Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

BACKGROUND AND AIMS: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood. METHODS: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. RESULTS: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up. CONCLUSIONS: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.

Experiences of participants in the co-design of a community-based health service for people with high healthcare service use.

BACKGROUND: Incorporating perspectives of health consumers, healthcare workers, policy makers and stakeholders through co-design is essential to design services that are fit for purpose. However, the experiences of co-design participants are poorly understood. The aim of this study is to explore the experiences and perceptions of people involved in the co-design of a new service for people with high healthcare service utilisation. METHODS: A methodology informed by the principles of grounded theory was used in this qualitative study to evaluate the experiences and perceptions of co-design participants. Participants were healthcare professionals, health managers and leaders and health consumers involved in the co-design of the new service in Tasmania, Australia. Semi-structured interviews were conducted, and data were iteratively and concurrently collected and analysed using constant comparative analysis. Audio/audio-visual recordings of interviews were transcribed verbatim. Transcripts, memos, and an audit trail were coded for experiences and perspectives of participants. RESULTS: There were thirteen participants (5 health professionals, 6 health managers and leaders, and 2 health consumers). Codes were collapsed into six sub-themes and six themes. Themes were bureaucracy hinders co-design, importance of consumers and diversity, importance of a common purpose, relationships are integral, participants expectations inform their co-design experience and learning from co-design. CONCLUSION: Most participants reported positive aspects such as having a common purpose, valuing relationships, and having a personal motivation for participating in co-design. However, there were factors which hindered the adaptation of co-design principles and the co-design process. Our research highlights that bureaucracy can hinder co-design, that including people with lived experience is essential and the need to consider various types of diversity when assembling co-design teams. Future co-design projects could use these findings to improve the co-design experience for participants, and ultimately the outcome for communities.

Effect of Intravenous Zoledronic Acid on Total Knee Replacement in Patients With Symptomatic Knee Osteoarthritis and Without Severe Joint Space Narrowing: A Prespecified Secondary Analysis of a Two-Year, Multicenter, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). METHODS: We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). RESULTS: Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). CONCLUSION: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.

Vitamin D supplementation for improving bone density in vitamin D-deficient children and adolescents: systematic review and individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin D supplements are widely used for improving bone health in children and adolescents, but their effects in vitamin D-deficient children are unclear. OBJECTIVES: This study aimed to examine whether the effect of vitamin D supplementation on bone mineral density (BMD) in children and adolescents differs by baseline vitamin D status and estimate the effect in vitamin D-deficient individuals. METHODS: This is a systematic review and individual participant data (IPD) meta-analysis. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MBASE, CINAHL, AMED, and ISI Web of Science (until May 27, 2020) for randomized controlled trials (RCTs) of vitamin D supplementation reporting bone density outcomes after ≥6 mo in healthy individuals aged 1-19 y. We used two-stage IPD meta-analysis to determine treatment effects on total body bone mineral content and BMD at the hip, femoral neck, lumbar spine, and proximal and distal forearm after 1 y; examine whether effects varied by baseline serum 25-hydroxyvitamin D [25(OH)D] concentration, and estimate treatment effects for each 25(OH)D subgroup. RESULTS: Eleven RCTs were included. Nine comprising 1439 participants provided IPD (86% females, mean baseline 25(OH)D = 36.3 nmol/L). Vitamin D supplementation had a small overall effect on total hip areal BMD (weighted mean difference = 6.8; 95% confidence interval: 0.7, 12.9 mg/cm2; I2 = 7.2%), but no effects on other outcomes. There was no clear evidence of linear or nonlinear interactions between baseline 25(OH)D and treatment; effects were similar in baseline 25(OH)D subgroups (cutoff of 35 or 50 nmol/L). The evidence was of high certainty. CONCLUSIONS: Clinically important benefits for bone density from 1-y vitamin D supplementation in healthy children and adolescents, regardless of baseline vitamin D status, are unlikely. However, our findings are mostly generalizable to White postpubertal girls and do not apply to those with baseline 25(OH)D outside the studied range or with symptomatic vitamin D deficiency (e.g., rickets). This study was preregistered at PROSPERO as CRD42017068772. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42017068772.

Association of knee and hip osteoarthritis with the risk of falls and fractures: a systematic review and meta-analysis.

OBJECTIVE: Studies evaluating the association of knee and hip osteoarthritis (OA) with falls and fractures have inconsistent findings. We aimed to investigate associations of symptomatic and radiographic knee and hip OA with risk of falls, recurrent falls, and fractures. METHODS: We conducted an electronic search of databases from inception to February 2023. Two authors independently screened studies, extracted data, and assessed the risk of bias using the Newcastle-Ottawa Scale tool in eligible studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Of 17 studies included (n = 862849), 2 had a high risk of bias. Among studies that evaluated falls or fractures as outcomes, 7/8 (87.5%) and 5/11 (45.5%) were self-reported, respectively. Both symptomatic knee and hip OA were associated with increased risk of recurrent falls (knee: OR = 1.55, 95% CI 1.10 to 2.18; hip: OR = 1.50, 95% CI 1.28 to 1.75) but not falls or fractures. Radiographic knee OA increased risk of falls (OR = 1.28, 95% CI 1.03 to 1.59) and did not significantly increase risk of recurrent falls (OR = 1.39, 95% CI 0.97 to 1.97) or fractures (OR = 1.22, 95% CI 0.99 to 1.52). Radiographic hip OA decreased the risk of recurrent falls (OR = 0.70, 95% CI 0.51 to 0.96) but had no statistically significant association with fractures (OR = 1.16, 95% CI 0.79 to 1.71). CONCLUSION: Symptomatic knee and hip OA were both associated with an increased risk of recurrent falls, and radiographic knee OA was associated with an increased risk of falls. No statistically significant associations of radiographic and symptomatic knee or hip OA with fractures were found.

Health Literacy predicts incident foot ulcers after 4 years - the SHELLED cohort study.

AIMS/HYPOTHESIS: To determine whether health literacy is associated with an index diabetes-related foot ulcer (DFU). METHODS: The SHELLED Study is a 4-year prospective study of people with diabetes aged over 40 with no history of DFU. The primary outcome was development of a first foot ulcer. Health Literacy was measured using the short form Test of Functional Health Literacy in Adults (s-TOFHLA) and nine domains of the Health Literacy Questionnaire (HLQ). RESULTS: Of 222 participants, 191 (86.0%) completed the study, of whom 13 (5.9%) developed an incident ulcer. In multivariable models, every unit increase in S-TOFHLA was associated with a reduced odds of foot ulcer development by 6% (OR 0.94, 95% CI 0.88 to 0.99). Better scores on two HLQ domains reduced the odds of foot ulcer (actively managing my health (OR 0.23, 95% CI 0.08 to 0.65) and understanding health information well enough to know what to do (OR 0.39, 95% CI 0.19 to 0.78). This was independent of baseline risk for foot disease. CONCLUSIONS/INTERPRETATION: These data provide novel evidence that health literacy is an important clinical risk factor for index foot ulceration. This is an area of potential focus for research and development of educational programs or policy aimed at reducing development of incident foot ulceration.

Longitudinal associations of objectively measured physical activity and sedentary time with leg muscle strength, balance and falls in middle-aged women.

We examined the longitudinal associations of accelerometer-measured physical activity and sedentary time with leg muscle strength (LMS), balance, and falls in middle-aged women. This was a 5-year cohort study among 308 women aged 36-56 years. We used linear mixed-effects models to examine associations of baseline and change in accelerometer-measured sedentary time, light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) with baseline and 5-year change in LMS and balance (timed up and go test [TUG], functional reach test [FRT], lateral reach test [LRT], and step test [ST]), and negative binomial/Poisson and log-binomial regression as appropriate to assess associations with falls after 5-year follow-up. Greater baseline MVPA was associated with better baseline LMS (ß = 4.65 kg/SD, 95% CI: 1.37, 7.93) and TUG (ß = -0.09 s/SD, 95% CI: -0.18, -0.01) but not with change in them over 5 years. Baseline MVPA was not associated with FRT at baseline but associated with a greater decrease in FRT (ß = -0.87 cm/SD, 95% CI: -1.57, -0.17). Increased MVPA over 5 years was associated with less deterioration in FRT (ß = 0.88 cm/SD, 95% CI: 0.14, 1.61). Increased sedentary time over 5 years was associated with a larger decrease in FRT (ß = -0.82 cm/SD, 95% CI: -1.58, -0.07). Higher baseline LPA was associated with higher falls risk (IRR = 1.27, 95% CI: 1.02, 1.57). Higher baseline MVPA may benefit LMS and balance, while increasing MVPA in the medium term has little effect on change in these outcomes in mid-life. Detrimental association of LPA with falls may be due to greater exposures to environmental hazards.HighlightsOur study for the first time examined the longitudinal associations of objectively measured physical activity and sedentary time with leg muscle strength, balance and falls in middle-aged women.Higher baseline moderate-to-vigorous physical activity (MVPA) may be beneficial for muscle strength and balance at baseline but increasing MVPA in the medium term has little effect on change in LMS or balance outcomes in middle-aged women.Higher baseline light physical activity (LPA) was associated with an increased risk of falls.The detrimental association of LPA with falls may be due to a greater exposure to environmental hazards in midlife, which needs to be clarified in future research.

Which clinical research questions are the most important? Development and preliminary validation of the Australia & New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network Research Question Importance Tool (ANZMUSC-RQIT).

BACKGROUND AND AIMS: High quality clinical research that addresses important questions requires significant resources. In resource-constrained environments, projects will therefore need to be prioritized. The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network aimed to develop a stakeholder-based, transparent, easily implementable tool that provides a score for the 'importance' of a research question which could be used to rank research projects in order of importance. METHODS: Using a mixed-methods, multi-stage approach that included a Delphi survey, consensus workshop, inter-rater reliability testing, validity testing and calibration using a discrete-choice methodology, the Research Question Importance Tool (ANZMUSC-RQIT) was developed. The tool incorporated broad stakeholder opinion, including consumers, at each stage and is designed for scoring by committee consensus. RESULTS: The ANZMUSC-RQIT tool consists of 5 dimensions (compared to 6 dimensions for an earlier version of RQIT): (1) extent of stakeholder consensus, (2) social burden of health condition, (3) patient burden of health condition, (4) anticipated effectiveness of proposed intervention, and (5) extent to which health equity is addressed by the research. Each dimension is assessed by defining ordered levels of a relevant attribute and by assigning a score to each level. The scores for the dimensions are then summed to obtain an overall ANZMUSC-RQIT score, which represents the importance of the research question. The result is a score on an interval scale with an arbitrary unit, ranging from 0 (minimal importance) to 1000. The ANZMUSC-RQIT dimensions can be reliably ordered by committee consensus (ICC 0.73-0.93) and the overall score is positively associated with citation count (standardised regression coefficient 0.33, p<0.001) and journal impact factor group (OR 6.78, 95% CI 3.17 to 14.50 for 3rd tertile compared to 1st tertile of ANZMUSC-RQIT scores) for 200 published musculoskeletal clinical trials. CONCLUSION: We propose that the ANZMUSC-RQIT is a useful tool for prioritising the importance of a research question.

Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-synovitis in Knee Osteoarthritis.

OBJECTIVE: The objective of this study is to investigate whether quantitatively measured infrapatellar fat pad (IPFP) signal intensity alteration is associated with joint effusion-synovitis in people with knee osteoarthritis (OA) over two years. METHODS: Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed effects models assessed the associations between IPFP signal intensity alteration and effusion-synovitis over two years. RESULTS: In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. CONCLUSION: Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.

Calcium and vitamin D for increasing bone mineral density in premenopausal women.

BACKGROUND: Osteoporosis is a condition where bones become fragile due to low bone density and impaired bone quality. This results in fractures that lead to higher morbidity and reduced quality of life. Osteoporosis is considered a major public health concern worldwide. For this reason, preventive measurements need to be addressed throughout the life course. Exercise and a healthy diet are among the lifestyle factors that can help prevent the disease, the latter including intake of key micronutrients for bone, such as calcium and vitamin D. The evidence on whether supplementation with calcium and vitamin D improves bone mineral density (BMD) in premenopausal women is still inconclusive. In this age group, bone accrual is considered to be the goal of supplementation, so BMD is relevant for the future stages of life. OBJECTIVES: To evaluate the benefits and harms of calcium and vitamin D supplementation, alone or in combination, to increase the BMD, reduce fractures, and report the potential adverse events in healthy premenopausal women compared to placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 12 April 2022. SELECTION CRITERIA: We included randomised controlled trials in healthy premenopausal women (with or without calcium or vitamin D deficiency) comparing supplementation of calcium or vitamin D (or both) at any dose and by any route of administration versus placebo for at least three months. Vitamin D could have been administered as cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Outcomes included total hip bone mineral density (BMD), lumbar spine BMD, quality of life, new symptomatic vertebral fractures, new symptomatic non-vertebral fractures, withdrawals due to adverse events, serious adverse events, all reported adverse events and additional withdrawals for any reason. MAIN RESULTS: We included seven RCTs with 941 participants, of whom 138 were randomised to calcium supplementation, 110 to vitamin D supplementation, 271 to vitamin D plus calcium supplementation, and 422 to placebo. Mean age ranged from 18.1 to 42.1 years. Studies reported results for total hip or lumbar spine BMD (or both) and withdrawals for various reasons, but none reported fractures or withdrawals for adverse events or serious adverse events. Results for the reported outcomes are presented for the three comparisons: calcium versus placebo, vitamin D versus placebo, and calcium plus vitamin D versus placebo. In all comparisons, there was no clinical difference in outcomes, and the certainty of the evidence was moderate to low. Most studies were at risk of selection, performance, detection, and reporting biases. Calcium versus placebo Four studies compared calcium versus placebo (138 participants in the calcium group and 123 in the placebo group) with mean ages from 18.0 to 47.3 years. Calcium supplementation may have little to no effect on total hip or lumbar spine BMD after 12 months in three studies and after six months in one study (total hip BMD: mean difference (MD) -0.04 g/cm2, 95% confidence interval (CI) -0.11 to 0.03; I2 = 71%; 3 studies, 174 participants; low-certainty evidence; lumbar spine BMD: MD 0 g/cm2, 95% CI -0.06 to 0.06; I2 = 71%; 4 studies, 202 participants; low-certainty evidence). Calcium alone supplementation does not reduce or increase the withdrawals in the trials (risk ratio (RR) 0.78, 95% CI 0.52 to 1.16; I2 = 0%; 4 studies, 261 participants: moderate-certainty evidence). Vitamin D versus placebo Two studies compared vitamin D versus placebo (110 participants in the vitamin D group and 79 in the placebo group), with mean ages from 18.0 to 32.7 years. These studies reported lumbar spine BMD as a mixture of MDs and percent of change and we were unable to pool the results. In the original studies, there were no differences in lumbar BMD between groups. Vitamin D alone supplementation does not reduce or increase withdrawals for any reason between groups (RR 0.74, 95% CI 0.46 to 1.19; moderate-certainty evidence). Calcium plus vitamin D versus placebo Two studies compared calcium plus vitamin D versus placebo (271 participants in the calcium plus vitamin D group and 270 in the placebo group; 220 participants from Woo 2007 and 50 participants from Islam 2010). The mean age range was 18.0 to 36 years. These studies measured different anatomic areas, one study reported total hip BMD and the other study reported lumbar spine BMD; therefore, data were not pooled for this outcome. The individual studies found no difference between groups in percent of change on total hip BMD (-0.03, 95% CI -0.06 to 0; moderate-certainty evidence), and lumbar spine BMD (MD 0.01, 95% CI -0.01 to 0.03; moderate-certainty evidence). Calcium plus vitamin D supplementation may not reduce or increase withdrawals for any reason (RR 0.82, 95% CI 0.29 to 2.35; I2 = 72%; 2 studies, 541 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Our results do not support the isolated or combined use of calcium and vitamin D supplementation in healthy premenopausal women as a public health intervention to improve BMD in the total hip or lumbar spine, and therefore it is unlikely to have a benefit for the prevention of fractures (vertebral and non-vertebral). The evidence found suggests that there is no need for future studies in the general population of premenopausal women; however, studies focused on populations with a predisposition to diseases related to bone metabolism, or with low bone mass or osteoporosis diagnosed BMD would be useful.

Effect of Curcuma longa extract on serum inflammatory markers and MRI-based synovitis in knee osteoarthritis: secondary analyses from the CurKOA randomised trial.

BACKGROUND: Curcuma longa (CL) extract is modestly effective for relieving knee symptoms in knee osteoarthritis (OA) patients; however, its mechanism of action is unclear. PURPOSE: We aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. METHODS: Secondary analyses were conducted on the CL for knee OA (CurKOA) trial, which compared CL (n = 36) and placebo (n = 34) over 12 weeks for the treatment of knee OA. Systemic inflammatory markers (TNFα, IL6, and hsCRP) and a cartilage extracellular matrix degradative enzyme (MMP-3) were measured. A subgroup of participants (CL, n = 7; placebo, n = 5) underwent CE-MRI at baseline and a 12-week follow-up. RESULTS: Over 12 weeks, there were no between-group differences in change in hsCRP, IL-6, and TNFα levels. MMP-3 levels decreased in both CL (-1.31 ng/ml [95%CI: -1.89 to -0.73]) and placebo (-2.34 ng/ml [95%CI: -2.95 to -1.73]) groups, with the placebo group having a slightly greater decrease (1.03 ng/ml [95%CI: 0.19 to 1.88]). Most (10 of 12) sub-study participants had normal synovial thickness scores at baseline. One participant had mild synovitis in each of the placebo and CL groups. Synovitis status was stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. CONCLUSION: This is the first study that explored the effect of CL treatment on local and systemic inflammation using biochemical markers and CE-MRI outcomes on knee OA patients. Secondary analyses from this pilot study suggest that CL is unlikely to have clinically significant effects on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo. The mechanism of action for CL effect on pain remains unclear.

Navigating the maze of osteoarthritis treatment: A qualitative study exploring the experience of individuals with osteoarthritis in Tasmania, Australia.

OBJECTIVE: Using a qualitative design this study aimed to (1) explore the experience of people living with osteoarthritis (OA), (2) gain an understanding of their navigation of the health system and, (3) explore their opinions on the role of exercise and joint replacement surgery for the management of OA. METHODS: Purposive sampling was used to recruit 26 participants with knee OA, aged 45 years and over, from Tasmania, Australia. Semi-structured interviews were audio-recorded, transcribed, coded, and thematically analysed to document participant understanding and experience of OA and their opinions on the role of exercise and surgery in managing OA. RESULTS: Of the 26 participants, 80% (n = 21) were female with a mean age of 66 years. The main theme identified was that individuals with knee OA were navigating a maze of OA treatments. Three related subthemes were that participants: (i) perceived their general practitioner did not have an ongoing role in their OA care, (ii) self-directed their management and, (iii) sampled from a 'smorgasbord' of treatment options, including low-value care options. Two other major themes were: the role of exercise for OA management, and surgery as a last resort. CONCLUSION: Our findings suggest that OA patients may not be choosing consistent, high-value care for their OA. This highlights the importance of an evidence-based multi-disciplinary approach to guide patients to self-manage their OA and support their navigation of the health system. Reducing emphasis on the pathway to surgery and streamlining access to conservative management strategies may assist people to receive high-value care.

Association of Calcaneal Bone Marrow Lesions and Plantar Fascia Imaging Biomarkers With Chronic Plantar Heel Pain: A Case-Control Study.

OBJECTIVE: To determine associations between chronic plantar heel pain (CPHP) and imaging biomarkers derived from magnetic resonance imaging (MRI) and ultrasonography. METHODS: We compared 218 participants with CPHP with 100 age- and sex-matched population controls. We assessed imaging biomarkers on MRI (calcaneal bone marrow lesions [BMLs], plantar fascia [PF] signal and thickness, spurs, and fat pad signal) and B-mode/power Doppler ultrasound (PF thickness, echogenicity, and vascularity). Covariate data collected included demographic characteristics, disease history, clinical measures, and physical activity by accelerometry. Data were analyzed using multivariable conditional logistic regression. RESULTS: Plantar calcaneal BML size (mm2 , odds ratio [OR] 1.03 [95% confidence interval (95% CI) 1.02-1.05]), larger plantar spurs (OR for spurs >5 mm 2.15 [95% CI 1.13-4.10]), PF signal (OR for signal penetrating >50% of the dorsoplantar width 12.12 [95% CI 5.36-27.42]), PF thickness (mm, OR for MRI 3.23 [95% CI 2.36-4.43] and ultrasound OR 3.78 [95% CI 2.69-5.32]), and echogenicity (diffusely hypoechoic OR 7.89 [95% CI 4.02-15.48] and focally hypoechoic OR 24.92 [95% CI 9.60-64.69]) were independently associated with CPHP. PF vascularity was uncommon, occurring exclusively in cases (cases with signal n = 47 [22%]). Combining imaging biomarkers into 1 model, plantar BMLs and PF imaging biomarkers, but not fat pad signal or heel spurs, were independently associated with CPHP. CONCLUSION: Calcaneal BMLs and PF imaging biomarkers are associated with CPHP. Further research is required to understand whether these different markers represent distinct phenotypes of heel pain, and if so, whether there are specific treatment implications.

Associations Between Dietary Intake of Vitamin K and Changes in Symptomatic and Structural Changes in Patients With Knee Osteoarthritis.

OBJECTIVE: To investigate associations of dietary vitamin K intake with changes in knee symptoms and structures in patients with knee osteoarthritis (OA). METHODS: Participants with symptomatic knee OA were enrolled (n = 259) and followed up for 2 years (n = 212). Baseline dietary vitamin K intake was calculated from a validated food frequency questionnaire. Knee symptoms were assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Knee cartilage defects, bone marrow lesions, and effusion-synovitis volume were measured from magnetic resonance imaging (MRI) scans. Univariable and multivariable linear regressions were used for analyses. RESULTS: A higher vitamin K intake quartile was significantly associated with a greater decrease in the total WOMAC score and dysfunction score over 24 months. The subgroup analyses showed in patients with severe baseline visual analog scale (VAS) pain that a higher vitamin K intake quartile was associated with more improvement in all WOMAC scores. There were no overall significant associations between vitamin K intake and changes in MRI features. In subgroup analysis, vitamin K intake was negatively associated with changes in tibiofemoral, patellar, and total cartilage defects in participants with a severe baseline radiographic grade and was negatively associated with change in total and patellar cartilage defects in participants with severe baseline VAS pain and in female patients. CONCLUSION: The association of higher vitamin K intake with decreased knee symptoms over 24 months in patients with knee OA suggests that clinical trials examining the effect of vitamin K supplementation for knee OA symptoms are warranted. Whether there is an effect on knee structure is unclear.

Associations between body composition, physical activity, and diet and radial bone microarchitecture in older adults: a 10-year population-based study.

Bone strength is important to prevent osteoporotic fractures and determined by bone mass and microarchitecture. This study suggests that having higher lean mass and lower fat mass, avoiding western dietary patterns, and improving steps per day may all be important for maintaining bone mass and microarchitecture in aging. PURPOSE: To describe associations between exposures of lean mass and fat mass, dietary patterns, serum 25-hydroxyvitamin D (25(OH)D), physical activity and grip strength, and bone outcome measures including bone mineral density and microarchitecture in older adults. METHODS: Data on 201 older adults (mean age 72 years, female 46% at 10.7-year follow-up (phase 4) from a population-based cohort study collected at baseline and follow-up at 2.6 (phase 2), 5.1 (phase 3), and 10.7 years (phase 4) were analyzed. Exposures were lean and fat mass, dietary patterns, physical activity (steps per day), serum 25(OH)D concentrations, and grip strength during follow-ups. Bone measures at phase 4 including areal bone mineral density (aBMD) at the spine, hip, and whole body by dual-energy X-ray absorptiometry, and radial cortical and trabecular bone microarchitecture by high-resolution peripheral computed tomography (HRpQCT). The cumulative average values of exposures were calculated. Multivariable linear regression was used to analyze associations between exposures and bone measures. RESULTS: Lean mass was beneficially associated with the hip, spine, and total body aBMD, radial cortical and trabecular bone area, and trabecular number and separation (ß ranged from - 0.39/standard deviation (SD) to 0.73/SD). Fat mass was detrimentally associated with radial compact cortical and inner transitional zone bone area, vBMD, and porosity (ß ranged from - 0.21 to 0.22/SD). Western dietary pattern scores were detrimentally associated with radial total and cortical bone vBMD and porosity (ß ranged from - 0.20 to 0.20/SD). Steps per day were beneficially associated with inner transitional zone area and thickness (ß = 0.12/SD and 0.19/SD), but no other measures. Grip strength and serum 25(OH)D were not associated with any radial bone measures. CONCLUSIONS: Lean mass was beneficially associated with aBMD, radial bone area, and trabecular bone microarchitecture. Fat mass had detrimental associations with radial bone area, vBMD, and porosity. A western dietary pattern was detrimental for radial bone microarchitecture while more steps per day (but not grip strength or 25(OH)D) appeared beneficial.

Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS).

BACKGROUND: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. METHODS: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0-3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12618001656224 . Registered on 08 October 2018.

Effect of zoledronic acid with or without methylprednisolone on 3D bone area and bone shape in patients with symptomatic knee osteoarthritis: A post-hoc analysis of the ZAP2 trial.

OBJECTIVE: To evaluate the effect of annual infusions of zoledronic acid (ZA) with or without a single injection of methylprednisolone, compared to placebo, on quantitative magnetic resonance imaging 3-D bone area and bone shape in participants with symptomatic knee osteoarthritis (OA). METHODS: This was a post-hoc analysis of the ZAP2 trial. Active appearance modelling was used to assess bone area (mm2) and femur bone shape (B-score) in 262 participants (mean 61.8 ± 8.0 years, 51% female) at baseline, 6, and 24 months. Radiographic joint space narrowing (JSN) was measured at baseline. An 'OA shape' was defined as a B-score of >1.96. RESULTS: At baseline 65% of participants demonstrated an OA shape. Treatment with ZA plus methylprednisolone but not ZA alone, compared to placebo, was associated with significantly slower expansion in bone area at the medial femoral (-33.9 mm2, 95% confidence interval [CI] -61.8 to -6.0) and lateral femoral (-22.0 mm2, 95%CI -40.7 to -3.4) compartments over 24 months. B-score increased in all groups, with no significant between-group differences. There were significant interactions of JSN (grade 0 vs grade 1-2) and B-score (≤1.96 vs >1.96) with treatment effect on bone area (p < 0.05), such that ZA plus methylprednisolone slowed the expansion of medial and lateral femoral bone area over 24 months in participants with JSN grade 1-2 or a B-score of >1.96. CONCLUSIONS: ZA plus methylprednisolone may retard expansion of bone area over 24 months, but ZA alone may not. Neither ZA with or without methylprednisolone slowed progression of bone shape over 6 or 24 months.

Cognition, educational attainment and diabetes distress predict poor health literacy in diabetes: A cross-sectional analysis of the SHELLED study.

OBJECTIVES: To identify factors that predict poor health literacy amongst people with diabetes. DESIGN: Cross-sectional analysis of baseline data from a prospective study of diabetic foot disease. SETTING: Patients attending a tertiary hospital diabetes outpatient clinic in Tasmania, Australia. PARTICIPANTS: 222 people with diabetes mellitus, aged >40 years, with no history of foot ulceration, psychotic disorders or dementia. OUTCOME MEASURES: Health literacy was measured using the short form Test of Functional Health Literacy in Adults (functional health literacy), and the Health Literacy Questionnaire (HLQ), which measures nine domains of health literacy. Predictors included demographic characteristics, cognition, diabetes distress, depression, and educational attainment. RESULTS: In multivariable analysis, greater educational attainment (OR 0.88, 95% CI 0.76, 0.99) and poorer cognition (OR 0.71, 95% CI 0.63, 0.79) were associated with poorer functional health literacy. Age was negatively associated with domains of appraisal of health information and ability to find good health information (both beta = -0.01). Educational attainment was positively associated with four domains, namely having sufficient information to manage my health, actively managing my health, appraisal of and ability to find good health information (beta ranging from +0.03 to 0.04). Diabetes distress was negatively associated with five domains: having sufficient information to manage my health, social support for health, ability to actively engage with healthcare providers, navigating the healthcare system and ability to find good health information (beta ranging from -0.14 to -0.18). CONCLUSION: Poorer cognition and poorer educational attainment may be detrimental for an individual's functional health literacy, and education, diabetes distress and older age detrimental across multiple health literacy domains. Clinicians and policy makers should be attuned to these factors when communicating with people with diabetes and in designing healthcare systems to be more health-literacy friendly in order to improve diabetes outcomes.

A prospective cohort study on cam morphology and its role in progression of osteoarthritis.

BACKGROUND: Cam morphology contributes to the development of hip osteoarthritis (OA) but is less studied in the general population. This study describes its associations with clinical and imaging features of hip OA. METHODS: Anteroposterior hip radiographs of 1019 participants from the Tasmanian Older Adult Cohort (TASOAC) were scored at baseline for α angle (cam morphology) in both hips. Using the Altman's atlas, radiographic hip OA (ROA) was assessed at baseline. Hip pain and right hip structural changes were assessed on a subset of 245 magnetic resonance images (MRI) at 5 years. Joint registry data for total hip replacement (THR) was acquired 14 years from baseline. RESULTS: Of 1906 images, cam morphology was assessed in 1016 right and 890 left hips. Cross-sectionally, cam morphology modestly associated with age (prevalence ratio [PR]: 1.02 P = .03) and body mass index (BMI) (PR: 1.03-1.07, P = .03) and strongly related to male gender (PR: 2.96, P < .001). Radiographically, cam morphology was prevalent in those with decreased joint space (PR: 1.30 P = .03) and osteophytes (PR: 1.47, P = .03). Longitudinally, participants with right cam and high BMI had more hip pain (PR: 17.9, P = .02). At the end of 5 years of follow-up these participants were also more likely to have structural changes such as bone marrow lesions (BMLs) (PR: 1.90 P = .04), cartilage defects (PR: 1.26, P = .04) and effusion-synovitis at multiple sites (PR: 1.25 P = .02). Cam morphology at baseline in either hip predicted up to threefold risk of THR (PR: 3.19, P = .003) at the end of 14 years. CONCLUSION: At baseline, cam morphology was linked with age, higher weight, male gender, early signs of radiographic OA such as joint space narrowing (JSN) and osteophytes (OST). At follow-up, cam predicted development of hip BMLs, hip effusion-synovitis, cartilage damage and THR. These findings suggest that cam morphology plays a significant role in early OA and can be a precursor or contribute to hip OA in later life.

Associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and changes in tibiofemoral joint structures in patients with knee osteoarthritis.

BACKGROUND: To describe the longitudinal associations between the morphological parameters of proximal tibiofibular joint (PTFJ) and joint structural changes in tibiofemoral compartments in patients with knee osteoarthritis (OA). METHODS: The participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. PTFJ morphological parameters were measured on coronal and sagittal MRI. The contacting area (S) of PTFJ and its projection areas onto the horizontal (load-bearing area, Sτ), sagittal (lateral stress-bolstering area, Sφ), and coronal plane (posterior stress-bolstering area, Sυ) were assessed. Knee structural abnormalities, including cartilage defects, bone marrow lesions (BMLs), and cartilage volume, were evaluated at baseline and after 2 years. Log binominal regression models and linear regression models were used to assess the associations between PTFJ morphological parameters and osteoarthritic structural changes. RESULTS: In the longitudinal analyses, the S (RR: 1.45) and Sτ (RR: 1.55) of PTFJ were significantly and positively associated with an increase in medial tibial (MT) cartilage defects. The Sτ (ß: - 0.07), Sυ (ß: - 0.07), and S (ß: - 0.06) of PTFJ were significantly and negatively associated with changes in MT cartilage volume. The Sτ (RR: 1.55) of PTFJ was positively associated with an increase in MT BMLs, and Sφ (RR: 0.35) was negatively associated with an increase in medial femoral BMLs. CONCLUSIONS: This longitudinal study suggests that higher load-bearing area of PTFJ could be a risk factor for structural changes in medial tibiofemoral (MTF) compartment in knee OA. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01176344 Anzctr.org.au Identifier: ACTRN12610000495022 Date of registration: 7 May 2010.