O. Stannus

Circulating levels of IL-6 and TNF-α are associated with knee radiographic osteoarthritis and knee cartilage loss in older adults

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.

Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study

Objective To determine the association between inflammatory markers and change in knee pain over 5 years. Methods A total of 149 randomly selected subjects (mean 63 years, range 52–78; 46% female) was studied. Serum levels of high sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF–α) and interleukin (IL)-6 were measured at baseline and 2.7 years later. Knee pain was recorded using the Western Ontario and McMasters osteoarthritis index questionnaire at baseline and 5 years later. Knee radiographic osteoarthritis of both knees was assessed at baseline, and knee bone marrow lesions, joint effusion and cartilage defects were determined using T1 or T2-weighted fat saturated MRI. Results After adjustment for confounding variables, baseline hs-CRP was positively associated with change in total knee pain (β=0.33 per mg/l, p=0.032), as well as change in the pain at night in bed (β=0.12 per ml/pg, p=0.010) and while sitting/lying (β=0.12 per ml/pg, p=0.002). Change in hs-CRP was also associated with change in knee pain at night and when sitting/lying (both p<0.05). Baseline TNFα and IL-6 were associated with change in pain while standing (β=0.06 per ml/pg, p=0.033; β=0.16 per ml/pg, p=0.035, respectively), and change in TNFα was positively associated with change in total knee pain (β=0.66 ml/pg, p=0.020) and change in pain while standing (β=0.26 ml/pg, p=0.002). Adjustment for radiographic osteoarthritis or MRI-detected structural abnormalities led to no or minor attenuation of these associations. Conclusion Systemic inflammation is an independent predictor of worsening knee pain over 5 years.

The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study.

IntroductionThe associations between leptin, interleukin (IL)-6, and hip radiographic osteoarthritis (OA) have not been reported, and their roles in obesity-related hip OA are unclear. The aim of this study was to describe the associations between leptin, IL-6, and hip radiographic osteoarthritis (ROA) in older adults.MethodsA cross-sectional sample of 193 randomly selected subjects (mean age, 63 years; range, 52 to 78 years; 48% female subjects) were studied. Hip ROA, including joint-space narrowing (JSN) and osteophytes, was determined by anteroposterior radiograph. Serum levels of leptin and interleukin (IL)-6 were measured with radioimmunoassay. Fat mass was measured with dual-energy x-ray absorptiometry (DXA). Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated.ResultsIn multivariable analysis, hip JSN was associated with serum levels of leptin in the whole sample (β = 0.046 per μg/L, P = 0.024 for superior; β = 0.068 per μg/L, P = 0.004 for axial compartment) and IL-6 only in females (β = 0.241 per pg/ml, P = 0.002 for superior; β = 0.239 per pg/ml, P = 0.001 for axial compartment). The positive associations between body-composition measures (BMI, WHR, percentage total fat mass, and percentage trunk fat mass) and hip JSN in women became nonsignificant after adjustment for leptin but not for IL-6. No significant associations were found between leptin, IL-6, and the presence or severity of osteophytes.ConclusionsThis study suggests that metabolic and inflammatory mechanisms may play a role in the etiology of hip OA and that the associations between body composition and hip JSN are mediated by leptin, particularly in women.

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.

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.

Body fat predicts an increase and limb muscle strength predicts a decrease in leptin in older adults over 2·6 years.

Obesity is characterized by hyperleptinaemia, which is associated with diabetes, hypertension and coronary heart disease. The aim of this study was to determine if body fat and muscle measures predict the natural increase in leptin over 2·6 years in older adults.