F. Cicuttini

The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study

Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the worlds population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.

Genetic influences on osteoarthritis in women: a twin study.

Abstract Objectives: To assess the relative contribution of genetic and environmental factors to common forms of osteoarthritis of the hands and knees. Design: Classic twin study with unselected twins who were screened radiologically for osteoarthritis. Subjects: 130 identical and 120 non-identical female twins aged 48-70 recruited from a London based twin register and through a national media campaign. Main outcome measures: Similarity in identical compared with non-identical twin pairs for radiographic changes at the interphalangeal and first carpometacarpal joints of the hands and the tibiofemoral joint and patellofemoral joint of the knee expressed as intraclass correlations. Results: The intraclass correlations of radiographic osteophytes and narrowing at most sites and the presence of Heberdens nodes and knee pain were higher in the identical pairs. The intraclass correlation of the total radiographic osteoarthritis score in identical pairs (rMZ) was 0.64 (SE 0.05) compared with 0.38 (0.08) in non-identical pairs. The proportion of genetic variance of total osteoarthritis score (osteophytes and narrowing) with modelling techniques was estimated at 0.54 (95% confidence interval 0.43 to 0.65) and ranged from 0.39 to 0.65 for different sites and features (P<0.001) after adjustment for age and weight. Conclusions: These results demonstrate for the first time a clear genetic effect for radiographic osteoarthritis of the hand and knee in women, with a genetic influence ranging from 39-65%, independent of known environmental or demographic confounders. The results of this study should lead to further work on isolating the gene or genes involved in the pathogenesis of this common disabling disease. Key messages Key messages Although environmental factors have traditionally been thought to be the main influences, there are few data to support this Between 39% and 65% of osteoarthritis in the general population can be attributed to genetic factors Identification of the genes concerned could have a large impact on the disease in terms of prevention and new therapeutic approaches

Higher dynamic medial knee load predicts greater cartilage loss over 12 months in medial knee osteoarthritis

Objective Mechanical factors, in particular increased medial knee joint load, are believed to be important in the structural progression of knee osteoarthritis. This study evaluated the relationship of medial knee load during walking to indices of structural disease progression, measured on MRI, in people with medial knee osteoarthritis. Methods A longitudinal cohort design utilising a subset of participants (n=144, 72%) enrolled in a randomised controlled trial of lateral wedge insoles was employed. Medial knee load parameters including the peak knee adduction moment (KAM) and the KAM impulse were measured at baseline using three-dimensional gait analysis during walking. MRI at baseline and at 12 months was used to assess structural indices. Multiple regression with adjustment for covariates assessed the relationship between medial knee load parameters and the annual change in medial tibial cartilage volume. Binary logistic regression was used for the dichotomous variables of progression of medial tibiofemoral cartilage defects and bone marrow lesions (BML). Results A higher KAM impulse, but not peak KAM, at baseline was independently associated with greater loss of medial tibial cartilage volume over 12 months (β=29.9, 95% CI 6.3 to 53.5, p=0.01). No significant relationships were seen between medial knee load parameters and the progression of medial tibiofemoral cartilage defects or BML. Conclusion This study suggests knee loading, in particular the KAM impulse, may be a risk factor for loss of medial tibial cartilage volume. As knee load is modifiable, load-modifying treatments may potentially slow disease progression.

Sex and site differences in cartilage development: a possible explanation for variations in knee osteoarthritis in later life.

OBJECTIVE To test the hypothesis that sex-related and joint compartment-related differences in the risk of osteoarthritis (OA) of the knee might be associated with variations in cartilage development, we investigated knee cartilage volume in healthy children. METHODS We studied 92 children who were randomly selected from among students in grades 3-12 of a single school in Hobart, Tasmania (49 boys, 43 girls; age range 9-18 years). Articular cartilage thickness and volume were determined at the patella, medial tibial compartment, and lateral tibial compartment by magnetic resonance imaging (MRI). Sagittal T1-weighted fat-suppressed MRI images were obtained and processed on an independent computer work station. RESULTS Males had significantly more knee cartilage than females. Sex accounted for 6-36% of the variation in cartilage thickness and volume, which was statistically significant at all sites. Even after adjustment for age, body mass index, bone area, and physical activity, males had 16-31% higher cartilage volume; this was most marked at the medial tibial site. In addition, lateral tibial thickness was greater than medial tibial thickness (5.9 versus 3.6 mm; P < 0.0001) and lateral tibial volume was greater than medial tibial volume (2,823 versus 2,299 microl; P < 0.0001). Furthermore, physical activity was a significant explanatory factor for cartilage volume at all sites (R2 7-14% depending on site; all P < 0.05). The most consistent activity association was with vigorous activity in the previous 2 weeks (difference between any vigorous activity versus none 22-25% greater; all P < 0.05). CONCLUSION Sex- and joint compartment-related differences in cartilage development may be one explanation for variations in the pattern of knee OA seen in later life. Furthermore, the physical activity associations suggest that cartilage development is amenable to modification.

Does knee malalignment increase the risk of development and progression of knee osteoarthritis? A systematic review

OBJECTIVE To systematically review the evidence for a relationship between malalignment of the knee joint and progression and/or development of knee osteoarthritis (OA). METHODS Electronic searches of Medline, EMBase, and CINAHL were performed up to July 2008 using medical subject headings and free-text words. We included radiographic or magnetic resonance imaging (MRI) studies that met a set of predefined criteria. Two independent reviewers extracted the data and assessed the methodologic quality of the selected studies. Due to both heterogeneity and a limited number of studies, the results were summarized using a best evidence synthesis. RESULTS Fourteen studies met our inclusion criteria and 8 were considered high quality. We found limited evidence for an association between knee malalignment and incident knee OA, because only 1 cohort study examined this relationship. However, there was strong evidence based on 4 high-quality cohort studies that knee malalignment is an independent risk factor for progression of radiographic knee OA. This finding was further supported by 2 high-quality MRI cohort studies that found a relationship between varus and valgus alignment and structural progression of knee OA. CONCLUSION Malalignment of the knee joint was found to be an independent risk factor for the progression of knee OA. Given the paucity of investigation into the relationship between knee malalignment and risk of incident OA, further high-quality cohort studies are needed, and these may have important implications for the prevention of knee OA.

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.

Users of oestrogen replacement therapy have more knee cartilage than non-users

BACKGROUND Osteoarthritis (OA) is increasingly prevalent in the years after menopause. Epidemiological data suggest that the use of oestrogen replacement therapy (ERT) may protect against knee OA. AIM To test the hypothesis that long term ERT (longer than five years) is associated with increased knee cartilage in postmenopausal women. METHODS The study involved 81 women (42 current users (⩾ five years) of ERT and 39 who had never used it). Articular cartilage volumes were determined by processing images acquired in the sagittal plane using a T1 weighted fat suppressed magnetic resonance sequence on an independent work station. RESULTS After bone size had been accounted for, ERT users had higher tibial cartilage volume than non-users. Total tibial cartilage volume was 7.7% (0.23 ml) greater in the group of ERT users (2.98 (0.47) ml; mean (SD)) than in the untreated group (2.75 (0.50) ml). The difference, after adjustment for the significant explanatory factors (years since menopause, body mass index, age at menopause, and smoking), between the ERT users and non-users increased from 0.23 ml to 0.30 ml (95% confidence interval 0.08 to 0.52, p=0.008). These differences persisted after exclusion of women with OA. CONCLUSIONS After adjustment for multiple confounders, women using long term ERT have more knee cartilage than controls. This may indicate that ERT prevents loss of knee articular cartilage.

Lateral wedge insoles for medial knee osteoarthritis: 12 month randomised controlled trial

Objective To assess the effect of lateral wedge insoles compared with flat control insoles on improving symptoms and slowing structural disease progression in medial knee osteoarthritis. Design Randomised controlled trial. Setting Community in Melbourne, Australia. Participants 200 people aged 50 or more with clinical and radiographic diagnosis of mild to moderately severe medial knee osteoarthritis. Interventions Full length 5 degree lateral wedged insoles or flat control insoles worn inside the shoes daily for 12 months. Main outcome measures Primary symptomatic outcome was change in overall knee pain (past week) measured on an 11 point numerical rating scale. Primary structural outcome was change in volume of medial tibial cartilage from magnetic resonance imaging scans. Secondary clinical outcomes included changes in measures of pain, function, stiffness, and health related quality of life. Secondary structural outcomes included progression of medial cartilage defects and bone marrow lesions. Results Between group differences did not differ significantly for the primary outcomes of change in overall pain (−0.3 points, 95% confidence intervals −1.0 to 0.3) and change in medial tibial cartilage volume (−0.4 mm3, 95% confidence interval −15.4 to 14.6), and confidence intervals did not include minimal clinically important differences. None of the changes in secondary outcomes showed differences between groups. Conclusion Lateral wedge insoles worn for 12 months provided no symptomatic or structural benefits compared with flat control insoles. Trial registration Australian New Zealand Clinical Trials Registry ACTR12605000503628 and ClinicalTrials.gov NCT00415259.

Incidence and risk factors for deep surgical site infection after primary total hip arthroplasty : a systematic review

Although deep surgical site infection (SSI) is a major complication of primary total hip arthroplasty (THA), there are conflicting data regarding the incidence of deep SSI, and no comprehensive evaluation of the associated risk factors has been undertaken. We performed a systematic review of the literature; undertaking computer-aided searches of electronic databases, assessment of methodological quality, and a best-evidence synthesis. The incidence of SSI ranged from 0.2% before discharge to 1.1% for the period up to and including 5 years post surgery. Greater severity of a pre-existing illness and a longer duration of surgery were found to be independent risk factors for deep SSI. There is a need for high-quality, prospective studies to further identify modifiable risk factors for deep SSI after THA.

Tibial and femoral cartilage changes in knee osteoarthritis

BACKGROUND Despite the increasing interest in using knee cartilage volume as an outcome measure in studies of osteoarthritis (OA), it is unclear what components of knee cartilage will be most useful as markers of structure in the tibiofemoral (TF) joint. OBJECTIVE To compare the changes that occur in femoral and tibial cartilage volume in normal and osteoarthritic knees and how they relate to radiological grade. METHODS 82 subjects (44 female, 38 male, age range 35–69 years) with a spectrum of radiological knee OA were examined. Each subject had femoral and tibial cartilage volume in the medial and lateral TF joint determined from T1 weighted fat saturated magnetic resonance images of the knee. Radiological grade of OA was determined from standing knee radiographs. RESULTS There was strong correlation between femoral and tibial cartilage volume measured in both the medial (R=0.75, p<0.001) and lateral TF joint (R=0.77, p<0.001). Similar correlations persisted when those with normal and those with OA joints were examined separately at both the medial and lateral TF joint. For each increase in radiological grade of joint space narrowing (0–3), there was a mean (SD) reduction in tibial cartilage volume of 1.00 (0.32) ml in the medial compartment and 0.53 (0.25) ml in the lateral compartment, after adjusting for differences in bone size. Similar changes were seen in the femoral cartilage. CONCLUSIONS The amounts of tibial and femoral cartilage are strongly related. It may be that for TF joint disease, measuring tibial cartilage alone may be adequate, given that measurements of the total femoral cartilage are less reproducible and the difficulties inherent in identifying the most appropriate component of femoral cartilage to measure.