Objective: To determine whether cartilage volume loss is an independent predictor of knee replacement. Design: Prospective community based, four year prospective cohort study. Methods: 123 subjects ...with mild to moderate symptomatic radiographic knee osteoarthritis were recruited by either advertising, the Victorian branch of the Arthritis Foundation of Australia, treating general practitioners, orthopaedic surgeons, or rheumatologists; 113 completed the study. Magnetic resonance imaging was carried out at baseline and at 2 years on the symptomatic knee. Rate of change in tibial cartilage volume was calculated. Subjects were then followed up at year 4 to determine whether they had undergone a knee replacement. Results: The rate of tibial cartilage loss over two years was an independent predictor of knee replacement at four years. For every 1% increase in the rate of tibial cartilage loss there was a 20% increase risk of undergoing a knee replacement at four years (95% confidence interval, 10% to 30%). Those in the highest tertile of tibial cartilage loss had 7.1 (1.4 to 36.5) higher odds of undergoing a knee replacement than those in the lowest tertile. WOMAC score at baseline, female sex, and tibial bone size (but not age and radiographic score) were also predictors of knee replacement. Conclusions: The data suggest that treatment targeted at reducing the rate of knee cartilage loss in subjects with symptomatic osteoarthritis may delay knee replacement. This has important implications in terms of prevention and therapeutic interventions in osteoarthritis.
To examine the association of metabolic syndrome (MetS) and its components with knee pain severity trajectories.
Data from a population-based cohort study were utilised. Baseline blood pressure, ...glucose, triglycerides and high-density lipoprotein (HDL) cholesterol were measured. MetS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. Radiographic knee osteoarthritis (ROA) was assessed by X-ray. Pain severity was measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire at each time-point. Group-based trajectory modelling was used to identify pain trajectories and multi-nominal logistic regression was used for analysis. Mediation analysis was performed to assess whether body mass index (BMI)/central obesity mediated the association between MetS, its components and pain trajectories.
Among 985 participants (Mean ± SD age: 62.9 ± 7.4, 50% female), 32% had MetS and 60% had ROA. Three pain trajectories were identified: ‘Minimal pain’ (52%), ‘Mild pain’ (33%) and ‘Moderate pain’ (15%). After adjustment for potential confounders, central obesity increased risk of belonging to both ‘Mild pain’ and ‘Moderate pain’ trajectories as compared to the ‘Minimal pain’ trajectory group, but MetS relative risk ratio (RRR): 2.26, 95%CI 1.50–3.39, hypertriglyceridemia (RRR: 1.75, 95%CI 1.16–2.62) and low HDL (RRR: 1.67, 95%CI 1.10–2.52) were only associated with ‘Moderate pain’ trajectory. BMI/central obesity explained 37–70% of these associations. Results were similar in those with ROA.
MetS and its components are predominantly associated with worse pain trajectories through central obesity, suggesting that the development and maintenance of worse pain trajectories may be caused by MetS.
Cell therapies are being investigated as potential disease modifying treatment options for osteoarthritis (OA). Progenza (PRG) comprises in vitro expanded mesenchymal stem cells derived from human ...donor adipose tissue combined with cell culture supernatant. The primary objective of this first-in-human study was to evaluate the safety and tolerability of PRG.
We conducted a single centre, randomized, double-blind, placebo-controlled, single ascending dose study. Twenty patients aged 40-65 years with symptomatic Kellgren-Lawrence grade 1-3 knee OA were treated in two cohorts and randomized 4:1 to PRG or placebo. Cohort 1: 3.9 million cells (PRG 3.9M, n = 8) or placebo (n = 2) and cohort 2: 6.7 million cells (PRG 6.7M, n = 8) or placebo (n = 2). Each patient received a single intra-articular injection and was followed-up for 12 months.
The study population comprised 20 patients (placebo, n = 4; PRG 3.9M, n = 8; PRG 6.7M, n = 8). All patients reported at least one treatment-emergent adverse event (TEAE). The majority of events 143/169 (84.6%) were mild with 34 (20.1%) being considered by the investigator to be treatment related. There were no serious AEs or withdrawals due to AEs during the study. There was a statistically significant within group improvement in VAS pain scores from baseline at all timepoints for the PRG combined group, with highly significant improvements seen at months 3, 6, 9 and 12 (p ≤ 0.005) while VAS pain scores in the placebo group showed marginal improvement. A statistically significant improvement was also seen in WOMAC pain subscale scores from baseline at all timepoints for the PRG combined group while a marginal improvement in the placebo group was not statistically significant. Between screening and month 12, there was no decrease in average lateral tibial cartilage volume in the PRG 3.9M group while the placebo group showed a statistically significant cartilage loss. This difference between the placebo and PRG 3.9M group was statistically significant (LSM difference 106.47 mm
, 95% CI 13.56 mm
, 199.37 mm
, p = 0.028).
When administered as a single intra-articular injection to patients with symptomatic knee OA, PRG was safe and well tolerated. Furthermore, measurable improvements in symptoms and knee structure outcomes warrant further studies on PRG's potential for disease modification in OA. Trial registration ANZCTR, ACTRN12615000439549. Date registered: 7th May 2015, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368355.
Summary Objective The role of inflammation in osteoarthritis (OA) pathogenesis is unclear, and the associations between inflammatory cytokines and cartilage loss have not been reported. We determined ...the associations between serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), knee radiographic OA (ROA) and cartilage loss over 2.9 years in older adults. Methods A total of 172 randomly selected subjects (mean 63 years, range 52–78, 47% female) were studied at baseline and approximately 3 (range 2.6–3.3) years later. IL-6 and TNF-α were assessed by radioimmunoassay. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed at baseline and follow-up to determine knee cartilage volume. Knee ROA of both knees was assessed at baseline. Results At baseline, quartiles of IL-6 and TNF-α were associated with increased prevalence of medial tibiofemoral joint space narrowing (OARSI grade ≥1) in multivariate analyses odds ratio (OR): 1.42 and 1.47 per quartile, respectively, both P < 0.05. Longitudinally, baseline IL-6 predicted loss of both medial and lateral tibial cartilage volume ( β : −1.19% and −1.35% per annum per quartile, P < 0.05 and P < 0.01, respectively), independently of TNF-α. Change in IL-6 was associated with increased loss of medial and lateral tibial cartilage volume ( β : −1.18% and −1.06% per annum per quartile, both P < 0.05) and change in TNF-α was also negatively associated with change in medial cartilage volume ( β : −1.27% per annum per quartile, P < 0.05). Conclusions Serum levels of IL-6 and TNF-α are associated with knee cartilage loss in older people suggesting low level inflammation plays a role in the pathogenesis of knee OA.
To identify distinct pain trajectories over 10.7 years and to examine predictors of identified pain trajectories in an older population and those with radiographic knee osteoarthritis (ROA).
963 ...participants (aged 50–80 years) from a population-based cohort had baseline demographic, psychological, lifestyle and comorbidities data collected. T1-and T2-weighted magnetic resonance imaging (MRI) of the right knee was performed to measure knee structural pathology-cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis. Group-based trajectory modelling (GBTM) was applied to identify trajectories of knee pain over 10.7 years measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).
Three distinct pain trajectories were defined: ‘Minimal pain’ (n = 501, 52%), ‘Mild pain’ (n = 329, 34%) and ‘Moderate pain’ (n = 165, 14%). In multivariable analysis, having cartilage defects, BMLs and effusion-synovitis were associated with an increased risk of being in the ‘Mild pain’ (relative risk RR: 1.40 to 1.92) and ‘Moderate pain’ trajectory (RR: 1.72 to 2.26), compared with the ‘Minimal pain’ trajectory. Being obese and having more painful sites were associated with ‘Mild pain’ and ‘Moderate pain’ trajectories, while unemployment, lower education level and presence of emotional problems were associated with ‘Moderate pain’ trajectory group. Similar results were found for those with ROA.
Distinct pain trajectories identified suggest that homogeneous subgroups exist, which might be useful for phenotypic assessment for pain management, particularly in knee osteoarthritis. Structural pathology was associated with worse pain trajectories, suggesting that peripheral stimuli are critical for the development and maintenance of pain severity. Environmental and psychological factors may exacerbate pain perception.
Maintaining mobility is an important aspect of health and well-being in older men. This literature review describes several modifiable and nonmodifiable risk factors impacting bone, muscle, and joint ...health. Exercise and nutritional interventions may help to prevent the progressive deterioration in bones, muscles, and joints impacting mobility in later life. Limitations in mobility are increasingly recognized as a major public health problem due to an aging population and growing number of older individuals affected by disabling comorbidities. Despite increasing numbers and debilitating consequences, there are no guidelines providing recommendations on strategies to maintain mobility for healthy aging among older men. This narrative review aims to fill this literature gap. PubMed, Scopus, and Google Scholar databases were searched using predefined search terms. Primary studies, exploratory analyses, cross-sectional surveys, meta-analyses, evidence-based clinical reviews, and guidelines from nationally recognized societies focusing on mobility in older men and key elements including bone, muscle and joint health, and balance were selected. Several modifiable and nonmodifiable risk factors have been reported in the literature that impact bone, muscle, and joint health and predispose older men to falls and fractures. The most common conditions impacting bones, muscles, and joints are osteoporosis, sarcopenia, and osteoarthritis, respectively. In addition to being key contributors to disability in the elderly, these conditions are all associated with a higher mortality risk. Although more studies are required, current evidence supports the use of various nonpharmacological (mainly exercise and nutrition) and/or pharmacological treatment modalities to help prevent and/or reverse these conditions. Incorporating lifestyle interventions involving exercise and nutrition at a younger age can help prevent the age-related, progressive deterioration in bones, muscles, and joints that can reduce mobility in later life. Established barriers to physical activities (e.g., poor health, social isolation) in men are important to consider for optimizing outcomes.
Summary Objective Whether meniscal extrusion and bone marrow lesions (BMLs) are independently associated with the risk of knee osteoarthritis (OA) is unknown. Methods Data was extracted from the ...Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren–Lawrence (KL) grade ≤ 1, n = 2120) or presence (KL ≥ 2, n = 2249) of radiographic OA (ROA). Baseline meniscal extrusion and tibial BMLs were assessed. Tibial plateau cartilage volume was assessed at baseline and 72 months, while radiographic disease was assessed at baseline and 48 months. Total knee replacement (TKR) was assessed at 72 months. Results In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage volume loss (medial tibia: −2.1%/annum vs −1.5%; lateral: −2.6%/annum vs −1.6%; both P < 0.001), progressive ROA and TKR (Odds ratio (OR) range 1.4–1.8; 95% CI range 1.1–2.9). The presence of a baseline BML was associated with accelerated cartilage volume loss (medial tibia: −2.1%/annum vs −1.6%; lateral: −1.9%/annum vs −1.6%; P ≤ 0.02), progressive ROA and joint replacement (OR range 1.5–2.4; 95% CI range 1.1–3.4). In those with no ROA, a baseline medial meniscal extrusion was associated with accelerated cartilage volume loss (medial tibia: −2.1%/annum vs −1.2%, P < 0.001), and a baseline medial BML with incident ROA (OR 1.7, 95% CI 1.1 to 2.9). Conclusions The presence of baseline meniscal extrusion and BMLs are associated with incident and progressive knee of each other (OA) and represent important structural targets for the treatment and prevention of knee OA.
Osteoarthritis is a leading cause of disability with no cure. The incidence of osteoarthritis is sexually dimorphic: women have a higher rate of osteoarthritis than men after the age of 50. Research ...has investigated the contribution of sex hormones, reproductive factors and hormone supplementation to osteoarthritis. It has been recognized that different joints are susceptible to different risk factors for osteoarthritis. We reviewed the evidence for the effect of endogenous sex hormones, reproductive factors and hormone supplementation on joint-specific osteoarthritis of the knee, hip and hand. Although the role of these hormonal factors in the pathogenesis of osteoarthritis is complex, data suggest that endogenous hormones and reproductive factors have a role in the pathogenesis of osteoarthritis, especially knee osteoarthritis, with uncertainty for the effect of exogenous hormones. From the available data, it is hard to conclude whether this is a direct effect of hormonal factors, or whether other factors related to these hormonal factors, i.e. obesity and inflammation, have a role in this association. Further studies should consider the mediation effect of body weight and inflammation, change in body weight throughout life, circulatory levels of all endogenous hormones and circulatory levels of hormones after hormone supplementation in this complex relationship.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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