Growth hormone predicts bone density in elderly women.

Evidence is accumulating that the risk of osteoporosis may be influenced by environmental factors during intrauterine and early postnatal life; such programming might be mediated through modification of the GH/IGF-1 axis during critical periods in its development. To address this issue, we explored the relationships among birth weight, circulating GH profile, bone density, and bone loss rate in a group of British women. The study population consisted of 38 women 60-75 years old resident in Hertfordshire for whom detailed birth records were available. Twenty-four-hour circulating GH profiles were obtained during an inpatient stay on a metabolic ward, after an overnight rest. The circulating profile of GH was characterised by estimating the peak, median, trough, and total concentrations from 72 samples measured sequentially over 24 h in each subject. Bone mineral density was assessed at the lumbar spine and femoral neck at baseline and at follow-up 4 years later. Lumbar spine bone mineral content (BMC) and density (BMD) were positively associated with all measures of GH concentration, although relationships were strongest for BMC with trough GH (r = 0.47, P < 0.01). Associations persisted after adjustment for age, body mass index, smoking, alcohol consumption, physical activity, and osteoarthritis score in multiple regression models. However, associations of GH concentration with femoral neck BMC were weak, and there was no association between any measure of GH concentration and bone loss at either site. Total (integrated) daily GH concentration tended to increase (P = 0.08) with rising birth weight, while IGF-1 concentration fell (P = 0.05) with rising birth weight, suggesting a role for the GH/IGF-1 axis in the programming of adult bone mass among women.

Neonatal anthropometry: the thin-fat Indian baby. The Pune Maternal Nutrition Study.

OBJECTIVE: To examine body size and fat measurements of babies born in rural India and compare them with white Caucasian babies born in an industrialised country. DESIGN: Community-based observational study in rural India, and comparison with data from an earlier study in the UK, measured using similar methods. SUBJECTS: A total of 631 term babies born in six rural villages, near the city of Pune, Maharashtra, India, and 338 term babies born in the Princess Anne Hospital, Southampton, UK. MEASUREMENTS: Maternal weight and height, and neonatal weight, length, head, mid-upper-arm and abdominal circumferences, subscapular and triceps skinfold thicknesses, and placental weight. RESULTS: The Indian mothers were younger, lighter, shorter and had a lower mean body mass index (BMI) (mean age, weight, height and BMI: 21.4 y, 44.6 kg, 1.52 m, and 18.2 kg/m(2)) than Southampton mothers (26.8 y, 63.6 kg, 1.63 m and 23.4 kg/m(2)). They gave birth to lighter babies (mean birthweight: 2.7 kg compared with 3.5 kg). Compared to Southampton babies, the Indian babies were small in all body measurements, the smallest being abdominal circumference (s.d. score: -2.38; 95% CI: -2.48 to -2.29) and mid-arm circumference (s.d. score: -1.82; 95% CI: -1.89 to -1.75), while the most preserved measurement was the subscapular skinfold thickness (s.d. score: -0.53; 95% CI: -0.61 to -0.46). Skinfolds were relatively preserved in the lightest babies (below the 10th percentile of birthweight) in both populations. CONCLUSIONS: Small Indian babies have small abdominal viscera and low muscle mass, but preserve body fat during their intrauterine development. This body composition may persist postnatally and predispose to an insulin-resistant state.

Does birth weight predict adult serum cortisol concentrations? Twenty-four-hour profiles in the United kingdom 1920-1930 Hertfordshire Birth Cohort.

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.

Intrauterine programming of adult body composition.

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.

Occupational physical activities and osteoarthritis of the knee.

OBJECTIVE: To assess the risk of knee osteoarthritis (OA) associated with kneeling, squatting, and other occupational activities. METHODS: We compared 518 patients who were listed for surgical treatment of knee OA and an equal number of control subjects from the same communities who were matched for sex and age. Histories of knee injury and occupational activities were ascertained at interview, height and weight were measured, and the hands were examined for Heberden's nodes. Data were analyzed by conditional logistic regression. RESULTS: After adjustment for body mass index (BMI), history of knee injury, and the presence of Heberden's nodes, risk was elevated in subjects who reported prolonged kneeling or squatting (odds ratio [OR] 1.9; 95% confidence interval [95% CI] 1.3-2.8), walking >2 miles/day (OR 1.9; 95% CI 1.4-2.8), and regularly lifting weights of at least 25 kg (OR 1.7; 95% CI 1.2-2.6) in the course of their work. The risks associated with kneeling and squatting were higher in subjects who also reported occupational lifting, and appeared to interact multiplicatively with the risk conferred by obesity. People with a BMI of > or =30 kg/m2 whose work had entailed prolonged kneeling or squatting had an OR of 14.7 (95% CI 7.2-30.2), compared with subjects with a BMI <25 kg/m2 who were not exposed to occupational kneeling or squatting. CONCLUSION: There is now strong evidence for an occupational hazard of knee OA resulting from prolonged kneeling and squatting. One approach to reducing this risk may lie in the avoidance of obesity in people who perform this sort of work.

Risk factors for the incidence and progression of radiographic knee osteoarthritis.

OBJECTIVE: Preventive strategies against knee osteoarthritis (OA) require a knowledge of risk factors that influence the initiation of the disorder and its subsequent progression. This population-based longitudinal study was performed to address this issue. METHODS: Ninety-nine men and 255 women aged > or =55 years had baseline interviews and weight-bearing knee radiographs in 1990-1991. Repeat radiographs were obtained in 1995-1996 (mean followup duration 5.1 years, median age at followup 75.8 years). Risk factors assessed at baseline were tested for their association with incident and progressive radiographic knee OA by logistic regression. RESULTS: Rates of incidence and progression were 2.5% and 3.6% per year, respectively. After adjusting for age and sex, the risk of incident radiographic knee OA was significantly increased among subjects with higher baseline body mass index (odds ratio [OR] 18.3, 95% confidence interval [95% CI] 5.1-65.1, highest versus lowest third), previous knee injury (OR 4.8, 95% CI 1.0-24.1), and a history of regular sports participation (OR 3.2, 95% CI 1.1-9.1). Knee pain at baseline (OR 2.4, 95% CI 0.7-8.0) and Heberden's nodes (OR 2.0, 95% CI 0.7-5.7) were weakly associated with progression. Analyses based on individual radiographic features (osteophyte formation and joint space narrowing) supported differences in risk factors for either feature. CONCLUSION: Most currently recognized risk factors for prevalent knee OA (obesity, knee injury, and physical activity) influence incidence more than radiographic progression. Furthermore, these factors might selectively influence osteophyte formation more than joint space narrowing. These findings are consistent with knee OA being initiated by joint injury, but with progression being a consequence of impaired intrinsic repair capacity.

Fluoride in drinking water and risk of hip fracture in the UK: a case-control study.

BACKGROUND: Although the benefits of water fluoridation for dental health are widely accepted, concerns remain about possible adverse effects, particularly effects on bone. Several investigators have suggested increased rates of hip fracture in places with high concentrations of fluoride in drinking water, but this finding has not been consistent, possibly because of unrecognised confounding effects. METHODS: We did a case-control study of men and women aged 50 years and older from the English county of Cleveland, and compared patients with hip fracture with community controls. Current addresses were ascertained for all participants; for those who agreed to an interview and who passed a mental test, more detailed information was obtained about lifetime residential history and exposure to other known and suspected risk factors for hip fracture. Exposures to fluoride in water were estimated from the residential histories and from information provided by water suppliers. Analysis was by logistic regression. FINDINGS: 914 cases and 1196 controls were identified, of whom 514 and 527, respectively, were interviewed. Among those interviewed, hip fracture was strongly associated with low body-mass index (p for trend <0.001) and physical inactivity (p for trend <0.001). Estimated average lifetime exposure to fluoride in drinking water ranged from 0.15 to 1.79 ppm. Current residence in Hartlepool was a good indicator for high lifetime exposure to fluoride. After adjustment for potential confounders, the odds ratio associated with an average lifetime exposure to fluoride > or =0.9 ppm was 1.0 [95% CI 0.7-1.5]. INTERPRETATION: There is a low risk of hip fracture for people ingesting fluoride in drinking water at concentrations of about 1 ppm. This low risk should not be a reason for withholding fluoridation of water supplies.

Occupational lifting is associated with hip osteoarthritis: a Japanese case-control study.

OBJECTIVE: Hip osteoarthritis (OA) is a frequent cause of pain and disability in Western countries, but the disorder is less common in Japan. A case-control study in Britain found obesity, hip injury, and occupational lifting to be associated with hip OA among men and women. However, there are few epidemiological studies concerning factors associated with hip OA in Japan. We performed a comparable case-control study of the disorder in Japan, and contrasted the findings with those from Britain. METHODS: The study was carried out in 2 health districts in Wakayama Prefecture, Japan. Cases were men and women aged > or = 45 years listed for total hip arthroplasty due to OA over one year, and who did not have an established cause of secondary OA (e.g., rheumatoid arthritis, ankylosing spondylitis). For each case, a control was selected randomly from the general population and was individually matched to the case for age, sex, and district of residence. Cases and controls were interviewed with a structured questionnaire about medical history, physical activity, socioeconomic factors, and occupation. Measurements were made of height and weight. RESULTS: One hundred fourteen cases (103 women, 11 men) were compared with 114 controls. We found no relationship between obesity and hip OA (OR = 1.0, 95% CI 0.5-1.9; highest vs lowest thirds of distribution of body mass index). There was, however, a statistically significant association between occupational lifting and hip OA, such that regular lifting of 25 kg in the individual's first job (OR = 3.6, 95% CI 1.3-9.7) or of 50 kg in their main job (OR = 4.0, 95% CI 1.1-14.2) was associated with increased risk of hip OA. These associations remained after adjustment for potential confounding variables. In contrast, those subjects who spent > 2 h each day sitting during their first job were significantly less likely to have the disorder (crude OR = 0.5, 95% CI 0.3-0.9). This association also remained statistically significant after adjustment for potential risk factors. CONCLUSION: Our findings support the hypothesis that occupational physical activity, particularly the lifting of very heavy loads in the workplace at regular intervals, predisposes to hip OA in both Britain and Japan. The lack of association between obesity or hand involvement and hip OA in Japan suggests that the contribution of constitutional and mechanical risk factors to this disorder might differ in different populations. However, attention to manual handling in the workplace would appear an important aspect of preventive strategies against hip OA in Western and Oriental populations.

The Southampton examination schedule for the diagnosis of musculoskeletal disorders of the upper limb.

OBJECTIVES: Following a consensus statement from a multidisciplinary UK workshop, a structured examination schedule was developed for the diagnosis and classification of musculoskeletal disorders of the upper limb. The aim of this study was to test the repeatability and the validity of the newly developed schedule in a hospital setting. METHOD: 43 consecutive referrals to a soft tissue rheumatism clinic (group 1) and 45 subjects with one of a list of specific upper limb disorders (including shoulder capsulitis, rotator cuff tendinitis, lateral epicondylitis and tenosynovitis) (group 2), were recruited from hospital rheumatology and orthopaedic outpatient clinics. All 88 subjects were examined by a research nurse (blinded to diagnosis), and everyone from group 1 was independently examined by a rheumatologist. Between observer agreement was assessed among subjects from group 1 by calculating Cohen's kappa for dichotomous physical signs, and mean differences with limits of agreement for measured ranges of joint movement. To assess the validity of the examination, a pre-defined algorithm was applied to the nurse's examination findings in patients from both groups, and the sensitivity and specificity of the derived diagnoses were determined in comparison with the clinic's independent diagnosis as the reference standard. RESULTS: The between observer repeatability of physical signs varied from good to excellent, with kappa coefficients of 0.66 to 1.00 for most categorical observations, and mean absolute differences of 1.4 degrees -11.9 degrees for measurements of shoulder movement. The sensitivity of the schedule in comparison with the reference standard varied between diagnoses from 58%-100%, while the specificities ranged from 84%-100%. The nurse and the clinic physician generally agreed in their diagnoses, but in the presence of shoulder capsulitis the nurse usually also diagnosed shoulder tendinitis, whereas the clinic physician did not. CONCLUSION: The new examination protocol is repeatable and gives acceptable diagnostic accuracy in a hospital setting. Examination can feasibly be delegated to a trained nurse, and the protocol has the benefit of face and construct validity as well as consensus backing. Its performance in the community, where disease is less clear cut, merits separate evaluation, and further refinement is needed to discriminate between discrete pathologies at the shoulder.

Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.

Determinants of bone loss in elderly men and women: a prospective population-based study.

While several studies have described the rate and pattern of involutional bone loss in women, far less information is available for men. Furthermore, the roles of lifestyle and body build in determining bone loss rate in both sexes have been largely extrapolated from cross-sectional studies. We addressed this issue in a population-based longitudinal study which sought to ascertain rates of bone loss at the femoral neck and lumbar spine in a cohort of men and women aged 60-75 years at baseline, and to relate this loss to anthropometric and lifestyle variables. We additionally investigated the capacity of biochemical markers of bone turnover to predict bone loss rates in these subjects. Women lost bone at all sites; this ranged from 0.20%/year at the lumbar spine to 1.43%/year at the femoral trochanteric region. By contrast, men lost only 0. 20%/year at the trochanteric region, and gained at the lumbar spine (0.33%/year) and at Ward's triangle (0.27%/year) over the 4-year period. Anthropometric measurements were associated with bone loss in both sexes; lower baseline body mass index (BMI) and a greater rate of loss of adiposity over the follow-up period were both associated with greater bone loss at all proximal femoral sites. These attained statistical significance after Bonferroni correction at the total proximal femur among both men (r = 0.29), p<0.01) and women (r = 0.31, p<0.05). Lifestyle factors associated with lower rates of bone loss (after adjustment for BMI) included alcohol consumption at the femoral neck among women (p = 0.007) and physical activity at the lumbar spine among men (p = 0.05). Serum parathyroid hormone, 25-hydroxyvitamin D and biochemical markers of bone turnover did not predict bone loss after adjustment for adiposity.

Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men.

Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61-72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.

Quality of life in patients with vertebral fractures: validation of the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). Working Party for Quality of Life of the European Foundation for Osteoporosis.

Vertebral fractures may be minor or lead to pain, decreased physical function, immobility, social isolation and depression, which together contribute to quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with vertebral fractures. This questionnaire, QUALEFFO, includes questions in the domains pain, physical function, social function, general health perception and mental function. QUALEFFO was validated in a multicenter study in seven countries. The study was done in 159 patients aged 55-80 years with clinical osteoporosis, i.e., back pain and other complaints with at least one vertebral fracture and lumbar bone mineral density T-score <-1. Patients with a recent vertebral fracture were excluded because of unstable disease. Controls were age- and sex-matched, and did not have chronic back pain or vertebral fractures. Subjects with conditions exerting a major influence on quality of life were excluded. The QUALEFFO was administered twice within 4 weeks and compared with a generic questionnaire, the Short Form 36 of the Medical Outcomes Study (SF-36). Standard spinal radiographs were made for assessment of vertebral height. Seven questions were removed from the analysis because of low response rate, linguistic ambiguities or redundancy. The 41 remaining questions were analyzed for repeatability, internal consistency and the capacity to discriminate between patients with vertebral fractures and controls. Comparison with the SF-36 was performed within similar domains by conditional logistic regression and by receiver operating characteristic (ROC) curves. The repeatability of QUALEFFO was good (kappa statistics 0.54-0.90) and 26 of 41 questions had a kappa score >/=0.70. The internal consistency of the five domains was adequate, with Crohnbach alpha around 0.80. All except five questions discriminated significantly between patients and controls. The median scores of QUALEFFO were significantly higher in patients with vertebral fractures than in controls in all five domain (p<0. 001), which is consistent with decreased quality of life in patients with osteoporosis. Spinal radiographs were assessed using the McCloskey-Kanis algorithm. According to this, 124 patients (78%) had vertebral fractures of >/=3 SD severity, in contrast with 7 controls (4%). Significant correlations existed between scores of similar domains of QUALEFFO and the SF-36, especially for pain, physical function and mental function. All five domains within each questionnaire discriminated significantly between fracture cases and controls. The odds ratios for pain and social function were greater for QUALEFFO, while general health perception was more discriminating using the SF-36. The ROC curve analysis of QUALEFFO indicated that all five domains were significantly predictive of vertebral fractures. When comparing similar domains of the two questionnaires, QUALEFFO domains demonstrated significantly better performance for pain, physical function and social function. The QUALEFFO total score and SF-36 physical composite score showed similar performance. In conclusion, QUALEFFO is repeatable, coherent and discriminates well between patients with vertebral fractures and control subjects. The results of this study confirm the decreased quality of life in patients with vertebral fractures.

Repeatability and validity of an upper limb and neck discomfort questionnaire: the utility of the standardized Nordic questionnaire.

The repeatability and validity of a questionnaire for upper limb and neck complaints were assessed in a population of 105 hospital outpatients with a range of upper limb and neck disorders (including cervical spondylosis, adhesive capsulitis, lateral epicondylitis, carpal tunnel syndrome and Raynaud's phenomenon). Subjects were asked to complete a modified Nordic-style upper limb and neck discomfort questionnaire on two occasions closely spaced in time. The repeatability of their responses was assessed by calculating a kappa coefficient (kappa), and the sensitivity and specificity of component items in the questionnaire were determined for specific diagnostic categories of upper limb and neck disorder. Symptom reports for pain in the upper limb and neck, pain interfering with physical activities, neurological symptoms and blanching were all found to be highly repeatable (kappa = 0.63-0.90). A number of regional pain reports proved to be very sensitive in relation to specific upper limb disorders, but, with the exception of reported finger blanching in patients with Raynaud's phenomenon, none proved to have a good specificity (range = 0.33-0.38). We conclude that a modified Nordic-style questionnaire is repeatable and sensitive, and is likely to have a high utility in screening and surveillance. However a complementary examination schedule of adequate specificity and repeatability is essential to establish a clinical diagnosis.

The epidemiology of Paget's disease in Britain: is the prevalence decreasing?

To estimate changes in the age- and gender-specific prevalence of Paget's disease in Britain, we performed a radiographic survey of the disorder in 10 British centers, using sampling and radiographic methods identical to a study performed in 1974. In each center, a sample of abdominal radiographs of people aged 55 years and over was taken from stored films within the radiology department of the principal general hospital. The radiographs were identified by screening radiographic records over the period 1993-1995. Any abdominal radiograph in a subject aged 55 years and over which included the entire pelvis, sacrum, femoral heads, and all lumbar vertebrae was studied. The radiographs were evaluated by a trained observer and the consultant radiologist who participated in the original 1974 survey. Nine thousand eight hundred and twenty-eight radiographs (4625 men, 5203 women) were assessed in the 10 towns. The overall age/gender standardized prevalence rate was 2%, with a male/female ratio of 1.6. Prevalence increased steeply with age among men and women, rising to 6.9% of men and 5.8% of women aged 85 years and over. The prevalence of Paget's disease in the 10 towns in 1994 was only 40% of that observed during the 1974 study. The decline in prevalence was apparent in all 10 centers, but was most marked in those with high rates in the original study. This survey of Paget's disease in 10 British towns suggests a prevalence of 2.5% among men and 1.6% among women aged 55 years and over. Age-adjusted prevalence rates declined steeply between 1974 and 1994. These declines suggest an environmental contribution to the etiology of this disorder that requires further investigation.

Hormone replacement therapy, other reproductive variables and symptomatic hip osteoarthritis in elderly white women: a case-control study.

BACKGROUND: Recent epidemiological studies suggest that post-menopausal hormone replacement therapy might reduce the risk of hip osteoarthritis (OA) in women. However, the association of the disorder with other reproductive variables is controversial. We addressed this issue in a population-based case control study among 413 female cases and 413 age- and sex-matched controls. METHODS: A total of 413 women listed for hip replacement because of primary OA over an 18 month period were compared with an equal number of controls selected from the general population and individually matched for age and general practice. Information about reproductive variables was obtained by questionnaire administered at interview. RESULTS: The risk of hip OA was significantly elevated among women who had had an oophorectomy (OR = 1.9, 95% CI 1.0-3.7). After adjustment for body mass index, the presence of Heberden's nodes, previous hip injury and past leisure sporting activity (all independent risk factors for hip OA), and for other reproductive variables, there was a non-significant, protective effect of long-term hormone replacement therapy, such that > or =5 yr of use was associated with a 40% reduction in risk (OR = 0.6, 95% CI 0.2-1.8). Paradoxically, short-term HRT use (up to 5 yr duration) was associated with an excess risk of hip OA (OR = 1.7, 95% CI 0.9-3.3). There was no association between the risk of hip OA and use of oral contraceptives, parity or hysterectomy. CONCLUSIONS: These data are consistent with previous studies suggesting a protective effect of long-term hormone replacement therapy on the risk of hip OA. By contrast, an elevation of risk in short-term users was demonstrated. Our results also suggest that risk is increased among women who have undergone unilateral or bilateral oophorectomy. Studies are required to investigate the mechanisms underlying these associations.

Osteoarthritis of the hip and occupational lifting.

To test the hypothesis that occupational lifting is a cause of hip osteoarthritis, the authors examined associations with lifting and other occupational activities in a case-control study. The study was performed in two English health districts (Portsmouth and North Staffordshire) from 1993 to 1995. A total of 611 patients (210 men and 401 women) listed for hip replacement because of osteoarthritis over an 18-month period were compared with an equal number of controls selected from the general population and individually matched for age, sex, and general practice. Information about suspected risk factors was obtained by a questionnaire administered at interview and a short physical examination. Analysis was by conditional logistic regression. After adjustment for potential confounders, the risk in men increased progressively with the duration and heaviness of occupational lifting. Relative to those with low exposure, men who had regularly lifted weights in excess of 50 kg for 10 years or longer had an odds ratio of 3.2 (95% confidence interval 1.6-6.5). No comparable association was found in women. Of the other occupational activities examined, only frequent climbing of stairs showed a pattern suggestive of a causal relation. These findings are consistent with the results of other studies, and there is now a strong case for regarding hip osteoarthritis as an occupational disease in men whose work has involved prolonged and frequent heavy lifting.

Programming of growth hormone secretion and bone mineral density in elderly men: a hypothesis.

Epidemiological studies suggest that retarded growth in infancy is associated with low adult bone mass. The mechanism underlying this association is unknown, but the programming of GH secretion or sensitivity by environmental influences during early development may play a role. We examined this issue in a sample of 37 healthy men, aged 63-73 yr, whose weight gain in infancy had been recorded. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of the GH secretory profile, insulin-like growth factor I (IGF-I), IGF-binding protein-1 and -3, and GH-binding protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual energy x-ray absortiometry. There was a statistically significant association between peak GH concentration (r = 0.46; P < 0.01) and fasting IGF-I concentration (r = 0.46; P < 0.01) with femoral neck bone density. After allowing for the peak GH concentration, median GH was negatively (P < 0.05) associated with bone mineral density. Weight at 1 yr was not related to peak GH, but was strongly related to the median GH concentration (r = 0.42; P = 0.01). These observations are consistent with a dual effect of GH secretion on bone density. High peak GH values drive IGF-I production and maintain bone mineralization in adult life. However, integrated GH secretion, after adjusting for the effect of pulse amplitude, is negatively associated with bone density in adult life. This particular characteristic of the GH secretory profile correlates with growth during infancy and might be programmed by environmental factors during intrauterine or early postnatal life.