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Showing papers by "Cyrus Cooper published in 2001"


Journal ArticleDOI
17 Jan 2001-JAMA
TL;DR: The data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year, and the presence of prevalent vertebral fractures increases this risk.
Abstract: ContextVertebral fractures significantly increase lifetime risk of future fractures, but risk of further vertebral fractures in the period immediately following a vertebral fracture has not been evaluated.ObjectiveTo determine the incidence of further vertebral fracture in the year following a vertebral fracture.Design and SettingAnalysis of data from 4 large 3-year osteoporosis treatment trials conducted at 373 study centers in North America, Europe, Australia, and New Zealand from November 1993 to April 1998.SubjectsPostmenopausal women who had been randomized to a placebo group and for whom vertebral fracture status was known at entry (n = 2725).Main Outcome MeasureOccurrence of radiographically identified vertebral fracture during the year following an incident vertebral fracture.ResultsSubjects were a mean age of 74 years and had a mean of 28 years since menopause. The cumulative incidence of new vertebral fractures in the first year was 6.6%. Presence of 1 or more vertebral fractures at baseline increased risk of sustaining a vertebral fracture by 5-fold during the initial year of the study compared with the incidence in subjects without prevalent vertebral fractures at baseline (relative risk [RR], 5.1; 95% confidence interval [CI], 3.1-8.4; P<.001). Among the 381 participants who developed an incident vertebral fracture, the incidence of a new vertebral fracture in the subsequent year was 19.2% (95% CI, 13.6%-24.8%). This risk was also increased in the presence of prevalent vertebral fractures (RR, 9.3; 95% CI, 1.2-71.6; P = .03).ConclusionOur data indicate that women who develop a vertebral fracture are at substantial risk for additional fracture within the next year.

1,701 citations


Journal ArticleDOI
01 Dec 2001-Bone
TL;DR: Varying patterns of fracture incidence were observed with increasing age; whereas some fractures became more common in later life (vertebral, distal forearm, hip, proximal humerus, rib, clavicle, pelvis), others were more frequent in childhood and young adulthood.

1,017 citations


Journal ArticleDOI
TL;DR: Obesity interacted more than additively with each of Heberden's nodes, earlier knee injury and meniscectomy, giving strong support to public health initiatives aimed at reducing the burden of knee OA by controlling obesity.
Abstract: OBJECTIVES: To assess the risk of knee osteoarthritis (OA) attributable to obesity, and the interactions between obesity and other established causes of the disorder. METHODS: We performed a population-based case–control study in three health districts of England (Southampton, Portsmouth and North Staffordshire). A total of 525 men and women aged 45 y and over, consecutively listed for surgical treatment of primary knee OA, were compared with 525 controls matched by age, sex and family practitioner. RESULTS: Relative to a body mass index (BMI) of 24.0–24.9 kg/m2, the risk of knee OA increased progressively from 0.1 (95% CI 0.0–0.5) for a BMI<20 kg/m2 to 13.6 (95% CI 5.1–36.2) for a BMI of 36 kg/m2 or higher. If all overweight and obese people reduced their weight by 5 kg or until their BMI was within the recommended normal range, 24% of surgical cases of knee OA (95% CI 19–27%) might be avoided. As a risk factor for knee OA obesity interacted more than additively with each of Heberden's nodes, earlier knee injury and meniscectomy. In comparison with subjects of normal weight, without Heberden's nodes, and with no history of knee injury, people with a combination of obesity, definite Heberden's nodes and previous knee injury had a relative risk of 78 (95% CI 17–354). CONCLUSIONS: Our findings give strong support to public health initiatives aimed at reducing the burden of knee OA by controlling obesity. People undergoing meniscectomy or with a history of knee injury might be a focus for targeted advice.

469 citations


Journal ArticleDOI
TL;DR: The association between birth weight and adult body composition (bone, lean, and fat mass) in a cohort of 143 men and women, aged 70-75 yr, who were born in Sheffield, UK, and still lived there remained statistically significant after adjustment for age, sex, and adult height.
Abstract: Epidemiological studies suggest an association between weight in infancy and the risk of osteoporosis in later life. The extent to which this reflects environmental influences on skeletal growth and metabolism before birth or during the first year of postnatal life remains uncertain. We therefore examined the association between birth weight and adult body composition (bone, lean, and fat mass) in a cohort of 143 men and women, aged 70-75 yr, who were born in Sheffield, UK, and still lived there. The subjects underwent assessment of body composition by dual energy x-ray absorptiometry. Neonatal anthropometric information included birth weight, birth length, head size, and abdominal circumference. There were significant (P < 0.01) positive associations between birth weight and adult, whole body, bone, and lean mass among men and women. These were mirrored in significant (P < 0.03) associations between birth weight and bone mineral content at the lumbar spine and femoral neck. Associations between birth weight and whole body fat were weaker and not statistically significant. The associations of birth weight with whole body bone mineral and lean mass remained statistically significant after adjustment for age, sex, and adult height. They also remained significant after adjustment for cigarette smoking, alcohol consumption, dietary calcium intake, and physical inactivity. These data are in accord with previous observations that anthropometric measures in infancy are associated with skeletal size in adulthood. The presence of these relationships at birth adds to the evidence that bone and muscle growth may be programmed by genetic and/or environmental influences during intrauterine life.

370 citations


Journal ArticleDOI
11 Apr 2001-JAMA
TL;DR: Use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture, and use of statin dosage less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture.
Abstract: bral fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and 1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of 0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95% CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for durations of more than 12 months. Conclusion In this study, use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture. JAMA. 2001;285:1850-1855 www.jama.com

288 citations


Journal ArticleDOI
TL;DR: It is estimated that 71 000 adult men and women sustain a distal forearm fracture in Britain each year, compared with previous British surveys, where the pattern of incidence with age appears to have changed in women.
Abstract: Fracture of the distal forearm is one of the most frequent osteoporotic fractures. However, there are few data concerning its incidence in Britain. The aim of this study was to determine the incidence of distal forearm fracture in adult British men and women. Six centers took part in the study: Aberdeen, Hull, Nottingham, Portsmouth, Southampton and Truro. At each center, men and women aged 35 years and over with an incident distal forearm fracture and who resided in the catchment area of the main hospital at that center, were identified during a 12 month period. Incident fractures were identified from all possible point-of-contact sources in each locality, including accident and emergency records, fracture clinics, ward listings and plaster room registers. The population at risk was defined geographically according to postcode and the denominator obtained from 1991 census data mapped to these postcodes. During the 12 month study period, 3161 individuals with distal forearm fracture were identified. The age-adjusted incidence, age 35 years and over, was 36.8/10 000 person-years in women and 9.0/10 000 person-years in men. In women, the incidence of fracture increased progressively with age from the perimenopausal period, while in men the incidence remained low until later life. Fractures were more frequently left-sided (55.6%) and 19.4% of subjects required hospitalization. On the basis of these data we estimate that 71 000 adult men and women sustain a distal forearm fracture in Britain each year. Compared with previous British surveys the pattern of incidence with age appears to have changed in women, the reason for this is unclear.

282 citations


Journal ArticleDOI
TL;DR: The increasing burden of osteoporotic fractures urgently requires effective preventive strategies aimed at maximizing peak bone density, preventing excessive bone loss, and reducing the risk of falls.
Abstract: Osteoporotic fractures represent a significant public health burden, which is set to increase in future generations. Lifetime risk is high and lies within the range of 40% to 50% in women and 13% to 22% in men. Life expectancy is increasing worldwide, and it is estimated that the number of individuals aged 65 years and older will increase from the current figure of 323 million to 1555 million by the year 2050. These demographic changes alone can be expected to cause the number of hip fractures occurring worldwide to increase from 1.66 million in 1990 to 6.26 million in 2050. Based on current trends, hip fracture rates might increase in the United Kingdom from 46,000 in 1985 to 117,000 in 2016. The societal cost of these fractures is high; cost-effectiveness analyses showed cost-effectiveness in treating high-risk patients with antiresorptive drugs, particularly if administered as soon as possible after a first fragility fracture.

265 citations


Journal ArticleDOI
TL;DR: Observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.
Abstract: Evidence is accumulating that intrauterine growth and development may influence an individual's risk of osteoporosis in later adult life. To examine maternal and paternal influences on intrauterine skeletal growth, we used dual-energy X-ray absorptiometry to measure the neonatal bone mineral content (BMC) and bone mineral density (BMD) of 145 infants born at term. Independently of the infant's duration of gestation at birth, the birthweights of both parents and the height of the father were positively correlated with neonatal whole body BMC. Women who smoked during pregnancy had infants with a lower whole body BMC and BMD; overall, there was a 7.1-g (11%) average difference between whole body BMC of infants whose mothers did and did not smoke during pregnancy (p = 0.005). Women with thinner triceps skinfold thicknesses (reflecting lower fat stores) and those who reported a faster walking pace and more frequent vigorous activity in late pregnancy also tended to have infants with a lower BMC and BMD (p values for BMC; 0.02, 0.03, and 0.05, respectively). Maternal thinness and faster walking pace but not maternal smoking or parental birthweight also were associated with lower bone mineral apparent density (BMAD). The influences on skeletal growth and mineralization were independent of placental weight, a marker of the placental capacity to deliver nutrients to the fetus. These observations point to a combination of genetic and intrauterine environmental influences on prenatal skeletal development and suggest that environmental modulation, even at this early stage of life, may reduce the risk of osteoporosis in adulthood.

234 citations


Journal ArticleDOI
TL;DR: The data provide evidence against a strong association between neck pain and the examined occupational physical activities, and suggest that psychosocial factors may be more important.
Abstract: Objectives This study determined the prevalence of neck pain and its relation to occupation and occupational activities in the general population. Methods A questionnaire was mailed to 21 201 subjects aged 16-64 years, randomly selected from the patient registers of general practices in England, Scotland, and Wales, and to 993 subjects randomly selected from pay records of the armed services. Information was collected on occupation, workplace physical activities, neck pain in the past week and year, headaches, and feelings of tiredness or stress. Associations were explored by logistic regression, the resultant odds ratios being converted to prevalence ratios (PR). Results Among 12 907 respondents, 4348 and 2528 reported neck pain in past year (1421 with pain interfering with normal activities) and week, respectively. Symptoms were the most prevalent among male construction workers [past week and year 24% and 38% (pain interfering with activities 11%), respectively], followed by nurses, armed services members, and the unemployed. Generally the age-standardized prevalence of neck pain varied little by occupation. Work with arms above the shoulders for >1 hours/day was associated with a significant excess of symptoms [PR 1.3-1.7 (women) and 1.2-1.4 (men)], but no associations existed for typing, lifting, vibratory tool use, or professional driving. Stronger neck-pain associations were found with frequent headaches (PR 2.3-2.8) and frequent tiredness or stress (PR 2.2-2.5) than with occupational activities. Conclusions The data provide evidence against a strong association between neck pain and the examined occupational physical activities. They suggest that psychosocial factors may be more important.

178 citations


Journal ArticleDOI
TL;DR: P prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and ‘other’ limb fractures; however, they do not predict distal forearm fractures.
Abstract: The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

177 citations


Book ChapterDOI
01 Jan 2001
TL;DR: Osteoporosis is a complex, multifactorial chronic disorder, in which a variety of pathophysiologic mechanisms lead to a progressive reduction in bone strength and an increased risk of fracture.
Abstract: Publisher Summary The purposes of this review are to summarize epidemiologic data concerning the frequency of osteoporosis and osteoporosis-related fractures, and to determine the impact that the condition has on society. Osteoporosis is a complex, multifactorial chronic disorder, in which a variety of pathophysiologic mechanisms lead to a progressive reduction in bone strength and an increased risk of fracture. Although viewed for many years as a major public health problem, the exact burden posed by osteoporosis is only now being rigorously assessed. Whether the disorder is defined by low bone mass or by the occurrence of specific fractures, osteoporosis is clearly a common condition. Thus, a third of postmenopausal white women in the United States can be expected to have osteoporosis in the lumbar spine, proximal femur, or midradius at any point in time, while the lifetime risk of a hip, spine, or distal forearm fracture from age 50 years onward in this group approaches 40%. However, the relative absence of symptoms until fractures occur makes effective therapeutic intervention difficult to implement. The public health burden will worsen dramatically in future decades, and the evaluation of strategies to prevent these fractures, both in individuals and in populations, has become an urgent priority.

Journal ArticleDOI
TL;DR: The results suggest that genetic influences on adult bone size and mineral density may be modified by undernutrition in utero.
Abstract: Studies of the association between polymorphisms of the gene for the vitamin D receptor (VDR) and adult bone mass have been inconsistent, pointing to the possibility that gene--environment interactions may vary in different populations. We have demonstrated previously an association between weight in infancy (a marker of the intrauterine and early post-natal environment) and each of adult bone mass and VDR genotype. We therefore sought to extend these observations in an elderly UK cohort and to investigate the possibility of an interaction between these genetic and early environmental markers of later osteoporosis risk. One hundred and sixty-five men and 126 women aged 61--73 years for whom birth records were available underwent bone mass measurements at baseline and follow-up 4 years later. Whole-blood samples were obtained, DNA extracted using standard techniques and polymorphisms in the VDR and collagen type I alpha 1 (Col IA1) genes identified. In the cohort as a whole, there were no significant associations between either birthweight or VDR genotype and bone mineral density (BMD) or bone loss rate at either site. However, the relationship between lumbar spine BMD and VDR genotype varied according to birthweight. Among individuals in the lowest third of birthweight, spine BMD was higher (P = 0.01) in individuals of genotype 'BB' after adjustment for age, sex and weight at baseline. In contrast, spine BMD was reduced (P = 0.04) in individuals of the same genotype who were in the highest third of the birthweight distribution. A significant (P = 0.02) statistical interaction was also found between VDR genotype and birthweight as determinants of BMD. Similar but slightly weaker associations were seen between lumbar spine bone mineral content (BMC) and VDR genotype in the lowest birthweight tertile. When examining the relationship between Col1A1 genotype and bone mass, lumbar spine BMC was higher in individuals of genotype 'Ss' or 'ss' in the lowest birthweight tertile (P = 0.02) after adjustment for age, sex and weight at baseline. These results suggest that genetic influences on adult bone size and mineral density may be modified by undernutrition in utero.

Journal ArticleDOI
TL;DR: The results suggest that intrauterine diet restriction reduces life span in rats and contrasts with the well-recognised increase in life span produced by postweaning diet restriction.
Abstract: Background: Postweaning diet restriction is associated with prolongation of life span, reduced age-related disease and slower ageing. The effects of diet restriction imposed prior t


Journal ArticleDOI
TL;DR: It is concluded that use of keyboards was associated with discomfort at the shoulder and wrist or hand, but risk estimates were lower than generally reported in workplace surveys.
Abstract: The objective of this study was to examine the relationship between upper limb symptoms and keyboard use in a population survey. A questionnaire was mailed to 21,201 subjects aged 16-64 years, selected at random from the registers of 34 British general practices. Information was collected on occupation and on regular use of keyboards (for >4 h in an average working day), pain in the upper limbs and neck, numbness or tingling in the upper limbs, headaches, and feelings of tiredness or stress. Associations were explored by logistic regression, with the resultant odds ratios converted into prevalence ratios (PRs). Among 12,262 respondents, 4899 held non-manual occupations. These included 1871 regular users of keyboards (e.g. computer operators, data processors, clerks, administrators, secretaries and typists). Pain in the neck or upper limbs and sensory symptoms were common in the non-manual workers overall (with 1 week period prevalences of 30 and 15%, respectively), and were associated with older age, smoking, headaches and tiredness or stress. After adjustment for these factors, regular keyboard use was significantly associated with pain in the past week in the shoulders (PRs 1.2-1.4) and the wrists or hands (PR 1.4), but not with elbow pain or sensory symptoms over the same period, or with neck or upper limb pain that prevented normal activities in the past year. Disabling symptoms were somewhat less prevalent among symptomatic keyboard users than among other symptomatic workers. We conclude that use of keyboards was associated with discomfort at the shoulder and wrist or hand, but risk estimates were lower than generally reported in workplace surveys. Previous estimates of risk in the occupational setting may have been biased by shared expectations, concerns, or other aspects of illness behaviour.

Journal ArticleDOI
TL;DR: Restriction in range of movement was predictive of the presence of OA in these new presenters to primary care with hip pain, and the results of this examination could be used to inform decisions regarding radiography.
Abstract: Objectives. The primary objective was to test the hypothesis that new attenders in primary care with hip pain and radiographic osteoarthritis (OA) have a decreased range of movement compared with those without OA. The secondary objective was to define the planes of movement and thresholds that were the most discriminatory for OA. Methods. Men and women aged 40 yr and over presenting with a new episode of hip pain were recruited from 36 general practices across the UK. A standardized radiographic and clinical examination was performed. The discriminating ability of the range of movement for each plane to identify those with radiographic OA was assessed using receiver operating characteristic curves. Results. New hip pain attenders with radiographic OA had restricted movement at the hip compared with those without radiographic change. Restriction in internal rotation was the most predictive and flexion the least predictive of radiographic OA. At this cut-off, restriction in any single plane had a sensitivity of 86% for moderate and 100% for severe OA (specificity was 54 and 42% respectively). Restriction in all three planes had greater discrimination (sensitivity was 33% for mild to moderate OA and 54% for severe OA; specificity was 93 and 88% respectively). Conclusions. Restriction in range of movement was predictive of the presence of OA in these new presenters to primary care with hip pain, and the results of this examination could be used to inform decisions regarding radiography.

Journal ArticleDOI
TL;DR: In this paper, the authors presented guidelines for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society.
Abstract: The burden of non-vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non-vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one-third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non-vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

Journal ArticleDOI
TL;DR: The targeting of high-risk patients will be important for implementing preventative strategies in a cost-effective manner and to estimate the number of fractures attributed to oral corticosteroid use.
Abstract: Aims The objective of this study was to estimate the number of fractures attributed to oral corticosteroid use. Methods Information was obtained from the General Practice Research Database which contains medical records of general practitioners in the UK. The total number of corticosteroid-related fractures during a course of treatment was estimated using the formula for attributable risk among the exposed. Results A total of 244 235 patients was prescribed an oral corticosteroid. The rate of hip fractures increased exponentially with age in both males and females. The excess number of hip fracture cases among females aged 85 years or older using 7.5 mg prednisolone per day or more was 1.4 cases per 100 patients per year. About 47% of all hip and 72% of all vertebral fractures that occurred can be attributed to oral corticosteroid use. Among 10 000 female users of higher doses, 99.7 nonvertebral, 31.6 hip and 45.8 vertebral fractures can be attributed to use of oral corticosteroids. Conclusions The targeting of high-risk patients will be important for implementing preventative strategies in a cost-effective manner.

Journal ArticleDOI
TL;DR: In this paper, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33).
Abstract: bral fractures, the ORs were 1.01 (95% CI, 0.80-1.27), 0.59 (95% CI, 0.31-1.13), and 1.15 (95% CI, 0.62-2.14), respectively. Relative to nonuse, a statin dosage of less than 20 mg/d (standardized to simvastatin) was associated with an adjusted OR of fracture of 1.13 (95% CI, 0.96-1.33); this OR was 1.07 (95% CI, 0.82-1.38) at dosages of 20 to 39.9 mg/d and 0.85 (95% CI, 0.47-1.53) at dosages of 40 mg/d or more. The adjusted OR was 0.71 (95% CI, 0.50-1.01) for statin use durations of 0 to 3 months, 1.31 (95% CI, 0.87-1.95) for durations of 3 to 6 months, 1.14 (95% CI, 0.82-1.58) for durations of 6 to 12 months, and 1.17 (95% CI, 0.99-1.40) for durations of more than 12 months. Conclusion In this study, use of statins at dosages prescribed in clinical practice was not associated with a reduction in risk of fracture. JAMA. 2001;285:1850-1855 www.jama.com

Journal Article
TL;DR: Normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life and may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life.
Abstract: Epidemiological studies suggest that environmental influences such as maternal nutrition, programme skeletal growth during intrauterine and early postnatal life. However, the mechanism whereby the skeletal growth trajectory is modified remains unclear. We have addressed this using a rat model of maternal protein insufficiency to investigate the cellular mechanisms involved in the programming of bone development. The aims of this study were to determine whether colony formation (colony forming unit-fibroblastic, CFU-F), proliferation, and differentiation of bone marrow stromal cells from offspring of female rats maintained on normal (18% casein) or low (9% casein) protein was altered and, whether their responses to growth hormone (GH), 1,25(OH)(2)D3, and IGF-1 differed. Dams were fed an 18% casein (control) diet or 9% casein (low protein) diet from conception until the end of pregnancy. Offspring were then fed a normal protein diet until harvest at 8, 12, and 16 weeks after birth. At 8 weeks, total CFU-F and alkaline phosphatase-positive CFU-F were significantly (P < 0.01) reduced in the low protein group compared to controls. At 12 weeks, no significant differences were observed in colony formation. Modulation of osteoblast proliferation and differentiation by IGF-1 and GH was observed (P < 0.01) in the control group at 8 weeks and the low protein group at 12 weeks. Alkaline phosphatase specific activity was significantly decreased at 8 weeks (P < 0.001) in the low protein group. At 12 and 16 weeks this was reversed, with significantly increased specific activity in the low protein group. These results suggest that normal proliferation and differentiation of mesenchymal stem cells were delayed by maternal protein restriction during early life. Furthermore, these results suggest that, with skeletal maturity, \"catch-up\" or a physiological shift in bone cell activity was present in the low protein group. These alterations in mesenchymal stem cell function by the early environment may represent an important candidate mechanism for the programming of osteoporosis and associated consequences in later life.

Journal ArticleDOI
TL;DR: Use of hand-guided mowers, concrete breakers, chain saws, and jig saws was significantly associated with symptoms, and the risk of sensory symptoms was elevated in laborers and plant operatives.
Abstract: Background: Although some occupational sources of hand-transmitted vibration (HTV) have been extensively investigated, the risks associated with others are poorly characterized. Methods: A questionnaire was mailed to a community sample of 12,240 men aged 16- 64 years and 906 men from the armed forces. Questions covered current occupation, sources of HTV, numbness or tingling in the fingers in the past week, and finger blanching. In the 5,364 respondents who had been at work in the past week, associations between symptoms and exposures were examined by logistic regression, with odds ratios converted into prevalence ratios (PRs). Results: Altogether, 513 men (10%) reported cold-induced finger blanching and 769 (14%) sensory symptoms in the fingers. The risk of blanching was increased in builders (PR 2.4, 95% CI 1.0-5.2), carpenters and joiners (PR 1.9, 95% CI 1.0-3.4), motor mechanics (PR 2.3, 95% CI 1.1-4.6), and laborers (PR 2.8, 95% CI 1.3-6.0); while the risk of sensory symptoms was elevated in laborers (PR 4.0, 95% CI 2.3-6.6) and plant operatives (PR 3.5, 95% CI 1.9-5.9). Use of hand-guided mowers, concrete breakers, chain saws, and jig saws was significantly associated with symptoms. Conclusions: Little attention has been paid to the risks of vibration injury in construction workers, woodworkers, motor mechanics, and laborers, or to the risks from mowers, jig saws and several other common vibratory tools. These should be a focus for further investigation and preventive measures.

Journal ArticleDOI
TL;DR: Symptoms in manual workers who had been employed in manual occupations for a year or more and who reported the last week as being representative of their job accords with the pattern of transmission of HTV to the upper limb, although a confounding effect from other ergonomic risk factors cannot be discounted.
Abstract: Workers exposed to hand-transmitted vibration (HTV) often experience aches and pains in the upper limbs, but there have been few studies of the pattern and severity of symptoms, or their relationship to the estimated dose of vibration. As part of a wider survey of vibration, we mailed a questionnaire about exposures to HTV and pain in the neck and upper limbs to a sample of men selected at random from the registration lists of 34 British general practices and the pay records of the armed services. Analysis was confined to the 1856 male respondents who had been employed in manual occupations for a year or more and who reported the last week as being representative of their job. Inquiry was made about pain in the neck, shoulder, elbow and wrist/hand over the past week and past year (including pains that limited normal activity). Subjects were classed according to their lifetime exposure to HTV and their estimated average daily vibration dose [A(8) r.m.s.] in the previous week. A total of 283 men had a minimum estimated A(8) greater than a proposed action level of 2.8 m/s2, and in this group symptoms were about twice as prevalent as in manual workers who had never used vibratory tools. The excess risk was somewhat higher for distal sites than for proximal ones (e.g. the prevalence ratio for hand/wrist pain in the past week was 2.7 versus 1.8 for neck pain). This accords with the pattern of transmission of HTV to the upper limb, although a confounding effect from other ergonomic risk factors cannot be discounted.


Journal ArticleDOI
TL;DR: Patients on long-term oral corticosteroids have an increased risk of low bone mass and fragility fractures and quantitative ultrasound of the calcaneus may provide evidence of microarchitectural changes not detected by dual-energy X-ray absorptiometry (DXA).
Abstract: Patients on long-term oral corticosteroids have an increased risk of low bone mass and fragility fractures. Fracture risk rises soon after commencement of corticosteroid therapy and it is possible that these agents adversely influence bone architecture disproportionately to their effect on bone mass. The best means of assessing bone status in patients using corticosteroids remains uncertain, but quantitative ultrasound of the calcaneus may provide evidence of microarchitectural changes not detected by dual-energy X-ray absorptiometry (DXA). Patients with Crohn's disease have an increased risk of low bone mineral density (BMD), the etiology of which is multifactorial but includes corticosteroid use. We studied 118 consecutive patients with Crohn's disease, 21 of whom used continuous oral corticosteroids, 70 of whom were intermittent users, and 27 who had never used the drug. All patients received DXA of the lumbar spine, hip and calcaneus and quantitative ultrasound (QUS) of the calcaneus. The different techniques were compared using a femoral neck T-score < or = -1.5 as the threshold of corticosteroid-induced osteoporosis. When compared with the femoral neck T-score, there were no significant differences between the predictive values of lumbar spine DXA, calcaneal DXA or calcaneal QUS to identify low femoral neck BMD. However, the absolute T-score required to give similar discriminatory capacity to femoral neck T-score varied substantially (T= -0.81 to -1.5) between the different measurement techniques and sites.

Journal ArticleDOI
TL;DR: Case-control and cohort studies conducted in Norway, Sweden, Italy, Italy and Norway did not show an association between calcium intake and the risk of hip fractures, and recent epidemiologic studies suggest that calcium may be a threshold element.
Abstract: Calcium intake may affect bone accretion in childhood and adolescence, the development of peak bone mass in young adulthood, and the rate of bone loss in postmenopausal and elderly women. Some of the earliest evidence between calcium intake and fracture was from Europe. In Yugoslavia, the fracture rate was much higher and the bone mineral density was much lower in a population living in a low-calcium intake area than those living in a high-calcium intake area [14]. Recent epidemiologic studies conducted in Europe suggest that calcium may be a threshold element. In a population where the dietary calcium intake is high, little association was observed between calcium intake and bone mineral density. For instance, Cooper et al. did not find an association between the relative risk of hip fracture and calcium intake in the UK [15]. Such negative findings were replicated in a nested case-control study by Wickham et al. [16]. The results of other epidemiologic studies that have been conducted are mostly negative, and in the countries in which these studies were conducted, calcium intake was fairly high. Case-control and cohort studies conducted in Norway [17], Sweden [18], Italy [19] and Norway [20] did not show an association between calcium intake and the risk of hip fractures. The MEDOS study is a multicenter case-control study con

Journal ArticleDOI
TL;DR: Bisphosphonates represent a class of potent anti-resorptive agents, which have been shown to reduce fracture rate at vertebral and non-vertebral sites, and other agents such as calcitonin, PTH and fluoride are of less certain benefit in preventing fracture.
Abstract: The high rate of osteoporotic fracture in Western populations has resulted in a significant burden in terms of morbidity, mortality and health care costs. The use of DXA has made the diagnosis of osteoporosis easier and identified a subgroup of individuals who are at a higher risk of fracture. It is a useful tool in determining therapy in those at greatest risk of fracture. However, widespread use of such treatments is low and greater uptake remains an elusive goal. There are now many different treatments that reduce fracture rate, and can accompany lifestyle measures such as smoking cessation, diet and exercise. Dietary supplementation with calcium has been shown to reduce the risk of vertebral fracture, and the combination of calcium with vitamin D has been shown to reduce fracture at non-vertebral sites, including the hip. Although ERT, SERMs and tibolone all retard bone loss, prospective fracture prevention has only been shown for SERMs and then only at the spine. Bisphosphonates represent a class of potent anti-resorptive agents, which have been shown to reduce fracture rate at vertebral and non-vertebral sites. Other agents such as calcitonin, PTH and fluoride are of less certain benefit in preventing fracture.



Journal ArticleDOI
17 Mar 2001-BMJ
TL;DR: The medical community has been reluctant to endorse these products, principally glucosamine and chondroitin preparations in osteoarthritis, but recent lay publications enthusiastically promote the benefits of these products.
Abstract: EDITOR—Several recent lay publications enthusiastically promote the benefits of glucosamine and chondroitin preparations in osteoarthritis.1 This has led to a surge of interest among patients and spectacular success in the marketplace; sales in the United States approach $1bn. The medical community has been reluctant to endorse these products, principally …