Showing papers by "Cyrus Cooper published in 2004"
TL;DR: Fractures were more common among boys than girls, with peak incidences at 14 and 11 years of age, respectively, and at childhood peak, incidence rates were only surpassed later in life at 85 years of life among women and never among men.
Abstract: A population-based British cohort study, including 6% of the population, was used to derive age- and sex-specific incidence rates of fractures during childhood. Fractures were more common among boys than girls, with peak incidences at 14 and 11 years of age, respectively. At childhood peak, incidence rates were only surpassed later in life at 85 years of age among women and never among men. Introduction: Fractures account for 25% of accidents and injuries in childhood; however, the descriptive epidemiology of childhood fractures remains uncertain. Materials and Methods: Age- and sex-specific incidence rates for fractures at various skeletal sites were derived from the General Practice Research Database (a population-based British cohort containing computerized medical records of 7,000,000 residents) between 1988 and 1998. Results: A total of 52,624 boys and 31,505 girls sustained one or more fractures over the follow-up period, for a rate of 133.1/10,000 person-years. Fractures were more common in boys (161.6/10,000 person-years) than girls (102.9/10,000 person-years). The most common fracture in both sexes was that of the radius/ulna (30%). Fracture incidence was greater among boys than girls at all ages, with the peak incidence at 14 years of age among boys and 11 years of age among girls. Marked geographic variation was observed in standardized fracture incidence, with significantly (p Conclusions: Fractures are a common problem in childhood, with around one-third of boys and girls sustaining at least one fracture before 17 years of age. Rates are higher among boys than girls, and male incidence rates peak later than those among females. At their childhood peak, the incidence of fractures (boys, 3%; girls, 1.5%) is only surpassed at 85 years of age among women and never among men. The most common site affected in both genders is the radius/ulna. Studies to clarify the pathogenesis of these fractures, emphasizing bone fragility, are now required.
572 citations
TL;DR: Upper limb pain is common in the general population and is often associated with physical signs suggestive of specific upper-limb disorders, which have a substantial impact on physical function and use of health care.
Abstract: Objective: To determine the prevalence, interrelation, and impact of musculoskeletal disorders of the upper limb in the general population. Methods: A total of 9,696 randomly selected adults of working age were surveyed in a 2-stage cross-sectional study involving a screening questionnaire and a standardized physical examination in symptomatic subjects. Age- and sex-specific prevalence rates were estimated for several musculoskeletal disorders and for nonspecific pain in the upper limbs. The overlap and impact on daily activities and healthcare utilization were explored. Results: Among 6,038 first-stage responders, 3,152 reported upper limb symptoms and 1,960 were subsequently examined. Of subjects with pain, 44.8% had 1 or more specific soft-tissue disorders. Site-specific prevalence rates were as follows: shoulder tendinitis 4.5% among men and 6.1% among women; adhesive capsulitis 8.2% among men and 10.1% among women; lateral epicondylitis 1.3% among men and 1.1% among women; de Quervain's disease 0.5% among men and 1.3% among women; other tenosynovitis of the hand or wrist, 1.1% among men and 2.2% among women. Specific disorders tended to cluster (P Conclusion: Upper limb pain is common in the general population and is often associated with physical signs suggestive of specific upper-limb disorders. These disorders have a substantial impact on physical function and use of health care.
542 citations
TL;DR: Only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes.
Abstract: Objective: To assess whether use of oral glucocorticoids is associated with cardiovascular and cerebrovascular morbidity.
Design and setting: Nested case–control study within a cohort of patients (⩾ 50 years old) with at least one prescription for oral or non-systemic glucocorticoids. Data were from the general practice research database.
Patients: 50 656 patients were identified with a first record for ischaemic heart disease ( International classification of diseases , ninth revision (ICD-9) codes 410, 411, 413, and 414), ischaemic stroke or transient ischaemic attack (ICD-9 codes 430–436), or heart failure (ICD-9 code 428) between 1988 and 1998. One control was matched to each case by sex, age, general practice, underlying disease, and calendar time.
Main outcome measure: Odds ratio (OR) of cardiovascular or cerebrovascular events in patients using oral glucocorticoids compared with non-users.
Results: There was a significant association between ever use of oral glucocorticoids and any cardiovascular or cerebrovascular outcome (adjusted OR 1.25, 95% confidence interval (CI) 1.21 to 1.29). The association was stronger for current use of oral glucocorticoids than for recent or past use. Among current users, the highest ORs were observed in the group with the highest average daily dose, although the dose–response relation was not continuous. Current use was associated with an increased risk of heart failure (adjusted OR 2.66, 95% CI 2.46 to 2.87), which was consistent between patients with rheumatoid arthritis, patients with chronic obstructive pulmonary disease, and patients without either of the two conditions. Also, current use was associated with a smaller increased risk of ischaemic heart disease (OR 1.20, 95% CI 1.11 to 1.29).
Conclusions: Oral glucocorticoid use was identified as a risk factor for heart failure. However, the evidence remains observational and only a randomised controlled trial of glucocorticoid treatment versus other disease modifying agents is likely to distinguish the importance of the underlying disease activity from its treatment in predicting cardiovascular outcomes.
431 citations
TL;DR: In this article, the relationship between bone mineral density (BMD) change and fracture risk in postmenopausal osteoporotic women receiving antiresorptive treatment was analyzed.
225 citations
TL;DR: The consistently reported positive relation between birth weight and adult body mass index may reflect prenatal and maternal influences on fat-free mass rather than on fat mass in older people, suggesting the postnatal environment may be more influential than prenatal factors in the development of obesity in later life.
196 citations
TL;DR: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.
Abstract: Background: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). Methods: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. Results: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. Conclusion: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.
181 citations
TL;DR: Birth weight is associated with sarcopenia in men and women, independently of adult height and weight, and the influence of infant growth on long-term muscle strength appears to be mediated through adult size.
Abstract: Background. Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia. Methods. We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size. Results. Grip strength was most strongly associated with birth weight in men (r ¼ 0.19, p , .001) and women (r ¼ 0.16, p , .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results. Conclusions. Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.
173 citations
01 Jan 2004
TL;DR: Significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD is described.
Abstract: Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.
137 citations
TL;DR: In this article, the role of the LRP5 gene in determining normal population variation of BMD was examined using family-based and case-control approaches, and a significant association and suggestive linkage between LRP-5 gene polymorphisms and BMD in >900 individuals with a broad range of bone phenotypes was found.
Abstract: Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD.
127 citations
University of Manchester1, University of Lübeck2, Southampton General Hospital3, Ruhr University Bochum4, Lund University5, National and Kapodistrian University of Athens6, University of Aberdeen7, Humboldt State University8, University of Göttingen9, Charles University in Prague10, Royal Cornwall Hospital11
TL;DR: Although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.
Abstract: Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR]=1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR=1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR=3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR=1.2; 95%CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR=1.6; 95%CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.
120 citations
Journal Article•
TL;DR: Heavy weight in the past appears to represent a risk factor for knee OA among women in Japan, as reported in Britain, although characteristic activities for work vary.
Abstract: OBJECTIVE: Risk of knee osteoarthritis (OA) associated with constitutional factors, history of joint injuries, and occupational factors was assessed in a case-control study among women in Japan. Results were contrasted with a comparable study in Britain. METHODS: The study covered 3 health districts in Japan. Cases were women aged >/= 45 years old, diagnosed with knee OA by orthopedic physicians utilizing radiography. No cases displayed established causes of secondary OA. Controls selected randomly from the general population were individually matched to each case for age, sex, and residential district. Subjects were interviewed using structured questionnaires to determine medical history, including history of joint injury, physical activity, socioeconomic factors, and occupation. Height and weight were measured. RESULTS: Interviews were obtained from 101 female cases and controls. The highest third of heaviest body weight in the past [high (> 62.0 kg) vs low (
TL;DR: Bone density was higher in newly diagnosed diabetic subjects, with relationships stronger in women than men (p<0.001), and hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.
Abstract: Previous studies have suggested that the high bone density often observed in type 2 diabetic patients may be explained by insulin resistance. We explored this hypothesis in the Hertfordshire Cohort Study. A total of 465 men and 444 women aged 59 to 71 years and with no prior diagnosis of diabetes attended a clinic where a glucose tolerance test was performed and bone density measured at the femoral neck and lumbar spine. Biochemical markers of bone turnover (serum osteocalcin and urinary mean c-terminal cross-linking telopeptide of type II collagen) were measured in 163 men. According to WHO criteria, 83 men and 134 women were diagnosed with impaired glucose tolerance and a further 33 men and 32 women were diagnosed as having type 2 diabetes. Bone density was higher in newly diagnosed diabetic subjects, with relationships stronger in women (p<0.001) than men (p<0.05) and attenuated by adjustment for body mass index. In both sexes, we observed positive correlations between the total femur and femoral neck bone mineral density with measures of insulin resistance (r=0.17–0.22), with stronger results observed in women. These relationships did not apply after adjustment for body mass index. Glucose status did not lead to differences in osteocalcin level or c-terminal cross-linking telopeptide of type II collagen levels. Our findings suggest that hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.
TL;DR: The DASH was a more discriminating measure than the GAT in assessing upper limb ability in this sample population of patients with early rheumatoid arthritis, and handgrip strength is an accurate indicator ofupper limb ability.
Abstract: Objective: To explore the relationship in individuals with early rheumatoid arthritis (RA) between self-report upper limb function, therapist-assessed upper limb function and therapist-assessed measures of structural impairment (handgrip, active hand motion and metacarpophalangeal (MCP) joint ulnar deviation).Design: Thirty-six patients with early RA were recruited across seven outpatient occupational therapy departments.Outcome measures: Upper limb functional activity and ability was measured using the Disability of the Arm, Shoulder and Hand (DASH) questionnaire and the Grip Ability Test (GAT). Upper limb impairment was assessed by bilateral power handgrip using the MIE Digital Grip Analyser, goniometry measures of bilateral metacarpophalangeal (MCP) joint ulnar deviation and bilateral active motion of the wrist.Results: Strong correlations (>0.7) were seen between the self-report DASH questionnaire and the therapist-rated GAT assessment. Bilateral power handgrips were also strongly correlated with both...
Ghent University Hospital1, Katholieke Universiteit Leuven2, University of Florence3, Southampton General Hospital4, University of Oxford5, Amgen6, Université catholique de Louvain7, University of Sheffield8, Eli Lilly and Company9, Oregon Health & Science University10, University of Cologne11, Geneva College12
TL;DR: Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds.
TL;DR: Being female, unemployed, a blue‐collar worker, or a smoker were independent risk factors for such extensive pain, but the strongest association was with psychological ill‐health.
Abstract: Little is known about the distribution and determinants of pain at multiple sites in the neck and upper limb. To investigate the prevalence, pattern, and clustering of such pains and the association of extensive involvement with putative risk factors, we mailed a questionnaire to a community sample of 9696 working-aged adults. Age-sex specific prevalence rates for pain were estimated and the frequency of bilateral involvement, pairwise overlap at different sites, and extent to which reports clustered within individuals were explored. Associations of multi-site involvement with age, gender, psychological health, smoking, and employment status were assessed by logistic regression. Among 6038 responders, 2657 reported at least a day of neck or upper limb pain in the past 7 days, including 1843 whose symptoms rendered normal activities difficult or impossible. Pain was frequently bilateral or in the dominant arm. Significant associations were seen for pain at anatomically adjacent sites. Pain affecting every site considered (neck, shoulders, elbows, wrists/hands) was far more common than might be expected if each site were statistically independent (observed/expected ratio 8750). Being female, unemployed, a blue-collar worker, or a smoker were independent risk factors for such extensive pain, but the strongest association was with psychological ill-health (odds ratio for worst vs. best third of the SF-36 low vitality score, 30.3, 95% CI 7.1-129.0). Neck and upper limb pain commonly cluster, and frequently display symmetry and adjacent patterns of involvement. Extensive neck and upper limb pain is far more strongly associated with poor mental vitality than localised pain.
TL;DR: These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility and carry a higher absolute risk for hip fracture than spinal fractures in contrast to women.
Abstract: Based on data searches and life-table analyses, we determined the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture after sustaining a Colles' or spine fracture and searched for potential gender-related differences. In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility.
TL;DR: Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone, and this excess risk disappeared after adjustment for indicators of asthma severity.
Abstract: Inhaled corticosteroids are widely used in the long-term management of asthma in children. Data on the relationship between inhaled corticosteroid therapy and osteoporotic fracture are inconsistent. We address this issue in a large population-based cohort of children aged 4-17 years in the UK (the General Practice Research Database). The incidence rates of fracture among children aged 4-17 years taking inhaled corticosteroids (n=97,387), taking bronchodilators only (n=70 984) and a reference group (n=345,758) were estimated. Each child with a non-vertebral fracture (n=23,984) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. Fracture incidence was increased in children using inhaled corticosteroids, as well as in those receiving bronchodilators alone. With an average daily beclomethasone dose of 200 microg or less, the crude fracture risk relative to nonusers was 1.10 [95% confidence interval (CI), 0.96-1.26]; with dosage of 201-400 microg, it was 1.23 (95% CI, 1.08-1.39); and with dosages over 400 microg, it was 1.36 (95% CI, 1.11-1.67). This excess risk disappeared after adjustment for indicators of asthma severity. The increased risk of fracture associated with use of inhaled corticosteroids is likely to be the result of the underlying illness, rather than being directly attributable to inhaled corticosteroid therapy.
TL;DR: Serum ALP may be a good indicator of Paget's disease in epidemiologic studies and was an excellent marker of the disease but the majority of those affected had normal ALP.
Abstract: Serum ALP may be a good indicator of Paget's disease in epidemiologic studies. Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP. Introduction: Evidence from radiographic surveys of limited skeletal sites has shown that Paget's disease of bone (PDB) is common in the elderly and has a distinct geographic variation. There is no information, however, about the relation of serum alkaline phosphatase (ALP) activity, a marker of the disease, and its prevalence in the population. Materials and Methods: We analyzed data from a well-defined Dutch population cohort (the Rotterdam study) with the following specific aims: (1) to assess the relationship between serum ALP activity and prevalence of radiographically diagnosed PDB, (2) to estimate the overall prevalence of the disease in the Netherlands, and (3) to assess the appearance of the disease with time. Using a nested case-control design, subjects with an increased serum ALP and normal serum liver enzymes were matched for gender and age (1 to 6) with subjects with normal serum ALP activity. Radiographs of the thoracic and lumbar spine, pelvis, proximal femurs, knees, wrists, and hands were taken. Results and Conclusions: PDB was diagnosed in 20.5% of subjects with elevated serum ALP activity and in 2.3% in those with normal serum ALP activity, increasing with age in both groups. The relative risk (RR) for PDB in the presence of raised serum ALP activity was 10.9 (95% CI, 4.8, 24.9). The estimated prevalence of PDB in the population was 3.6%, and the large majority (about 86%) had normal serum ALP activity, contrasting findings in bone clinics where the opposite is the case. Finally, in subjects with normal and raised serum ALP activity but no PDB at baseline, radiographs taken 6-9 years later showed no evidence of the disease. This study demonstrated that serum ALP activity is a sensitive marker of PDB in men and women >55 years of age, but the majority of those affected have normal serum ALP activity.
01 Jan 2004
TL;DR: This article reviewed the patterns of occurrence of Paget's disease according to age, gender, ethnic group, and geographical location, and discussed the aetiological implications of the epidemiological data.
Abstract: Summary Paget’s Disease of Bone (PDB), first described by James Paget in 1877, is characterized by rapid bone remodeling and the formation of bone that is structurally abnormal. The aetiology is unknown, although both genetic and environmental factors have been implicated. PDB is more prevalent among men than women, and prevalence increases progressively with age, reaching around 15% in elderly men in Britain. In this article, we review the patterns of occurrence of Paget’s disease according to age, gender, ethnic group, and geographical location. We also discuss recent work documenting mortality rates and secular trends for the disorder over the last two decades, and discuss the aetiological implications of the epidemiological data.
TL;DR: It is suggested that common diversity in the GH1 region predisposes to osteoporosis via effects on the level of GH expression and the interaction with infant weight suggests that early environment may influence the effect of GH1 genotype on bone loss.
Abstract: Epidemiological studies point to the importance of gene-environment interactions during early life as determinants of later osteoporosis and fracture. We examined associations between common single nucleotide polymorphisms in the human GH (GH1) gene and weight in infancy, adult bone mass and bone loss rates, and circulating GH profiles. Two hundred and five men and 132 women, aged 61–73 yr, in the Hertfordshire Cohort Study were included; bone mineral density was measured by dual energy x-ray absorptiometry over 4 yr. Twenty-four-hour circulating GH profiles were constructed in a subset of 71 men and women. Genomic DNA was examined for two single nucleotide polymorphisms in the GH gene (one in the promoter region and one in intron 4). Homozygotes at loci GH1 A5157G and T6331A displayed low baseline bone density and accelerated bone loss; there was also a significant (P = 0.04) interaction among weight at 1 yr, GH1 genotype, and bone loss rate. There was a graded association between alleles and circulating...
TL;DR: A systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome, found that the effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain.
Abstract: Summary
background The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome.
methods We searched electronic databases to identify articles, abstracts and conference proceedings to March 2002. We also checked reference lists in included studies and expert reviews. Two reviewers independently extracted the data on study design and change in BMD. The results of individual trials were combined by fixed effects model meta-analysis using weighted mean difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and other sites.
findings Eighteen trials that included 700 patients met the inclusion criteria. Maximum follow-up was for 12 weeks (1 trial), 6 months (14 trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial). Reporting quality of both study design and results was poor. Ten trials (458 subjects) were included in the meta-analysis. We excluded those eight trials from which sufficient data could not be extracted. We found a mean change in BMD, at the lumbar spine with GH treatment, of 0·01 g/cm2 after 6 and 12 months, 0·02 g/cm2 after 18 months and 0·03 g/cm2 after 24 months. Statistical significance at the 0·05 level was just achieved at 6 and 12 months but was significant at 18 and 24 months. These changes are small and may be influenced by bias.
conclusion There is evidence of a small effect of GH replacement on bone mineral density in adults with GH deficiency. The clinical importance of this is uncertain.
TL;DR: Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture, and further work is needed to develop novel therapeutic and preventative strategies to reduce the burden of osteOPorotic fractures in the population.
Abstract: Undernutrition and other adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the GH/IGF-1 and HPA axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have suggested that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Finally, childhood growth rates have been directly linked to the risk of hip fracture many decades later. Further work is needed to use this approach to develop novel therapeutic and preventative strategies to reduce the burden of osteoporotic fractures in the population.
TL;DR: The results suggest that the relationship between plasma leptin and bone mass is similar in men and women and that it is mediated through the strong association of both variables with adiposity, rather than through a direct association of leptin on bone cell function.
Abstract: Several studies have shown an association between circulating leptin concentration and bone mineral density, but most studies are cross-sectional in design and report findings in women only. We performed a population-based longitudinal study relating baseline plasma leptin concentration to bone mass at the lumbar spine and femoral neck and to change in bone density at these sites over four years in a cohort of 302 men and women aged 60–75 years born and still resident in Hertfordshire, UK. Baseline plasma leptin concentration was strongly positively correlated with body mass index (men: r = 0.71, P < 0.000l; women: r = 0.79, P < 0.0001) and with bone mineral content, bone mineral density, and volumetric bone mineral density at all sites (r = 0.24–0.36, P < 0.001) in both sexes; associations with change in bone density were markedly weaker and inconsistent. Adjustment for adult lifestyle determinants of osteoporosis made little difference to our results, but the associations of leptin with bone mass were no longer significant after adjustment for body mass index. These results suggest that the relationship between plasma leptin and bone mass is similar in men and women and that it is mediated through the strong association of both variables with adiposity, rather than through a direct association of leptin on bone cell function.
TL;DR: The health care costs of symptomatic vertebral fractures occurring in women aged 50 years and above in the UK are examined to determine whether these costs need to be set against the costs of fracture prevention.
TL;DR: GH-CSH genotype adds substantially to, but does not account for, the associations between low body weight, at birth and in infancy, and the metabolic syndrome, while birth weight and 1-yr weight associations with metabolic syndrome traits were independent of the CSH1.01 effects.
Abstract: Low rates of fetal and infant growth are associated with the metabolic syndrome and cardiovascular disease in later life. We investigated common genetic variation in the GH-CSH gene cluster on chromosome 17q23 encoding GH, placental lactogens [chorionic somatomammotropins (CSH)], and placental GH variant in relation to fetal and infant growth and phenotypic features of the metabolic syndrome in subjects aged 59-72 yr from Hertfordshire, UK. Allele groups T, D1, and D2 of a locus herein designated CSH1.01 were examined in relation to GH-CSH single nucleotide polymorphisms and to specific phenotypes. Average birth weights were similar for all genotype groups. Men with T alleles were significantly lighter at 1 yr of age, shorter as adults, and had higher blood pressures, fasting insulin (T/T 66% higher than D2/D2) and triglyceride concentrations, and insulin and glucose concentrations during a glucose tolerance test. Birth weight and 1-yr weight associations with metabolic syndrome traits were independent of the CSH1.01 effects. Common diversity in GH-CSH correlates with low 1-yr weight and with features of the metabolic syndrome in later life. GH-CSH genotype adds substantially to, but does not account for, the associations between low body weight, at birth and in infancy, and the metabolic syndrome.
TL;DR: Although Indo-Asian women appear to have lower spinal BMD than Caucasians, these differences disappear when BMAD values are calculated, suggesting lower BMD values in Asians may be a size-related artefact.
Abstract: Background: Indo-Asian immigrants are known to be at high risk of metabolic bone disease, but the prevalence of osteoporosis in this population is unknown.
Aim: To compare the bone mineral at the lumbar spine and femoral neck of Indo-Asian immigrant women with that of age-matched Caucasian women.
Design: Retrospective analysis.
Methods: Women of Indo-Asian origin referred for bone density scans in the last five years were identified. The skeletal status of each was compared with an age-matched Caucasian control for bone mineral content (BMC), bone mineral density (BMD) and bone mineral apparent density (BMAD) at the lumbar spine and femoral neck, and hip axis length was measured.
Results: At the lumbar spine, Indo-Asians had a significantly lower BMD than Caucasians (0.834 vs. 0.913, p = 0.008), but there was no significant difference when BMAD values were calculated (0.123 vs. 0.122). At the femoral neck, there was no difference in BMD (0.728 vs. 0.712, p = 0.5), and BMAD values were significantly higher among Indo-Asians than Caucasians (0.393 vs. 0.319, p = 0.022). Hip axis length was significantly shorter among Indo-Asian women (10.3 vs. 10.7, p = 0.009).
Discussion: Although Indo-Asian women appear to have lower spinal BMD than Caucasians, these differences disappear when BMAD values are calculated. While BMD is an areal density, not taking into account the ‘depth’ of the bone, BMAD is an estimation of volumetric density. Hence lower BMD values in Asians may be a size-related artefact. Longitudinal studies may be required to evaluate the use of BMD as a marker for fracture risk in this population.
Journal Article•
Journal Article•