Miranda Davies-Tuck

The natural history of bone marrow lesions in community based adults with no clinical knee osteoarthritis

Objective: Although bone marrow lesions (BML) have been implicated in the pathogenesis of osteoarthritis, their natural history in a healthy population is unknown. This study in a healthy, pain-free population aimed to examine the natural history of BML; factors associated with incidence and progression of BML over 2 years and whether incident BML are associated with the development of pain. Methods: 271 subjects with no clinical knee osteoarthritis, being pain free at baseline, underwent magnetic resonance imaging of their dominant knee at baseline and 2 years later. The presence of BML was assessed. Results: In knees initially free of BML, incident BML developed in 14% of people over the study period. Increased body mass index (BMI; odds ratio (OR) 1.15, 95% CI 1.06 to 1.2, p = 0.001) was associated with incident BML. Those who developed a BML were more likely to develop knee pain compared with those in whom no BML developed (OR 4.2, 95% CI 1.2 to 15.1, p = 0.03). Among those in whom BML were present at baseline, 46% completely resolved. There was no association between age, gender and BMI and persistence of BML over 2 years. Conclusion: In this healthy population, the rate of incident BML is lower than previously described in a population with osteoarthritis. Incident BML are associated with increased BMI and the development of pain. Approximately half the BML present at baseline resolved. These data suggest that in pain-free people with no clinical knee osteoarthritis, BML are reversible and may provide a target for interventions aimed at the prevention of knee osteoarthritis.

Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women - a prospective cohort study

IntroductionGiven the emerging evidence that osteoarthritis (OA) may have a vascular basis, the aim of this study was to determine whether serum lipids were associated with change in knee cartilage, presence of bone marrow lesions (BMLs) at baseline and the development of new BMLs over a 2-year period in a population of pain-free women in mid-life.MethodsOne hundred forty-eight women 40 to 67 years old underwent magnetic resonance imaging (MRI) of their dominant knee at baseline and 2.2 (standard deviation 0.12) years later. Cartilage volume and BMLs were determined for both time points. Serum lipids were measured from a single-morning fasting blood test approximately 1.5 years prior to the MRI.ResultsThe incidence of BML at follow-up was associated with higher levels of total cholesterol (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.01, 3.36; P = 0.048) and triglycerides (OR 8.4, 95% CI 1.63, 43.43; P = 0.01), but not high-density lipoprotein (HDL) (P = 0.93), low-density lipoprotein (LDL) (P = 0.20) or total cholesterol/HDL ratio (P = 0.17). No association between total cholesterol, triglycerides, HDL, LDL or total cholesterol/HDL ratio and presence of BMLs at baseline or annual change in total tibial cartilage volume was observed.ConclusionsIn this study of asymptomatic middle-aged women with no clinical knee OA, serum cholesterol and triglyceride levels were associated with the incidence of BMLs over 2 years. This provides support for the hypothesis that vascular pathology may have a role in the pathogenesis of knee OA. Further work is warranted to clarify this and whether treatments aimed at reducing serum lipids may have a role in reducing the burden of knee OA.

Relationship between obesity and foot pain and its association with fat mass, fat distribution, and muscle mass

To examine the relationship between obesity, body composition, and foot pain as assessed by the Manchester Foot Pain and Disability Index (MFPDI).

Comparison of peak knee adduction moment and knee adduction moment impulse in distinguishing between severities of knee osteoarthritis

BACKGROUND The peak knee adduction moment is a valid proxy for medial knee joint loading. However as it only measures load at one instance of stance, knee adduction moment impulse, a measure that takes into account both the magnitude and duration of the stance phase, may provide more comprehensive information. This study directly compared the abilities of peak knee adduction moment and knee adduction moment impulse to distinguish between knee osteoarthritis severities. METHODS 169 participants with medial knee osteoarthritis completed radiographic and magnetic resonance imaging, the Western Ontario and McMaster Universities Arthritis Index to assess pain and a three-dimensional gait analysis. Participants were classified using four dichotomous classifications: Kellgren-Lawrence grading, alignment, medial tibiofemoral bone marrow lesions, and pain. FINDINGS When using Kellgren-Lawrence grade and alignment classifications, the area under the receiver operator curves were significantly greater for knee adduction moment impulse than for peak knee adduction moment. Based on analysis of covariance, knee adduction moment impulse was significantly different between Kellgren-Lawrence grade and alignment groups while peak knee adduction moment was not significantly different. Both peak knee adduction moment and knee adduction moment impulse distinguished between bone marrow lesion severities while neither measure was significantly different between pain severity groups. INTERPRETATIONS Findings suggest knee adduction moment impulse is more sensitive at distinguishing between disease severities and may provide more comprehensive information on medial knee joint loading. Future studies investigating biomechanics of knee osteoarthritis should include knee adduction moment impulse in conjunction with peak knee adduction moment.

Change in knee angle influences the rate of medial tibial cartilage volume loss in knee osteoarthritis

OBJECTIVES Identifying factors that influence the rate of cartilage loss at the knee may help to prevent or delay the progression of knee osteoarthritis (OA). Changes in knee alignment alter knee joint load and may affect the rate of cartilage loss. The aim of this study was to determine whether change in knee alignment between baseline and 2 years is associated with a change in knee cartilage volume in knee OA in the subsequent 2.5 years. METHODS Seventy-eight adults with symptomatic knee OA were recruited using a combined strategy. Radiographs were performed at time 0 and 2 years to determine change in knee alignment, measured on a continuous scale. Magnetic Resonance Imaging was performed at 2 and 4.5 years to determine annual percentage change in medial and lateral tibial cartilage volumes. RESULTS In multivariate analyses, for every 1 degrees change toward genu valgum, there is an associated 0.44% reduction in the rate of annual medial tibial cartilage volume loss (95% CI: -0.85%, -0.04%, P=0.03). Similarly, because our measures of change in alignment and cartilage volume were continuous, these results also implied that for every 1 degrees change toward genu varum, there was an associated 0.44% increase in the rate of annual medial tibial cartilage volume loss. Change in knee angle did not significantly affect the rate of loss of the lateral tibial cartilage volume (P=0.95). CONCLUSION Our results have demonstrated that progressive change toward genu valgum reduced the annual rate of medial tibial cartilage volume loss in people with knee OA, without expediting the rate of lateral tibial cartilage volume loss. These findings suggest that methods to reduce varus alignment may delay the progression of medial tibiofemoral OA and warrant further investigation.

Development of bone marrow lesions is associated with adverse effects on knee cartilage while resolution is associated with improvement--a potential target for prevention of knee osteoarthritis: a longitudinal study.

IntroductionTo examine the relationship between development or resolution of bone marrow lesions (BMLs) and knee cartilage properties in a 2 year prospective study of asymptomatic middle-aged adults.Methods271 adults recruited from the Melbourne Collaborative Cohort Study, underwent a magnetic resonance imaging scan (MRI) of their dominant knee at baseline and again approximately 2 years later. Cartilage volume, cartilage defects and BMLs were determined at both time points.ResultsAmong 234 subjects free of BMLs at baseline, 33 developed BMLs over 2 years. The incidence of BMLs was associated with progression of tibiofemoral cartilage defects (OR 2.63 (95% CI 0.93, 7.44), P = 0.07 for medial compartment; OR 3.13 (95% CI 1.01, 9.68), P = 0.048 for lateral compartment). Among 37 subjects with BMLs at baseline, 17 resolved. Resolution of BMLs was associated with reduced annual loss of medial tibial cartilage volume (regression coefficient -35.9 (95%CI -65, -6.82), P = 0.02) and a trend for reduced progression of medial tibiofemoral cartilage defects (OR 0.2 (95% CI 0.04, 1.09), P = 0.06).ConclusionsIn this cohort study of asymptomatic middle-aged adults the development of new BMLs was associated with progressive knee cartilage pathology while resolution of BMLs prevalent at baseline was associated with reduced progression of cartilage pathology. Further work examining the relationship between changes and BML and cartilage may provide another important target for the prevention of knee osteoarthritis.

Sex hormones and structural changes in osteoarthritis: A systematic review

AIM To systematically review the evidence for a relationship between sex hormones and structural changes in osteoarthritis (OA). METHODS Electronic searches of MEDLINE were performed in November-December 2010 and in February 2011 for studies of sex hormones and OA that met a predefined set of criteria. Both controlled trials and observational studies were eligible for inclusion. Two independent reviewers extracted the data and assessed the methodological quality of the included studies. Due to the heterogeneity of the studies, we were unable to perform a best evidence synthesis. However we have provided summaries for each section. RESULTS Twenty-seven studies were included in this review, of which 11 were considered high quality. The evidence suggests an association between endogenous oestrogen and cartilage turnover and radiographic OA, and between testosterone and cartilage volume. There is also evidence for an association between exogenous oestrogen and cartilage and bone turnover, although its effects on radiographic and MRI structure as well as joint replacement are unclear. The evidence also supports an association between oestrogen receptor α and β gene polymorphisms and OA. CONCLUSION Although the heterogeneity of the studies means that there is insufficient evidence to form strong conclusions, the available evidence supports an effect of endogenous and exogenous oestrogen as well as oestrogen receptor polymorphisms on joint health.

Dietary fatty acid intake affects the risk of developing bone marrow lesions in healthy middle-aged adults without clinical knee osteoarthritis: a prospective cohort study

IntroductionFatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.MethodsTwo hundred ninety-seven middle-aged adults without clinical knee OA underwent magnetic resonance imaging (MRI) of their dominant knee at baseline. BMLs were assessed. Of the 251 participants with no BMLs in their knee at baseline, 230 underwent MRI of the same knee approximately 2 years later. Intakes of fatty acids were estimated from a food frequency questionnaire.ResultsIncreased consumption of saturated fatty acids was associated with an increased incidence of BMLs over 2 years after adjusting for energy intake, age, gender, and body mass index (odds ratio of 2.56 for each standard deviation increase in dietary intake, 95% confidence interval 1.03 to 6.37, P = 0.04). Intake of monounsaturated or polyunsaturated fatty acids was not significantly associated with the incidence of BMLs.ConclusionsIncreased fatty acid consumption may increase the risk of developing BMLs. As subchondral bone is important in maintaining joint integrity and the development of OA, this study suggests that dietary modification of fatty acid intake may be one strategy in the prevention of knee OA which warrants further investigation.

Imaging of knee osteoarthritis

New imaging modalities are broadening the possibilities in osteoarthritis (OA) research, and are offering new insights to help better understand the pathogenesis of this disease. Although knee radiographs are widely employed in epidemiological and clinical studies to assess structural pathology, joint radiographs provide limited outcome measures in knee OA, and other more valid, reliable and sensitive imaging modalities are now available. In particular, magnetic resonance imaging can directly visualize articular cartilage and other joint structures, such as bone and soft tissue, that are now recognized as part of the disease process. This chapter will examine imaging modalities in the assessment of knee OA, and the impact of these on our understanding of the pathogenesis of this disease.

Association of weight gain with incident knee pain, stiffness, and functional difficulties: a longitudinal study.

To examine the longitudinal association between significant weight change and change in knee symptoms (pain, stiffness, and function), and to determine whether the effects differ in those who are obese and those with osteoarthritis (OA).