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Objective: To describe the associations of glucose homeostasis and metabolic syndrome (MetS) measures with knee cartilage defects and cartilage volume in young adults., Methods: Fasting blood biochemistry, waist circumference and blood pressure measures were collected 4-5 years prior to knee magnetic resonance imaging (MRI) scans. Blood measures included levels of glucose, insulin, triglyceride and high-density lipoprotein cholesterol (HDL-C). Homeostatic model assessment 2-insulin resistance (HOMA2-IR), HOMA2-beta cell function (HOMA2-β), HOMA2-insulin sensitivity (HOMA-S) and MetS were calculated or defined. Knee cartilage defects and cartilage volume were measured from MRI scans. Data were analysed using log binomial or linear regressions., Results: Among 328 participants (47.3% were females, aged 26-36 years at baseline), 40 (12.7%) had hyperglycaemia and 21 (6.7%) had MetS. Glucose homeostasis measures (except fasting glucose) were associated with tibiofemoral cartilage defects (fasting insulin: relative risk (RR) 1.05, 95% confidence interval (CI) 1.01 to 1.08; HOMA2-IR: 1.44, 1.08 to 1.92; HOMA2-β: 2.59, 1.33 to 5.07; HOMA2-S: 0.36, 0.18 to 0.72), but not patellar cartilage defects. There were no associations between glucose homeostasis measures and knee cartilage volume. High waist circumference (RR 2.32, 95% CI 1.18 to 4.54) and low HDL-C (RR 1.99, 95% CI 1.08 to 3.69) were associated with tibiofemoral cartilage defects, but no other associations were observed between MetS or its components and cartilage defects or volume., Conclusion: Insulin resistance, high waist circumference and low HDL-C were associated with higher risk of tibiofemoral cartilage defects, suggesting glucose homeostasis and some MetS components may affect early cartilage damage in young adults., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory., Objective: To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels., Design, Setting, and Participants: A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013., Interventions: Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years., Main Outcomes and Measures: Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI)., Results: Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text]., Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis., Trial Registration: clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022.

Introduction: Recent evidence suggests that bone marrow lesions (BMLs) play a pivotal role in knee osteoarthritis (OA). The aims of this study were to determine: 1) whether baseline BML presence and/or severity predict site-specific cartilage defect progression and cartilage volume loss; and 2) whether baseline cartilage defects predict site-specific BML progression., Methods: A total of 405 subjects (mean age 63 years, range 52 to 79) were measured at baseline and approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee was performed to measure knee cartilage volume, cartilage defects (0 to 4), and BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial (LT), and lateral femoral (LF) sites. Logistic regression and generalized estimating equations were used to examine the relationship between BMLs and cartilage defects and cartilage volume loss., Results: At all four sites, baseline BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P < 0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P < 0.05) at the same site. In multivariable analysis, there was a significant relationship between BML severity and defect progression at all four sites (OR 1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF, LT, and LF sites (β -22.1 to -42.0, all P < 0.05). Additionally, baseline defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7, all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at the MT and LT sites when both larger defects and BMLs were present at baseline (all P < 0.05)., Conclusions: Baseline BMLs predicted site-specific defect progression and cartilage volume loss in a dose-response manner suggesting BMLs may have a local effect on cartilage homeostasis. Baseline defects predicted site-specific BML progression, which may represent increased bone loading adjacent to defects. These results suggest BMLs and defects are interconnected and play key roles in knee cartilage volume loss; thus, both should be considered targets for intervention.

Although knee malalignment is a risk factor for the progression of unicompartmental knee osteoarthritis (OA), it is unclear how this relationship is mediated. Cartilage defects are known to predate cartilage loss and the onset of knee OA, and it may be that knee malalignment increases the risk of unicompartmental knee cartilage defects. Knee radiographs and MRI were performed on a total of 202 subjects, 36.6% of whom had radiographic knee OA, to determine the relationship between static knee alignment and knee cartilage defects. Analyses were performed for the entire cohort, as well as for healthy and OA subgroups. For every 1 degrees increase in a valgus direction, there was an associated reduced risk of the presence of cartilage defects in the medial compartment of subjects with knee OA (p = 0.02), healthy subjects (p = 0.002), and the combined (p < 0.001) group. Moreover, for every 1 degrees increase in a valgus direction, there was an associated increased risk of the presence of lateral cartilage defects in the OA group (p = 0.006), although the relationship between change toward genu valgum and lateral compartment cartilage defects did not persist for the healthy group (p = 0.16). This cross-sectional study has demonstrated that knee alignment is associated with the risk for compartment specific knee cartilage defects in both healthy and arthritic people. Given that the natural history of cartilage volume reduction appears to be predated by the presence of cartilage defects, whether knee alignment affects the longitudinal progression from cartilage defects to cartilage loss requires further examination., ((c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: To examine the associations between meniscal tear, knee structure, osteoarthritis (OA) risk factors, radiographic change, and symptoms in a largely non-osteoarthritic cohort., Methods: This cross-sectional study included 294 subjects with mean age 47 (SD 6) years, body mass index (BMI) 28 (SD 5), and 58% were female. Meniscal tear, knee cartilage defect score, quantitative tibial and femoral cartilage volume, and tibial plateau bone area were determined using T1-weighted fat saturated magnetic resonance images., Results: In multivariable analysis, prevalence of meniscal tear was significantly associated with age (OR 1.06 to 1.12/year, all p < 0.05), BMI (OR 1.06 to 1.11/kg/m(2), all p < 0.05 with the exception of the lateral anterior horn), sex (women vs men: OR 4.14 to 4.23, p < 0.01 at the medial and lateral meniscal body site), and family history of OA (OR 1.97 to 2.01, p < 0.05 at the lateral meniscal anterior and posterior horns). Meniscal tear was associated with a higher tibiofemoral cartilage defect score at lateral body and all medial sites, lower tibial and femoral cartilage volume at the lateral compartment, markedly higher prevalent radiographic OA at medial compartment, and greater tibial bone area. Moreover, meniscal tear at the lateral posterior and anterior horns was significantly associated with WOMAC pain, stiffness, and function scores., Conclusion: Meniscal tear at specific sites shares risk factors with knee OA. Importantly, meniscal tear is associated with cartilage defect, loss of cartilage volume, alteration in bone size, and prevalence of radiographic OA, suggesting that meniscal tear in non-OA subjects appears to be an early event in the disease process, and may be a risk factor for knee cartilage damage and articular structural changes.

Objective: It remains unclear whether malalignment of the knee is a cause of knee OA or a marker of disease progression. We investigated whether baseline malalignment of the knee predicts subsequent change in knee cartilage volume and chondral defects in subjects with and without radiographic knee osteoarthritis (OA)., Methods: A convenience sample of 315 male and female subjects (mean age 45 yrs, range 26-61) was followed up for a mean period of 2.4 years. Anatomic knee alignment was assessed on a standing anterior-posterior semiflexed view of the right knee and defined as the angle subtended by a line drawn through the midshaft of the femur with respect to one drawn through the midshaft of the tibia. T1-weighted fat saturation magnetic resonance imaging scans were performed on the same knee at baseline and followup for cartilage volume and chondral defects., Results: Knee alignment was normally distributed in this sample with a mean of 178.2 degrees (SD 1.9 degrees). Fifty-five percent of subjects were < 178.5 degrees, while 14% were > 180 degrees. After adjustment for age, sex, body mass index, previous knee injury, and OA family history, neither category of alignment at baseline was associated with subsequent loss of lateral and medial tibial cartilage volume. Similarly, there was no association between malalignment and progression of chondral defects. The results remained the same when stratified by radiographic OA status., Conclusion: Our adequately powered study shows that baseline knee alignment is not associated with subsequent loss of cartilage volume or progression of chondral defects over 2 years. Further studies with a longterm followup are needed, but these results suggest malalignment is primarily a marker of disease progression.

Objectives To describe associations between MRI markers with knee symptoms in young adults. Methods Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008–2010) and at the 6- to 9-year follow-up (CDAH-3; 2014–2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. Results The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s. d. 2.72) and 43.27 (s. d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P  < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P  = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P  = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P  = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P  = 0.001] and knee symptoms assessed after 6–9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P  < 0.001] and 6–9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P  = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6–9 years. Conclusion BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults. [ABSTRACT FROM AUTHOR]

Background: Previous studies have been inconsistent concerning the association between smoking and risk of osteoarthritis (OA). This study aimed to explore the associations of smoking status and change in cartilage volume of OA in two longitudinal cohorts. Methods: Subjects from the Osteoarthritis Initiative cohort (OAI, n = 593) and the Tasmanian Older Adult Cohort (TASOAC, n = 394) were included in this study. For both cohorts, participants were classified into three groups based on their smoking status, namely 'never', 'former', and 'current' smokers. The outcome measures were the annual rate of change of tibiofemoral cartilage volume over 2 years in OAI and of tibial cartilage volume over 2.6 years in TASOAC. Potential confounders were balanced using the inverse probability of treatment weighting (IPTW) method. Results: Overall, 42.3% and 37.4% of participants were former smokers, and 5.7% and 9.3% were current smokers in the OAI and TASOAC cohorts, respectively. Compared to never smokers, neither former nor current smoking was associated with risk of the annual rate of change of tibiofemoral cartilage volume in OAI (former smoker: β=-0.068%/year, 95% confidence interval [CI] -0.824 to 0.688, p = 0.860; current smoker: β=-0.222%/year, 95% CI -0.565 to 0.120, p = 0.204) and tibial cartilage volume in TASOAC (former smoker: β = 0.001%/year, 95% CI -0.986 to 0.989, p = 0.998; current smoker: β=-0.839%/year, 95% CI -2.520 to 0.844, p = 0.329). Conclusions: Our findings from two independent cohorts consistently showed that smoking was not associated with knee cartilage loss in older adults. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most prevalent joint disorder characterized by joint structural pathological changes with the loss of articular cartilage as its hallmark. Tools that can predict cartilage loss would help identify people at high risk, thus preventing OA development. The recent advance of the metabolomics provides a new avenue to systematically investigate metabolic alterations in disease and identify biomarkers for early diagnosis. Using a metabolomics approach, the current study aimed to identify serum metabolomic signatures for predicting knee cartilage volume loss over 10 years in the Tasmania Older Adult Cohort (TASOAC). Cartilage volume was measured in the medial, lateral, and patellar compartments of the knee by MRI at baseline and follow-up. Changes in cartilage volume over 10 years were calculated as percentage change per year. Fasting serum samples collected at 2.6-year follow-up were metabolomically profiled using the TMIC Prime Metabolomics Profiling Assay and pairwise metabolite ratios as the proxies of enzymatic reaction were calculated. Linear regression was used to identify metabolite ratio(s) associated with change in cartilage volume in each of the knee compartments with adjustment for age, sex, and BMI. The significance level was defined at α = 3.0 × 10−6 to control multiple testing. A total of 344 participants (51% females) were included in the study. The mean age was 62.83 ± 6.13 years and the mean BMI was 27.48 ± 4.41 kg/m2 at baseline. The average follow-up time was 10.84 ± 0.66 years. Cartilage volume was reduced by 1.34 ± 0.72%, 1.06 ± 0.58%, and 0.98 ± 0.46% per year in the medial, lateral, and patellar compartments, respectively. Our data showed that the increased ratios of hexadecenoylcarnitine (C16:1) to tetradecanoylcarnitine (C14) and C16:1 to dodecanoylcarnitine (C12) were associated with 0.12 ± 0.02% reduction per year in patellar cartilage volume (both p < 3.03 × 10−6). In conclusion, our data suggested that alteration of long chain fatty acid β-oxidation was involved in patellar cartilage loss. While confirmation is needed, the ratios of C16:1 to C14 and C12 might be used to predict long-term cartilage loss. [ABSTRACT FROM AUTHOR]

Introduction: Inflammation has been suggested to be involved in the pathogenesis of osteoarthritis and pain. We sought to explore the associations between inflammatory serum markers and magnetic resonance imaging-defined long-term structural change and pain trajectory. Methods: A total of 169 randomly selected participants (mean age 63 years; 47% female) from a prospective cohort study were included in this study. Circulating levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (CRP) were measured at baseline. A knee MRI scan was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and at 10.7 years. Knee pain at four visits was measured by the WOMAC pain questionnaire, and pain trajectories were identified using group-based trajectory modelling. Linear, log-binomial and multi-nominal logistic regression were used for the analyses. Results: IL-6 was associated with lateral but not medial tibial CV loss (β = − 0.25% per annum, per standard deviation [SD] log pg/ml; P < 0.05) in the multivariate analysis. IL-6 was also associated with a 'Moderate pain' trajectory (relative risk ratio 1.93 per SD log pg/ml; 95% confidence interval 1.02–3.65) relative to the 'Minimal pain' trajectory group. There was no significant association of TNF-α and CRP with CV loss and pain trajectory groups with the exception of a beneficial relationship between CRP and medial tibial CV loss (β = 0.20% per annum, per SD log mg/l). No association between inflammatory markers and change in BML size was observed. Conclusions: IL-6 was independently associated with compartment-specific CV loss and worse pain trajectory, but the other markers studied were not, suggesting that components of inflammation are implicated in the pathogenesis of cartilage loss and developing a worse pain course. [ABSTRACT FROM AUTHOR]

Objective To describe the association between change in subchondral bone marrow lesions (BMLs) and change in tibiofemoral cartilage volume and knee symptoms in patients with symptomatic knee OA. Methods In total, 251 participants (mean 61.7 years, 51% female) were included. Tibiofemoral cartilage volume was measured at baseline and 24 months, and BML size at baseline, 6 and 24 months. Knee pain and function scores were evaluated at baseline, 6 and 24 months. Change in total and compartment-specific BML size was categorized according to the Least Significance Criterion. Linear mixed-effects models were used to evaluate the associations of change in BMLs over 6 and 24 months with change in cartilage volume over 24 months and knee symptoms over 6 and 24 months. Results Total BML size enlarged in 26% of participants, regressed in 31% and remained stable in 43% over 24 months. Compared with stable BMLs in the same compartment, enlarging BMLs over 24 months were associated with greater cartilage loss (difference: −53.0mm3, 95% CI: −100.0, −6.0), and regressing BMLs were not significantly associated with reduced cartilage loss (difference: 32.4mm3, 95% CI: −8.6, 73.3) over 24 months. Neither enlargement nor regression of total BML size over 6 and 24 months was associated with change in knee pain and function over the same time intervals. Conclusions In subjects with symptomatic knee osteoarthritis and BMLs, enlarging BMLs may lead to greater cartilage loss but regressing lesions are not associated with reduced cartilage loss while neither is associated with change in knee symptoms. [ABSTRACT FROM AUTHOR]

Objective To describe associations of body composition, physical activity and physical performance with knee cartilage thickness and subchondral bone area in young adults. Methods Body composition, physical activity and physical performance were measured 4–5 years prior to knee MRI. Cartilage thickness and bone area were measured quantitatively from MRI. Associations were assessed using linear regression analysis, with mediators being identified using mediation analysis. Results Participants (n = 186) were 31–41 years of age when the MRI was acquired and 48% were female. Greater lean mass was positively associated with cartilage thickness [β = 6.52 μm/kg (95% CI 0.86, 12.18)] and bone area [β = 13.37 mm2/kg (95% CI 5.43, 21.31)]. Physical performance measures were positively associated with cartilage thickness [long jump: β = 2.44 μm/cm (95% CI 0.70, 4.18); hand grip strength: 7.74 μm/kg (95% CI 1.50, 13.98); physical work capacity: 1.07 μm/W (95% CI 0.29, 1.85)] and bone area [long jump: β = 3.99 mm2/cm (95% CI 0.64, 7.34); hand grip strength: 19.06 mm2/kg (95% CI 7.21, 30.92); leg strength: 3.18 mm2/kg (95% CI 1.09, 5.28); physical work capacity: 3.15 mm2/W (95% CI 1.70, 4.60)]. Mediation analysis suggested these associations were mediated by lean mass (effect mediated: 27–95%). Conclusion Greater lean mass and better physical performance measured 4–5 years prior were associated with greater knee cartilage thickness and subchondral bone area in young adults, and the associations of physical performance were largely mediated by lean mass. These findings suggest lean mass may play an important role in maintaining knee joint health in young adults. [ABSTRACT FROM AUTHOR]

Objective To examine the association of metabolic syndrome (MetS) and its components with knee cartilage volume loss and bone marrow lesion (BML) change. Methods Longitudinal data on 435 participants from a population-based cohort study were analysed. Blood pressure, glucose, triglycerides and high-density lipoprotein (HDL) were collected. MetS was defined based on the National Cholesterol Education Program–Adult Treatment Panel III criteria. MRI of the right knee was performed to measure cartilage volume and BML. Radiographic knee OA was assessed by X-ray and graded using the Altman atlas for osteophytes and joint space narrowing. Results Thirty-two percent of participants had MetS and 60% had radiographic knee OA. In multivariable analysis, the following were independently associated with medial tibial cartilage volume loss: MetS, β = −0.30%; central obesity, β = −0.26%; and low HDL, β = −0.25% per annum. MetS, hypertriglyceridaemia and low HDL were also associated with higher risk of BML size increase in the medial compartment (MetS: relative risk 1.72, 95% CI 1.22, 2.43; hypertriglyceridaemia: relative risk 1.43, 95% CI 1.01, 2.02; low HDL: relative risk 1.67, 95% CI 1.18, 2.36). After further adjustment for central obesity or BMI, MetS and low HDL remained statistically significant for medial tibial cartilage volume loss and BML size increase. The number of components of MetS correlated with greater cartilage volume loss and BML size increase (both P for trend <0.05). There were no statistically significant associations in the lateral compartment. Conclusion MetS and low HDL are associated with medial compartment cartilage volume loss and BML size increase, suggesting that targeting these factors has the potential to prevent or slow knee structural change. [ABSTRACT FROM AUTHOR]

Objectives. Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. Methods. A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. Results. Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ≤ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). Conclusion. Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities. [ABSTRACT FROM AUTHOR]

Importance: Observational studies suggest that vitamin D supplementation is associated with benefits for knee osteoarthritis, but current trial evidence is contradictory.Objective: To compare the effects of vitamin D supplementation vs placebo on knee pain and knee cartilage volume in patients with symptomatic knee osteoarthritis and low vitamin D levels.Design, Setting, and Participants: A multicenter randomized, double-blind, placebo-controlled clinical trial in Tasmania and Victoria, Australia. Participants with symptomatic knee osteoarthritis and low 25-hydroxyvitamin D (12.5-60 nmol/L) were enrolled from June 2010 to December 2011. The trial was completed in December 2013.Interventions: Participants were randomly assigned to receive monthly treatment with oral vitamin D3 (50,000 IU; n = 209) or an identical placebo (n = 204) for 2 years.Main Outcomes and Measures: Primary outcomes were change in tibial cartilage volume (assessed using magnetic resonance imaging [MRI]) and change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score (0 [no pain] to 500 [worst pain]) from baseline to month 24. Secondary outcomes were cartilage defects and bone marrow lesions (assessed using MRI).Results: Of 413 enrolled participants (mean age, 63.2 years; 50% women), 340 (82.3%) completed the study. The level of 25-hydroxyvitamin D increased more in the vitamin D group (40.6 nmol/L) than in the placebo group (6.7 nmol/L) (P < .001) over 2 years. There were no significant differences in annual change of tibial cartilage volume or WOMAC pain score. There were no significant differences in change of tibiofemoral cartilage defects or change in tibiofemoral bone marrow lesions. Adverse events (≥ 1 per patient) occurred in 56 participants in the vitamin D group and in 37 participants in the placebo group (P = .04). [table: see text].Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and low serum 25-hydroxyvitamin D levels, vitamin D supplementation, compared with placebo, did not result in significant differences in change in MRI-measured tibial cartilage volume or WOMAC knee pain score over 2 years. These findings do not support the use of vitamin D supplementation for preventing tibial cartilage loss or improving WOMAC knee pain in patients with knee osteoarthritis.Trial Registration: clinicaltrials.gov Identifier: NCT01176344; anzctr.org.au Identifier: ACTRN12610000495022. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is a major clinical and public health problem, with no current medications approved as having disease modifying effects. HMG-CoA reductase inhibitors, or "statins", a drug class widely used to prevent cardiovascular events, could potentially affect OA progression via a number of mechanisms including their effects on lipid metabolism and inflammation. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether atorvastatin reduces the progression of knee structural changes and symptoms over 2 years in patients with symptomatic knee OA.Methods/design: 350 patients with symptomatic knee OA will be recruited through the OA Clinical Trial Network (in Melbourne, Hobart and Adelaide). They will be randomly allocated to the two arms of the study, receiving either 40 mg of atorvastatin or identical placebo once daily for 2 years. Magnetic resonance imaging of the knee will be performed at baseline and 2 years later. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is annual percentage change in knee cartilage volume. Secondary outcomes include progression of cartilage defects, bone marrow lesions, knee pain and function. The primary analysis will be by intention to treat, but per protocol analyses will also be performed.Discussion: The study will provide high-quality evidence to address whether atorvastatin has a novel disease modifying effect in OA by delaying the structural and symptomatic progression of knee OA. Thus, the trial has major public health and clinical importance, as if found to be beneficial, atorvastatin could produce substantial cost savings by delaying and possibly reducing the need for joint replacement surgery, and provide marked improvements in quality of life for people with OA.Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000190707 , registered on 18 February 2013. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe the cross-sectional and longitudinal relationship between hip bone marrow lesions (BMLs), high cartilage signal, and hip and knee pain. One hundred ninety-eight participants in the Tasmanian Older Adult Cohort Study with right hip MRI conducted at two time points, approx. 2.3 years apart, were included. Short T1 Inversion Recovery MR images were used to quantitatively measure hip BML size and determine high cartilage signal presence. Hip and knee pain were individually assessed using the Western Ontario and McMaster Universities Osteoarthritis index pain score. Fifty-five participants (28 %) had either femoral and/or acetabular BMLs. Cross-sectionally, the presence of large femoral, acetabular, or any hip BMLs was associated with higher odds of hip pain (OR = 4.42, 95% CI = 1.37-19.7; OR = 5.23, 95% CI = 1.17-22.9; OR = 4.43, 95% CI = 1.46-13.2, respectively). High cartilage signal was strongly associated with hip BMLs (OR = 6.45, 95% CI = 3.37-12.6), but not with pain. Longitudinally, incident acetabular (Mean diff = +5.90, 95% CI = +3.78 to +8.15) and femoral BMLs (Mean diff = +1.18, 95% CI = 0.23-1.94) were associated with worsening hip pain, while resolving femoral BMLs were associated with a decrease in knee pain (Mean diff = −3.18, 95% CI = −5.99 to −0.50). The evidence is consistent for hip, but not knee pain, and strongly suggests that large hip BMLs are associated with hip pain. Furthermore, high cartilage signal is asymptomatic, but strongly associated with hip BMLs. These findings suggest that hip BMLs play an important role in hip osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective. Cartilage loss is a key pathological feature of OA and can be assessed indirectly using radiography or directly through MRI. A number of cross-sectional studies have suggested that primary generalized osteoarthritis (PGOA) may be a distinct disease, but despite the high frequency of involvement of the hip and the knee joints in OA, very few studies have looked at the radiographic association between these two joints, and none has done so using MRI. The aim of this study was to examine the association of hip and knee cartilage measured by both radiography and MRI.Methods. We studied 151 participants from the Tasmanian Older Adult Cohort (TASOAC) study, who were selected randomly from the southern Tasmanian electoral rolls. MRI was used to assess hip and knee cartilage volume and radiography was used to assess joint space narrowing (JSN). Correlation analyses were used to compare cartilage volume measurements and JSN.Results. In adjusted analysis, there was a consistent, positive association between knee and hip cartilage volume that was best for total knee cartilage volume (r = 0.16–0.40, all P < 0.05). In contrast, there was at best a weak correlation, depending on the site, between hip and knee JSN (r = −0.01 to 0.21).Conclusion. Hip and knee cartilage volume are more strongly associated than hip and knee JSN, suggesting a commonality of cartilage volume at different anatomic sites. The weaker radiographic association may reflect less measurement error with MRI or the contribution of multiple structures to joint space in the knee. [ABSTRACT FROM PUBLISHER]

Objectives. There have been no reported studies of the association between parity and cartilage in young individuals. The aim of this study was to describe the association between parity, cartilage volume and cartilage defects in women aged 31–41 years.Methods. Cross-sectional study of 144 women, mean age 36 years and BMI 25 kg/m2, who were participants in an established prospective study. Parity was assessed using a questionnaire. Knee (medial tibial, lateral tibial and patellar) cartilage volume, cartilage defects (grade 0–4 depending on the severity of cartilage thickness loss at tibial and patellar sites) and tibial bone area were assessed using T1-weighted fat-suppressed MRI.Results. The prevalence of cartilage defects (grade &geq;2) in this population was 13%. Parity was associated with a higher risk of cartilage defects at the patellar [prevalence ratio (PR) per birth 1.52, 95% CI 1.05, 2.21; PR parous vs nulliparous 1.93, 95% CI 0.66, 5.65], but not tibial sites, after adjustment for confounders including age, BMI, smoking, physical activity, knee injury and tibial bone area. This association between parity and patellar cartilage defects was stronger for those women who had three or more births (vs nulliparous, PR 5.27, 95% CI 1.39, 20.01). There were no significant associations between parity and cartilage volume.Conclusion. Parity was associated with knee cartilage defects primarily at the patellar site in this sample of young women. This association was more apparent with increasing number of live births, suggesting a possible adverse effect of parity on knee cartilage. [ABSTRACT FROM PUBLISHER]

Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. [ABSTRACT FROM PUBLISHER]

Objective. Although there is a well-established sex difference in the prevalence and severity of OA, the mechanism for this is not clear. The aim of this study was to examine the potential role of BMD and BMC in explaining gender differences in knee cartilage volume.Methods. A total of 153 subjects aged 25–60 years, 81% female, were recruited. MRI was performed of the dominant knee. Cartilage volume was measured using validated methods. Total body BMD and content was measured using DXA.Results. Total body BMC and BMD was significantly associated with medial cartilage volume in both sexes. However, the associations were stronger in men for BMC (B = 0.52; 95% CI 0.21, 0.83; P for difference = 0.001) and BMD (B = 2242; 95% CI 443, 4041; P for difference = 0.05). Similar results were obtained in the lateral tibial compartment. No significant association was obtained between total body BMD and BMC and patella cartilage volume in either men or women.Conclusions. In this relatively healthy population, we found a positive relationship between total body BMD and BMC and tibial cartilage volume in the medial and lateral compartments. These relationships were stronger in men than women. Thus, the results of this study may provide some insight into the sex differences in knee cartilage volume, which may in turn facilitate our understanding of the pathogenesis of OA. [ABSTRACT FROM PUBLISHER]

Objectives. The presence of bone marrow lesions (BMLs) has been linked to pain and progression of knee OA. The aim of this study was to determine the relationship between BMLs and longitudinal change in tibial cartilage volume and risk of knee joint replacement in subjects with knee OA.Methods. One hundred and nine men and women with symptomatic knee OA were recruited. The same knee was imaged using MRI at baseline and ∼2 years later. Tibial cartilage volume and BMLs were measured. Knee joint replacement over 4 years was determined.Results. The mean age of the subjects at baseline was 63.2 (s.d. 10.3) years. BMLs were present in 66% of the subjects. Cross-sectionally, BMLs were negatively associated with both medial (regression coefficient −121.4; 95% CI −183.8, −859.1; P < 0.001) and lateral (regression coefficient −142.1; 95% CI −241.8, −42.4; P = 0.01) tibial cartilage volume data. Longitudinally, for every 1-score increase in baseline BML severity (range 0–4), the annual total tibial cartilage loss was increased by 1.14% (95% CI 0.29%, 1.87%; P = 0.01). The risk of knee joint replacement over 4 years increased with increasing BML score (odds ratio 1.57; 95% CI 1.04, 2.35; P = 0.03).Conclusion. The prevalence and severity of BMLs are associated with less tibial cartilage volume and greater cartilage loss over 2 years. Moreover, severity of BMLs was positively associated with risk of knee joint replacement over 4 years. This provides further support for the importance of BMLs in identifying those with OA most likely to progress. Identifying factors that prevent or reduce the severity of BMLs may provide an important target in the prevention of disease progression and treatment of OA, and the subsequent need for arthroplasty. [ABSTRACT FROM PUBLISHER]

Objective. Obesity is an important risk factor for knee OA. Evidence suggests that fat and muscle have differential effects on the pathogenesis of disease. The aim of this study was to examine the relationship between body composition and knee structure, including knee cartilage volume, defects and bone marrow lesions (BMLs).Methods. A total of 153 subjects aged 25–60 years, 81% females, were recruited across a range of BMI (18–55 kg/m2) for a study examining the relationship between obesity and musculoskeletal disease. MRI was performed of the dominant knee. Cartilage volume, defects and BMLs were measured using validated methods. Body composition was measured using dual X-ray absorptiometry.Results. There was an 81 (95% CI: 69, 94) mm3 increase in cartilage volume for every 1 kg increase in skeletal muscle mass. Fat mass was not significantly associated with cartilage volume. Fat mass, but not skeletal muscle mass, was a risk factor for cartilage defects and BMLs. For every 1 kg increase in total body fat there was an increased risk of cartilage defects (OR = 1.31, 95% CI: 1.04, 1.64) and BMLs (OR = 1.09, 95% CI: 1.01, 1.18).Conclusions. In this relatively healthy population, fat mass was associated with increased cartilage defects and BMLs, which are features of early knee OA. In contrast, skeletal muscle mass was positively associated with cartilage volume, which may be due to coinheritance, a commonality of environmental factors associated with cartilage accrual or a protective effect of increased muscle. [ABSTRACT FROM PUBLISHER]

The article presents a study which examined the relationship between tibial bone area and tibial subchondral bone mineral density (BMD) with the development of cartilage defect and loss of cartilage volume. According to the authors, bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss while tibial subchondral BMD predicted medial defect development but not cartilage loss. They suggest that subchondral bone changes leading to cartilage damage involve multiple mechanisms.

The article focuses on the study that determines the associations between serum levels of vitamin D, sunlight exposure, and knee cartilage loss cross-sectionally and longitudinally in older adults. Both sunlight exposure and serum 25 D levels are linked with decreased knee cartilage loss. Such result is best observed by using a whole range of 25 D levels than predefined cut points. It is implied that achieving vitamin D sufficiency may protect and retard cartilage loss in knee osteoarthritis.

The article presents a study which aims to examine the effects of smoking on change in knee cartilage volume and increases in knee cartilage defects and to test for interaction between smoking and family history of osteoarthritis (OA). It concludes that smoking causes knee cartilage loss and defect development primarily in individuals with a family history of knee OA.

The aim of this study was to describe clinical, structural and biochemical factors associated with knee pain in younger subjects. A cross-sectional convenience sample of 371 male and female subjects (mean age, 45 years, range 26–61) was studied. Knee pain was assessed by questionnaire. Chondral defects, cartilage volume, and bone area of the right knee were determined using T1-weighted fat saturation magnetic resonance imaging (MRI). X-ray was performed on the same knee for the assessment of radiographic features of osteoarthritis. The urinary C-terminal cross-linking telopeptide of type II collagen (CTX-II) was measured by enzyme-linked immunosorbent assay (ELISA). Height and weight were measured by standard protocols and body mass index (BMI) was calculated. The prevalence of knee pain was 35% in this sample. Chondral defect scores (particularly femoral and patellar but not tibial) were significantly associated with knee pain in a dose–response fashion (all p<0.01). Cartilage volume and bone area were not associated with knee pain in multivariate analysis in this sample. Urinary CTX-II was higher in subjects with knee pain ( p=0.04), but this became nonsignificant after adjustment for BMI and osteophytes (both of which were significant) suggesting potential mechanisms of effect. In conclusion, knee pain is significantly associated with non-full thickness chondral defects (particularly femoral and patellar), osteophytes, CTX-II, and obesity but not other factors. MRI and biochemical measures can add to radiographs in defining unexplained knee pain in younger subjects. [ABSTRACT FROM AUTHOR]

Pain in osteoarthritis is multifactorial, but a disconnect between radiographic features and symptoms hampers our understanding of pain. New imaging data suggest that pain arises from virtually all structures in the joint and that cartilage loss is only a minor contributor to pain symptoms but is important for disease progression. [ABSTRACT FROM AUTHOR]

The article discusses the causes of knee cartilage defects. It was reported that the widespread and severity of knee cartilage defects goes up with increasing age and body mass index associated with tibiofemoral osteophytes, increased tibial bone area, decreased knee cartilage volume and increased type II collagen breakdown. In addition, weight loss may help improve knee cartilage defects.

Background: MRI slices of 1.5 mm thickness have been used in both cross sectional and longitudinal studies of osteoarthritis, but is difficult to apply to large studies as most techniques used in measuring knee cartilage volumes require substantial post-image processing. The aim of this study was to determine the optimal sampling of 1.5 mm thick slices of MRI scans to estimate knee cartilage volume in males and females for cross-sectional and longitudinal studies. Methods: A total of 150 subjects had a sagittal T1-weighted fat-suppressed MRI scan of the right knee at a partition thickness of 1.5 mm to determine their cartilage volume. Fifty subjects had both baseline and 2-year follow up MRI scans. Lateral, medial tibial and patellar cartilage volumes were calculated with different samples from 1.5 mm thick slices by extracting one in two, one in three, and one in four to compare to cartilage volume and its rate of change. Agreement was assessed by means of intraclass correlation coefficient (ICC) and Bland & Altman plots. Results: Compared to the whole sample of 1.5 mm thick slices, measuring every second to fourth slice led to very little under or over estimation in cartilage volume and its annual change. At all sites and subgroups, measuring every second slice had less than 1% mean difference in cartilage volume and its annual rate of change with all ICCs ≥ 0.98. Conclusion: Sampling alternate 1.5 mm thick MRI slices is sufficient for knee cartilage volume measurement in cross-sectional and longitudinal epidemiological studies with little increase in measurement error. This approach will lead to a substantial decrease in post-scan processing time. [ABSTRACT FROM AUTHOR]

Resistin acts as an endogenous ligand of Toll-like receptor (TLR)-4 that triggers major inflammatory pathways and mediates inflammatory processes. The role of resistin in osteoarthritis (OA) pathogenesis is unclear. The aim of this study is to describe the longitudinal associations of serum levels of resistin with knee synovitis measures and structural abnormalities in patients with knee OA. A prospective cohort study. Patients (n = 200) with symptomatic knee OA (mean age 63.1 years, range 49-79; female 46.5%) participated. All measures were performed at baseline and 2 years later. Serum resistin was measured using enzyme-linked immunosorbent assay. Infrapatellar fat pad (IPFP) high signal intensity alteration and effusion synovitis were measured from magnetic resonance imaging (MRI). Knee structures including cartilage volume, cartilage defects, and bone marrow lesions (BMLs) were also assessed by MRI semiquantitatively or quantitatively. Linear or logistic mixed effects regression analyses were used in longitudinal analyses. Serum resistin was positively associated with high signal intensity alteration measures of IPFP as well as the presence [relative risk = 1.06, 95% confidence interval (CI) 1.02, 1.10] and volume (β = 0.77, 95% CI 0.01, 1.53) of effusion synovitis in multivariable analyses. Serum levels of resistin were also positively associated with higher tibiofemoral cartilage defect (β = 1.98, 95% CI 0.34, 3.57) and BML scores (β = 3.18, 95% CI 0.99, 5.37) after adjustment for covariates. Higher serum levels of resistin are associated with knee synovitis surrogate measures and structural abnormalities, suggesting that obesity may promote OA not only by increasing weight loading on joints but also by triggering 1 or more inflammatory pathways. [ABSTRACT FROM AUTHOR]

Objectives Aspirin, widely used in the prevention of cardiovascular disease, in low dose, has anti-inflammatory and vasculoprotective effects: both of these processes contribute to the pathogenesis of osteoarthritis. We examined whether use of low dose aspirin affects change in knee cartilage volume in osteoarthritis. Methods Participants from the Melbourne osteoarthritis cohort were classified as users and non-users of aspirin, according to baseline use (≤300 mg/day). Their knees were imaged twice over 2 years. Tibial cartilage volumes were measured and change calculated. Results Twenty one (18%) of 117 eligible participants were aspirin users. Annual change in medial tibial cartilage volume was −43 mm 3 (95% confidence intervals (CI) −93, 10) in aspirin users and −101 mm 3 (95% CI −125, −77) in non-users ( p = 0.043 for difference) after adjusting for age, gender, BMI and radiographic severity. Similar results were seen for annual percentage loss (1.9% vs 5.4%, p = 0.034). No difference was observed for lateral tibial cartilage change and annual change ( p = 0.98, 0.87 respectively) Conclusion Low dose aspirin use was associated with reduced medial tibial cartilage loss over 2 years in people with knee osteoarthritis. This data is hypothesis generating and clinical trials are required to confirm efficacy. If this hypothesis is confirmed, low dose aspirin may be used to reduce the progression of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Patellofemoral knee osteoarthritis (OA) is a common disease, and a significant cause of knee pain, however few data have examined longitudinal change at the patellofemoral joint. The aim of this study was to examine factors affecting change in patella cartilage over a longer time period than previously examined. Study design: Longitudinal study of 77 subjects (58% female) with knee OA underwent magnetic resonance imaging (MRI), with a repeat MRI of the same knee obtained approximately 4.5 years later. Main outcome measures: Annual change in patella cartilage volume, and annual percentage change over 4.5 years. Results: After adjusting for age, gender, BMI and patella bone volume at baseline, cartilage change was observed at the rate of 2.5% (95% confidence interval, 2.0, 3.0) per annum over 4.5 years. Cartilage was lost at a higher rate in women compared to men after accounting for age, BMI or bone volume at baseline (3.3% vs. 1.4%, respectively, p =0.03). Increased patella bone volume was associated with increased patella cartilage loss (p =0.02). No measures of radiographic severity of disease affected change in cartilage volume. Conclusions: The increased rate of cartilage loss in women may contribute to the increased prevalence of disease, although the underlying mechanism requires further study. Increased patella bone volume was also associated with increased patella cartilage loss. Whether this is due to biomechanical factors will need to be determined. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Knee osteoarthritis (OA) is a major cause of pain and disability in women, becoming a major health problem in mid to later life. A better understanding of factors contributing to deleterious structural knee changes may be important for preventing OA. In men, occupations associated with frequent knee bending have been shown to be associated with damage to knee cartilage. This has not been examined in women. The aim of this study was to examine the effect of occupational specific knee activities on tibial and patella cartilage morphology among healthy females. Methods: 96 females aged 26–62 years with no history of knee injury or symptoms were recruited as part of a study of community-based study of lifestyle factors on knee health. Occupational activity data examining the frequency of tasks such as heavy lifting, knee bending, stair climbing, walking and standing were obtained by questionnaire. Tibial and patella cartilage volumes and defects were measured from magnetic resonance imaging using validated methods. Results: Heavy lifting/bending/squatting, knee bending, stair climbing and walking were all associated with an increased risk of patella, but not tibial, cartilage defects (odds ratio 1.8–2.9; p ≤0.05) after adjustment for potential confounders, including knee alignment and radiographic joint space narrowing. There was a trend towards knee bending being associated with a reduction in patella cartilage volume (p =0.07). Conclusion: Our results demonstrate that asymptomatic adult females with occupations requiring frequent knee bending have patella, but not tibial cartilage damage. These findings suggest that vocational tasks requiring knee bending are detrimental to the structure of cartilage in females and may be an area to consider in the prevention of knee OA. [Copyright &y& Elsevier]