J L Newton

Is osteoarthritis a metabolic disorder

BACKGROUNDnObesity is associated with an increased risk of developing osteoarthritis (OA), even in non-weight bearing joints. High levels of adipose tissue-associated inflammation may explain this association.nnnSOURCES OF DATA AND AREAS OF DEBATEnPublished evidence looking at the associations between components of Metabolic Syndrome (MetS) and knee, hip or hand OA and the higher mortality described with knee OA.nnnEMERGING POINTSnDevelopment of MetS and OA shares a relationship with adipose tissue-associated inflammation. This review supports this inflammatory pathway being part of the shared mechanism behind obesity as a risk factor for OA and the recently described OA-associated increased mortality.nnnTIMELY AREAS FOR DEVELOPMENTnIn an era of an obesity epidemic, this review identifies a need for well-designed cohort studies assessing early metabolic changes in populations at high risk of OA and MetS, and to identify risk factors for increased mortality in patients with OA.

Stress Fractures in the Young Athlete: A Pictorial Review

Stress fractures are an uncommon but important source of pain and disability in young athletes. The presentation and differential diagnosis of stress fractures in young athletes differs from that of older athletes. This pictorial review outlines the pathogenesis and imaging features of stress fractures. Other pathologies that can mimic stress fractures and the advantages of the use of magnetic resonance imaging will be discussed. An imaging algorithm for a suspected stress fracture is suggested.

Painful knee but not hand osteoarthritis is an independent predictor of mortality over 23 years follow-up of a population-based cohort of middle-aged women.

To assess whether joint pain or radiographic osteoarthritis (ROA) of the knee and hand is associated with all-cause and disease-specific mortality in middle-aged women. Methods Four subgroups from the prospective community-based Chingford Cohort Study were identified based on presence/absence of pain and ROA at baseline: (Pain−/ROA−; Pain+/ROA−; Pain−/ROA+; Pain+/ROA+). Pain was defined as side-specific pain in the preceding month, while side-specific ROA was defined as Kellgren–Lawrence grade ≥2. All-cause, cardiovascular disease (CVD) and cancer-related mortality over the 23-year follow-up was based on information collected by the Office for National Statistics. Associations between subgroups and all-cause/cause-specific mortality were assessed using Cox regression, adjusting for age, body mass index, typical cardiovascular risk factors, occupation, past physical activity, existing CVD disease, glucose levels and medication use. Results 821 and 808 women were included for knee and hand analyses, respectively. Compared with the knee Pain−/ROA− group, the Pain+/ROA− group had an increased risk of CVD-specific mortality (HR 2.93 (95% CI 1.47 to 5.85)), while the knee Pain+/ROA+ group had an increased HR of 1.97 (95% CI 1.23 to 3.17) for all-cause and 3.57 (95% CI 1.53 to 8.34) for CVD-specific mortality. We found no association between hand OA and mortality. Conclusion We found a significantly increased risk of all-cause and CVD-specific mortality in women experiencing knee pain with or without ROA but not ROA alone. No relationship was found between hand OA and mortality risk. This suggests that knee pain, more than structural changes of OA is the main driver of excess mortality in patients with OA.

Association of familial and sporadic rheumatoid arthritis with a single corticotropin‐releasing hormone genomic region (8q12.3) haplotype

OBJECTIVEnRheumatoid arthritis (RA) is a common disabling autoimmune disease with a complex genetic component. We have previously described linkage of a region of chromosome 8q12.3 with RA and association of the microsatellite marker CRHRA1 with RA in 295 affected sibling-pair families. In the current study we aimed to physically link the RA-associated marker with the corticotropin-releasing hormone (CRH) candidate gene, and to examine the genomic region for additional short tandem repeat (STR) genetic markers in order to clarify the association with RA.nnnMETHODSnWe examined the association of 2 STR markers with disease in the original 295 multicase families and in a cohort of 131 simplex families to refine our understanding of this genetic region in disease susceptibility in sporadic and familial RA. Genomic library screening and sequencing were used to generate physical sequences in the CRH genomic region. Bioinformatic analysis of the sequence flanking the CRH structural gene was used to screen for additional STRs and other genetic features. Genotyping was carried out using a standard fluorescence approach. Estimations of haplotype frequencies were performed to assess linkage disequilibrium. The transmission disequilibrium test was performed using TRANSMIT.nnnRESULTSnPhysical cloning and sequencing analyses identified the genomic region linking the CRHRA1 marker and the CRH structural locus. Moreover, we identified a further STR, CRHRA2, which was in strong linkage disequilibrium with CRHRA1 (P = 4.0 x 10(-14)). A haplotype, CRHRA1*10;CRHRA2*14, was preferentially carried by unaffected parents at a frequency of 8.6% compared with the expected frequency of 3.1%. This haplotype was overtransmitted in the multiply affected families (P = 0.0077) and, similarly, in the simplex families (P = 0.024). Combined analysis of both family cohorts confirmed significant evidence for linkage (P = 4.9 x 10(-4)) and association (P = 5.5 x 10(-3)) for this haplotype with RA.nnnCONCLUSIONnIn demonstrating significant linkage disequilibrium between these 2 markers, we have refined the disease-associated region to a single haplotype and confirmed the significance of this region in our understanding of the genetics of RA.

Behavioural physical activity interventions in participants with lower-limb osteoarthritis: a systematic review with meta-analysis

Objective To assess effectiveness of osteoarthritis interventions to promote long-term physical activity behaviour change. Design A systematic review and meta-analysis. Protocol registration PROSPERO CRD4201300444 5 (http://www.crd.york.ac.uk/prospero/). Study selection Randomised controlled trials (RCTs) comparing physical activity interventions with placebo, no/or minimal intervention in community-dwelling adults with symptomatic knee or hip osteoarthritis. Primary outcomes were change in physical activity or cardiopulmonary fitness after a minimum follow-up of 6u2005months. Data extraction Outcomes were measures of physical activity (self-reported and objectively measured) and cardiovascular fitness. Standard mean differences between postintervention values were used to describe the effect sizes. Results 27u2005984 titles were screened and 180 papers reviewed in full. Eleven RCTs satisfied inclusion criteria, total study population of 2741 participants, mean age 62.2. The commonest reasons for study exclusion were follow-up less than 6u2005months and no physical activity measures. The majority of included interventions implement an arthritis self-management programme targeting coping skills and self-efficacy. Seven studies used self-report measures, the pooled effect of these studies was small with significant heterogeneity between studies (SMD 0.22 with 95% CI −0.11 to 0.56, z=1.30 (p=0.19) I2 statistic of 85%). Subgroup analysis of 6–12u2005month outcome reduced heterogeneity and increased intervention effect compared to control (SMD 0.53, 95% CI 0.41 to 0.65, z=8.84 (p<0.00001) I2 of 66%). Conclusions Arthritis self-management programmes achieve a small but significant improvement in physical activity in the short term. Effectiveness of intervention declines with extended follow-up beyond 12u2005months with no significant benefit compared to control. The small number of studies (11 RCTs) limited ability to define effective delivery methods. Investigation of behavioural lifestyle interventions for lower limb osteoarthritis populations would benefit from consensus on methodology and outcome reporting. This includes use of validated physical activity reporting tools and planning for long-term follow-up.

Imaging in the Assessment and Management of Overuse Injuries in the Foot and Ankle

Overuse injuries of the ankle and foot are common in the general and athletic populations. The wide spectrum of overuse injuries includes ligamentous injuries, soft tissue and osseous impingement, osteochondral lesions, tendon injuries, and stress fractures. Some conditions such as impingement syndromes and stress fractures may be missed on initial physical examination, and patients with such injuries often present to a sports or orthopedic clinic with persistent symptoms. With the increasing participation in sports, health-care professionals involved in the care of athletes at all levels must have a thorough understanding of overuse conditions of the foot and ankle, and the use of imaging in the management of these conditions. This article covers the clinical presentation, pertinent anatomy, imaging features, and management of overuse injuries of the foot and ankle.

Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women.

Abstract Context and objective: We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women. Materials and methods: Five hundred and ninety-three women with no baseline KOA underwent 5-year knee radiographs over 20-years and were asked about knee pain a month before each assessment. A repeated measures logistic regression model was used where the outcomes were recorded at 5, 10, 15 and 20-years follow-up. Results: The highest quartile of sCOMP was associated with increased risk of RKOA with overall OR of 1.97 (95% CI: 1.33–2.91) over 20 years when compared with the lowest sCOMP quartile. The association with painful KOA was similar and also independent, but only when the fourth and third sCOMP quartiles were compared. Discussion and conclusion: This study demonstrates that sCOMP levels are predictive of subsequent structural changes and incidence of painful KOA, independently of age and BMI.

Adipokines as potential prognostic biomarkers in patients with acute knee injury

Abstract This review considers adipokines as predictive biomarkers for early onset post-traumatic knee osteoarthritis (KOA). Serum concentrations of leptin and resistin can predict radiographic changes and are elevated in early KOA, with higher leptin concentrations independently associated with more severe knee changes. Plasma concentrations of resistin are chronically elevated after injury. Leptin, resistin, chemerin and vistfatin induce catabolic enzymes associated with cartilage degeneration. Available literature on adipokines in post-traumatic KOA pathogenesis suggests that they could contribute to risk prediction of early onset post-traumatic KOA. Further research is needed to further understand the association between adipokines, synovitis and long-term outcomes in this population.

Chronic inflammation is a feature of Achilles tendinopathy and rupture

Background Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified the importance of inflammation in the development and progression of tendon disease. These mechanisms remain poorly understood in disease of energy-storing tendons such as the Achilles. Using tissue biopsies from patients, we investigated if inflammation is a feature of Achilles tendinopathy and rupture. Methods We studied Achilles tendon biopsies from symptomatic patients with either mid-portion tendinopathy or rupture for evidence of abnormal inflammatory signatures. Tendon-derived stromal cells from healthy hamstring and diseased Achilles were cultured to determine the effects of cytokine treatment on expression of inflammatory markers. Results Tendinopathic and ruptured Achilles highly expressed CD14+ andu2009CD68+ cellsu2009and showed a complex inflammation signature, involving NF-κB, interferon and STAT-6 activation pathways. Interferon markers IRF1 and IRF5 were highly expressed in tendinopathic samples. Achilles ruptures showed increased PTGS2 and interleukin-8 expression. Tendinopathic and ruptured Achilles tissues expressed stromal fibroblast activation markers podoplanin and CD106. Tendon cells isolated from diseased Achilles showed increased expression of pro-inflammatory and stromal fibroblast activation markers after cytokine stimulation compared with healthy hamstring tendon cells. Conclusions Tissue and cells derived from tendinopathic and ruptured Achilles tendons show evidence of chronic (non-resolving) inflammation. The energy-storing Achilles shares common cellular and molecular inflammatory mechanisms with functionally distinct rotator cuff positional tendons. Differences seen in the profile of ruptured Achilles are likely to be attributable to a superimposed phase of acute inflammation and neo-vascularisation. Strategies that target chronic inflammation are of potential therapeutic benefit for patients with Achilles tendon disease.

Physical activity during adolescence and the development of cam morphology: a cross-sectional cohort study of 210 individuals

Introduction Cam morphology is a strong risk factor for the development of hip pain and osteoarthritis. It is increasingly thought to develop in association with intense physical activity during youth; however, the aetiology remains uncertain. The study aim was to characterise the effect of physical activity on morphological hip development during adolescence. Methods Cross-sectional study of individuals aged 9–18 years recruited from Southampton Football Club Academy (103 male) with an age-matched control population (52 males and 55 females). Assessments included questionnaires and 3 Tesla MRI of both hips. Alpha angle, epiphyseal extension and epiphyseal tilt were measured on radial images. Results Alpha angle and epiphyseal extension increased most rapidly between ages 12 and 14 years. Soft-tissue hypertrophy at the femoral head-neck junction preceded osseous cam morphology and was first evident at age 10 years. The greatest increase and highest absolute values of alpha angle and epiphyseal extension were colocalised at 1 o’clock. Maximum alpha angles were 6.7 degrees greater in males than females (p=0.005). Compared with individuals who play no regular sport, alpha angles were 4.0 degrees higher in individuals who play sport for a school or club (p=0.041) and 7.7 degrees higher in individuals competing at a national or international level (p=0.035). There was no association with leg dominance . Conclusions Sporting activity during adolescence is strongly associated with the development of cam morphology secondary to epiphyseal hypertrophy and extension with a dose-response relationship. Males participating in competitive sport are at particularly elevated risk of developing cam morphology and secondary hip pathology.