection with 80 mg methylprednisolone acetate, the index knee joint was aspirated and the fluid obtained was forwarded for assessment of SF WBC count. RESULTS: Information on SF WBC count was available for 55 subjects. An increase in WBC count category (≤100, 101-250, and 251-1,000 cells/mm3 ) was associated with an increase in synovial tissue volume (P = 0.028) and with other MRI-based measures of disease severity. Also, with each increase in SF WBC count category, there was a greater reduction in KOOS score after steroid injection (for WBC count of ≤100 cells/mm3 [referent], mean ± SD 12.5 ± 15.2; for WBC count of 101-250 cells/mm3 , mean ± SD 21.3 ± 20.6 [ß coefficient 0.279, P = 0.049]; for WBC count of 251-1,000 cells/mm3 , mean ± SD 29.3 ± 15.2 [ß coefficient 0.320, P = 0.024]). CONCLUSION: Although all participants in the analysis had SF WBC counts within the "normal" range, total SF WBC count appears to be a biomarker for synovitis on MRI and may also predict response to antiinflammatory treatment.

Avoiding perforations in endodontics.

PRECIS: While it will be impossible to eliminate all iatrogenic errors in endodontics, by focusing on key areas during the endodontic process, we can reduce the potential for problems for ourselves and our patients.