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Background Physical fatigability, the level of fatigue experienced while undertaking specified physical tasks, increases with age throughout adulthood. These age-related changes, which reflect reductions in energy availability, precipitate declines in activity participation and function. Higher levels of fatigue are also related to increased risk of disability and premature mortality so it is imperative to identify modifiable risk factors across life associated with physical fatigability. Cross-sectional analyses suggest that obesity and inflammation may be associated with increased risk of high physical fatigability. However, whether these inter-related factors act on the same pathway is unclear and requires further investigation in longitudinal studies. We thus aimed to examine the associations of body mass index (BMI) and inflammatory markers from midlife with subsequent levels of perceived physical fatigability in a nationally representative sample. Methods Up to 2095 men and women from the MRC National Survey of Health and Development, a British cohort followed-up prospectively since birth in 1946, who had valid physical fatigability scores on the Pittsburgh Fatigability Scale (PFS) at age 68 years were included in analyses. Linear regression models were used to assess associations of BMI from age 43 and inflammatory markers (C-reactive protein (CRP) and interleukin-6 (IL-6)) at age 60–64 with continuous PFS scores at age 68. Adjustments were made for sex (where no evidence of interaction was found), long-term limiting illness, physical activity and symptoms of anxiety and depression. All analyses were performed using STATA v14.2. Results Women had higher mean PFS scores than men (16.0 (SD=9.3) vs 13.4 (SD=9.0), p Conclusion These findings highlight the potentially important influence of inflammatory and other cardio-metabolic processes on physical fatigability. They suggest that both BMI and inflammation from midlife may be important targets for intervention to reduce the burden of this commonly reported symptom in older populations.

Physical fatigability, the level of fatigue experienced while undertaking specified physical tasks, increases with age. These age-related changes, which reflect reductions in energy availability, precipitate declines in function and activity participation. Cross-sectional analyses suggest that obesity and inflammation may be modifiable risk factors for fatigability which require further investigation in longitudinal studies. Using data on 2095 participants from the MRC National Survey of Health and Development, a nationally representative British birth cohort, we aimed to assess whether body mass index (BMI) and inflammatory markers were associated with physical fatigability and, if so, whether these act on shared pathways. Linear regression models were used to relate BMI from age 36 and inflammatory markers (C-reactive protein (CRP) and interleukin-6 (IL-6)) at age 60–64 to physical fatigability scores on the Pittsburgh Fatigability Scale (PFS) at age 68. Women had higher mean PFS scores than men (16.0 (SD=9.3) vs 13.4 (SD=9.0), p

Background Obesity and chronic low-grade inflammation have both been implicated in the onset of physical fatigue. However, few studies have investigated the independence of these associations in older community-dwelling populations. We therefore aimed to investigate the associations of body mass index (BMI) and inflammatory markers at age 60–64 with perceived physical fatigability at age 68 and to assess whether any such associations were independent of each other and potential confounding factors. A secondary aim was to investigate whether any association with BMI extended back into earlier adulthood. Methods Participants of the MRC National Survey of Health and Development (N = 1580) had BMI and levels of interleukin-6 (IL-6) and C-reactive protein (CRP) measured during clinical assessments at age 60–64. These were related to self-perceived physical fatigability assessed at age 68 using the Pittsburgh Fatigability Scale (PFS) (total score:0 (no physical fatigue)–50 (extreme physical fatigue)). Resuts Women had higher mean PFS scores than men (mean (SD): 16.0 (9.1) vs 13.2 (8.9), p

ObjectiveLow back pain (LBP) is a common musculoskeletal disorder, but it is still unclear which individuals develop it. The authors examined the contribution of genetic factors, lumbar disc degeneration (LDD) and other risk factors in a female sample of the general population.Material and MethodsA cross-sectional study was conducted among 2256 women (371 and 698 monozygotic and dizygotic twin pairs and 29 sibling pairs and 60 singletons) with a mean age of 50 years (18–84). A self-reported validated questionnaire was used to collect back pain data. Risk factors including body weight, smoking, occupation, physical exercise and MRI assessed LDD were measured. Data analysis included logistic regression and variance decomposition.ResultsThe major factors associated with LBP included genetic background, with OR approximately 6 if the monozygotic co-twin had LBP, or 2.2 if she was a dizygotic co-twin. In addition, LDD and overweight were highly significantly (pConclusionsThe main risk factors for reported episodes of severe and disabling LBP in UK women include the degree of LDD as assessed by MRI, being overweight and genetic heritability.

Objectives Lumbar disc degeneration (LDD) is prevalent, age-related and contributes to low back pain. Crosssectional LDD as determined by MRI scan is known to be highly heritable. The authors postulated that the rate of progression might also be controlled by genetic factors. Methods A 10-year follow-up of MRI-determined LDD was performed in 234 pairs of twin volunteers in the UK and Australia, comprising 90 monozygotic pairs and 144 dizygotic same-sex twin pairs. Of the total sample, 95% were female. The mean age at baseline was 53.3 years (range 32.3–69.5). The rate of progression was calculated and, because the effect of age was non-linear, the sample was divided into age strata and heritability estimated for each trait’s progression. Results All MRI-determined traits worsened signifi cantly over the period of follow-up (p

While there is an acknowledged need for biomarkers to progress arthritis research, imaging biomarkers for the spine have lagged behind those for peripheral joint osteoarthritis. Progress has been slow for a number of reasons. First and perhaps most importantly, there is currently no international agreement on definition of spine osteoarthritis (OA), either histologically or on imaging. Secondly, spine OA comprises two main pathologies, and debate continues as to whether they are separate entities or linked: degenerative disc disease and facet joint arthritis. Imaging those neighbouring joints is not straightforward and usually requires separate imaging investigations. Thirdly, it is only just becoming clear to what extent changes on imaging are associated with the main clinical problem - back pain. To compound the problem, the organisation of clinical services usually means that different specialties tend to focus on different anatomical areas, so a combined approach is not commonly adopted. Systematic evaluation of facet joints in epidemiological study is still in its infancy. Regardless of these hurdles, we have attempted in this review to summarise the state of play of imaging biomarkers in the spine with the emphasis on degenerative disc disease. MR imaging clearly leads the way and there exists a variety of specialist techniques such as T1rho and which may offer spine research imaging biomarkers in the future.

ObjectiveOsteoarthritis (OA) and osteoporosis are often considered to lie at opposite ends of a spectrum of bone phenotypes. Lumbar degenerative disc disease (LDD) may be associated with low back pain (LBP) and is similar in many ways to OA. LDD is reported in small studies to be associated with increased spine bone mineral density (BMD). The present work aimed to confirm this association in a large population sample using MRI and explore the relationship further, in particular to determine whether it is mediated genetically.MethodsA population based sample (N=908, age range 32–74 years) of UK female twins having MRI of the lumbar spine was used in this study. LDD traits and summary measures and their relationship with BMD at the lumbar spine and hip were examined using multivariate multiple regression and maximum likelihood based variance decomposition.ResultsThere was a significant positive correlation between LDD and BMD at the lumbar spine and hip, which remained significant after adjustment for confounders. Both traits were highly heritable and the associations between them were mediated genetically.ConclusionsA clear, significant and independent association of BMD at hip and lumbar spine with LDD was found which is, in part, genetically mediated. The association with the non-axial site, the hip, is of particular interest and suggests a systemic bone effect. This should encourage the search for pleiotropic genes to help in the understanding of the bone–cartilage relationship. Moreover, genetic variants identified could provide novel therapeutic targets in the management of LBP.

Study design Cross-sectional open population based study (nested in a prospective cohort study). Objective To explore the association of the different individual radiographic features, including osteophytes and disc space narrowing, with self-reported low back pain (LBP). Different definitions of lumbar disc degeneration with self-reported LBP and disability were considered in a large open population sample. Furthermore, in order to disentangle the discrepancies in reported strength of the associations, we characterized the frequency of the different individual radiographic features of lumbar disc degeneration and definitions of lumbar disc degeneration, as well as their association with LBP status, by age, gender, and vertebral level. Summary of background data Currently within the literature, there have been no studies that have explored different definitions of lumbar disc degeneration and their association with LBP within one study sample. Methods The intervertebral disc spaces (L1/2 to L5-S1) were evaluated for the presence and severity of anterior osteophytes and disc space narrowing using a semiquantitative score (grade 0-3). Logistic regression was used to determine the association between these individual radiographic features of lumbar disc degeneration and different definitions of lumbar disc degeneration for LBP. Results Lumbar radiographs were scored for 1204 men, and 1615 women. Osteophytes were the most frequent radiographic feature observed, with men having the greatest frequency. Disc space narrowing was more frequent in women than men. Both radiographic features increased in frequency with age.Disc space narrowing appeared more strongly associated with LBP than osteophytes, especially in men (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.8). Disc space narrowing at 2 or more levels appeared more strongly associated with LBP than disc space narrowing at only 1 level (OR = 2.4; 95% CI: 1.6-3.4). After excluding level L5-S1, the strength of almost all associations increased. Conclusion We are the first to report different possible lumbar disc degeneration definitions and their associations with LBP. Disc space narrowing at 2 or more levels appeared more strongly associated with LBP than other radiographic features, especially after excluding level L5-S1.

Lumbar disc degeneration (LDD) is a common cause of back pain, which is a major public health problem in Western countries. It is a common cause of work absenteeism, and its prevalence is increasing. LDD is known to be influenced by genetic factors, with estimated heritability of >70%. Little is known, however, of the genetic processes underlying the development of disc degeneration. A number of genetic loci have been investigated through a candidate gene approach. Many early reports of candidate gene associations in LDD, however, have not been replicated (1). LDD has much in common with osteoarthritis (OA) of the knee. The pathologic changes are similar in cartilage and disc and, furthermore, rapid progression of OA of the knee is predicted by LDD (2). The gene GDF5 is known to be involved in digit growth and certain monogenic disorders of skeletal development, and it was recently identified as playing a role in height (3). There is good evidence that variants in or near the GDF5 gene predispose to knee OA (4–7) and are associated with hip geometry and fracture risk (8). In addition, the gene promotes growth and repair in animal intervertebral disc tissue in vitro (9). The GDF5 gene, therefore, is a good candidate for influencing human intervertebral disc degeneration. The variant rs143383 is found in the 5′-untranslated region of the GDF5 gene on chromosome 20 at position 104 and represents a change of base from T to C. This is the most widely studied single-nucleotide polymorphism (SNP) for GDF5 and, because funding restricted our study to a single SNP, we selected this one to study for association with LDD.

A life course approach to ageing relies on maintaining participation rates in national birth cohorts and other long-term longitudinal studies. This reduces the risk of selective attrition biasing associations between lifetime risk factors and health outcomes in later life and ensures the studies remain as representative as possible of the original population. We report the participation patterns for a postal questionnaire and home visit at 68–69 years of study members in the MRC National Survey of Health and Development, the oldest and longest-running British birth cohort study. We investigated how participation varied by lifetime and recent contact, health status, previous clinical feedback and study engagement, taking account of prior socioeconomic and cognitive characteristics. Overall participation and home visit participation remained high (94 and 80%, respectively) and there were no gender differences. Participation was higher in those with higher levels of prior contact and lower in those with the poorest health status. Having previously received clinical feedback on actionable blood results was associated with reduced home visit participation but other forms of clinical feedback were not associated with subsequent participation. Activities that fostered study engagement were associated with increased home visit participation. These findings inform strategies to maintain participation in life course studies. Electronic supplementary material The online version of this article (doi:10.1007/s10654-016-0217-8) contains supplementary material, which is available to authorized users.

for hip and knee osteoarthritis. Studies of TJR patient-reported outcomes and the scope of outcomes examined typically include pain and physical function with limited points of follow-up. The inter-relationships of social and community participation, a recognized and important concept to patients with TJR, with impairments (e.g. symptoms etc.) and activity limitations over the year of recovery following TJR have not been evaluated. This research addresses this gap. Methods: Participants (hip: n=437; knee: 494) completed measures presurgery and at 10-14 days, 1, 3, 6 and 12 months post-surgery. The survey included impairments (physical: HOOS/KOOS symptoms and Chronic Pain Grade; mood: Hospital Anxiety and Depression Scale, fatigue); activity limitations (HOOS/KOOS activities of daily living + sports/leisure activities); and, participation restrictions (Jette Late Life Disability + Calderdale community mobility). Using structural equation modeling, we evaluated the longitudinal inter-relationships of patient-reported outcomes of impairments, activity limitations and participation restrictions. Measures of overall model fit were assessed. Results: Hip group: age range from 31-86 years (mean=63) with 55% female; Knee group: age range from 35-88 years (mean=65) with 65% female. Significant improvements in the dimensions of physical impairments (PI), activity limitation (AL) and participation restriction (PR) scores were observed over time with the exception of mood. Both within and across time, PI was associated with AL and AL was associated with PR. However, improvements were lagged over time with earlier improvements in physical impairments and later improvements in participation. All analyses were adjusted for age, sex, BMI, hip vs. knee and low back pain. Conclusions: Given the lagged inter-relationship of physical impairments, activity limitations and participation restrictions, the provision and timing of interventions that target all these areas are critical to maximizing outcome following TJR. Current care pathways that tend to focus on short term follow-up with limited attention to social and community participation should be re-evaluated in order to maximize people’s outcome following TJR.