Showing papers by "Cyrus Cooper published in 2002"

The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis.

Abstract: Studies of oral corticosteroid dose and loss of bone mineral density have reported inconsistent results. In this meta-analysis, we used information from 66 papers on bone density and 23 papers on fractures to examine the effects of oral corticosteroids on bone mineral density and risk of fracture. Strong correlations were found between cumulative dose and loss of bone mineral density and between daily dose and risk of fracture. The risk of fracture was found to increase rapidly after the start of oral corticosteroid therapy (within 3 to 6 months) and decrease after stopping therapy. The risk remained independent of underlying disease, age and gender. We conclude that oral corticosteroid treatment using more than 5 mg (of prednisolone or equivalent) daily leads to a reduction in bone mineral density and a rapid increase in the risk of fracture during the treatment period. Early use of preventive measures against corticosteroid-induced osteoporosis is recommended.

Epidemiology of osteoporosis

Abstract: Osteoporosis is a major public health problem through its association with fracture. The problem may be alleviated substantially by appropriate early intervention before fracture occurs. This chapter discusses the epidemiology of osteoporosis and addresses the following questions: How should osteoporosis be defined? What is the incidence and prevalence of osteoporosis and fracture? Is there geographical variation in the occurrence of osteoporosis? What are the risk factors for osteoporosis and do they explain the occurrence of osteoporosis and osteoporotic fracture?

Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS).

Abstract: Vertebral fracture is one of the major adverse clinical consequences of osteoporosis; however, there are few data concerning the incidence of vertebral fracture in population samples of men and women. The aim of this study was to determine the incidence of vertebral fracture in European men and women. A total of 14,011 men and women aged 50 years and over were recruited from population-based registers in 29 European centers and had an interviewer-administered questionnaire and lateral spinal radiographs performed. The response rate for participation in the study was approximately 50%. Repeat spinal radiographs were performed a mean of 3.8 years following the baseline film. All films were evaluated morphometrically. The definition of a morphometric fracture was a vertebra in which there was evidence of a 20% (+4 mm) or more reduction in anterior, middle, or posterior vertebral height between films--plus the additional requirement that a vertebra satisfy criteria for a prevalent deformity (using the McCloskey-Kanis method) in the follow-up film. There were 3174 men, mean age 63.1 years, and 3,614 women, mean age 62.2 years, with paired duplicate spinal radiographs (48% of those originally recruited to the baseline survey). The age standardized incidence of morphometric fracture was 10.7/1,000 person years (pyr) in women and 5.7/1,000 pyr in men. The age-standardized incidence of vertebral fracture as assessed qualitatively by the radiologist was broadly similar-12.1/1,000 pyr and 6.8/1,000 pyr, respectively. The incidence increased markedly with age in both men and women. There was some evidence of geographic variation in fracture occurrence; rates were higher in Sweden than elsewhere in Europe. This is the first large population-based study to ascertain the incidence of vertebral fracture in men and women over 50 years of age across Europe. The data confirm the frequent occurrence of the disorder in men as well as in women and the rise in incidence with age.

A New Approach to the Development of Assessment Guidelines for Osteoporosis

Abstract: The diagnosis of osteoporosis is made from the measurement of BMD. DXA at the hip is the appropriate diagnostic site. Current clinical guidelines follow the principle that BMD measurements are indicated in individuals with risk factors for fracture and that treatment is recommended in those with a BMD below a critical value. In some countries reimbursement for the costs of treatment depend upon such thresholds for BMD. In Europe the critical value corresponds to a T-score of-2.5 SD, whereas in the USA less stringent criteria are used. It is evident, however, that fracture risk at any given T-score varies markedly according to age and other risk factors. This has led to the view that interventions should be targeted to those at high risk, irrespective of a fixed BMD threshold. In this sense, BMD is utlized as a risk assessment, since in many instances intervention thresholds will be less stringent than the diagnostic threshold. Thus, intervention thresholds need to differ from diagnostic thresholds and be based on fracture probabilities. A 10-year fracture probability appears to be an appropriate time frame. There are a number of problems to be overcome in the development of assessment guidelines. They need to take account of not only the risk of hip fracture but also that of other fractures which contribute significantly to morbidity, particularly in younger individuals. A promising approach is to weight fracture probabilities according to the disutility incurred compared with hip fracture probability. Account also needs to be taken of the large geographic variation in fracture probabilities worldwide. A further challenge for the future will be to identify risk factors that predict fracture with high validity in different regions of the world and their independent contributions, so that models of risk prediction can be constructed and ultimately validated in independent cohorts.

Does a fracture at one site predict later fractures at other sites? A British cohort study.

Abstract: The extent to which a fracture at one skeletal site predicts further fractures at other sites remains uncertain. We addressed this issue using information from the UK General Practice Research Database, which contains the medical records of general practitioners; our study population consisted of all patients aged 20 years or older with an incident fracture during 1988 to 1998. We identified 222 369 subjects (119 317 women, 103 052 men) who had sustained at least one fracture during follow-up. There was a 2- to 3-fold increase in the risk of subsequent fractures at different skeletal sites. A patient with a radius/ulna fracture had a standardized incidence ratio (SIR) of 3.0 (95% confidence interval 2.9-3.1) for fractures at a different skeletal site; for initial vertebral fracture, this ratio was 2.9 (2.8-3.1) and for initial femur/hip fracture it was 2.6 (2.5-2.7). The SIRs were generally higher among men than women. Men aged 65-74 years with a radius/ulna fracture or vertebral fracture had substantially higher rates of subsequent femur/hip fractures than expected; SIRs were 6.0 (3.4-9.9) and 13.4 (7.3-22.5). Corresponding SIRs among women of similar age were 3.3 (2.8-3.9) and 5.8 (4.1-8.1), respectively. Men and women aged 65 years or older with a vertebral fracture had a 5-year risk of femur/hip fracture of 6.7% and 13.3%, respectively. Our results indicate that fractures at any site are strong risk factors for subsequent fractures, among both elderly men and women.

Incidence of limb fracture across Europe: Results from the European prospective osteoporosis study (EPOS)

Abstract: The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Birth Weight, Childhood Size, and Muscle Strength in Adult Life: Evidence from a Birth Cohort Study

Abstract: Environmental influences during gestation may have long-term effects on adult muscle strength. It is not known how early in adult life such effects are manifest and whether they are modified by childhood body size. The authors examined the relation between birth weight and hand grip strength in a prospective national birth cohort of 1,371 men and 1,404 women from the Medical Research Council National Survey of Health and Development who were aged 53 years in 1999. A positive relation between birth weight and adult grip strength remained after adjustment first for adult height and weight and then additionally for childhood height and weight (p = 0.006 for men and p = 0.01 for women). The effects of birth weight on grip strength did not vary by childhood or current body size and were not confounded by social class. To the authors' knowledge, this is the first study to show that birth weight has an important influence on muscle strength in midlife independent of later body size and social class. It suggests that birth weight is related to the number of muscle fibers established by birth and that even in middle age compensating hypertrophy may be inadequate. As the inevitable loss of muscle fibers proceeds in old age, a deficit in the number of fibers could threaten quality of life and independence.

Intrauterine exposure to a maternal low protein diet reduces adult bone mass and alters growth plate morphology in rats.

Abstract: Epidemiological studies suggest that poor growth during fetal life and infancy is associated with decreased bone mass in adulthood. However, theses observations have not, to date, been corroborated in animal models. To address this issue we evaluated the influence of maternal protein restriction on bone mass and growth plate morphology among the adult offspring, using a rat model. Maternal protein restriction resulted in a reduction in bone area and BMC, but not BMD, among the offspring in late adulthood. The widened epiphyseal growth plate in the protein-restricted offspring is compatible with the programming of cartilage and bone growth by maternal nutrition in early life.

Sports injury, occupational physical activity, joint laxity, and meniscal damage

Abstract: OBJECTIVE: To investigate the risk factors for meniscal damage, an important determinant of knee osteoarthritis. METHODS: We studied 243 men and women aged 20-59 years in whom the diagnosis of a meniscal tear was confirmed for the first time at arthroscopy, over a 25 month period, in 2 British hospitals. Each case was compared with one or 2 community controls, matched by age and sex, who were registered with the same general practitioner. Information on exposure to risk factors was obtained by a structured questionnaire and physical examination. RESULTS: Meniscal tear was strongly associated with participation in sports during the 12 months preceding the onset of symptoms; the risk was particularly high for soccer (OR 3.7; 95% CI 2.1-6.6). Higher body mass index and occupational kneeling (OR 3.8; 95% CI 1.3-11.0) and squatting (OR 2.9; 95% CI 1.0-8.0) were associated with an increased risk of degenerative meniscal lesions, after adjustment for social class, joint laxity, and sports participation. Joint laxity was associated with degenerative meniscal lesions independently of occupational physical activity, sports, and obesity. CONCLUSION: Our results confirm the importance of sporting activities entailing knee torsion in acute meniscal tear. They also point to a role for occupational activity, adiposity, and joint laxity in the pathogenesis of degenerative meniscal lesions. Modifying these mechanical risk factors may serve to reduce the risk of meniscal injury and may also help to prevent later knee osteoarthritis.

Reliability of the Southampton examination schedule for the diagnosis of upper limb disorders in the general population

Abstract: Background: Epidemiological research in the field of soft tissue neck and upper limb disorders has been hampered by the lack of an agreed system of diagnostic classification. In 1997, a United Kingdom workshop agreed consensus definitions for nine of these conditions. From these criteria, an examination schedule was developed and validated in a hospital setting. Objective: To investigate the reliability of this schedule in the general population. Methods: Ninety seven adults of working age reporting recent neck or upper limb symptoms were invited to attend for clinical examination consisting of inspection and palpation of the upper limbs, measurement of active and passive ranges of motion, and clinical provocation tests. A doctor and a trained research nurse examined each patient separately, in random order and blinded to each other9s findings. Results: Between observer repeatability of the schedule was generally good, with a median κ coefficient of 0.66 (range 0.21 to 0.93) for each of the specific diagnoses considered. Conclusion: As expected, the repeatability of tests is poorer in the general population than in the hospital clinic, but the Southampton examination schedule is sufficiently reproducible for epidemiological research in the general population.

Health status in patients awaiting hip replacement for osteoarthritis

Abstract: Background: Hip osteoarthritis is a major cause of pain and disability, especially in the elderly. As part of a study investigating factors that could be associated with advanced osteoarthritis of the hip, we compared the health status of patients awaiting arthroplasty for hip osteoarthritis with controls. We further investigated the interaction of hip osteoarthritis with other variables (age, gender, social class and concurrent pain) in relation to health status. Methods: A case–control study was performed in two English health districts (Portsmouth and North Staffordshire) during 1993–1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period formed the case group and were compared with an equal number of controls selected from the general population and individually matched for age, gender and general practice. Cases and controls completed a structured interviewer-administered questionnaire, which included queries about their medical condition, occupation (from which a measure of social class was derived), and general health status using the SF36. Results: Physical function (t=32.1, P Conclusion: Patients awaiting hip-replacement because of osteoarthritis were more likely to be restricted in their physical and social life than adults in the general population, but mental state and vitality appear unimpaired in this group. This contrasts with findings from other chronic pain disorders. Manual social class is not linked to being on a waiting list for osteoarthritic hip replacement but does add to the burden on health status, particularly social functioning in those with osteoarthritis of the hip.

Polymorphism of the IGF2 gene, birth weight and grip strength in adult men

Abstract: Background: grip strength is a simple measure of skeletal muscle function but a powerful predictor of disability, morbidity and mortality. Recent evidence has shown that prenatal and infant growth influence grip strength in later life; this may reflect genetic influences on muscle size and function, although strong candidate genes have not been identified. IGF II has proliferative effects in adult muscle and is one of the major determinants of fetal growth; polymorphism in the IGF2 gene could therefore link early growth to adult grip strength. Objectives: to determine whether polymorphism of the IGF2 gene influences adult grip strength and mediates the association between size at birth and grip strength in later life. Methods: polymorphism of the ApaI marker in the IGF2 gene was determined for 693 Hertfordshire men and women born between 1920 and 1930 who had taken part in a study linking early growth to ageing. Grip strength was measured using isometric dynamometry. Genotyping assay development was undertaken in Southampton Genetic Epidemiology Laboratories (http://www.sgel.humgen.soton.ac.uk). Results: in univariate analyses, IGF2 genotype and birth weight were both significant predictors of adult grip strength in the men after adjustment for age and current height. Significant associations were not seen in the women. When IGF2 genotype and birth weight in men were studied simultaneously, both contributed significantly to grip strength after adjustment for age and adult height. Conclusions: these results show that polymorphism of the IGF2 gene and birth weight have independent effects on adult grip strength in men and suggest that IGF2 polymorphism does not explain the association between size at birth and grip in later life. This study provides preliminary evidence for independent genetic and early environmental programming of adult muscle strength.

Does Birth Weight Predict Adult Serum Cortisol Concentrations? Twenty-Four-Hour Profiles in the United Kingdom 1920–1930 Hertfordshire Birth Cohort

Abstract: Low birth weight and weight in infancy are associated with adult insulin resistance and type 2 diabetes. A proposed mechanism is programming of the hypothalamic-pituitary-adrenal axis by intrauterine undernutrition, leading to persistently elevated cortisol concentrations. We examined 24-h serum cortisol profiles (samples every 20 min) in 83 healthy elderly men and women whose birth weight and infant weight were recorded. Variables derived from these profiles included trough, peak, and area under the curve concentrations; the time of onset, rate of rise, duration, and peak of the early morning cortisol rise; postprandial secretion; and regularity of secretion (approximate entropy). None of these parameters was related to birth weight, weight at 1 yr, or change in weight SD score between birth and 1 yr. Consistent with other studies, 0730-0900 h cortisol concentrations were higher in men and women of lower birth weight, although this was not statistically significant (P = 0.08). Our findings do not support the hypothesis that reduced intrauterine and infant growth are associated with continuously raised cortisol concentrations in old age. Programmed effects on the hypothalamic-pituitary-adrenal axis may influence reactivity rather than resting secretion.

The Epidemiology of Corticosteroid-Induced Osteoporosis: a

Abstract: Studies of oral corticosteroid dose and loss of bone mineral density have reported inconsistent results. In this meta-analysis, we used information from 66 papers on bone density and 23 papers on fractures to examine the effects of oral corticosteroids on bone mineral density and risk of fracture. Strong correlations were found between cumulative dose and loss of bone mineral density and between daily dose and risk of fracture. The risk of fracture was found to increase rapidly after the start of oral corticosteroid therapy (within 3 to 6 months) and decrease after stopping therapy. The risk remained independent of underlying disease, age and gender. We conclude that oral corticosteroid treatment using more than 5 mg (of prednisolone or equivalent) daily leads to a reduction in bone mineral density and a rapid increase in the risk of fracture during the treatment period. Early use of preventive measures against corticosteroid-induced os- teoporosis is recommended.

Recent developments in the epidemiology of osteoporosis

Abstract: Osteoporosis is a widespread condition, often unrecognised in clinical practice, which may have devastating health consequences through its association with fragility fractures. Osteoporotic fractures represent an enormous public health burden. The total number of fractures, and hence the cost to society, will increase dramatically over the next 50 years as a result of demographic changes in the number of elderly people. This article reviews the latest advances in our knowledge of epidemiologic aspects of osteoporosis, including the epidemiology of fragility fracture, the determinants of fracture risk, and genetic, intrauterine, and environmental risk factors for osteoporosis. Novel relationships between breast cancer and bone mineral density will also be discussed.

Raynaud's phenomenon, vibration-induced white finger, and difficulties in hearing

Abstract: Background: An association has previously been reported between finger blanching and hearing difficulties, but only in workers with exposure to noise and hand transmitted vibration (HTV). Aims: To explore the association in a community sample, including cases who lacked occupational exposure to noise or HTV. Method: A questionnaire was mailed to 12 606 subjects aged 35–64 years, chosen at random from the age–sex registers of 34 British general practices. Inquiry was made about years of employment in noisy jobs, lifetime exposure to HTV, hearing difficulties and tinnitus, and lifetime history of cold induced finger blanching. Subjects were classed as having severe hearing difficulty if they used a hearing aid or found it difficult or impossible to hear conversation in a quiet room. Associations of finger blanching with hearing difficulties and tinnitus were analysed by logistic regression. Results: Among 8193 respondents were 185 who reported severe hearing difficulty and 1151 who reported finger blanching. After adjustment for age and years of work in noisy jobs, hearing difficulty was about twice as common in men and women who reported finger blanching, including those who had never been importantly exposed to noise and in those never exposed to HTV. Conclusions: These data support an association between finger blanching and hearing loss, which is not explained by confounding occupational exposure to noise, and suggest that it may extend to causes of blanching other than vibration induced white finger. Further investigations are warranted to confirm the association and explore possible mechanisms, such as sympathetic vasoconstriction in the cochlea.

Defining Incident Vertebral Deformities in Population Studies: A Comparison of Morphometric Criteria

Abstract: Various morphometric criteria have been used to define incident vertebral deformity. The aim of this analysis was to compare the relative validity of two established criteria and a novel method in which these criteria were combined. Men and women aged 50 years and over were recruited from population registers across Europe and had lateral spinal radiographs performed using a standard protocol. A subsample of individuals had bone mineral density (BMD) at the spine or femoral neck. Subjects were followed prospectively and a subsample had repeat spinal radiographs a median of 3.8 years after the baseline survey. All radiographs were evaluated morphometrically in the radiology coordinating center in Berlin. Anterior, middle and posterior height were recorded in all vertebrae from T4 to L4. On the basis of these morphometric measurements incident vertebral deformity was defined using one of three methods: (i) the change method – a change in any vertebral height of 20% or more between films, plus the additional requirement that a vertebral body have changed in absolute vertebral height by 4 mm or more; (ii) the point prevalence method, where a vertebra satisfies criteria for a prevalent deformity (McCloskey–Kanis) on the follow-up, though not the baseline film; (iii) a combination of the height reduction and the point prevalence criteria. Paired films were also evaluated qualitatively by an experienced radiologist for the presence of incident vertebral deformity. Logistic regression was used to compare the three morphometric methods using known risk factors for vertebral deformity including age, baseline vertebral deformity and BMD, and the qualitative evaluation. Computer simulation was used to determine the potential degree of bias and loss of statistical efficiency due to misclassification for each of the three methods, using the radiologist’s assessment of incident deformity as the reference. Six thousand eight hundred subjects were included in this analysis. Of these 450 had sustained an incident vertebral deformity according to at least one of the three morphometric methods. The distribution of risk factors was similar in the subjects who satisfied only one morphometric criterion and those who satisfied neither. However, the subjects who satisfied both criteria had a very different distribution of risk factors: they were older, more likely to be female, more likely to have had a previous vertebral deformity and more likely to have an incident fracture in the opinion of an experienced radiologist. Using computer simulation, at low incidence levels, combining the criteria led to greater statistical efficiency and less bias in estimating associations with risk factors. Thus in this analysis the combination of the point prevalence and 20% change in height criterion for defining incident vertebral deformity showed a stronger relationship with clinical risk factors than either single criterion. Its application in population-based studies would increase the likelihood of detecting risk factors for incident vertebral deformity for a given sample size.

Early diet and growth: impact on ageing.

Abstract: The modification of ageing by nutritional intervention is well recognised. Post-weaning diet restriction is the only widely reproducible method to slow ageing, but the effects of prenatal and preweaning diet restriction have been less well characterised. There is some evidence that diet restriction instituted in utero or shortly after birth may have an opposite effect and be associated with increased ageing, and recent work suggests that it may shorten lifespan. Interest in this area has been rekindled by the growing body of epidemiological evidence showing that a number of age-related diseases are associated with poor growth and inadequate nutrition in early life. The relevance of this association to structural and functional ageing changes in different systems is now being considered. Work on musculo-skeletal ageing has demonstrated that loss of muscle strength and bone mass is greater in individuals who did not grow well in early life, and a range of studies suggests that maternal, developmental and nutritional factors are important. The underlying mechanisms remain speculative, and it remains to be determined whether they are system-specific or universal throughout the body. A new cohort of subjects aged between 60 and 70 years is being established to investigate how genetic factors interact with growth and nutritional influences to programme musculo-skeletal ageing in later life.

Osteoporosis in patients with inflammatory bowel disease

Abstract: Increased incidence of “fragility” fractures in patients with inflammatory bowel disease There is consistent evidence that patients with inflammatory bowel disease (IBD) have an increased risk of osteoporosis, defined by reduced bone mineral density (BMD).1 The important clinical end point of osteoporosis however, is fractures; these are associated with significant morbidity and mortality and healthcare costs. The retrospective cohort study of Bernstein et al shows a 40% increase in the risk of fracture among patients with IBD compared with age and sex matched controls.2 The increased risk was similar in patients with Crohn's disease (CD) and ulcerative colitis (UC). These results differ from a large Danish case control study which reported a 2.5-fold increase in the risk of fracture among women with CD but failed to demonstrate a statistically significant increased risk among men with CD or patients with UC.3 The literature on BMD in IBD is also discordant when comparing the risk of osteoporosis in patients with CD with those with UC.1 Further large studies of fracture in these disorders are required to quantify the risk in CD and UC. The reduction …

The relationship between endogenous estrogen, sex hormone-binding globulin, and bone loss in female residents of a rural Japanese community: the Taiji Study.

Abstract: The aim of this study was to clarify the relationship between endogenous estrogen, sex hormone-binding globulin (SHBG), and bone loss in pre-, peri-, and postmenopausal female residents of Taiji, a rural Japanese community. From a list of inhabitants aged 40 to 79 years, 200 participants—50 women in each of four age decades—were randomly selected, and baseline bone mineral density (BMD) at the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry in 1993. Total estradiol (total E2) and SHBG were measured, and SHBG-unbound E2 (UBE2) was calculated using SHBG and the percent SHBG-unbound fraction ratio. BMD was measured again 3 years later, in 1996. Participants with ovariectomy or hysterectomy were excluded, and the remaining participants were categorized into four groups: premenopausal (n= 38), perimenopausal (n= 14), postmenopausal group 1 (5 years or less since menopause; n= 18), and postmenopausal group 2 (6 years or more since menopause; n= 74). The mean value of total E2 was highest in the premenopausal group (49.1 pg/ml), followed by the perimenopausal group (26.4 pg/ml), and the postmenopausal groups (0.83 pg/ml in postmenopausal group 1 and 0.96 pg/ml in postmenopausal group 2). The means for UBE2 showed the same pattern across the groups. After the multiple regression analysis of BMD at follow-up and endogenous estrogens, in premenopausal women, there were no significant associations between BMD at follow-up and serum total E2 and UBE2. In perimenopausal women, however, serum total E2 and UBE2 were significantly correlated with trochanteric BMD at follow-up (P < 0.05); and in postmenopausal group 2, they were significantly correlated with lumbar spine and Ward's triangle BMD at follow-up (P < 0.001 at lumbar spine, P < 0.05 at Ward's triangle). Concerning the association between BMD at follow-up and SHBG, in the premenopausal group, serum levels of SHBG were negatively correlated with BMD at the femoral neck (P < 0.05). In regard to partial regression coefficients for the change rates of BMD over 3 years and serum estrogens and SHBG concentrations, in perimenopausal women, UBE2 was correlated with the change rate of BMD at Ward's triangle (P < 0.05), and in postmenopausal group 1, serum levels of SHBG were significantly negatively related to change in BMD at the trochanter (P < 0.01). No other relationships with change in BMD were observed at any sites. These findings suggest that serum E2, UBE2, and SHBG levels differentially predict BMD levels in groups of differing menstrual status. It would, however, be difficult to predict bone loss in middle-aged and elderly Japanese women over a 3-year period using these indices alone.

Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males.

Abstract: Ciliary neurotrophic factor (CNTF) administration reduces weight in leptin-resistant mice via the signalling pathway normally activated by leptin. A G>A null mutation in the CNTF gene results in complete absence of protein. We hypothesised that absence of CNTF could lead to diminished initiation of anorectic pathways, with consequent increase in body mass. In 575 Caucasian men aged 59-73 years, the A/A genotype (frequency 1.9%) was associated with a 10 kg increase in weight (P=0.03, 2 df) and 3 kg/m(2) greater BMI (P=0.02, 2 df). There was no effect in women. The CNTF G>A null mutation therefore confers a moderate effect on obesity in males of A/A genotype, who represent 1% of the general population.

Size at birth, adult intestinal calcium absorption and 1,25(OH)2 vitamin D

Abstract: Background: Adult bone mineral status is modified by early environmental influences, but the mechanism of this phenomenon is unknown. Intestinal calcium absorption and vitamin D metabolism are integrally involved in bone metabolism and may be programmed during early life. Aim: To examine the early‐life influences on calcium absorption and its control in 322 post‐menopausal female twins. Methods: Intestinal calcium absorption was assessed by the stable strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)2 vitamin D were measured and recalled birth weight recorded. Results: Fractional intestinal Sr absorption ( α Sr) was correlated with serum 1,25(OH)2 vitamin D ( p <0.001), but not with 25(OH) vitamin D. Birth weight was inversely associated with serum 1,25(OH)2 vitamin D ( p =0.04), the association being independent of serum calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated with α Sr ( p =0.03), this association being independent of age, season, customary calcium intake and serum 25(OH) vitamin D; however, when serum 1,25(OH)2 vitamin D was added into the model, the association became non‐significant, suggesting that the association was partially mediated via serum 1,25(OH)2 vitamin D. Discussion: We found a significant inverse association between birth weight and intestinal calcium absorption that is partially explained by an association between serum 1,25(OH)2 vitamin D and birth weight. This suggests a mechanism whereby the intra‐uterine environment might affect adult skeletal status.

Bone loss and inhaled glucocorticoids.

Abstract: Comparisons between patients with mild asthma and those with persistent asthma who are receiving high doses of inhaled glucocorticoids must include a careful evaluation of base-line characteristics.2 Table 2 of the article shows that the 28 women who did not use inhaled glucocorticoids weighed less than the 42 women who required more than eight puffs of inhaled glucocorticoids per day (mean [±SD], 140±20 vs. 154±40 lb), had nearly twice the level of physical activity (98±54 vs. 55±71 metabolic hours per week), had a lower incidence of past or current use of inhaled glucocorticoids (14±36 percent vs. 62±49 percent), and were less likely to have a history of oral-glucocorticoid use (36± 49 percent vs. 79±42 percent). All of these base-line differences appear to be statistically significant. It is as if we compared the bones of a busload of women soccer players with those of a busload of sedentary women. A relative lack of gravitational exercise can obviously contribute to bone loss, as shown most clearly in astronauts returning from zero gravity. Because the presence of persistent asthma limits one's ability to exercise, the resulting inactivity and other changes in variables reflecting the severity of asthma (e.g., weight, prednisone use, and airway inflammation) invalidate any reliable analysis of the effects of inhaled glucocorticoids on bone loss in groups that were so dissimilar at base line in the absence of a randomized scheme of treatment allocation.

The clinical grading of Raynaud's phenomenon and vibration-induced white finger: relationship between finger blanching and difficulties in using the upper limb.

Abstract: Objectives: To investigate the association between functional difficulties in using the upper limb and extent and frequency of finger blanching, and the merits of these markers in grading the severity of Raynaud's phenomenon (RP) and vibration-induced white finger (VWF) Methods: A questionnaire was mailed to a randomly selected community sample of 22,194 working-aged adults Information was collected on cold-induced finger blanching – including the extent and frequency of attacks in the past year, and on difficulty in using the upper limb in several everyday activities (eg doing up buttons, opening a tight screw-top jar, and pouring from a jug) Associations were examined by logistic regression with the resultant odds ratios converted into prevalence ratios (PRs) and 95% confidence intervals (95% CI) Results: Among 12,907 respondents were 1,359 who reported finger blanching and provided details of its extent and frequency Of these, 74% reported frequent attacks (50 or more over the year), and 12% reported extensive blanching (affecting nine or ten digits) After adjustment for potential confounders, subjects with finger blanching reported an excess of difficulties in using the limb Thus, in men with blanching the PR for difficulty with buttons was 47 (95% CI 39–58), and that for pouring from a jug was 38 (30–49) in comparison with men who had never had blanching Similar associations were found in women and in those men with exposure to hand-transmitted vibration The risk of reporting difficulties increased markedly with frequency of blanching – up to four- or fivefold in those with 50 or more attacks in the past year compared with those who had none; but differences by extent were less marked, with PRs ≤16 in those with nine to ten digits affected compared with one to two digits Conclusions: RP and VWF are both associated with difficulties in using the upper limb in everyday tasks Further investigation of potential reporting biases is warranted, but if the associations are causal, frequency of attacks influences impairment more than extent of disease More account may need to be taken of frequency of blanching episodes in assessing and in compensating subjects with VWF

Early Life Effects on Aging

Abstract: It is becoming increasingly apparent that the early environment both before birth and in infancy has profound effects on aging and long-term health. This is due to environmental programming whereby influences acting at critical periods of growth and development can permanently change structure and function with lifelong consequences. Many biological characteristics of the adult can be affected including the maximum size attained, the structure and function of different systems and the response to stimuli [1]. Nutrition is the most widely researched cause of environmental programming but other agents include physical factors such as temperature, light and noise.

The role of the growth hormone - insulin-like growth factor i axis in the aetiology of male idiopathic osteoporosis

Abstract: Objective. There is increasing evidence that nitric oxide (NO) may be important in the pathogenesis of systemic lupus erythematosus (SLE). One possible explanation for the differences observed in NO production between SLE patients and controls is variation in the 5' promoter region of the NOS2 gene, which controls NOS2 transcription. We studied the possible contribution of (CCTTT) n microsatellite polymorphism in the NOS2 promoter region to susceptibility to SLE and the clinical outcome of the disease. Methods. We analysed the distribution of the multiallelic (CCTTT) n repeat within the 5' upstream promoter region of the NOS2 gene, by a polymerase chain reaction-based method, in 117 SLE patients and 199 healthy subjects from southern Spain. Results. No statistically significant differences between SLE patients and healthy controls were observed with regard to the frequency of (CCTTT) n microsatellite repeats of any given length. Similarly, no associations were found with any of the clinical characteristics tested. Conclusion. We conclude that polymorphism in the NOS2 gene promoter does not play a relevant role in the pathogenesis of SLE in our population.