B. Antony

A longitudinal study of the association between infrapatellar fat pad maximal area and changes in knee symptoms and structure in older adults

Background The infrapatellar fat pad (IPFP) is of uncertain significance for knee osteoarthritis. The aim of this study was to describe the longitudinal associations between baseline IPFP maximal area and changes in knee pain, knee cartilage volume and cartilage defects in older adults. Methods 356 community-dwelling male and female adults aged 50–80 years were measured at baseline and approximately 2.6 years later. T1-weighted or T2-weighted fat-suppressed MRI was used to assess maximal IPFP area, cartilage volume and cartilage defects at baseline and/or follow-up. Knee pain was assessed by the self-administered Western Ontario McMaster Osteoarthritis Index questionnaire. Results After adjustment for confounders, IPFP maximal area in women was significantly and negatively associated with changes in knee pain (β: −0.18 to −0.86 for total knee pain, pain at night while in bed, pain when sitting/lying and pain when standing upright, all p<0.05) but not with other knee pain subscales. IPFP maximal area in women was beneficially associated with change in tibial cartilage volume per annum (β: +1.56% per cm2 at medial site; +0.86% per cm2 at lateral site, both p<0.05), but not with change in patellar cartilage volume. Further, it was significantly associated with reduced risks of increases in medial cartilage defects (relative risk: 0·46 at tibial site, relative risk: 0.59 at femoral site; both p<0.05) but not with increases at other sites in women. No significant associations were found in men. Conclusions While the associations are not fully consistent, IPFP maximal area appears to have a protective role for knee symptoms and cartilage damage in older female adults.

Effect of vitamin D supplementation on tibial cartilage volume and knee pain among patients with symptomatic knee osteoarthritis: a randomized clinical trial

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.

Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults

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

Cross-sectional and longitudinal associations between systemic, subchondral bone mineral density and knee cartilage thickness in older adults with or without radiographic osteoarthritis.

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

Signal intensity alteration in the infrapatellar fat pad at baseline for the prediction of knee symptoms and structure in older adults: a cohort study

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

Body fat is associated with increased and lean mass with decreased knee cartilage loss in older adults: a prospective cohort study.

Objective:To determine the associations between body composition at baseline and knee cartilage loss over 2.9 years in older adults.Methods:A total of 395 randomly selected subjects (mean 62 years, range 51–81, 50% female) were studied at baseline and 2.9 years later. T1-weighted fat-suppressed magnetic resonance imaging of the right knee was performed to determine knee cartilage volume and tibial bone area at baseline and follow-up. Height, weight and radiographic osteoarthritis were measured by standard protocols at baseline. Fat mass and lean mass were measured by dual-energy X-ray absorptiometry at baseline.Results:Tibial cartilage volume decreased by 2.0–2.7% per annum. In multivariable analysis, annual change in medial cartilage volume was negatively and significantly associated with body mass index (β: −0.14% per kg m−2, 95% confidence interval (CI): −0.25%, −0.02%), percentage total body fat (β: −0.19% per %, 95% CI: −0.30%, −0.07%) and percentage trunk fat (β: −0.10% per %, 95% CI: −0.19%, −0.02%), and positively associated with percentage lean mass (β: 0.20% per %, 95% CI: 0.08%, 0.32%). Change in lateral tibial cartilage volume was also significantly associated with percentage total body fat (β: −0.11% per %, 95% CI: −0.21%, −0.001%) and total lean mass (β: 0.13% per kg, 95% CI: 0.04%, 0.22%). These were independent of sex and age even though both were also significant predictors.Conclusions:Body fat adversely affects tibial cartilage loss over time, whereas lean mass is protective. Strategies aimed at reducing body fat but increasing lean mass may reduce knee cartilage loss in older people.

Association of Baseline Knee Bone Size, Cartilage Volume, and Body Mass Index with Knee Cartilage Loss Over Time: A Longitudinal Study in Younger or Middle-aged Adults

Objective. To determine the association of knee bone size, cartilage volume, and body mass index (BMI) at baseline with knee cartilage loss over 2 years in younger or middle-aged adults. Methods. A total of 324 subjects (mean age 45 yrs, range 26–61) were measured at baseline and about 2 years later. Knee cartilage volume and bone size were determined using T1-weighted fat-saturated magnetic resonance imaging. Results. In multivariable analysis, baseline knee bone size was negatively associated with annual change in knee cartilage volume at medial and lateral tibial sites (ß = −0.62% to −0.47%/cm2, all p < 0.001). The associations disappeared at medial tibial site after adjustment for baseline cartilage volume and became of borderline statistical significance at lateral tibial site after adjustment for both baseline cartilage volume and osteophytes (ß = −0.29, p = 0.059). Baseline knee cartilage volume was consistently and negatively associated with annual change in knee cartilage volume at all 3 medial tibial, lateral tibial, and patellar sites (ß = −4.41% to −1.37%/ml, all p < 0.001). Baseline BMI was negatively associated with an annual change in knee cartilage volume, but only in subjects within the upper tertile of baseline cartilage volume, even after adjusting for cartilage defects (ß = −0.16% to −0.34%/kg/m2, all p < 0.05). Conclusion. Our study suggests that both higher baseline tibial bone area and knee cartilage volume (most likely due to cartilage swelling) are associated with greater knee cartilage loss over 2 years. A higher BMI was associated with greater knee cartilage loss only in subjects with higher baseline cartilage volume.

Association between childhood overweight measures and adulthood knee pain, stiffness and dysfunction: a 25-year cohort study

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

Mass effect and signal intensity alteration in the suprapatellar fat pad: associations with knee symptoms and structure

OBJECTIVE To describe cross-sectional associations between mass effect or signal intensity alteration of the suprapatellar fat pad (SPFP) with knee symptoms and structure in older adults. METHODS A cross-sectional sample of 904 randomly selected subjects (mean 62.4 years, 49.9% female) was studied. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was used to assess mass effect or signal intensity alteration of SPFP, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. The Osteoarthritis Research Society International (OARSI) atlas was used to assess knee osteophyte, joint space narrowing (JSN) and radiographic osteoarthritis (ROA). Univariable and multivariable linear or logistic regression analyses were used to examine the associations. RESULTS After adjustment for confounders including age, sex, body mass index (BMI), disease status, tibial bone area and/or ROA, the presence of SPFP mass effect was significantly associated with any knee pain (OR: 2.39; 95% confidence interval (CI): 1.54, 3.70) and ROA (OR: 2.10; 95% CI: 1.33, 3.31) but not with cartilage volume, cartilage defects or BMLs. The presence of SPFP signal intensity alteration was significantly associated with any knee pain (OR: 1.90; 95% CI: 1.43, 2.53), ROA (OR: 1.83; 95% CI: 1.37, 2.45), any BMLs (OR: 1.55; 95% CI: 1.17, 2.06) but not with cartilage volume and cartilage defects. Significant associations with knee pain and BMLs were more evident in subjects with ROA. Presence of SPFP mass effect and/or signal intensity alteration combined was associated with any tibial cartilage defects (OR: 1.45; 95% CI: 1.04, 2.04). CONCLUSIONS SPFP mass effect and/or signal intensity alterations are deleteriously associated with knee pain, radiographic OA and BMLs in this cross-sectional study, suggesting that SPFP abnormalities may contribute to pain and structural abnormalities in the knee.

Cross-sectional and Longitudinal Associations between Knee Joint Effusion Synovitis and Knee Pain in Older Adults

Objective. To describe the cross-sectional and longitudinal associations between knee regional effusion synovitis and knee pain in older adults. Methods. Data from a population-based random sample (n = 880, mean age 62 yrs, 50% women) were used. Baseline knee joint effusion synovitis was graded (0–3) using T2-weighted magnetic resonance imaging (MRI) in the suprapatellar pouch, central portion, posterior femoral recess, and subpopliteal recess. Effusion synovitis of the whole joint was defined as a score of ≥ 2 in any subregion. Other knee structural (including cartilage, bone marrow, and menisci) lesions were assessed by MRI at baseline. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index questionnaire at baseline and 2.6 years later. Multivariable analyses were performed after adjustment for age, sex, body mass index, and other structural lesions. Results. The prevalence of effusion synovitis was 67%. Suprapatellar pouch effusion synovitis was significantly and independently associated with increased total and nonweight-bearing knee pain in both cross-sectional and longitudinal analyses (for an increase in total knee pain of ≥ 5, RR 1.26 per grade, 95% CI 1.04–1.52), and increased weight-bearing knee pain in longitudinal analysis only. Effusion synovitis in posterior femoral recess and central portion were independently associated with increases in nonweight-bearing pain (RR 1.63 per grade, 95% CI 1.32–2.01 and RR 1.29 per grade, 95% CI 1.01–1.65, respectively) in longitudinal analyses only. Conclusion. Knee joint effusion synovitis has independent associations with knee pain in older adults. Suprapatellar pouch effusion synovitis is associated with nonweight-bearing and weight-bearing knee pain, while posterior femoral recess and central portion effusion synovitis are only associated with nonweight-bearing pain.