Stephen Quinn

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

OBJECTIVEnThe 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.nnnMETHODSnA 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.nnnRESULTSnAt 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).nnnCONCLUSIONSnSerum 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.

Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial

Objectives To compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs). Methods Adults aged 50–80 years (n=59) with clinical knee osteoarthritis and knee BMLs were randomised to receive either ZA (5 mg/100 ml) or placebo. BMLs were determined using proton density-weighted fat saturation MR images at baseline, 6 and 12 months. Pain and function were measured using a visual analogue scale (VAS) and the knee injury and osteoarthritis outcome score (KOOS) scale. Results At baseline, mean VAS score was 54 mm and mean total BML area was 468 mm2. VAS pain scores were significantly reduced in the ZA group compared with placebo after 6 months (−14.5 mm, 95% CI −28.1 to −0.9) but not after 3 or 12 months. Changes on the KOOS scales were not significant at any time point. Reduction in total BML area was greater in the ZA group compared with placebo after 6 months (−175.7 mm2, 95% CI −327.2 to −24.3) with a trend after 12 months (−146.5 mm2, 95% CI −307.5 to +14.5). A greater proportion of those in the ZA group achieved a clinically significant reduction in BML size at 6 months (39% vs 18%, p=0.044). Toxicity was as expected apart from a high rate of acute phase reactions in treatment and placebo arms. Conclusions ZA reduces knee pain and areal BML size and increases the proportion improving over 6 months. Treatment of osteoarthritis may benefit from a lesion specific therapeutic approach. Clinical trial registration number ACTRN 12609000399291.

A randomised controlled trial of the effects of mindfulness practice on medical student stress levels.

Medical Education 2011: 45: 381–388

Long-term cognitive transitions, rates of cognitive change, and predictors of incident dementia in a population-based first-ever stroke cohort

Background and Purpose— There are few data on long-term cognitive outcomes after first-ever stroke. We aimed to study long-term cognitive transitions, rates of cognitive change, and factors associated with incident dementia and cognitive impairment–no dementia (CIND) 2 years after first-ever stroke. Methods— A population-based cohort of incident first-ever stroke cases (n=99; mean age, 69.9 years) and an age- and sex-matched comparison group (nonstrokes, n=99) were followed up for 2 years by 3 serial examinations. Rates of cognitive change were compared by repeated-measures analyses. Factors associated with incident dementia and CIND at 2 years were determined by multinomial logistic regression. Results— Significant stroke×time interactions were present for all cognitive domains, with stroke cases showing a greater rate of decline compared with nonstrokes. Stroke recurrence during follow-up was responsible for significantly greater global decline. Strokes with recurrence (P=0.02), age (P=0.004), and baseline cognitive impairment (P<0.001) were independently associated with incident dementia at 2 years. Strokes without recurrence (P=0.008), age (P=0.001), and baseline cognitive impairment (P<0.001) were independently associated with CIND at 2 years. Conclusions— Recurrent stroke contributes importantly to global cognitive decline after a first-ever stroke. Secondary stroke prevention will be important in ameliorating dementia related to stroke. Mechanisms underlying the progression of early cognitive impairment to dementia in stroke patients need further investigation.

Increasing incidence of ALS in Canterbury, New Zealand A 22-year study

Objective: We performed a prospective study of amyotrophic lateral sclerosis (ALS) in North Canterbury, New Zealand, from 1985 to 2006, to ascertain the incidence of ALS over that 22-year period, and to detect patterns of change in incidence. We also aimed to identify factors that influenced survival. Methods: A prospective database of all patients seen at the Department of Neurology at Christchurch Public Hospital formed the basis of this study. Additional cases were identified through hospital coding data and from neurologists’ private practice records. Kaplan-Meier life table analysis and Cox proportional hazards analyses were used for the survival analysis. Poisson regression and capture-recapture techniques were used to analyze incidence data. Results: ALS incidence rates steadily increased by 3% per year over the 22 years, from 1.6 to 3.3 per 100,000 per year. Older age, bulbar symptoms, and male sex adversely affected survival. The median survival from diagnosis was 17.6 months and from symptom onset 27.6 months. Contemporary supportive therapies such as noninvasive ventilation and percutaneous endoscopic gastrostomy did not extend survival. There was no disease clustering and no clues to etiology were revealed. Conclusions: We report the highest recorded incidence of amyotrophic lateral sclerosis (ALS) to date, with the incidence of ALS in Canterbury increasing over the 22 years of the study. We were unable to confirm improvement in survival using contemporary supportive therapies and confirmed older age, male sex, and bulbar onset as adverse prognostic factors. The increasing incidence is not explained by aging of the population. GLOSSARY: ALS = amyotrophic lateral sclerosis; CDHB = Canterbury District Health Board; CPH = Christchurch Public Hospital; EEC = El Escorial criteria; ICD = International Classification of Diseases; KM = Kaplan-Meier; MND = motor neuron diseases; NDD = neurology department database; NIV = noninvasive ventilation; PMA = progressive muscle atrophy; UMN = upper motor neuron.

Bone marrow lesions predict site-specific cartilage defect development and volume loss: a prospective study in older adults

IntroductionRecent evidence suggests that bone marrow lesions (BMLs) play a pivotal role in knee osteoarthritis (OA). The aims of this study were to determine: 1) whether baseline BML presence and/or severity predict site-specific cartilage defect progression and cartilage volume loss; and 2) whether baseline cartilage defects predict site-specific BML progression.MethodsA total of 405 subjects (mean age 63 years, range 52 to 79) were measured at baseline and approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee was performed to measure knee cartilage volume, cartilage defects (0 to 4), and BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial (LT), and lateral femoral (LF) sites. Logistic regression and generalized estimating equations were used to examine the relationship between BMLs and cartilage defects and cartilage volume loss.ResultsAt all four sites, baseline BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P < 0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P < 0.05) at the same site. In multivariable analysis, there was a significant relationship between BML severity and defect progression at all four sites (OR 1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF, LT, and LF sites (β -22.1 to -42.0, all P < 0.05). Additionally, baseline defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7, all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at the MT and LT sites when both larger defects and BMLs were present at baseline (all P < 0.05).ConclusionsBaseline BMLs predicted site-specific defect progression and cartilage volume loss in a dose-response manner suggesting BMLs may have a local effect on cartilage homeostasis. Baseline defects predicted site-specific BML progression, which may represent increased bone loading adjacent to defects. These results suggest BMLs and defects are interconnected and play key roles in knee cartilage volume loss; thus, both should be considered targets for intervention.

Tracking of bone mass from childhood to adolescence and factors that predict deviation from tracking

It has been hypothesized that bone density tracks but long term studies in children are lacking. As such, the aim of this study was to describe tracking of dual X-ray absorptiometry measures from age 8 to age 16 years, whether this was independent of change in body size and whether deviation from tracking could be predicted. 116 males and 67 females had anthropometric (height and weight), questionnaire (medication use, sports, breastfeeding), fitness (PWC(170)) and DXA measures (bone free lean mass [LM], fat mass [FM] and bone mass) at baseline and follow-up. BMC and aBMD were assessed at the spine and hip and total body and bone mineral apparent density (BMAD) at the spine and hip. We found all DXA measures tracked significantly after adjustment for change in height and change in weight (males: R(2): BMC 24-62%; aBMD 41-48%; BMAD 30-37%, females: R(2): BMC 45-72%; aBMD 36-56%; BMAD 30-48%). Factors that predicted subjects would deviate positively, that is improve in tertile or remain in the highest tertile of spine and hip aBMD included having been breastfed, increase in LM, PWC(170) at age 8 and sport participation in males. LM at age 8 was beneficial in males while in females; FM at age 8 predicted subjects would deviate positively. Boys who gained absolute and percent FM and girls who gained percent FM, were more likely to deviate negatively, that is, decrease in tertile or remain in the lowest tertile of spine and hip aBMD. ICS use at age 8 also predicted subjects, particularly males would not improve in bone mass relative to their peers. In conclusion, DXA measures track moderately to strongly from childhood to adolescence. This was independent of linear growth and sex indicating bone development and physical growth are under largely separate mechanistic control. Body composition was the main predictor of altered tracking but environmental factors also appear important.

Association between leptin, body composition, sex and knee cartilage morphology in older adults: the Tasmanian older adult cohort (TASOAC) study

OBJECTIVEnTo describe the associations between leptin, body composition, sex and knee cartilage volume/defects in older adults.nnnMETHODSnA cross-sectional sample of 190 randomly selected subjects (mean 63 years, range 52-78, 48% female) were studied. Knee cartilage volume and defects were determined using T1-weighted fat saturation MRI. Serum leptin levels were measured by radioimmunoassay. Fat and lean mass were measured by dual energy x ray absorptiometry (DXA). Body mass index (BMI) was calculated.nnnRESULTSnIn multivariable analysis, serum levels of leptin were negatively associated with total cartilage volume (beta: -541 mm3/log transformed unit, 95% CI -861 to -221) but not with prevalent knee cartilage defects. BMI was negatively associated with cartilage volume after adjustment for total lean mass and positively with prevalent knee cartilage defects. However, the association between BMI and cartilage volume disappeared after adjustment for leptin while the association between BMI and cartilage defects remained unchanged. Lastly, sex differences in total cartilage volume decreased substantially after adjustment for leptin (R2 from 51% to 30%).nnnCONCLUSIONSnThis cross-sectional study suggests cartilage volume loss with obesity and female sex is related to leptin and, thus, is hormonally mediated in older adults. By contrast, obesity related knee focal cartilage defects may be more related to non-hormonal factors.

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.

Subchondral Bone and Cartilage Damage - A Prospective Study in Older Adults

OBJECTIVEnThere is limited longitudinal evidence relating subchondral bone changes to cartilage damage and loss. The aim of this study was to describe the association between baseline tibial bone area and tibial subchondral bone mineral density (BMD) with tibial cartilage defect development and cartilage volume loss.nnnMETHODSnA total of 341 subjects (mean age 63 years, range 52-79 years) underwent measurement at baseline and approximately 2.7 years later. Tibial knee cartilage volume, cartilage defects (graded on a scale of 0-4), and bone area were determined using T1-weighted fat suppression magnetic resonance imaging. Tibial subchondral BMD was determined using dual x-ray absorptiometry.nnnRESULTSnIn multivariable analysis, baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 per 1 SD increase, 95% confidence interval [95% CI] 1.0, 2.6, and OR 2.4 per 1 SD increase, 95% CI 1.4, 4.0, respectively) and cartilage volume loss at the medial tibial site (beta = -34.9 per 1 SD increase, 95% CI -49.8, -20.1). In contrast, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase, 95% CI 1.2, 2.1) and was not associated with cartilage loss.nnnCONCLUSIONnThe results of this study demonstrated that bone area predicted medial and lateral cartilage defect development and medial cartilage volume loss, while subchondral BMD predicted medial defect development but not cartilage loss. These associations were independent of each other, indicating there are multiple mechanisms by which subchondral bone changes may lead to cartilage damage.