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Objective: To describe the associations between infrapatellar fat pad (IPFP) signal intensity alteration at baseline and knee symptoms and structural changes in older adults.Methods: A total of 874 subjects (mean 62.1 years, 50.1% female) selected randomly from local community were studied at baseline and 770 were followed up (only 357 had MRI at follow-up) over 2.6 years. T1-weighted or T2-weighted fat suppressed MRI was used to assess IPFP signal intensity alteration (0-3), cartilage volume, cartilage defects and bone marrow lesions (BMLs) at baseline and 2.6 years later. Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index questionnaire. Radiographic osteoarthritis (OA) was assessed.Results: In cross-sectional analyses, IPFP signal intensity alteration was significantly and positively associated with total knee pain as well as knee cartilage defects, BMLs and knee radiographic OA and negatively associated with patellar cartilage volume after adjustment for age, sex, body mass index and/or radiographic OA. Longitudinally, baseline signal intensity alteration within IPFP was significantly and positively associated with increases in knee pain when going upstairs/downstairs as well as increases in tibiofemoral cartilage defects and BMLs, and negatively associated with change in lateral tibial cartilage volume in multivariable analyses.Conclusions: IPFP signal intensity alteration at baseline was associated with knee structural abnormalities and clinical symptoms cross-sectionally and longitudinally in older adults, suggesting that it may serve as an important imaging biomarker in knee OA. [ABSTRACT FROM AUTHOR]

Objective: To describe the cross-sectional and longitudinal associations between knee regional effusion-synovitis and structural changes in older adults.Methods: A total of 977 subjects were randomly selected from the local community (mean 62 years, 50% female) at baseline and 404 were followed up 2.6 years later. T2-weighted MRI was used to assess knee effusion-synovitis in four subregions: suprapatellar pouch, central portion, posterior femoral recess and subpopliteal recess. Knee cartilage defects, cartilage volume and bone marrow lesions (BMLs) were measured using MRI at baseline and follow-up.Results: Cross-sectionally, effusion-synovitis in most subregions was significantly associated with a higher risk of cartilage defects, BMLs and reduced cartilage volume. Longitudinally, suprapatellar pouch effusion-synovitis at baseline predicted an increase in cartilage defects (p<0.01), loss of cartilage volume (p=0.04) and an increase in BMLs (p=0.02) in multivariable analyses. The significant associations of effusion-synovitis with cartilage volume and BMLs disappeared after adjustment for cartilage defects. Effusion-synovitis in whole knee joint (p<0.01) and subpopliteal recess (p<0.05) was consistently associated with longitudinal changes in cartilage defects but not in cartilage volume and BMLs.Conclusions: There are independent associations between knee joint effusion-synovitis and knee cartilage defects in both cross-sectional and longitudinal analyses, suggesting a potential causal relationship. The associations of effusion-synovitis with BMLs and cartilage volume were largely dependent on cartilage defects, suggesting potential causal pathways. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether offspring having at least one parent with a total knee replacement for severe primary knee osteoarthritis (OA) have an increased risk of worsening knee pain over 8 years as compared with controls with no family history of knee OA.Methods: A total of 219 participants (mean age 48 years, range 29-61 years) with 115 offspring and 104 controls participated in this study. Knee pain was respectively assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 2 years and 10 years. T1-weighted or T2-weighted fat saturated MRI of the right knee was performed to assess knee cartilage defects, bone marrow lesions, effusion, meniscal extrusion and tears.Results: Compared with controls, the prevalence of knee pain for offspring was similar at 2 years (56% vs 54%, p=0.764) and higher at 10 years (74% vs 54%, p=0.002). Over 8 years, offspring more frequently had an increase in total knee pain (66% vs 41% ≥1 point increase, p=0.003) and in all subscales apart from walking (all p<0.05). In multivariable analysis, after adjustment for confounders and structural factors, offspring had an elevated risk of worsening total knee pain (OR=2.16, 95% CI 1.14 to 4.12), as well as each subscale except for walking and standing (OR=1.95 to 3.30, all p<0.05).Conclusions: Offspring with a family history of knee OA have an increased risk of worsening knee pain, which is independent of structural factors, suggesting that genetic factors may be involved in the pathogenesis of knee pain. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA).Methods: A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score.Results: Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years.Conclusions: In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation.Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404). [ABSTRACT FROM AUTHOR]

Introduction There is a paucity of data examining the effects of weight change on knee joint structures and symptoms. This study examined the effect of weight change on change in knee cartilage volume and symptoms in an obese cohort. Methods 112 obese subjects (Body Mass Index ≥30 kg/m²) were recruited from various community sources to examine the effect of obesity on musculoskeletal health. Tibial cartilage volume, determined by MRI, and knee symptoms, determined by the Western Ontario and McMaster Osteoarthritis Index (WOMAC) were collected at baseline and an average of 2.3 years later. Results Percentage weight change was associated with change in medial tibial cartilage volume (β -1.2 mm³, 95% CI -2.3 to -0.1 mm³, p=0.03) that was consistent throughout the spectrum of weight loss through to mild weight gain. Percentage weight change was not associated with change in the lateral tibial (p=0.93) or patella ( p=0.32) cartilage volumes. Percentage weight change was associated with change in all WOMAC subscales (all p≤0.01): pain (β -1.8 mm, 95% CI -3.2 to -0.4 mm), stiffness (β -1.6 mm, 95% CI -2.5 to -0.7 mm) and function (β -6.9 mm, 95% CI -11.6 to -2.1 mm). Conclusions The linearity of effect implies that weight loss is associated with reduced medial cartilage volume loss and improved knee symptoms, while weight gain is associated with increased medial cartilage volume loss and worse knee symptoms. These results suggest that in obese people, small amounts of weight change may have the potential for a disease modifying effect on both knee joint structure and symptoms. While weight loss is an important primary management strategy in obese individuals, avoidance of further weight gain should also be a clinical goal. [ABSTRACT FROM AUTHOR]

Background There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. Objective To systematically review the literature for the relationship between serum CRP levels measured by a high sensitivity method (high sensitive CRP (hs-CRP)) and OA, as well as the correlation between circulating CRP levels and OA phenotypes. Methods MEDLINE, EMBASE and CINAHL databases were systematically searched from January 1992 to December 2012. Studies were included when they met the inclusion criteria and data from studies were extracted. Two independent reviewers assessed study quality using a modified Newcastle-Ottawa Quality Assessment Scale. Meta-analyses were performed to pool available data from included studies. Results 32 studies met the inclusion criteria. Serum hs-CRP levels in OA were modestly but statistically significantly higher than controls (mean difference=1.19 mg/L, 95% CI 0.64 to 1.73, p<0.001) with significant heterogeneity between studies. Levels were significantly associated with pain (r=0.14, 95% CI 0.09 to 0.20, p<0.001) and decreased physical function (r=0.25, 95% CI 0.13 to 0.39, p<0.001). No significant associations were found between hs-CRP levels and radiographic OA. Conclusions Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA. [ABSTRACT FROM AUTHOR]

Objective To describe the associations between overweight measures in childhood and knee pain, stiffness and dysfunction among adults 25 years later. Methods Subjects broadly representative of the Australian population (n=449, aged 31-41 years, female 48%) were selected from the Australian Schools Health and Fitness Survey of 1985. Height, weight and knee injury were recorded and knee pain was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Childhood height, weight and knee injury had been measured according to standard protocols 25 years earlier and body mass index (BMI) and percentage overweight were calculated. Results The prevalence of knee pain was 34% and overweight in childhood and adulthood was 7% and 48%, respectively. Overall, there were no significant associations between childhood overweight measures and total WOMAC knee pain, stiffness and dysfunction scores in adulthood. However, in men, overweight in childhood was associated with adulthood WOMAC pain (relative risk (RR) 1.72, 95% CI 1.11 to 2.69) and childhood weight and BMI were associated with WOMAC stiffness and dysfunction. Childhood weight, BMI and overweight were all associated with the presence of adulthood walking knee pain in men and the whole sample. Most of these associations were independent of adult overweight measures. Subjects who were overweight in both childhood and adult life had a significant increase in the risk and prevalence of adulthood walking pain (RR=2.42, 95% CI 1.06 to 5.53). Conclusions Childhood overweight measures were significantly associated with adulthood knee mechanical joint pain, stiffness and dysfunction among men, independent of adult overweight, suggesting that childhood overweight may lead to later knee symptoms in men. [ABSTRACT FROM AUTHOR]

Objective To investigate cross-sectional and longitudinal associations between serum leptin levels and knee cartilage thickness in older adults. Methods A prospective cohort of 163 randomly selected subjects (mean 63 years, range 52-78, 46% women) was studied. Knee cartilage thickness at medial tibial, lateral tibial, femoral and patellar sites was determined using T1-weighted fat-suppressed MRI. Serum leptin levels were measured by radioimmunoassay. Radiographic osteoarthritis, body fat (%), trunk fat (%), weight and height were measured, and body mass index (BMI) was calculated. Results Cross-sectionally, serum levels of leptin were negatively associated with femoral (β: -0.013, 95% CI -0.022 to -0.003), medial tibial (β: -0.009, 95% CI -0.018 to -0.001), lateral tibial (β: -0.012, 95% CI -0.021 to -0.003) and patellar (β: -0.014, 95% CI -0.026 to -0.002) cartilage thickness after adjustment for covariates. Moreover, BMI, trunk fat and total body fat were negatively associated with cartilage thickness, and the significant associations disappeared after further adjustment for leptin. Longitudinally, both baseline leptin and change in leptin were associated with greater changes in medial tibial cartilage thickness (β: -0.004, 95% CI -0.007 to -0.001 and β: -0.009, 95% CI -0.018 to -0.001, respectively) in multivariable analyses. Conclusions Serum levels of leptin are independently and consistently associated with reduced cartilage thickness cross-sectionally and longitudinally. In addition, the associations between adiposity measures and cartilage thickness are mediated by leptin, suggesting leptin may play a key role in cartilage thinning. [ABSTRACT FROM AUTHOR]

Objective Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5x10-7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA. [ABSTRACT FROM AUTHOR]

Objectives To investigate cross-sectional and longitudinal associations between systemic bone mineral density (BMD), subchondral BMD (sBMD) and knee cartilage thickness in older adults with or without radiographic osteoarthritis (ROA). Methods A prospective cohort of 158 randomly selected subjects (mean 63 years, 48% women) including 69 non-ROA and 89 ROA subjects were studied at baseline and 2.7 years later. Knee cartilage thickness was semi-automatically determined from T1-weighted fat-suppressed MRI. Knee cartilage volume was measured from MRI. Systemic BMD and sBMD were measured by dual-energy X-ray absorptiometry (DXA). Results Cross-sectionally, total body, total hip, spine BMD and/or lateral tibial sBMD were significantly and positively associated with femoral, lateral tibial and/or patellar cartilage thickness in subjects with ROA after adjustment for potential confounders. Longitudinally, a high total body BMD was associated with an increase in femoral cartilage thickness (β: 0.33 mm/g/cm², 95% CI 0.13 to 0.53); a high spine BMD was associated with increases in femoral and lateral tibial cartilage thickness (β: 0.25 mm/g/cm2, 95% CI 0.10 to 0.41; and β: 0.18 mm/g/cm2, 95% CI: 0.01 to 0.34, respectively) and a high medial tibial sBMD was associated with an increase in medial tibial cartilage thickness (β: 0.45 mm/g/cm², 95% CI 0.02 to 0.89) in subjects with ROA. In contrast, there were no significant associations between baseline systemic BMD, sBMD and cartilage volume loss, nor were there associations between BMD and cartilage thickness in subjects without ROA. Conclusions Both systemic and subchondral BMD are positively associated with increased cartilage thickness in subjects with ROA, suggesting BMD may play a protective role against cartilage loss in knee OA. [ABSTRACT FROM AUTHOR]

Introduction Meniscal tears are commonly found on MRI and increase the risk for radiographic knee osteoarthritis (OA). While meniscectomy is recommended when knee pain is severe or functionally disabling, it is unclear how to best treat meniscal tears without these symptoms. The aim of this longitudinal study was to examine the effect of weight change on knee cartilage and pain in a cohort of community-based adults with and without meniscal tears detected by MRI. Methods 250 adults with no history of knee OA or knee injury were recruited from the general community and weight-loss clinics. MRI of the knee, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), weight and height were measured at baseline and again at follow-up approximately 2 years later. Results Medial meniscal tears were present in 36 (18%) of the cohort. In those with medial meniscal tears, after adjustment for confounders, percentage weight change was significantly associated with percentage change in medial tibial cartilage volume (β 0.2% 95% CI 0.08% to 0.3% p=0.002) and knee pain (β 11.6% 95% CI 2.1% to 21.1% p=0.02). That is, for every 1% gain in weight, there was an associated 0.2% increased loss of medial tibial cartilage volume and 11.6% increase in pain. In those with no medial meniscal tear, neither change in medial tibial cartilage volume (β 0.02% 95% CI -0.01% to 0.10% p=0.53) or pain (β 1.9% 95% CI -2.2% to 6.1% p=0.36) were significantly associated with change in weight.Conclusions This study demonstrated that among adults with medial meniscal tears, weight gain is associated with increased cartilage loss and pain, while weight loss is associated with the converse. This suggests attention to weight is particularly important in the management of people with medial meniscal tears. [ABSTRACT FROM AUTHOR]

Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world's population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA. [ABSTRACT FROM AUTHOR]

Background Vitamin D is important for bone, cartilage and muscle function but there are few studies on its association with joint pain. Objective To investigate whether serum vitamin D predicts change in knee and hip pain in older adults. Methods Longitudinal population-based cohort study of randomly selected older adults (n=769) aged 50-80 years (mean 62 years); 50% were male. Serum 25-hydroxyvitamin D (25-OHD) was assessed at baseline by radioimmunoassay, and pain at baseline, 2.6 and/or 5 years using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire. We used linear regression with adjustment for age, sex, body mass index and season, then further adjusted for potential structural mechanisms (radiographic osteoarthritis, bone marrow lesions, chondral defects and muscle strength). Results Mean total knee WOMAC score was 3.2 (range 0-39). 4.2% of participants had moderate vitamin D deficiency at baseline (25-OHD 12.5-25 nmol/l). 25-OHD <25 nmol/l predicted change in knee pain (using total WOMAC score) over 5 years (ß=2.41, p=0.002) with a similar effect size for hip pain over 2.4 years (ß=2.20, p=0.083). Results were consistent within pain subscales, and the association was independent of demographic, anthropometric and structural covariates. No association was present when 25-OHD was analysed as a continuous measure. Conclusions Moderate vitamin D deficiency independently predicts incident, or worsening of, knee pain over 5 years and, possibly, hip pain over 2.4 years. Therefore correcting moderate vitamin deficiency may attenuate worsening of knee or hip pain in elderly people but giving supplements to those with a higher 25-OHD level is unlikely to be effective. [ABSTRACT FROM AUTHOR]

Objectives This study describes the longitudinal association between objectively assessed physical activity (PA) and knee structural change measured using MRI. Methods 405 community-dwelling adults aged 51-81 years were measured at baseline and approximately 2.7 years later. MRI of the right knee at baseline and follow-up was performed to evaluate bone marrow lesions (BMLs), meniscal pathology, cartilage defects, and cartilage volume. PA was assessed at baseline by pedometer (steps/day). Results Doing ≥10 000 steps/day was associated with BML increases (RR 1.97, 95% CI 1.19 to 3.27, p=0.009). Participants doing ≥ 10 000 steps/day had a 1.52 times (95% CI 1.05 to 2.20, p=0.027) greater risk of increasing meniscal pathology score, which increased to 2.49 (95% CI 1.05 to 3.93, p=0.002) in those with adverse meniscal pathology at baseline. Doing =10 000 steps/day was associated with a greater risk increasing cartilage defect score in those with prevalent BMLs at baseline (RR 1.36, 95% CI 1.03 to 1.69, p=0.013). Steps/day was protective against volume loss in those with more baseline cartilage volume but led to increased cartilage loss in those with less baseline cartilage volume. (p=0.046 for interaction). Conclusions PA was deleteriously associated with knee structural change, especially in those with pre-existing knee structural abnormalities. This suggests individuals with knee abnormalities should avoid doing ≥ 10 000 steps/day. Alternatives to weight-bearing activity may be needed in order to maintain PA levels required for other aspects of health. [ABSTRACT FROM AUTHOR]

Background Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications. Objective To review published evidence on safety and efficacy of IL-6i in inflammatory diseases. Methods We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov. Results Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable. Conclusions IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation. [ABSTRACT FROM AUTHOR]

Background Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. Methods Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. Results The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. Conclusions The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition. [ABSTRACT FROM AUTHOR]

Objective To determine the association between inflammatory markers and change in knee pain over 5 years. Methods A total of 149 randomly selected subjects (mean 63 years, range 52-78; 46% female) was studied. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF-α) and interleukin (IL)-6 were measured at baseline and 2.7 years later. Knee pain was recorded using the Western Ontario and McMasters osteoarthritis index questionnaire at baseline and 5 years later. Knee radiographic osteoarthritis of both knees was assessed at baseline, and knee bone marrow lesions, joint effusion and cartilage defects were determined using T1 or T2-weighted fat saturated MRI. Results After adjustment for confounding variables, baseline hs-CRP was positively associated with change in total knee pain (β=0.33 per mg/l, p=0.032), as well as change in the pain at night in bed (β=0.12 per ml/pg, p=0.010) and while sitting/lying (β=0.12 per ml/pg, p=0.002). Change in hs-CRP was also associated with change in knee pain at night and when sitting/lying (both p<0.05). Baseline TNFα and IL-6 were associated with change in pain while standing (β=0.06 per ml/pg, p=0.033; β=0.16 per ml/pg, p=0.035, respectively), and change in TNFα was positively associated with change in total knee pain (β=0.66 ml/pg, p=0.020) and change in pain while standing (β=0.26 ml/pg, p=0.002). Adjustment for radiographic osteoarthritis or MRI-detected structural abnormalities led to no or minor attenuation of these associations. Conclusion Systemic inflammation is an independent predictor of worsening knee pain over 5 years. [ABSTRACT FROM AUTHOR]

Objectives Apprentice thoroughbred racing jockeys have a higher fall rate than their more experienced counterparts. The authors describe rates of occurrence and investigate risk factors for falls among less-experienced thoroughbred flat racing jockeys in Australia who commenced their race riding career between August 2002 and July 2009. Methods Data on race-day falls were extracted from stewards' reports. Denominator data were provided by Racing Information Services Australia on races conducted in Australia. HRs were estimated using time-to-event (survival analysis) methods. Results Factors found to be associated with falls by less-experienced jockeys (as indicated by number of career rides or career stage) were older jockey age at commencement of career (p=0.001), fewer previous rides this meeting (p<0.001), fewer previous starts by the horse (p<0.001), younger horse age (p<0.001), lower race grade (p<0.001), lower prize money (p<0.001), shorter race distance (p<0.001) and drier track rating (p<0.001). Apprentice experience was inversely and strongly associated with increased rates of falls (p<0.001). Three indicators of less accomplished horses (lower race grade, fewer previous starts by the horse and less prize money at stake) and two race conditions (drier tracks and shorter race distance) were found to be associated with a progressively higher hazard of falls for less-experienced jockeys. Conclusions This study identified factors that preferentially contribute to falls by inexperienced jockeys. The authors suggest that consideration be given to restricting apprentice jockeys with little race-riding experience from riding horses that have not yet won a race (maiden) or that have had few previous race starts. [ABSTRACT FROM AUTHOR]

Objectives To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). Methods Adults aged 50-80 years (n = 59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale. Results At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm². VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (-14.5 mm, 95% CI -28.1 to -0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (-175.7 mm², 95% CI -327.2 to -24.3) with a trend after 12 months (-146.5 mm², 95% CI -307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms. Conclusions ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach. [ABSTRACT FROM AUTHOR]

The authors report a rare case of renal cell carcinoma (RCC) metastasis to the paranasal sinuses. The authors review RCC and its potential for sinonasal metastasis and discuss the variable presentation and need for clinical suspicion for early diagnosis and treatment. A 74-year-old man presented with numbness of the left side of the face, reduced visual acuity and ptosis 12 years after nephrectomy for RCC. Imaging studies showed a lesion in the left pterygopalatine fossa and the histological features supported the diagnosis of metastatic RCC. RCC metastasis to the paranasal sinuses is very rare and can present with various symptoms depending on the affected organ. These symptoms occasionally are the initial manifestation of renal RCC and it is very important to recognise them so that the patient receives the appropriate therapy to improve survival. [ABSTRACT FROM AUTHOR]

Abstract Objectives To assess the effectiveness of calcium supplementation for improving bone mineral density in healthy children and to determine if any effect is modified by other factors and persists after supplementation stops. Design Meta-analysis. Data sources Electronic bibliographic databases, hand searching of conference proceedings, and contacting authors for unpublished data. Review methods We included randomised placebo controlled trials of calcium supplementation in healthy children that lasted at least three months and had bone outcomes measured after at least six months of follow-up. Two reviewers independently extracted data and assessed quality. Meta-analyses predominandy used fixed effects models with outcomes eiven as standardised mean differences. Results We included 19 studies involving 2859 children. Calcium supplementation had no effect on bone mineral density at the femoral neck or lumbar spine. There was a small effect on total body bone mineral content (standardised mean difference 0.14, 95% confidence interval 0.01 to 0.27) and upper limb bone mineral density (0.14, 0.04 to 0.24). This effect persisted after the end of supplementation only at the upper limb (0.14, 0.01 to 0.28). There was no evidence that sex, baseline calcium intake, pubertal stage, edinicity, or level of physical activity modified the effect. Conclusions The small effect of calcium supplementation on bone mineral density in the upper limb is unlikely to reduce the risk of fracture, either in childhood or later life, to a degree of major public healm importance. [ABSTRACT FROM AUTHOR]

Objective: To describe the relation between spinal degenerative disease, allelic variation in the vitamin D receptor gene, and lifestyle factors in a population-based association study.Methods: Random population-based sample of 110 men and 172 women over 60 years of age participating in the Dubbo Osteoporosis Epidemiology Study who had spinal radiographs (performed according to a standardised approach), assessment of lifestyle factors, bone densitometry as well as blood taken for genotyping.Results: Spinal degenerative disease of varying severity was common in this sample. Multivariate analysis of genetic and lifestyle factors simultaneously strengthened the statistical significance of each indicating the presence of additive gene environment interaction. Allelic variation in the vitamin D receptor gene was associated with severity of osteophytosis (adjusted OR "TT" v "tt" 0.41, 95% CI 0.17, 0.97), presence of disc narrowing (adjusted OR "TT" v "tt" 0.45, 95% CI 0.20, 0.99) and weakly with presence of osteophytosis (adjusted OR "TT" v "tt" 0.47, 95% CI 0.19, 1.16) but not with severity of disc narrowing (OR "TT" v "tt" 1.05, 95% CI 0.40, 2.72) or apophyseal arthritis (OR "TT" v "tt" 0.63, 95% CI 0.24, 1.59). Adjustment for femoral neck bone density did not change these findings suggesting that the association is not mediated through bone density. Presence and severity of spinal degenerative disease increased with age at all sites. Current smoking increased both the presence (adjusted OR 9.70, 95% CI 2.08, 45.1) and severity (adjusted OR 2.91, 95% CI 1.16, 9.03) of spinal osteophytosis with intermediate values for past smokers. Severity of osteophytosis was also independently associated with body mass index and quadriceps strength consistent with a contributory effect of physical loading.Conclusions: In this elderly sample, both genetic and lifestyle factors were associated with the presence and severity of spinal degenerative disease. There were site specific differences in associations at the spine, which may be because of misclassification of disease status or may indicate possible environmental and genetic differences in the pathophysiology of spinal degenerative disease. Further studies are required to confirm these findings in different population samples and to further explore potential aetiological mechanisms particularly gene environment interaction. [ABSTRACT FROM AUTHOR]

Investigates the risk factors in predicting osteoporotic fractures by postural instability and bone density in Dubbo, New South Wales. Measurement on the incidence of fracture for individual subjects; Percentage on overall incidence of atraumatic fractures in men and women; Effectiveness of bone mineral density, body sway and muscle strength.

The authors reflect on the cardiovascular risks of calcium supplementation in older women and on research which has examined the use of calcium supplements in older women. They suggest that the increased risk of myocardial infarction associated with calcium supplementation outweighs a proven reduction in fracture that has been associated with calcium supplementation. They argue that based on available evidence it seems prudent to only use calcium supplementation in patients who are also being given treatment for osteoporosis with drugs including bisphopsphonates.

The article discusses research on the impact of vitamin D supplementation on bone mineral density in healthy children. Analyses indicate that vitamin D supplementation could lead to clinically useful improvements, especially in bone mineral density of the lumbar spine. Bone mineral density at the hip, lumbar spine and total body bone mineral content were the primary outcomes of the study. Findings suggest that vitamin supplementation had no significant effects on bone mineral content or on hip or forearm bone density.

Objectives Riding thoroughbred racehorses is a hazardous occupation. In this study, we investigated risk factors associated with falls by licensed thoroughbred racing jockeys participating in flat races conducted in Australia. Methods Data on race-day falls were extracted from stewards' reports. Denominator data were provided by Racing Information Services Australia on races conducted in Australia from August 2002 until July 2006. Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses were stratified by race grade (maiden, class, open/restricted). Results In multivariable analyses, factors associated with falls were female sex of jockey (IRR 1.11; 95% CI 1.00 to 1.23), being an apprentice jockey (IRR 1.51; 95% CI 1.39 to 1.63), being an amateur jockey (IRR 1.44; 95% CI 1.11 to 1.86), drier tracks (p<0.001), younger horse age (p<0.001), shorter race distance (p<0.001), lower field size (p=0.013) and lower race grade (p<0.001). The IRRs for five factors associated with falls differed by category of race grade: those for apprentice jockey (interaction p=0.003), higher prize money (interaction p<0.001) and shorter race distance (interaction p=0.041) were greater in lower race grades, while those for fewer previous rides this meeting (interaction p=0.027) and drier track rating (interaction p=0.035) were greater in higher race grades. Female jockeys had a significantly higher incidence of falls when riding horses under 4 years of age in open and restricted races (interaction p=0.038), and the effects of lower field size in maiden races, and of shorter races, were more pronounced for falls occurring before the race. Conclusions We identified a range of factors associated with falls to thoroughbred racing jockeys riding in flat races that adds to the evidence base for formulating strategies to improve occupational health and safety standards in the thoroughbred racing industry. [ABSTRACT FROM AUTHOR]