Factors affecting tibial plateau expansion in healthy women over 2.5 years: a longitudinal study

SummaryObjectiveThere is evidence for tibial bone area to increase in response to risk factors for knee osteoarthritis (OA) in healthy subjects and to increase over time in subjects with knee OA. We performed a cohort study to examine whether tibial plateau bone area changes over time in healthy subjects and identify factors influencing the change.DesignEighty-one healthy women (age range 50–76 years) underwent magnetic resonance imaging (MRI) on their dominant knee at baseline and approximately 2.5 years later. Tibial plateau bone area was measured at baseline and follow-up. Risk factors assessed at baseline were tested for their association with change in tibial plateau bone area over time using multiple linear regression.ResultsThe mean tibial plateau bone area increased from 1733±209 to 1782±203mm2 for the medial, and from 1090±152 to 1109±152mm2 for the lateral over the study period, representing an annual average increase rate of 1.2% (95% CI 0.03%, 1.6%) and 0.8% (95% CI 0.7%, 1.8%), respectively. Baseline tibial plateau bone area was inversely associated with the increase rate of tibial plateau bone area. There was a trend for static knee alignment to be related to the increase rate of tibial plateau bone area.ConclusionIn healthy women, tibial plateau bone area increases over time. Baseline tibial plateau bone area is the main factor affecting the rate of increase, with biomechanical factors, such as static anatomical alignment, likely to affect the expansion of tibial plateau. Further work will be needed to determine the effect of subchondral bone change in the pathogenesis of knee OA

Physician diagnosed arthritis, reported arthritis and radiological non-axial osteoarthritis

SummaryObjectiveTo determine the question that best predicts radiographic evidence of non-axial osteoarthritis (OA).DesignThe Melbourne Women's Mid-life Health Project (MWMHP), commenced in 1991, is a population-based prospective study of 438 Australian-born. Two hundred and fifty-seven (57%) women remained in longitudinal assessment in 2002 and 224 (87%) women agreed to undergo X-rays of their hands and knees between 2002 and 2003.MethodsAnnually participants were asked about aches and stiff joints and arthritis or rheumatism. In the eleventh year of follow-up X-rays were scored for evidence of OA using a validated scale, by two investigators who were blinded to questionnaire results. Information on hormone therapy use, physical activity, mood, smoking, body mass index (BMI) and age were obtained by both self-administered and face-to-face questionnaires.ResultsPatient reported physician diagnosed arthritis was the best predictor of radiological OA (ROA). The question had a specificity of 64%, a positive predictive value of 57% and a negative predictive value of 71%. Even the most reliable question about arthritis still had a relatively low specificity for radiologically diagnosed OA. Reporting symptoms were significantly more common in participants who were depressed, those who had a higher negative affect and those with a higher BMI.ConclusionIn large epidemiological studies where questionnaire assessment of OA is required, the greatest accuracy is achieved by asking about physician diagnosed arthritis. Concurrent application of a validated scale for mood is important

Obesity defined by body mass index and waist circumference and risk of total knee arthroplasty for osteoarthritis: a prospective cohort study

Objective: To examine the risk of total knee arthroplasty (TKA) due to osteoarthritis associated with obesity defined by body mass index (BMI) or waist circumference (WC) and whether there is discordance between these measures in assessing this risk. Methods: 36,784 participants from the Melbourne Collaborative Cohort Study with BMI and WC measured at 1990–1994 were included. Obesity was defined by BMI (≥30 kg/m2) or WC (men ≥102cm, women ≥88cm). The incidence of TKA between January 2001 and December 2018 was determined by linking participant records to the National Joint Replacement Registry. Results: Over 15.4±4.8 years, 2,683 participants underwent TKA. There were 20.4% participants with BMI-defined obesity, 20.8% with WC-defined obesity, and 73.6% without obesity defined by either BMI or WC. Obesity was classified as non-obese (misclassified obesity) in 11.7% of participants if BMI or WC alone was used to define obesity. BMI-defined obesity (HR 2.69, 95%CI 2.48–2.92), WC-defined obesity (HR 2.28, 95%CI 2.10–2.48), and obesity defined by either BMI or WC (HR 2.53, 95%CI 2.33–2.74) were associated with an increased risk of TKA. Compared with those without obesity, participants with misclassified obesity had an increased risk of TKA (HR 2.06, 95%CI 1.85–2.30). 22.7% of TKA in the community can be attributable to BMI-defined obesity, and a further 3.3% of TKA can be identified if WC was also used to define obesity. Conclusions: Both BMI and WC should be used to identify obese individuals who are at risk of TKA for osteoarthritis and should be targeted for prevention and treatment.Yuan Z. Lim, Yuanyuan Wang, Flavia M. Cicuttini, Graham G. Giles, Stephen Graves, Anita E. Wluka, Sultana Monira Hussai

Study protocol for a randomised controlled trial of diacerein versus placebo to treat knee osteoarthritis with effusion-synovitis (DICKENS)

Published online: 11 September 2022Background: There is an unmet need for treatments for knee osteoarthritis (OA). Effusion-synovitis is a common inflammatory phenotype of knee OA and predicts knee pain and structural degradation. Anti-inflammatory therapies, such as diacerein, may be effective for this phenotype. While diacerein is recommended for alleviating pain in OA patients, evidence for its effectiveness is inconsistent, possibly because studies have not targeted patients with an inflammatory phenotype. Therefore, we will conduct a multi-centre, randomised, placebo-controlled double-blind trial to determine the effect of diacerein on changes in knee pain and effusion-synovitis over 24 weeks in patients with knee OA and magnetic resonance imaging (MRI)-defined effusion-synovitis. Methods: We will recruit 260 patients with clinical knee OA, significant knee pain, and MRI-detected effusion-synovitis in Hobart, Melbourne, Adelaide, and Perth, Australia. They will be randomly allocated to receive either diacerein (50mg twice daily) or identical placebo for 24 weeks. MRI of the study knee will be performed at screening and after 24 weeks of intervention. The primary outcome is improvement in knee pain at 24 weeks as assessed by a 100-mm visual analogue scale (VAS). Secondary outcomes include improvement in volumetric (ml) and semi-quantitative (Whole-Organ Magnetic Resonance Imaging Score, 0–3) measurements of effusion-synovitis using MRI over 24 weeks, and improvement in knee pain (VAS) at 4, 8, 12, 16, and 20 weeks. Intention-to-treat analyses of primary and secondary outcomes will be performed as the primary analyses. Per protocol analyses will be performed as the secondary analyses. Discussion: This study will provide high-quality evidence to determine whether diacerein improves pain, changes disease trajectory, and slows disease progression in OA patients with effusion-synovitis. If diacerein proves effective, this has the potential to significantly benefit the substantial proportion (up to 60%) of knee OA patients with an inflammatory phenotype. Trial registration: Australian and New Zealand Clinical Trial Registry ACTRN 12618 00165 6224. Registered on 08 October 2018.Guoqi Cai, Graeme Jones, Flavia M. Cicuttini, Anita E. Wluka, Yuanyuan Wang, Catherine Hill, Helen Keen, Benny Antony, Xia Wang, Barbara de Graaff, Michael Thompson, Tania Winzenberg, Kathy Buttigieg and Dawn Aitke

Static knee alignment and its association with radiographic knee osteoarthritis

SummaryObjectivesAlthough knee alignment is associated with the progression of knee osteoarthritis (OA), it is unclear which features that characterize radiographic OA are related to alignment. The aim of this study was to examine the relationship between static knee joint alignment (measured as a continuous variable) and the radiographic features of knee OA (joint space narrowing and osteophytes).MethodsOne hundred and twenty one adults with symptomatic knee OA were recruited using a combined strategy including referral from specialist centres, arthritis support groups and media advertising. X-rays were performed to classify the severity of disease and to determine static knee alignment.ResultsIncreasing varus knee alignment was associated with increasing risk of medial compartment joint space narrowing (P<0.001) and osteophytes (P=0.005). Increasing valgus knee alignment was associated with an increased risk for lateral compartment joint space narrowing (P<0.001) and osteophytes (P=0.002).ConclusionThis study has demonstrated that the static knee angle, measured as a continuous variable, is an important determinant of the compartment-specific features of radiographic knee OA. Further work is required to determine whether interventions aimed at correcting these relatively minor levels of varus and valgus angulation will have an effect on the risk of tibiofemoral OA

Female reproductive and hormonal factors and incidence of primary total knee arthroplasty due to osteoarthritis

Objective: To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis (OA), and to determine whether the associations differ according to overweight/obesity status. Methods: This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive (OC) use, menopausal status, and hormone replacement therapy (HRT) were collected in 1990–1994. Incidence of TKA during 2001–2013 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. All analyses were adjusted for age, body mass index (BMI) at midlife, change in BMI (from early reproductive age to midlife), country of birth, physical activity, smoking, and education level. Results: Over the course of 12.7 years, 1,208 TKAs for OA were identified. Ever being pregnant was associated with increased risk of TKA (hazard ratio [HR] 1.32 [95% confidence interval (95% CI) 1.06–1.63]). Parity was positively associated with risk of TKA (P for trend = 0.003). OC users had increased risk of TKA compared with non-users (for OC use of <5 years, HR 1.25 [95% CI 1.08–1.45]; for OC use of ≥5 years, HR 1.17 [95% CI 1.00–1.37]). A 1-year increase in menstruation was associated with a 1% decrease in risk of TKA (HR 0.99 [95% CI 0.97–0.99]). These associations remained significant only in women of normal weight at early reproductive age. Current HRT users had increased risk of TKA compared with non-users (HR 1.37 [95% CI 1.14–1.64]); the association was significant only in non-obese women at midlife.Conclusion: Reproductive and hormonal factors were associated with risk of knee OA. These associations remained significant in women of normal weight at early reproductive age and in non-obese women at midlife. Further work is needed to understand the complex effect of these factors on knee OA.Sultana Monira Hussain, Yuanyuan Wang, Graham G. Giles, Stephen Graves, Anita E. Wluka, Flavia M. Cicuttin