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A J Silman

Publications and source records attributed to A J Silman.

At least 19 recordsLinked to original sources

Moderation of psychosocial risk factors through dysfunction of the hypothalamic-pituitary-adrenal stress axis in the onset of chronic widespread musculoskeletal pain: findings of a population-based prospective cohort study.

OBJECTIVE: To test the hypothesis that abnormalities in the hypothalamic-pituitary-adrenal (HPA) stress-response system would act as an effect moderator between HPA function and the onset of chronic widespread pain (CWP). METHODS: We conducted a population-based prospective cohort study. Current pain and psychosocial status were ascertained in 11,000 subjects. Of the 768 eligible subjects free of CWP but at future risk based on their psychosocial profile, 463 were randomly selected, and 267 (57.7%) consented to assessment of their HPA axis function. Diurnal function was measured by assessing levels of salivary cortisol in the morning (9:00 AM) and evening (10:00 PM). Serum cortisol levels were measured after an overnight low-dose (0.25 mg) dexamethasone suppression test and a potentially stressful clinical examination. All subjects were followed up 15 months later to identify cases of new-onset CWP. RESULTS: A total of 241 subjects (94.9%) completed the followup study, and 28 (11.6%) reported the new onset of CWP. High levels of cortisol post-dexamethasone (odds ratio [OR] 3.53, 95% confidence interval [95% CI] 1.17-10.65), low levels in morning saliva (OR 1.43, 95% CI 0.52-3.94), and high levels in evening saliva (OR 2.32, 95% CI 0.64-8.42) were all associated with CWP. These 3 factors were found to be independent and additive predictors of CWP (OR for all 3 factors 8.5, 95% CI 1.5-47.9) in analyses controlling for age, sex, depression, sleep disturbance, recent traumatic life events, and pain status. One or more of these 3 HPA factors identified 26 (92.9%) cases of new-onset CWP. CONCLUSION: Among a group of psychologically at-risk subjects, dysfunction of the HPA axis helps to distinguish those who will and will not develop new-onset CWP.

Adult↗

The role of psychosocial factors in predicting the onset of chronic widespread pain: results from a prospective population-based study.

OBJECTIVE: Chronic widespread pain (CWP) is strongly associated with psychosocial distress both in a clinical setting and in the community. The aim of this study was to determine the contribution of measures of psychosocial distress, health-seeking behaviour, sleep problems and traumatic life events to the development of new cases of CWP in the community. METHODS: In a population-based prospective study, 3171 adults aged 25-65 yrs free of CWP were followed-up 15 months later to identify those with new CWP. Baseline data were available on their scores from a number of psychological scales including Illness Attitude Scales (IAS), Somatic Symptom Checklist (SSC), Hospital Anxiety & Depression Scale, Sleep Problems Scale, and Life Events Inventory. RESULTS: 324 subjects [10%, 95% confidence interval (CI) 9.2, 11.3] developed new CWP at follow-up. After adjustment for age and sex, three factors independently predicted the development of CWP: scoring three or more on the SSC [odds ratio (OR) 1.8, 95% CI 1.1, 3.1], scoring eight or more on the Illness Behaviour subscale of the IAS (OR 3.3, 95% CI 2.3, 4.8), and nine or more on the Sleep Problem Scale (OR 2.7, 95% CI 1.6, 3.2). Subjects exposed to all three factors were at 12 times the odds of new CWP than those with low scores on all scales. CONCLUSION: Subjects are at substantial increased odds of developing CWP if they display features of somatization, health-seeking behaviour and poor sleep. Psychosocial distress has a strong aetiological influence on CWP.

Adult↗

A longitudinal study exploring pain control, treatment and service provision for individuals with end-stage lower limb osteoarthritis.

OBJECTIVE: To investigate the level of pain control, treatment and service provision amongst individuals with end-stage lower limb osteoarthritis who were on the waiting list for hip or knee joint replacement. METHODS: A total of 105 patients on a waiting list for primary knee or hip replacement from a regional orthopaedic centre in the UK were recruited. The study was longitudinal and based on direct interviews at baseline and 6 months, with a postal questionnaire at 3 months. Data were collected on pain by a visual analogue scale (VAS) and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. In addition, medication and the use of services and treatments were recorded. RESULTS: Participants experienced high levels of pain as measured by VAS [mean 7.0; 95% confidence interval (CI) 6.6-7.5] and WOMAC pain (mean 11.2; 95% CI 10.6-11.9). The majority of participants (78, 74%) was taking analgesics more than once a day. Primary care utilization was variable. Of the 74 (70%) participants who had consulted their GP in the previous 3 months, 41 (55%) had not discussed their pain or osteoarthritis during these consultations. Just below one-third of participants (31, 30%) reported to have received information on osteoarthritis. CONCLUSIONS: Pain appears to be difficult to manage in individuals with end-stage lower limb osteoarthritis. Individuals appeared not to be taking appropriate levels of analgesia in relation to levels of pain. Improvements are required in the provision of information on pain and osteoarthritis. Patients would benefit from more proactive management by health professionals (especially by GPs).

Adult↗

Pressure pain thresholds and tender point counts as predictors of new chronic widespread pain in somatising subjects.

BACKGROUND: Tender points are a general measure of distress both in the community and in clinic subjects. It has been suggested that multiple tender points should be regarded as the early stages of somatisation of distress. Similarly, recent evidence suggests that chronic widespread pain (CWP) is one manifestation of the somatisation of distress. OBJECTIVE: Given that a high tender point count and CWP are clinical hallmarks of the fibromyalgia syndrome, it was hypothesised that in somatising subjects, a high tender point count or a low pain threshold would predict the development of CWP in the future. METHODS: In this population-based prospective study, 245 adults aged 25-65 years, free of CWP, were identified on the basis of a detailed questionnaire on pain and a psychosocial questionnaire comprising the Somatic Symptom Checklist and the Illness Behaviour subscale of the Illness Attitude Scales. These subjects took part in a pain threshold examination with a Fischer pressure algometer. Tender point counts were computed by including all areas with a pain threshold<4 kg/cm2. Individuals were followed up at 15 months, at which time 231 (93% of subjects still living at their baseline address) provided data on pain status, using the same instruments. RESULTS: At follow-up, 26 (11%) subjects developed new CWP. Although subjects with a low baseline pain threshold were not at increased risk of developing symptoms, a high tender point count, adjusted for age, sex, baseline pain status and other confounding factors, predicted the development of new CWP. CONCLUSION: Subjects free of CWP are at an increased risk of its development if they have a high tender point count. However, a low-pressure pain threshold does not predict the onset of symptoms. Data from this population-based prospective study suggest that a low pain threshold in subjects with CWP is likely to be a secondary phenomenon as a result of pain or associated distress rather than the antecedent of symptoms.

Adult↗

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Age Factors↗

Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register.

BACKGROUND: Anti-tumour necrosis factor-alpha (TNF-alpha) therapies represent an important advancement in therapy for rheumatoid arthritis (RA). However, there remains a proportion of patients who do not improve despite therapy. These drugs are expensive and have the potential of serious toxicity. Therefore, it would be ideal to predict the patients who will respond, so that the use of these drugs can be targetted. OBJECTIVE: To identify the clinical factors present at the start of anti-TNF-alpha therapy that are associated with response at 6 months in patients with RA. METHODS: The British Society for Rheumatology (BSR) Biologics Register collects detailed data on all patients with a rheumatic disease receiving biologic therapy in the UK. We studied all patients with RA who had started etanercept (ETA) or infliximab (INF) and had achieved a minimum 6 months follow-up by 1 October, 2004. The disease status at the baseline and at 6 months was assessed using the Disease Activity Score (DAS28). The response was classified according to the European League against Rheumatism (EULAR) improvement criteria. The effect of baseline characteristics on response was studied using multivariate ordinal logistic regression. RESULTS: 2879 patients were included in this analysis (1267 ETA, 1612 INF). At the start of therapy, the mean age was 55 yrs, disease duration 14 yrs, baseline DAS28 6.7 and health assessment questionnaire (HAQ) 2.1. In all, 28% of ETA and 86% of INF patients were receiving methotrexate. After 6 months, 18% had a good EULAR response, of whom 9% were considered to be in remission and 50% had a moderate response. There was no overall difference in response rate between the two anti-TNF-alpha therapies. A higher baseline HAQ score correlated with a lower response rate while a better response was associated with the current use of NSAIDs and the use of methotrexate (MTX), although the latter only reached statistical significance with ETA [OR 1.82 (95% CI 1.38-2.40)]. There was a lower response rate among current smokers, particularly in patients receiving INF [OR 0.77 (95% CI 0.60-0.99)]. Age, disease duration, rheumatoid factor and the previous number of disease-modifying antirheumatic drugs (DMARDs) did not predict response to either drug. However, females were less likely to achieve remission. CONCLUSIONS: These data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies. However, the most disabled patients were less likely to respond, despite concurrent MTX. The benefits of NSAIDs may reflect the relative absence of comorbidities in patients who can tolerate these drugs or the continuing presence of reversible inflammatory symptoms. The association of smoking and poor outcome with INF is a novel finding and may reflect alterations in pharmacokinetics. The inability of other baseline disease characteristics to predict the outcome suggests that other factors, including potential genetic differences in drug metabolism, may be influencing the response to anti-TNF-alpha therapies.

Adult↗

Down regulation of multidrug resistance protein-1 expression in patients with early rheumatoid arthritis exposed to methotrexate as a first disease-modifying antirheumatic drug.

BACKGROUND: Methotrexate (MTX) is the current gold standard conventional disease-modifying antirheumatic drug (DMARD) and is effluxed from cells by several transmembrane proteins, including multidrug resistance protein-1 (MRP1). It is hypothesised that the overexpression of these proteins may mediate reduced efficacy of MTX. To date, it is unclear how expression of these proteins changes over time or after exposure to drugs. AIMS: To compare MRP1 expression in newly diagnosed patients with DMARD-naive rheumatoid arthritis with that in healthy controls and to investigate how MRP1 expression changed after exposure to MTX. METHODS: 18 newly diagnosed patients with DMARD-naive rheumatoid arthritis and 14 healthy controls were recruited. Peripheral blood mononuclear cell counts were taken at baseline and after 6 months' treatment with MTX. Cells were separated by density gradient centrifugation and MRP1 expression was measured using the QCRL-1 monoclonal antibody. RESULTS: MRP1 expression in patients did not seem to be up regulated compared with that in healthy controls. In patients who were positive for MRP1 at baseline (61%), treatment with MTX and folic acid led to a marked down regulation of MRP1 expression at 6 months. CONCLUSION: In patients with rheumatoid arthritis expressing MRP1, treatment with MTX and folic acid led to down regulation of MRP1 expression. Further studies are required to determine the mechanism behind this observation and whether MRP1 expression mediates altered efficacy to MTX.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To determine whether the rate of serious infection is higher in anti-tumor necrosis factor (anti-TNF)-treated rheumatoid arthritis (RA) patients compared with RA patients treated with traditional disease-modifying antirheumatic drugs (DMARDs). METHODS: This was a national prospective observational study of 7,664 anti-TNF-treated and 1,354 DMARD-treated patients with severe RA from the British Society for Rheumatology Biologics Register. All serious infections, stratified by site and organism, were included in the analysis. RESULTS: Between December 2001 and September 2005, there were 525 serious infections in the anti-TNF-treated cohort and 56 in the comparison cohort (9,868 and 1,352 person-years of followup, respectively). The incidence rate ratio (IRR), adjusted for baseline risk, for the anti-TNF-treated cohort compared with the comparison cohort was 1.03 (95% confidence interval 0.68-1.57). However, the frequency of serious skin and soft tissue infections was increased in anti-TNF-treated patients, with an adjusted IRR of 4.28 (95% confidence interval 1.06-17.17). There was no difference in infection risk between the 3 main anti-TNF drugs. Nineteen serious bacterial intracellular infections occurred, exclusively in patients in the anti-TNF-treated cohort. CONCLUSION: In patients with active RA, anti-TNF therapy was not associated with increased risk of overall serious infection compared with DMARD treatment, after adjustment for baseline risk. In contrast, the rate of serious skin and soft tissue infections was increased, suggesting an important physiologic role of TNF in host defense in the skin and soft tissues beyond that in other tissues.

Adalimumab↗

Predictors of persistent neck pain after whiplash injury.

OBJECTIVE: To establish the aetiological influences of persistent neck pain following a motor vehicle collision and to construct a model for use in the emergency department for identifying patients at high risk of persistent symptoms. DESIGN: Prospective cohort study. Patients recruited from hospital emergency departments were sent a questionnaire to gather information on various exposures. They were followed up at 1, 3, and 12 months to identify those with persistent symptoms. MAIN OUTCOME MEASURE: Persistent neck pain (pain at 1, 3, and 12 months after collision). RESULTS: The baseline survey included 765 patients. Subsequently, 480 completed a questionnaire at each follow up time point, of whom 128 (27%) reported neck pain on each occasion. Few collision specific factors predicted persistent neck pain. In contrast, a high level of general psychological distress, pre-collision history of widespread body pain, type of vehicle, whiplash associated symptoms, and initial neck disability best predicted the persistence of symptoms. Furthermore, these factors, in combination, accounted for more than a fivefold increase in the risk of persistent neck pain. CONCLUSION: The greatest predictors of persistent neck pain following a motor vehicle collision relate to psychological distress and aspects of pre-collision health rather than to various attributes of the collision itself. With these factors, and those relating to initial injury severity, it is possible to identify a subgroup of patients presenting with neck pain with the highest risk of persistent symptoms. Thus, it is possible to identify whiplash patients with a poor prognosis and to provide closer follow up and specific attention to management in these individuals.

Accidents, Traffic↗

The world of biologics.

In March 2002 the National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of anti-TNF therapy for patients with rheumatoid arthritis (RA). The guidelines recommended that all RA patients treated with these drugs should be enrolled on a national register which had been established by the British Society for Rheumatology (the BSRBR). A comparison cohort of RA patients treated with traditional disease modifying drugs (DMARDs) is also being recruited. The main role of the BSRBR is to study the long-term safety of biologic drugs. Up to the end of March 2005, 9508 patients with RA had been enrolled on the BSRBR. Four thousand, three-hundred and six had been treated with etanercept, 3561 with infliximab, 1500 with adalimumab and 141 with anakinra. With regards to anti-TNF drugs, 79% remained on their original drug at six months, 65% of whom could be classified as responders. Co-prescription with methotrexate was associated with a 70% response rate. Patients with a high baseline level of disability were less likely to respond. Overall the rates of serious infection were not increased in the anti-TNF versus the comparison cohort. However the rates of skin and soft tissue infection and of intracellular infections (eg, salmonella, listeria, legionella) were increased. There were 11 cases of tuberculosis (seven extra-pulmonary). There was concern about the high mortality rates among patients with baseline pulmonary fibrosis treated with anti-TNF therapy. It is unclear whether this is related to the drug or to the underlying disease. The rates of malignancy and mortality were not increased compared to the DMARD treated group in the short term. Further follow-up is needed to determine the long term safety of these drugs.

Antibodies, Monoclonal↗

Does physical trauma lead to an increase in the risk of new onset widespread pain?

OBJECTIVE: To determine the rate of new onset of widespread pain after a traumatic event (motor vehicle crash). METHODS: A prospective cohort study of persons registered with an insurance company who had or had not experienced a motor vehicle crash. All participants were sent a questionnaire to assess pre-crash (or for the non-crash group, prior) psychosocial factors and widespread pain. Participants reporting pre-crash (prior) widespread pain were excluded. At six months, participants were sent a follow up questionnaire to ascertain new prevalent widespread pain. RESULTS: 597 (51%) of participants returned a baseline questionnaire (465 crash and 132 non-crash). Among the cohort who had experienced a crash, the new onset rate of widespread pain six months later was low (8%), though in comparison with the non-crash group there was an increased risk (RR = 1.9 (95% CI, 0.8 to 4.8, adjusted for age and sex)); this was attenuated after adjustment for pre-crash (prior) psychological distress and somatic symptoms (RR = 1.4 (95% CI, 0.5 to 3.2)). CONCLUSIONS: The findings suggest that a motor vehicle crash (as an example of a physically traumatic event) is unlikely to have a major impact on the new onset of widespread pain. Any observed relation may, in part, be explained by psychological distress.

Accidents, Traffic↗

Radiographic features of lumbar disc degeneration and bone mineral density in men and women.

OBJECTIVES: To determine the association between individual radiographic features of lumbar disc degeneration and bone mineral density (BMD) at the spine and hip. METHODS SUBJECTS: were recruited from a population register for a screening survey of vertebral osteoporosis. BMD was assessed at the spine and hip using dual energy x ray absorptiometry. Lateral spinal radiographs were evaluated for features of lumbar disc degeneration. Each vertebral level from L1/2 to L4/5 was assessed for the presence and severity of osteophytes, end plate sclerosis, and disc space narrowing. Linear regression was used to determine the association between each of these features and BMD at the spine and hip, with adjustments for age, body mass index, and levels of physical activity. Analyses were done separately in men and women. RESULTS: 250 women and 256 men (mean age around 65 years) were studied. At the lumbar spine, after age adjustment there was an increase in BMD with increasing grade for all radiographic features of disc degeneration in both men and women. At the femoral neck, after age adjustment there was an increase in BMD with increasing osteophyte and end plate sclerosis grade though not disc space narrowing. Adjusting for body mass index and physical activity did not influence the strength of the associations. CONCLUSIONS: Radiographic features of lumbar disc degeneration are associated with an increase in BMD at the spine. Osteophytes and end plate sclerosis, but not disc space narrowing, are associated with an increase in BMD at the hip.

Age Factors↗

Rib fractures predict incident limb fractures: results from the European prospective osteoporosis study.

Population studies suggest that rib fractures are associated with a reduction in bone mass. While much is known about the predictive risk of hip, spine and distal forearm fracture on the risk of future fracture, little is known about the impact of rib fracture. The aim of this study was to determine whether a recalled history of rib fracture was associated with an increased risk of future limb fracture. Men and women aged 50 years and over were recruited from population registers in 31 European centres for participation in a screening survey of osteoporosis (European Prospective Osteoporosis Study). Subjects were invited to complete an interviewer-administered questionnaire that included questions about previous fractures including rib fracture, the age of their first fracture and also the level of trauma. Lateral spine radiographs were performed and the presence of vertebral deformity was determined morphometrically. Following the baseline survey, subjects were followed prospectively by annual postal questionnaire to determine the occurrence of clinical fractures. The subjects included 6,344 men, with a mean age of 64.2 years, and 6,788 women, with a mean age of 63.6 years, who were followed for a median of 3 years (range 0.4-5.9 years), of whom 135 men (2.3%) and 101 women (1.6%) reported a previous low trauma rib fracture. In total, 138 men and 391 women sustained a limb fracture during follow-up. In women, after age adjustment, those with a recalled history of low trauma rib fracture had an increased risk of sustaining 'any' limb fracture [relative hazard (RH)=2.3; 95% CI 1.3, 4.0]. When stratified by fracture type the predictive risk was more marked for hip (RH=7.7; 95% CI 2.3, 25.9) and humerus fracture (RH=4.5; 95% CI 1.4, 14.6) than other sites (RH=1.6; 95% CI 0.6, 4.3). Additional adjustment for prevalent vertebral deformity and previous (non-rib) low trauma fractures at other sites slightly reduced the strength of the association between rib fracture and subsequent limb fracture. In men, after age adjustment, there was a small though non-significant association between recalled history of rib fracture and future limb fracture. Our data highlight the importance of rib fracture as a marker of bone fragility in women.

Aged↗

Poor sleep and depression are independently associated with a reduced pain threshold. Results of a population based study.

To determine the relative contributions of psychological factors and sleep disturbance to reduced pain threshold we conducted a cross-sectional two-phase population-based study. A total of 424 subjects were recruited, stratified by pain and distress status. Subjects completed a postal questionnaire that asked about current pain and covered aspects of psychological status and sleep disturbance. Samples of subjects stratified by the extent of bodily pain they reported and psychological status were invited to participate in an examination of pain threshold. The association between psychological status, sleep disturbance and a low pain threshold was examined using ordinal regression. High levels of psychological distress (OR=1.6, 95% CI (1.02, 2.5)), disturbed sleep (OR=2.2, 95% CI (1.4, 3.5)) and high scores on the HAD depression scale (OR=2.1, 95% CI (1.3, 3.2)) were all associated with having a low pain threshold. In multivariate analysis disturbed sleep and depression remained independently associated with a low pain threshold. These relationships persisted after adjustment for pain status. This study had demonstrated that depression and poor sleep are associated with a reduced pain threshold.

Adult↗

Is musculoskeletal pain more common now than 40 years ago?: Two population-based cross-sectional studies.

OBJECTIVE: To test the hypothesis that the prevalence of specific musculoskeletal pain symptoms has increased over time in the northwest region of England. To meet this objective we have examined the difference in the prevalence of low back, shoulder and widespread pain between the 1950s and today using historical data collected by the Arthritis Research Campaign (arc). METHODS: Two cross-sectional surveys conducted over 40 yr apart in the northwest region of England. The status of two regional pain sites and widespread pain was determined using interview and questionnaire responses, for the earlier and later studies respectively. Subjects were classified positively if they reported low back pain, shoulder pain or widespread pain on the day of the survey. Rates were standardized to the Greater Manchester population. RESULTS: There were large differences in the prevalence of musculoskeletal pain between the two surveys. For all three symptoms examined prevalence increased from 2- to 4-fold between the two surveys. In both surveys low back pain was more common in women. Shoulder and widespread pain was less prevalent in women than in men in the earlier survey but by the time of the later survey women reported more pain at these sites. CONCLUSIONS: The prevalence of musculoskeletal pain is much higher than that reported over 40 yr ago. The change in prevalence is unlikely to be entirely due to the study design; other possible explanations such as the increased reporting or awareness of these symptoms is discussed.

Adolescent↗

Low grip strength is associated with bone mineral density and vertebral fracture in women.

OBJECTIVES: Grip strength has been reported to be associated with bone mass locally at the forearm and also at distant skeletal sites, including the spine and hip. Less is known about the association between low grip strength and risk of vertebral fracture. The aim of this study was to examine the association between low grip strength, bone mineral density at the hip and spine, and vertebral fracture in middle-aged and elderly European men and women. METHODS: Men and women aged 50 yr and over were recruited for participation in a screening survey of vertebral osteoporosis across Europe. Subjects who agreed to take part had an interviewer-administered questionnaire and lateral spinal radiographs performed. Subjects were assessed also for grip strength using a handgrip dynamometer (range 0-300 mmHg). A subsample of those recruited had bone mineral density measurements performed at the spine and femoral neck. Subjects had repeat lateral spine radiographs performed a mean of 3.8 yr following the baseline survey. Linear regression analysis was used to determine the association between low grip strength and bone mineral density at the hip and spine. Logistic regression was used to determine the association between grip strength and both prevalent and incident vertebral fracture. RESULTS: One thousand two hundred and sixty-five men and 1380 women with data concerning grip strength and bone mineral density were included in the analysis. In women, after age adjustment, compared with those with 'normal' grip, those with 'impaired' (231-299 mmHg) and low grip (<231 mmHg) had significantly lower bone mass at the spine and femoral neck. In men, those with low grip strength had a lower BMD at the spine and hip than those in the normal group. However, because of the small numbers with submaximal grip strength, the confidence intervals around all estimates included zero. Adjustment for body size and levels of physical activity had little effect on the results. In addition, among women, after adjustment for age, body mass index and physical activity levels, compared with those with normal grip, those with low grip strength had an increased risk of developing incident vertebral fracture (odds ratio = 2.67; 95% confidence interval 1.13, 6.30). Further adjustment for spine bone density had little influence on the association (odds ratio = 2.60). CONCLUSIONS: In women, low grip strength is associated with low bone mineral density at both the spine and hip and an increased risk of incident vertebral fracture. These associations cannot be explained by differences in body size or lifestyle.

Absorptiometry, Photon↗

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Accidental Falls↗

A history of the Arthritis Research Campaign Epidemiology Unit, 1954-2004.

The founders of the Arthritis Research Campaign (arc) Epidemiology Unit were Kellgren and Lawrence. Their initial work was conducted in miners and then in the general population. They pioneered standardized methods of interview, examination and X-ray evaluation. They also played a key role in the early development of classification criteria for use in epidemiological surveys. The second director, Philip Wood, focused on understanding the impact of rheumatic diseases on the individual and on society. He was largely responsible for the International Classification of Impairments Disabilities and Handicaps. In the last 30 yrs, developments in statistics, computing and genetics have enabled the basic questions of disease aetiology to be re-examined. The third director, Alan Silman, took over in 1988. The Unit now has three research divisions: Genetics and Genomics, Outcome Studies and Population Surveys.

Arthritis↗