Showing papers by "Cyrus Cooper published in 2003"

Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy.

Abstract: OBJECTIVE: To evaluate predictors of vertebral fractures, including a threshold for bone mineral density (BMD), in patients receiving oral glucocorticoids (GCs). METHODS: Data were obtained from 2 randomized clinical trials (prevention and treatment trials of risedronate) using similar methods, but different inclusion criteria were applied with regard to prior exposure to GCs. Predictors of vertebral fracture in the placebo group were identified using Cox regression with forward selection. The BMD threshold analysis involved a comparison of the 1-year fracture risk in postmenopausal women receiving placebo in the GC trials with that in postmenopausal women not taking GCs in 3 other trials. RESULTS: The study population comprised 306 patients with baseline and 1-year followup data on vertebral fractures (111 receiving placebo and 195 receiving risedronate). In the placebo group, the statistically significant predictors of incident fracture were the baseline lumbar spine BMD (for each 1-point decrease in T score, relative risk [RR] 1.85, 95% confidence interval [95% CI] 1.06-3.21) and the daily GC dose (for each 10-mg dose increase, RR 1.62, 95% CI 1.11-2.36). In the BMD threshold analysis, compared with nonusers of GCs, patients receiving GCs were younger, had a higher BMD at baseline, and had fewer prevalent fractures; nevertheless, the risk of fracture was higher in the GC users compared with nonusers (adjusted RR 5.67, 95% CI 2.57-12.54). The increased risk of fracture was observed in GC users regardless of whether osteoporosis was present. CONCLUSION: The daily, but not cumulative, GC dose was found to be a strong predictor of vertebral fracture in patients receiving GCs. At similar levels of BMD, postmenopausal women taking GCs, as compared with nonusers of GCs, had considerably higher risks of fracture.

Is grip strength a useful single marker of frailty

Abstract: Background: chronological age is widely used as a marker of frailty in clinical practice. However there can be wide variation in frailty between individuals of a similar age. Grip strength is a powerful predictor of disability, morbidity and mortality which has been used in a number of frailty scores but not as a single marker of frailty. Objective: to investigate the potential of grip strength as a single marker of frailty in older people of similar chronological age. Design: cross-sectional study with prospective collection of mortality data. Setting: North Hertfordshire, UK. Subjects: 717 men and women, aged 64–74, born and still living in North Hertfordshire, who took part in a previous study to investigate the relationship between size at birth and ageing processes in later life. Methods: the number of significant associations between grip strength and the ageing markers was compared with numbers between chronological age and the ageing markers. Results: in men, lower grip strength correlated significantly with ten ageing markers compared to chronological age which was significantly associated with seven. In women, there were six significant relationships for grip compared to three for age. The greater number of relationships between grip strength and ageing markers was not explained by the association between grip strength and age, and remained after adjustment for adult size. Conclusions: grip strength was associated with more markers of frailty than chronological age within the narrow age range studied. Grip strength may prove a more useful single marker of frailty for older people of similar age than chronological age alone. Its validity in a clinical setting needs to be tested.

The burden of musculoskeletal conditions at the start of the new millennium

Abstract: Musculoskeletal conditions are extremely common and include more than 150 different diseases and syndromes, which are usually associated with pain and loss of function. In the developed world, where these conditions are already the most frequent cause of physical disability, ageing of the most populous demographic groups will further increase the burden these conditions impose. In the developing world, successful care of childhood and communicable diseases and an increase in road traffic accidents is shifting the burden to musculoskeletal and other noncommunicable conditions. To help better prepare nations for the increase in disability brought about by musculoskeletal conditions, a Scientific Group meeting was held to map out the burden of the most prominent musculoskeletal conditions at the start of the Bone and Joint Decade. In particular, the Group gathered data on the incidence and prevalence of rheumatoid arthritis, osteoarthritis, osteoporosis, major limb trauma and spinal disorders. Data were collected and organized by world region, gender and age groups to assist with the ongoing WHO Global Burden of Disease 2000 study. The Group also considered what is known about the severity and course of these conditions, along with their economic impact. The most relevant domains to assess and monitor the consequences of these conditions were identified and used to describe health states for the different stages of the conditions. Instruments that measure these most important domains for the different conditions were recommended. It is clear from data collated that the impact from musculoskeletal conditions and trauma varies among different parts of the world and is influenced by social structure, expectation and economics, and that it is most difficult to measure impact in less developed nations, where the predicted increase is greatest.

Smoking and musculoskeletal disorders: findings from a British national survey

Abstract: Objectives: To explore the relation between smoking habits and regional pain in the general population. Methods: A questionnaire was mailed to 21 201 adults, aged 16–64 years, selected at random from the registers of 34 British general practices, and to 993 members of the armed services, randomly selected from pay records. Questions were asked about pain in the low back, neck, and upper and lower limbs during the past 12 months; smoking habits; physical activities at work; headaches; and tiredness or stress. Associations were examined by logistic regression and expressed as prevalence ratios (PRs). Results: Questionnaires were completed by 12 907 (58%) subjects, including 6513 who had smoked at some time, among whom 3184 were current smokers. Smoking habits were related to age, social class, report of headaches, tiredness or stress, and manual activities at work. After adjustment for potential confounders, current and ex-smokers had higher risks than lifetime non-smokers for pain at all of the sites considered. This was especially so for pain reported as preventing normal activities (with PRs up to 1.6 in current v never smokers). Similar associations were found in both sexes, and when analysis was restricted to non-manual workers. Conclusions: There is an association between smoking and report of regional pain, which is apparent even in ex-smokers. This could arise from a pharmacological effect of tobacco smoke (for example, on neurological processing of sensory information or nutrition of peripheral tissues); another possibility is that people with a low threshold for reporting pain and disability are more likely to take up and continue smoking.

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

Abstract: The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

Children and the risk of fractures caused by oral corticosteroids.

Abstract: Oral corticosteroids are known to increase the risk of fracture in adults, but their effects in children remain uncertain. The medical records of general practitioners in the United Kingdom (from the General Practice Research Database) were used to estimate the incidence rates of fracture of children ages 4-17 years taking oral corticosteroids (n = 37,562) and of control children taking nonsystemic corticosteroids (n = 345,748). Each child with a fracture (n = 22,846) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. The average duration of treatment was 6.4 days (median, 5 days). The risk of fracture was increased in children with a history of frequent use of oral corticosteroids; children who received four or more courses of oral corticosteroids had an adjusted odds ratio (OR) for fracture of 1.32 (95% CI, 1.03-1.69). Of the various fracture types, the risk of humerus fracture was doubled in children who received four or more courses of oral corticosteroids (adjusted OR, 2.17 [1.01-4.67]). Fracture risk was also increased among children using 30 mg prednisolone or more each day (adjusted OR for fracture, 1.24 [1.00-1.52]) and among those receiving four or more courses of oral corticosteroids (OR, 1.32 [1.03-1.69]). Children who stopped taking oral corticosteroids had a comparable risk of fracture to those in the control group. Our findings suggest that children who require more than four courses of oral corticosteroid as treatment for underlying disease are at increased risk of fracture. It is not entirely clear whether this relates directly to oral corticosteroid use or the underlying disease and its severity. Irrespective of these issues, this group of children is at increased risk of fracture.

Risk factors for incident neck and shoulder pain in hospital nurses.

Abstract: Aim: To assess the incidence and risk factors for neck and shoulder pain in nurses. Methods: A longitudinal study of neck and shoulder pain was carried out in female nurses at two hospitals in England. Personal and occupational risk factors were assessed at baseline. The self reported incidence of symptoms in the neck and shoulder region was ascertained at three-monthly intervals over two years. A Cox regression model was used to estimate hazard ratios (HRs) for incident neck/shoulder pain during follow up in nurses who had been pain free for at least one month at baseline. Results: The baseline response rate was 56%. Of 903 women who were pain free at baseline, 587 (65%) completed at least one follow up while still in the same job. During an average of 13 months, 34% of these (202 women) reported at least one episode of neck/shoulder pain. The strongest predictor of pain in the neck/shoulder was previous history of the symptom (HRs up to 3.3). For physical exposures at work, the highest risks (HRs up to 1.7) were associated with specific patient handling tasks that involved reaching, pushing, and pulling. Nurses who reported low mood or stress at baseline were more likely to develop neck/shoulder pain later (HR 1.5). Workplace psychosocial factors (including job demands, satisfaction, and control) were not associated with incident neck/shoulder symptoms. Conclusions: Neck/shoulder pain is common among hospital nurses, and patient handling tasks that involve reaching and pulling are the most important target for risk reduction strategies.

Temporal analysis of rat growth plates: cessation of growth with age despite presence of a physis.

Abstract: Despite the continued presence of growth plates in aged rats, longitudinal growth no longer occurs. The aims of this study were to understand the reasons for the cessation of growth. We studied the growth plates of femurs and tibiae in Wistar rats aged 62-80 weeks and compared these with the corresponding growth plates from rats aged 2-16 weeks. During skeletal growth, the heights of the plates, especially that of the hypertrophic zone, reflected the rate of bone growth. During the period of decelerating growth, it was the loss of large hydrated chondrocytes that contributed most to the overall decrease in the heights of the growth plates. In the old rats we identified four categories of growth plate morphology that were not present in the growth plates of younger rats: (a). formation of a bone band parallel to the metaphyseal edge of the growth plate, which effectively sealed that edge; (b). extensive areas of acellularity, which were resistant to resorption and/or remodeling; (c). extensive remodeling and bone formation within cellular regions of the growth plate; and (d). direct bone formation by former growth plate chondrocytes. These processes, together with a loss of synchrony across the plate, would prevent further longitudinal expansion of the growth plate despite continued sporadic proliferation of chondrocytes.

The use of conventional and complementary treatments for knee osteoarthritis in the community

Abstract: Objectives. The aim of the survey was to assess the prevalence of clinically diagnosed knee osteoarthritis (OA) in two general practice populations in the Wessex region (practice A: a deprived urban population and practice B: an affluent rural population) and to assess both conventional and complementary therapy use in these two populations. Methods. All patients over 55 yr with a clinical diagnosis of knee OA, as identified from the practice computerized records, were sent a questionnaire about their knee pain and their use of conventional and complementary treatments. Results. A total of 4566 patients over 55 yr were registered in the two practices. Of these, 828 (18.13%) had a clinical diagnosis of knee OA and 240 (29%) patients were asymptomatic at the time of survey. Physiotherapy was under-utilized with only 13.1% of patients having received either hospital- or GP-based physiotherapy. There was a high prevalence of non-steroidal anti-inflammatory drug (NSAID) use, being significantly more in the affluent population (P < 0.05). In the affluent population there were statistically more social class groups 1–3a; statistically more NSAIDs, glucosamine and chondroitin sulphate were also used. The median amount spent on complementary medicine per month was £5.00, with the affluent population spending significantly more (P < 0.05). Conclusions. In this population, physiotherapy is an under-utilized treatment for knee OA, in spite of its recommendation as first-line treatment in all guidelines. Complementary medicines and therapies are commonly used, particularly in affluent populations.

Impact of ergonomic intervention on back pain among nurses.

Abstract: Objectives This study assessed the impact of ergonomic intervention on rates of low-back pain among hospital nurses. Methods Altogether 1239 female nurses from two hospitals in southern England completed a baseline postal questionnaire about low-back pain and associated risk factors. Between 18 and 28 months after the baseline survey, major intervention was implemented at one hospital to minimize unassisted patient handling and high-risk nursing tasks. At the other, no intervention was initiated, and efforts to improve patient handling were more limited. Thirty-two months after the baseline survey, a second postal survey was carried out in both hospitals (1167 respondents) to reassess the prevalence of symptoms and risk factors. Results After adjustment for nonoccupational risk factors, prevalent low-back pain at baseline was associated with low job satisfaction and the performance of patient-handling activities without mechanical aids. After the intervention, the prevalence of occupational risk factors was somewhat lower, but similar improvements occurred at the comparison hospital. At the intervention site the prevalence of symptoms increased slightly (from 27% to 30%), whereas at the comparison site there was no change, the prevalence remaining constant at 27%. Calculations based on the association of risk factors with symptoms at baseline and the observed changes in their prevalence indicated that the change in risk factors was insufficient to produce a substantial reduction in back pain. Conclusions These findings cast doubt on the means by which many hospitals are attempting to improve the ergonomics of nursing activities. More effective methods of implementing changes in work systems are needed.

Evidence of sustained skeletal benefits from impact-loading exercise in young females: a 3-year longitudinal study.

Abstract: The skeletal effects from intensive exercise throughout puberty are undefined. Forty-five female gymnasts and 52 controls were studied over 3 years, including a heredity aspect. The effects of size, maturity, exercise, and diet were identified using a multilevel regression model. Results demonstrated sustained skeletal benefits resulting from exercise throughout all stages of pubertal development. Introduction: Weight-bearing exercise is beneficial for peak bone mass development. However, whether skeletal benefits achieved with exercise are maintained if training remains intensive throughout the pubertal years is not entirely clear. The influence of familial resemblance for bone mass remains undefined in physically active versus inactive children. The aim of this study was to investigate the long-term influences of impact-loading exercise on bone quantity and quality in young females after controlling for growth, maturation, and hereditary factors. Materials and Methods: At baseline, 45 gymnasts (G) and 52 normally active controls (C) 8-17 years of age were recruited. Anthropometry, diet, physical activity, and quantitative ultrasound (QUS) were measured annually for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) were taken three times at 1-year intervals. A multilevel regression model was fitted, and the independent effects of body size, maturity, physical activity, and diet were identified over time. To assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross-sectional measurements of anthropometry, QUS, and BMC/BMD. Results and Conclusions: Gymnasts were smaller and lighter (as were their mothers) than controls, but they had significantly higher QUS and axial and appendicular BMC and BMD, with >170 g more bone mineral in TB across puberty (after adjustment for maturity [years from peak height velocity], height, weight, energy, and protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD, depending on skeletal site. These results provide evidence of sustained skeletal benefits from impact-loading exercise, which are unlikely to result entirely from heredity, throughout pubertal years

Knee disorders in the general population and their relation to occupation.

Abstract: Background: Hospital based studies of occupational risk factors for knee disorders are complicated by the possibility of selective referral to hospital of people whose work is made difficult by their symptoms. Aims: To explore the extent of such bias and to assess the association of meniscal injury with occupational activities. Methods: A questionnaire was mailed to a community sample of 2806 men aged 20–59 years in southern England. This asked about lifetime occupational and sporting activities, and any history of knee symptoms lasting 24 hours or longer. Rates of hospital referral were compared in symptomatic men according to their occupational activities. In a nested case-control investigation, the occupational activities of 67 men who reported meniscectomy were compared with those of 335 controls. Results: Among 1404 men who responded to the questionnaire, the lifetime prevalence of knee symptoms was 54%, and in 70% of cases the symptoms had started suddenly, usually while playing sport. Symptomatic men whose work entailed kneeling or squatting were more likely to be referred to an orthopaedic surgeon than the average (28% and 31% versus 24%), especially if they experienced locking of the knee (69% and 73% versus 43%). In the nested case-control study, meniscectomy was associated with playing soccer and work that involved regular kneeling or squatting. Conclusions: Results suggest that hospital referral for knee symptoms is influenced to some extent by patients' occupational activities. Playing soccer is confirmed as a strong risk factor for knee cartilage injury.

Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses

Abstract: Introduction: the role of the increase in bone mineral density (BMD) in fracture risk reduction observed in osteoporotic patients treated with antiresorptive drugs is unclear. We examined the effects of study selection, the use of summary statistics or individual patient data (IPD) as the basis for the analyses, and the choice of BMD values used on the outcome of meta-analyses. Materials and Methods: to evaluate the effects of study selection, we performed Poisson regression analyses using the results from a number of published studies. To evaluate the effects of using individual patient data instead of summary statistics, we simulated the IPD for vertebral fracture to match the summary statistics for published trials and compared these results with those based on meta-regression using summary statistics. We also evaluated the effect of varying the BMD increase with treatment (3-8%) used in predicting the fracture risk reductions in these simulations. Results: the Poisson regression, which found a statistically significant relationship between nonvertebral fracture risk and spinal BMD when 18 trials of varying designs, duration, and sample size were included in the analysis (p = 0.02), was no longer significant when the analysis was based on the 7 large studies that were placebo-controlled, at least 3 years in duration (at least 1000 patient-years). Meta-analyses of simulated IPD from 12 trials of six antiresorptive agents gave accurate results regardless of the proportion of vertebral risk reduction assumed to be related to BMD change, whereas meta-regression based on summary statistics always produced an estimate around 50%. When the actual data from two risedronate studies were analyzed, the meta-regression based on summary statistics demonstrated a stronger correlation between BMD change and fracture risk reduction than the results based on the IPD analysis. In predicting the fracture risk reduction, the use of the average BMD gain (3%) observed in all studies in the calculations produced an overall fracture risk reduction very similar to the one observed clinically. In contrast, the use of a large BMD gain (8%) produced a substantially higher estimated fracture risk reduction and resulted in a high proportion of fracture risk reduction being attributed to BMD change. Conclusions: many factors may influence the outcome of meta-analyses, and caution should be used in interpreting the results of such analyses when exploring the relationship between BMD changes and fracture risk reduction with antiresorptive therapy of osteoporosis.

The relative importance of whole body vibration and occupational lifting as risk factors for low-back pain

Abstract: Aims: To explore the impact of occupational exposure to whole body vibration (WBV) on low back pain (LBP) in the general population and to estimate the burden of LBP attributable to occupational WBV in comparison with that due to occupational lifting. Methods: A questionnaire including sections on WBV at work, LBP, and potential risk factors was mailed to a community sample of 22 194 men and women of working age. Sources and durations of exposure to occupational WBV were ascertained for the past week and personal vibration doses (eVDV) were estimated. Analysis was confined to subjects reporting exposures in the past week as typical of their work. Associations of LBP with eVDV, driving industrial vehicles, and occupational lifting were explored by logistic regression and attributable numbers were calculated. Results: Significant associations were found between daily lifting of weights greater than 10 kg at work and LBP, troublesome LBP (which made it difficult to put on hosiery), and sciatica (prevalence ratios 1.3 to 1.7); but the risk of these outcomes in both sexes varied little by eVDV and only weak associations were found with riding on industrial vehicles. Assuming causal associations, the numbers of cases of LBP in Britain attributable to occupational WBV were estimated to be 444 000 in men and 95 000 in women. This compared with an estimated 940 000 male cases and 370 000 female cases of LBP from occupational lifting. Conclusions: The burden of LBP in Britain from occupational exposure to WBV is smaller than that attributable to lifting at work.

Umbilical venous IGF-1 concentration, neonatal bone mass, and body composition.

Abstract: IGF-1 is a key growth factor during fetal life. Using DXA, we found that the concentration of IGF-1 in umbilical cord serum is strongly related to neonatal whole body bone mineral content, lean mass, and fat mass. However IGF-1 did not explain the relationships of maternal smoking, fat mass, and physical activity with neonatal bone mass. The study supports a direct role for circulating IGF-1 in growth of the fetal skeleton. Introduction: Evidence is accumulating that the risk of osteoporosis in later life may be determined in part by environmental influences during intrauterine and early postnatal life. We previously reported that maternal birthweight, smoking, fat stores, and physical activity during pregnancy predict neonatal bone mass. While the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis is an important determinant of postnatal skeletal growth, there are few data relating the concentration of growth factors in umbilical cord blood to bone mineral content (BMC) and other indices of body composition in the newborn infant. Materials and Methods: We conducted a population-based study in a cohort of full-term, newborn infants whose mothers were characterized for lifestyle, body composition, and nutrition through their normal pregnancies. In a sample of 119 infants from the cohort, we related cord serum IGF-1 and insulin-like growth factor binding protein (IGFBP)-3 concentrations to neonatal body composition measured by DXA and evaluated the extent to which this cytokine mediates the previously reported effects of maternal diet and lifestyle on neonatal bone mass. Results: There were strong positive associations between cord serum IGF-1 concentration and whole body BMC (r = 0.38, p < 0.001), whole body lean mass (r = 0.40, p < 0.001), and whole body fat mass (r = 0.50, p < 0.001) after adjusting for gestational age and sex. There was no association between cord serum IGF-1 and BMC adjusted for bone size. Neither cord serum IGF-1 nor IGFBP-3 explained the relationships that we previously reported between maternal influences and neonatal bone mass. Conclusions: Cord serum IGF-1 is more closely related to the size of the neonatal skeleton than to its degree of mineralization. Documented maternal determinants of neonatal bone mass seem to mediate their effects independently of variations in cord serum IGF-1 in healthy pregnancies.

Analysis of environmental factors in familial versus sporadic Paget's disease of bone--the New England Registry for Paget's Disease of Bone.

Abstract: A registry for Paget's Disease (PD) was created to study the environmental and familial features of this disorder. This study examines the first 202 people enrolled. Those with a family history of PD (20%) suffered earlier deformity and fracture, and tended to have grandparents born abroad. These findings suggest heritage is important in PD; the role of environment remains unclear. Introduction: The New England Registry for Paget's Disease of Bone is a database that was created to explore the distribution and determinants of disease frequency. Methods: Using a case-series design, we explored the association of environmental factors in expression of the disease, comparing those patients with familial Paget's disease to those with sporadic Paget's disease (PD). Results and Conclusions: Analysis of the first 202 patients enrolled in the registry revealed a positive family history (FH) in 41 (20%). Significant findings in this cohort included an earlier age of onset (51 years FH+ versus 59 years FH?, p < 0.05), a trend to a higher incidence of bone deformity (49% versus 33%, p < 0.1), and an increased fracture rate (27% versus 11%, p < 0.05). Persons with a FH of PD were less likely to record the United States or Canada as their grandparents' birthplace (p < 0.01), and sibships tended to be larger (p < 0.05). A history of measles infection, childhood exposure to pets, milk ingestion, year of immigration to the United States, birth order, level of education, and functional status did not distinguish the two groups. The database confirms the high prevalence of familial PD and supports the theory that heritable factors are important in the pathogenesis of this focal disorder of bone metabolism.

Weight from birth to 53 years: a longitudinal study of the influence on clinical hand osteoarthritis.

Abstract: Objective. To determine the influence of body weight throughout the life course on the development of clinical hand osteoarthritis (OA). Methods. A British national survey was used to perform a prospective cohort study of 1,467 men and 1,519 women born in 1946. Weight was measured at birth and at subsequent followup visits through childhood and adulthood. The main outcome measure was the odds ratio for the presence of hand OA at the age of 53 years. Results. Two hundred eighty men (19%) and 458 women (30%) had OA in at least 1 hand joint. Hand OA was significantly associated with increased weight at ages 26 years, 43 years, and 53 years and with decreased weight at birth in men. Birth weight and adult weight showed independent effects, such that men with the highest risk for OA represented those who had been heaviest at age 53 years and lightest at birth. These findings were not explained by grip strength. There was no significant relationship between weight and hand OA in women. Conclusion. The results of this study show that increased adult weight is associated with, and may precede, development of hand OA in men. An association between hand OA and weight was not observed in women. The relationship between hand OA and decreased birth weight is a new finding and may reflect the persisting influence of prenatal environmental factors on adult joint structure and function.

Weight from birth to 53 years: A longitudinal study of the influence on clinical hand osteoarthritis

Abstract: OBJECTIVE To determine the influence of body weight throughout the life course on the development of clinical hand osteoarthritis (OA). METHODS A British national survey was used to perform a prospective cohort study of 1,467 men and 1,519 women born in 1946. Weight was measured at birth and at subsequent followup visits through childhood and adulthood. The main outcome measure was the odds ratio for the presence of hand OA at the age of 53 years. RESULTS Two hundred eighty men (19%) and 458 women (30%) had OA in at least 1 hand joint. Hand OA was significantly associated with increased weight at ages 26 years, 43 years, and 53 years and with decreased weight at birth in men. Birth weight and adult weight showed independent effects, such that men with the highest risk for OA represented those who had been heaviest at age 53 years and lightest at birth. These findings were not explained by grip strength. There was no significant relationship between weight and hand OA in women. CONCLUSION The results of this study show that increased adult weight is associated with, and may precede, development of hand OA in men. An association between hand OA and weight was not observed in women. The relationship between hand OA and decreased birth weight is a new finding and may reflect the persisting influence of prenatal environmental factors on adult joint structure and function.

Efficacy and safety of oral weekly ibandronate in the treatment of postmenopausal osteoporosis.

Abstract: Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53–80 yr old; time since menopause > 3 yr) with postmenopausal osteoporosis [lumbar spine (L1–L4) bone mineral density (BMD) T-score < 2] to demonstrate the noninferiority of an oral weekly (20 mg) ibandronate regimen compared with an oral daily (2.5 mg) ibandronate regimen. All patients received daily calcium (500 mg) and vitamin D (400 IU). The primary analysis was the relative change in lumbar spine (L1–L4) BMD from baseline after 48 wk in the perprotocol population. Daily and weekly ibandronate significantly increased spinal BMD by 3.47 and 3.53%, respectively, and provided substantial and similar decreases in biochemical markers of bone turnover. In the primary analysis, noninferiority of the weekly regimen to the daily regimen was demonstrated, with the boundary of the one-sided confidence interval, 0.96%, within both the 1.65% prespecified margin and a more stringent margin of 1.10%. These results demonstrate that oral weekly ibandronate provides the same efficacy and safety as oral daily ibandronate in women with postmenopausal osteoporosis. (J Clin Endocrinol Metab 88: 4609–4615, 2003)

Predictors of hip joint replacement in new attenders in primary care with hip pain.

Abstract: BACKGROUND: Studies investigating the factors associated with need for total hip replacement should ideally be based on prospective investigation of new attenders in primary care AIM: To determine the incidence of listing for total hip replacement, and its predictors, among attenders in primary care with a new episode of hip pain DESIGN OF STUDY: Prospective multicentre cohort study SETTING: One hundred and ninety-five patients (mean age = 63 years, 68% female) with new episode of hip pain, attending primary care between November 1994 and October 1997 At the first visit, patients were evaluated for indices of pain and disability, range of hip movement, and radiographic changes of osteoarthritis METHOD: General practitioner participants were recruited from the membership of the Primary Care Rheumatology Society to recruit all consecutive attenders with a new episode of hip pain Annual follow-up was carried out to determine which patients were being 'put on a waiting list' for total hip replacement RESULTS: Seven per cent of patients were put on a waiting list for total hip replacement within 12 months and 23% of patients within four years At presentation, pain duration, pain severity, (including the need to use a stick) and restriction of internal rotation were the major clinical predictors of being put on a waiting list Radiographic predictors of osteoarthritis performed similarly to the clinical measures A simple scoring system based on both radiographic severity and two of the clinical measures was derived that identified groups at high likelihood of being put on a waiting list (sensitivity = 76%) with a low false-positive rate (specificity = 95%) CONCLUSION: New primary care attenders with pain are frequently accepted for total hip replacement soon after their first attendance--a decision that can be predicted by simple clinical measures

Neutropenia and agranulocytosis in England and Wales: incidence and risk factors.

Abstract: The objectives of this study were to estimate the incidence of idiosyncratic neutropenia and agranulocytosis in England and Wales and to evaluate their risk factors and outcomes. The study was conducted using data from the General Practice Research Database. All cases of idiosyncratic neutropenia or agranulocytosis were identified and the incidence was estimated. This was followed by a nested case-control study, estimating odds ratios with drug exposure from conditional logistic regression. From 1987 to 1999, 3,224 patients with idiosyncratic neutropenia (50 with agranulocytosis) were identified. The incidences of neutropenia and agranulocytosis were estimated to be 120 and 7 cases per million people per year, respectively. The adjusted odds ratios for neutropenia were 34.7 (95% confidence interval 12.0-99.7) for current users of thyroid inhibitors, 9.5 (4.4-20.8) for users of disease-modifying antirheumatic drugs, and 7.6 (4.9-11.9) for users of aminosalicylates. Other drugs with statistically significantly increased risks of neutropenia included antibacterial drugs, non-opioid analgesics, NSAIDs, antidepressants, ulcer-healing drugs, and anti-epileptics. The increase in risk of neutropenia predominantly occurred during the first months of treatment. For most drugs investigated in this study, there was no relationship to daily dose. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and mostly explained by the underlying disease state. In conclusion, the highest risks of neutropenia were generally found in patients starting treatment. The excess 1-year mortality was low among neutropenia and agranulocytosis cases and can be mostly explained by the underlying disease state.

Use of alpha-blockers and the risk of hip/femur fractures.

Abstract: OBJECTIVE: To study the association between use of alpha-blockers and risk of hip/femur fractures. DESIGN: Population-based case-control study. SETTING: General Practice Research Database. SUBJECTS: Cases were defined as men, aged 40 years and older with a first diagnosis for hip/femur fracture. Controls were matched 1 : 1 on gender, year of birth and general practitioner-practice. RESULTS: In all, 4571 cases and an equal number of controls were identified. Current use of alpha-blockers (prazosin, doxazosin, indoramin, terazosin, alfuzosin and tamsulosin) was compared with non-use of alpha-blockers. Current use of alpha-blockers on the index date was associated with an increased risk of hip/femur fracture [adjusted odds ratio (OR) 1.9, 95% confidence interval (CI): 1.1-3.0] in the overall analysis. The effect was particularly strong for first prescriptions within a treatment episode (adjusted OR 5.1, 95% CI: 1.0-31.7) and during the first month of treatment (adjusted OR 4.1, 95% CI: 0.7-23.9). Stratification according to indication of use showed that current use of alpha-blockers was not associated with hip/femur fracture in men with a diagnosis of benign prostatic hyperplasia (adjusted OR 1.0, 95% CI: 0.4-2.5), but was associated in men who used alpha-blockers for cardiovascular disease (adjusted OR 2.8, 95% CI: 1.4-5.4). CONCLUSION: Current use of alpha-blockers was associated with an increased risk of hip/femur fracture and with the start of a new treatment episode. The effect seemed to be confined to patients who used alpha-blockers for cardiovascular disease. Caution with respect to first-dose effects related to the initiation of a new episode of alpha-blocker treatment is advised.

PTH/PTHrP activity and the programming of skeletal development in utero.

Abstract: There is increasing evidence that nutritional deficiency in utero adversely affects bone development and the risk of developing osteoporosis in later life. Although the mechanisms involved are unknown, circumstantial evidence points to an important role of PTH/PTHrP activity. It is recognized that PTH and PTHrP are critically involved in regulating fetal calcium homeostasis, actions that are mediated at least in part by PPR. As well as playing a central role in the maintenance of calcium homeostasis in the fetus, studies in transgenic mice show that PTH, PTHrP, and PPR exert similar effects on skeletal development in utero, acting to increase the size of the trabecular envelope and decrease that of the cortical envelopes. Taken together, these observations raise the possibility that stimulation of PTH/PTHrP activity in the fetus in response to calcium deficiency acts to increase the size of the trabecular envelope but to reduce that of the cortical envelope. Although any increase in trabecular bone at birth is likely to be relatively transient, a decrease in size of the cortical envelope may have a persistent effect on the trajectory of bone growth in subsequent childhood. Consistent with this proposal, preliminary findings from birth cohort studies suggest that maternal calcium intake and cord blood calcium levels are positively related to bone mass of the offspring as assessed later in childhood. Further studies are justified to determine whether alterations in fetal PTH/ PTHrP activity caused by calcium stress lead to a reduction in size of the cortical envelope at birth that persists into childhood and later adult life and to identify modifiable maternal factors that are responsible for these changes.

PASSCLAIM – Bone health and osteoporosis

Abstract: Background: The EC Concerted Action PASSCLAIM aims to produce a generic tool for assessing the scientific support for health-related claims for foods and food components. Aim: The task of the ITGB Working Group was to critically evaluate the categories of scientific evidence needed to support claims in relation to bone health and osteoporosis. Methods: A framework was developed to describe the chain of evidence that is required to link the consumption of a food or food component to bone health outcomes. Techniques available for interrogating each link in the chain were identified and their strengths and weaknesses considered. This framework was used to determine intermediate markers of health outcome with respect to osteoporosis and to debate the level of evidence that would be required to substantiate claims of enhanced function or reduced disease risk. Results: Use of this framework with osteoporotic fracture as the health endpoint resulted in the following judgements based on current knowledge: 1) bone mineral density (BMD) is an intermediate marker of bone health which, for people of any age and sex, can provide evidence of enhanced function; 2) for people over 50 years living in populations with a high incidence of fracture, BMD is an intermediate marker of osteoporotic fracture risk which can provide evidence of an increased probability of reduced disease risk; 3) because osteoporosis is defined as a state of increased fracture risk due to low bone mass and deterioration in bone microarchitecture, a claim of a definite reduction in osteoporosis or fracture risk requires similar substantiation to claims that fractures are prevented or treated, including clinical trials and animal studies; 4) data from lower in the chain of evidence, such as bone turnover and calcium bioavailability, are not, by themselves, sufficiently strongly related to bone health endpoints to provide evidence of enhanced function or reduced disease risk but can provide supporting information. Conclusions: In the light of existing scientific knowledge, a framework has been developed as a tool for considering the scientific support for claims relating to bone health and osteoporosis. To provide a working example, the framework has been used to assess the current position with osteoporotic fracture as the health endpoint. This experience will contribute to the formulation under PASSCLAIM of a generic tool for assessing the scientific support of health claims on foods.

Syndrome of symptomatic adult acetabular dysplasia (SAAD syndrome)

Abstract: Objectives: To determine the prevalence of acetabular dysplasia in subjects presenting with hip pain to primary care and its relationship with radiographic osteoarthritis (OA) of the hip. Design: Cross sectional analysis of a prospective cohort. Setting: 35 general practices across the UK. Subjects: 195 patients (63 male, 132 female) aged 40 years and over presenting with a new episode of hip pain Results: The prevalence of acetabular dysplasia in this study of new presenters with hip pain was high (32%). There was no significant relationship between acetabular dysplasia and radiographic OA overall. Conclusions: The high prevalence of acetabular dysplasia across all grades of OA severity suggests that dysplasia itself may be an important cause of hip pain (“symptomatic adult acetabular dysplasia”).