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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. [ABSTRACT FROM AUTHOR]

Background: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim: To describe the association between SES and time to THR and TKR. Methods: One thousand and seventy‐two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area‐level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut‐point. Results: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2–13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non‐significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. [ABSTRACT FROM AUTHOR]

Objective To describe the impact of OA on health-related quality of life (HRQoL) in the forms of health state utilities (HSUs) and health-dimension scores, and to compare the longitudinal changes in HRQoL for people with and without OA, using an Australian population-based longitudinal cohort. Methods Participants of the Tasmanian Older Adult Cohort with data on OA diagnosis and HRQoL were included [interviewed at baseline (n  = 1093), 2.5 years (n  = 871), 5 years (n  = 760) and 10 years (n  = 562)]. HRQoL was assessed using the Assessment of Quality of Life four-dimensions and analysed using multivariable linear mixed regressions. Results Compared with participants without OA, HSUs for those with OA were 0.07 (95% confidence interval: 0.09, 0.05) units lower on average over 10 years. HSUs for participants with knee and/or hip OA were similar to those with other types of OA at the 2.5 year follow-up and then diverged, with HSUs of the former being up to 0.09 units lower than the latter. Those with OA had lower scores for psychological wellness, independent living and social relationships compared with those without OA. Independent living and social relationships were mainly impacted by knee and/or hip OA, with the effect on the former increasing over time. Conclusion Interventions to improve HRQoL should be tailored to specific OA types, health dimensions, and times. Support for maintaining psychological wellness should be provided, irrespective of OA type and duration. However, support for maintaining independent living could be more relevant to knee and/or hip OA patients living with the disease for longer. [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]

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]

Objective. To identify novel biomarker(s) for predicting advanced knee OA. Methods. Study participants were derived from the Newfoundland Osteoarthritis Study and the Tasmania Older Adult Cohort Study. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA. Metabolic profiling was performed on fasting plasma. Four thousand and eighteen plasma metabolite ratios that were highly correlated with that in SF in our previous study were generated as surrogates for joint metabolism. Results. The discovery cohort included 64 TKR cases and 45 controls and the replication cohorts included a cross-sectional cohort of 72 TKR cases and 76 controls and a longitudinal cohort of 158 subjects, of whom 36 underwent TKR during the 10-year follow-up period. We confirmed the previously reported association of the branched chain amino acids to histidine ratio with advanced knee OA (P = 9.3 x 10-7) and identified a novel metabolic marker--the lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio--that was associated with advanced knee OA (P = 1.5 x 10-7) after adjustment for age, sex and BMI. When the subjects of the longitudinal cohort were categorized into two groups based on the optimal cut-off of the ratio of 0.09, we found the subjects with the ratio ≽0.09 were 2.3 times more likely to undergo TKR than those with the ratio <0.09 during the 10-year follow-up (95% CI: 1.2, 4.3, P = 0.02). Conclusion. We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change. [ABSTRACT FROM AUTHOR]

Highlights • Osteodynapenia but not osteosarcopenia increased the risk of fracture. • Osteodynapenia did not lead to a significantly greater fracture risk compared to having osteopenia or dynapenia alone. • Osteosarcopenia but not osteodynapenia increased the risk of mortality. • Osteosarcopenia did not lead to a significantly greater mortality risk compared to having osteopenia or sacropenia alone. Abstract Aim: To determine whether older adults with low muscle mass (sarcopenia) and strength (dynapenia), in the presence of osteoporosis/osteopenia, have an increased risk of fracture and mortality over 10 years, compared to those with low muscle or low bone mass alone or with neither condition. Methods: 1032 participants (52% women; mean age 62.9 ± 7.4 years) were prospectively followed for 10 years. Mortality was ascertained from the death registry and fractures were self-reported. Baseline appendicular lean mass (ALM) was assessed using dual-energy X-ray absorptiometry and normalised to body mass index (BMI). Hand grip strength (HGS) was assessed by dynamometer. Osteosarcopenia and osteodynapenia were defined as having T-scores of the total hip and/or lumbar spine bone mineral density (BMD) < –1 combined with being in the lowest 20% of the sex-specific distribution for ALM/BMI or HGS respectively. Results: Incident fracture risk was significantly higher in participants who were osteodynapenic (RR = 2.07, 95% CI: 1.26–3.39), dynapenic alone (RR = 1.74, 95% CI: 1.05–2.87), and osteopenic alone (RR = 1.63, 95% CI: 1.15–2.31), compared to those without dynapenia or osteopenia. Mortality risk was significantly higher only in participants with osteosarcopenia (RR = 1.49, 95% CI: 1.01–2.21) compared to those without sarcopenia or osteopenia. However, osteosarcopenia and osteodynapenia did not lead to a significantly greater fracture or mortality risk compared to having these conditions on their own. Conclusion: These findings suggest that the combined effect of osteopenia and sarcopenia or dynapenia on fracture and mortality risk, respectively, may not be greater than that of each individual condition. [ABSTRACT FROM AUTHOR]

• In addition to inter-individual differences, intra-individual variability in physical activity is associated with knee pain and functional limitation. • When participants engaged in more physical activity than their average level, they had lower knee pain and functional limitation. • Conversely, having higher functional limitations compared with an individual's average was associated with lower levels of physical activity. To describe the associations between interindividual (between-person) and intraindividual (within-person) variability in physical activity (PA) and knee pain and functional limitation among older adults. We also investigated the potential bidirectional association of between-person and within-person variability in knee pain and functional limitation with PA. Participants (N = 1064; 51% women; mean age 63 ± 7.4 years) were measured at baseline, 2.5, and 5 years. PA was measured using pedometers. Knee pain and functional limitation were assessed using the WOMAC scale. A two-part hurdle model, with adjustment for confounders, estimated the association of between-person and within-person variability in PA with knee pain/functional limitation (as the outcome). Linear mixed effect regression models described the association of between-person and within-person variability in knee pain and functional limitation with PA (as the outcome). Between-person effects showed that participants with a higher 5-year average PA had lower average WOMAC scores (β= –1.17, 95% CI: –1.82, –0.51). Within-person effects showed that at time-points when participants had a higher PA level than average, they also had lower WOMAC scores (β= –0.85, 95% CI: –1.36, –0.35). Conversely, both between-person (β= –15.6, 95% CI: –22.5, –8.8) and within-person increase (β= –7.4, 95% CI: –13.5, –1.4) in WOMAC scores were associated with lower PA. These findings suggest that PA and knee pain/dysfunctional contribute to the development of one another. Pain can lead to changes in inter- and intraindividual PA levels, but the reverse is also possible – changes in PA results in changes in inter- and intraindividual pain/dysfunctional levels. [ABSTRACT FROM AUTHOR]

To determine the effect of vitamin D supplementation and maintaining sufficient serum vitamin D on depressive symptoms in patients with knee osteoarthritis (OA) and vitamin D deficiency. A prespecified secondary analysis of a multicentre, randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to receive oral vitamin D 3 (50,000 IU, n = 209) or placebo (n = 204) monthly for 24 months. In addition, participants who completed the trial were classified into 2 groups according to their serum 25(OH)D levels at month 3 and 24 as follows: not consistently sufficient (serum 25(OH)D ≤ 50 nmol/L at month 3 and/or 24), and consistently sufficient (serum 25(OH)D > 50 nmol/L at both month 3 and 24). Multilevel mixed-effect models were used to compare differences of change in PHQ-9 scores between groups. This clinical trial was conducted in participants with symptomatic knee OA and vitamin D deficiency from June 2010 to December 2013 in Tasmania and Victoria, Australia. The primary outcome was the depressive symptoms change over 24 months, which was measured using the Patient Health Questionnaire (PHQ-9, 0-27). Of 599 participants who were screened for eligibility, 413 participants were enrolled (mean age: 63.2 years; 50.3% female) and 340 participants (intervention n = 181, placebo n = 159, 82.3% retention rate) completed the study. The baseline prevalence of depression (PHQ-9 score ≥5) was 25.4%. Depressive symptoms improved more in the vitamin D supplementation group compared to the placebo group [β: −0.66, 95% confidence interval (CI): −1.22 to −0.11, P for difference =.02] and in the participants who maintained vitamin D sufficiency compared to those who did not (β: −0.73, 95% CI: −1.41 to −0.05, P for difference =.04) over 24 months. These findings suggest that vitamin D supplementation and maintaining adequate vitamin D levels over 24 months may be beneficial for depressive symptoms in patients with knee OA. [ABSTRACT FROM AUTHOR]