Feasibility and acceptability of using jumping mechanography to detect early components of sarcopenia in community-dwelling older women.

OBJECTIVE: To determine the feasibility and acceptability of using peak power and force, measured by jumping mechanography (JM), to detect early age-related features of sarcopenia in older women. METHODS: Community-dwelling women aged 71-87 years were recruited into this cross-sectional study. Physical function tests comprised the short physical performance battery (SPPB), grip strength and, if SPPB score≥6, JM. JM measured peak weight-adjusted power and force from two-footed jumps and one-legged hops respectively. Questionnaires assessed acceptability. RESULTS: 463 women were recruited; 37(8%) with SPPB⟨6 were ineligible for JM. Of 426 remaining, 359(84%) were able to perform ≥1 valid two-footed jump, 300(70%) completed ≥1 valid one-legged hop. No adverse events occurred. Only 14% reported discomfort. Discomfort related to JM performance, with inverse associations with both power and force (p⟨0.01). Peak power and force respectively explained 8% and 10% of variance in SPPB score (13% combined); only peak power explained additional variance in grip strength (17%). CONCLUSIONS: Peak power and force explained a significant, but limited, proportion of variance in SPPB and grip strength. JM represents a safe and acceptable clinical tool for evaluating lower-limb muscle power and force in older women, detecting distinct components of muscle function, and possibly sarcopenia, compared to those evaluated by more established measures.

Developmental aspects of a life course approach to healthy ageing.

We examine the mechanistic basis and wider implications of adopting a developmental perspective on human ageing. Previous models of ageing have concentrated on its genetic basis, or the detrimental effects of accumulated damage, but also have raised issues about whether ageing can be viewed as adaptive itself, or is a consequence of other adaptive processes, for example if maintenance and repair processes in the period up to reproduction are traded off against later decline in function. A life course model places ageing in the context of the attainment of peak capacity for a body system, starting in early development when plasticity permits changes in structure and function induced by a range of environmental stimuli, followed by a period of decline, the rate of which depends on the peak attained as well as the later life conditions. Such path dependency in the rate of ageing may offer new insights into its modification. Focusing on musculoskeletal and cardiovascular function, we discuss this model and the possible underlying mechanisms, including endothelial function, oxidative stress, stem cells and nutritional factors such as vitamin D status. Epigenetic changes induced during developmental plasticity, and immune function may provide a common mechanistic process underlying a life course model of ageing. The life course trajectory differs in high and low resource settings. New insights into the developmental components of the life course model of ageing may lead to the design of biomarkers of later chronic disease risk and to new interventions to promote healthy ageing, with important implications for public health.

Prevalence of Falls in an Urban Community-Dwelling Older Population of Cape Town, South Africa.

OBJECTIVE: Falls are a major cause of disability and mortality in older adults. Studies on falls in this population have mainly been conducted in high income countries, and scant attention has been given to the problem in low and middle income countries, including South Africa. The aim of the study was to establish a rate for falls in older adults in South Africa. DESIGN: A cross-sectional survey with a 12-month follow-up survey. SETTING: Three purposively selected suburbs of Cape Town: Plumstead, Wynberg Central and Gugulethu. PARTICIPANTS: Eight hundred and thirty seven randomly sampled ambulant community-dwelling subjects aged ≥ 65 years grouped according to ethnicity in three sub-samples: black Africans, coloureds (people of mixed ancestry) and whites. MEASUREMENTS: Data were collected on socio-demographic and health characteristics, and history of falls using a structured questionnaire and a protocol for physical assessments and measurements. RESULTS: Of the total baseline (n=837) and follow-up (n=632) survey participants, 76.5% and 77.2 % were females with a mean (S.D) age of 74 years (6.4) and 75 years (6.2), respectively. Rates of 26.4% and 21.9% for falls and of 11% and 6.3% for recurrent falls, respectively, were calculated at baseline and follow-up. Fall rates differed by ethnic sub-sample at baseline: whites 42 %, coloureds 34.4% and black Africans 6.4 % (p=0.0005). Rates of 236, 406 and 354 falls per 1000 person years were calculated for men, women and both genders, respectively. Recurrent falls were more common in women than in men. CONCLUSION: Falls are a significant problem in older adults in South Africa. Effective management of falls and falls prevention strategies for older people in South Africa, need to be developed and implemented.

Osteoporosis and sarcopenia in older age.

Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition. This article is part of a Special Issue entitled "Muscle Bone Interactions".

Peripheral quantitative computed tomography measures are associated with adult fracture risk: the Hertfordshire Cohort Study.

Peripheral quantitative computed tomography (pQCT) captures novel aspects of bone geometry that may contribute to fracture risk and offers the ability to measure both volumetric bone mineral density (vBMD) and a separation of trabecular and cortical compartments of bone, but longitudinal data relating measures obtained from this technique to incident fractures are lacking. Here we report an analysis from the Hertfordshire Cohort Study, where we were able to study associations between measures obtained from pQCT and DXA in 182 men and 202 women aged 60-75 years at baseline with incident fractures over 6 years later. Among women, radial cortical thickness (HR 1.72, 95% CI 1.16, 2.54, p=0.007) and cortical area (HR 1.91, 95% CI 1.27, 2.85, p=0.002) at the 66% slice were both associated with incident fractures; these results remained significant after adjustment for confounders (age, BMI, social class, cigarette smoking and alcohol consumption, physical activity, dietary calcium, HRT and years since menopause). Further adjustment for aBMD made a little difference to the results. At the tibia, cortical area (HR 1.58, 95% CI 1.10, 2.28, p=0.01), thickness (HR 1.49, 95% CI 1.08, 2.07, p=0.02) and density (HR 1.64, 95% CI 1.18, 2.26, p=0.003) at the 38% site were all associated with incident fractures with the cortical area and density relationships remaining robust to adjustment for the confounders listed above. Further adjustment for aBMD at this site did lead to attenuation of relationships. Among men, tibial stress-strain index (SSI) was predictive of incident fractures (HR 2.30, 95% CI 1.28, 4.13, p=0.005). Adjustment for confounding variables and aBMD did not render this association non-significant. In conclusion, we have demonstrated relationships between measures of bone size, density and strength obtained by pQCT and incident fracture. These relationships were attenuated but in some cases remained significant after adjustment for BMD measures obtained by DXA, suggesting that some additional information may be conferred by this assessment.

Birth weight and growth from infancy to late adolescence in relation to fat and lean mass in early old age: findings from the MRC National Survey of Health and Development.

OBJECTIVE: High birth weight and greater weight gain in infancy have been associated with increased risk of obesity as assessed using body mass index, but few studies have examined associations with direct measures of fat and lean mass. This study examined associations of birth weight and weight and height gain in infancy, childhood and adolescence with fat and lean mass in early old age. SUBJECTS: A total of 746 men and 812 women in England, Scotland and Wales from the MRC National Survey of Health and Development whose heights and weights had been prospectively ascertained across childhood and adolescence and who had dual energy X-ray absorptiometry measures at age 60-64 years. METHODS: Associations of birth weight and standardised weight and height (0-2 (weight only), 2-4, 4-7, 7-11, 11-15, 15-20 years) gain velocities with outcome measures were examined. RESULTS: Higher birth weight was associated with higher lean mass and lower android/gynoid ratio at age 60-64 years. For example, the mean difference in lean mass per 1 standard deviation increase in birth weight was 1.54 kg in males (95% confidence interval=1.04, 2.03) and 0.78 kg in females (0.41, 1.14). Greater weight gain in infancy was associated with higher lean mass, whereas greater gains in weight in later childhood and adolescence were associated with higher fat and lean mass, and fat/lean and android/gynoid ratios. Across growth intervals greater height gain was associated with higher lean but not fat mass, and with lower fat/lean and android/gynoid ratios. CONCLUSION: Findings suggest that growth in early life may have lasting effects on fat and lean mass. Greater weight gain before birth and in infancy may be beneficial by leading to higher lean mass, whereas greater weight gain in later childhood and adolescence may be detrimental by leading to higher fat/lean and android/gynoid ratios.

Psychological well-being and incident frailty in men and women: the English Longitudinal Study of Ageing.

BACKGROUND: Observations that older people who enjoy life more tend to live longer suggest that psychological well-being may be a potential resource for healthier ageing. We investigated whether psychological well-being was associated with incidence of physical frailty. METHOD: We used multinomial logistic regression to examine the prospective relationship between psychological well-being, assessed using the CASP-19, a questionnaire that assesses perceptions of control, autonomy, self-realization and pleasure, and incidence of physical frailty or pre-frailty, defined according to the Fried criteria (unintentional weight loss, weakness, self-reported exhaustion, slow walking speed and low physical activity), in 2557 men and women aged 60 to ≥ 90 years from the English Longitudinal Study of Ageing (ELSA). RESULTS: Men and women with higher levels of psychological well-being were less likely to become frail over the 4-year follow-up period. For a standard deviation higher score in psychological well-being at baseline, the relative risk ratio (RR) for incident frailty, adjusted for age, sex and baseline frailty status, was 0.46 [95% confidence interval (CI) 0.40-0.54]. There was a significant association between psychological well-being and risk of pre-frailty (RR 0.69, 95% CI 0.63-0.77). Examination of scores for hedonic (pleasure) and eudaimonic (control, autonomy and self-realization) well-being showed that higher scores on both were associated with decreased risk. Associations were partially attenuated by further adjustment for other potential confounding factors but persisted. Incidence of pre-frailty or frailty was associated with a decline in well-being, suggesting that the relationship is bidirectional. CONCLUSIONS: Maintaining a stronger sense of psychological well-being in later life may protect against the development of physical frailty. Future research needs to establish the mechanisms underlying these findings.

Is grip strength a good marker of physical performance among community-dwelling older people?

INTRODUCTION: There is increasing interest in physical performance as it relates to both the current and future health of older people. It is often characterised using the Short Physical Performance Battery including assessment of gait speed, chair rises and standing balance. However this battery of tests may not be feasible in all clinical settings and simpler measures may be required. As muscle strength is central to physical performance, we explored whether grip strength could be used as a marker of the Short Physical Performance Battery. OBJECTIVE: To examine associations between grip strength and components of the Short Physical Performance Battery in older community dwelling men and women. METHODS: Grip strength measurement and the Short Physical Performance Battery were completed in 349 men and 280 women aged 63-73 years taking part in the Hertfordshire Cohort Study (HCS). Relationships between grip strength and physical performance (6m timed-up-and-go [TUG], 3m walk, chair rises and standing balance times) were analysed using linear and logistic regression, without and with adjustment for age, anthropometry, lifestyle factors and co-morbidities. RESULTS: Among men, a kilo increase in grip strength was associated with a 0.07s (second) decrease in 6m TUG, a 0.02s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001 for all). Among women, a kilo increase in grip strength was associated with a 0.13s decrease in 6m TUG, a 0.03s decrease in 3m walk time, and a 1% decrease in chair rises time (p<0.001). Higher grip strength was associated with better balance among men (p=0.01) but not women (p=0.57). Adjustment for age, anthropometry, lifestyle and co-morbidities did not alter these results. CONCLUSIONS: Grip strength is a good marker of physical performance in this age group and may be more feasible than completing a short physical performance battery in some clinical settings.

The relationship of dietary patterns with adult lung function and COPD.

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns. The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis. Using regression analysis, after controlling for confounders, a "prudent" pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with forced expiratory volume in 1 s (FEV(1)) (trend p-value <0.001 in males, 0.008 in females) (difference in FEV(1) between top and bottom quintiles of pattern score, 0.18 L (95% CI 0.08-0.28 L) in males, 0.08 L (95% CI 0.00-0.16 L) in females). This pattern was also positively associated with forced vital capacity (FVC) in both sexes. Males with a higher "prudent" pattern score had a higher FEV(1)/FVC (trend p-value 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile 0.46, 95% CI 0.26-0.81; trend p-value 0.012). Associations in males were stronger in smokers than nonsmokers (interaction p-value for FEV(1)/FVC 0.002). A "prudent" dietary pattern may protect against impaired lung function and COPD, especially in male smokers.

The effects of aerobic exercise on metabolic risk, insulin sensitivity and intrahepatic lipid in healthy older people from the Hertfordshire Cohort Study: a randomised controlled trial.

AIMS/HYPOTHESIS: We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial. METHODS: Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up. RESULTS: We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a non-significant reduction in zMS in the exercise group compared with controls (0.07 [95% CI -0.03, 0.17], p = 0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11-0.92], p = 0.035) compared with controls. Results were similar in per-protocol analyses. CONCLUSIONS/INTERPRETATION: Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe. TRIAL REGISTRATION: Controlled-trials.com ISRCTN60986572 FUNDING: Medical Research Council.

Grip strength and cardiovascular drug use in older people: findings from the Hertfordshire Cohort Study.

BACKGROUND: reduced grip strength is associated with adverse health consequences, and there is interest in identifying modifiable influences. Cardiovascular drugs are commonly used by older people, but their effect on muscle strength is unclear. METHODS: we investigated associations between cardiovascular drug use and grip strength among 1,572 men and 1,415 women, aged 59-73, who participated in the Hertfordshire Cohort Study. RESULTS: Forty-five percent of participants were taking a cardiovascular drug. Furosemide was associated with average decreases in grip strength of 3.15 kg (95% confidence interval [CI] 0.90, 5.39, P < 0.01) among men and 2.35 kg (95% CI 0.93, 3.77, P < 0.01) among women after adjustment for age and height. Corresponding differences for nitrates were 1.84 kg (95% CI 0.29, 3.39, P = 0.02) among men and 3.66 kg (95% CI 1.99, 5.33, P < 0.01) among women. Calcium channel blockers and fibrates were associated with reduced grip among women. Statins were not associated with grip. The associations between grip strength and nitrate use in men and nitrate and fibrate use in women were robust to additional adjustment for co-morbidity. CONCLUSIONS: use of some cardiovascular drugs is associated with reduced grip strength in older people. These findings have potential implications for the functional ability of older people treated with these drugs.

Bone health and deterioration in quality of life among participants from the Hertfordshire cohort study.

UNLABELLED: We utilised the Hertfordshire cohort study to examine relationships between bone density at baseline and SF-36 status 4 years later. We found deterioration in the mental health domain over follow-up in osteoporotic men (but not women) compared with other groups (relative rate ratio=5.78, 95% confidence interval (CI) 1.78-19.2). INTRODUCTION: Osteoporosis is associated with decreased quality of life, although it has been difficult to evaluate the confounding effects of fracture and co-morbidity. Having previously shown that male osteoporotics have poorer health than counterparts with normal bone mineral density, even after adjustment for co-morbidity and prior fracture, we assessed quality of life in both groups 4 years apart. METHODS: Four hundred and ninety-eight men and 468 women completed questionnaires detailing lifestyle factors, co-morbidities and quality of life (SF-36) before undergoing bone density measurements at the lumbar spine and total femur. At follow-up 4 years later, 322 men and 320 women were reassessed. RESULTS: Multinomial logistic regression confirmed deterioration in mental health over follow-up in osteoporotic men compared with other groups (relative rate ratio=5.78, 95% CI 1.78-19.2). These patterns were not apparent among women. CONCLUSIONS: Men with lower bone density at baseline had poorer quality of life some 4 years later, even after adjustment for co-morbidity and fracture. This may reflect secondary osteoporosis in men (due to alcohol or hypogonadism).

The SF-36: a simple, effective measure of mobility-disability for epidemiological studies.

BACKGROUND: Mobility disability is a major problem in older people. Numerous scales exist for the measurement of disability but often these do not permit comparisons between study groups. The physical functioning (PF) domain of the established and widely used Short Form-36 (SF-36) questionnaire asks about limitations on ten mobility activities. OBJECTIVES: To describe prevalence of mobility disability in an elderly population, investigate the validity of the SF-36 PF score as a measure of mobility disability, and to establish age and sex specific norms for the PF score. METHODS: We explored relationships between the SF-36 PF score and objectively measured physical performance variables among 349 men and 280 women, 59-72 years of age, who participated in the Hertfordshire Cohort Study (HCS). Normative data were derived from the Health Survey for England (HSE) 1996. RESULTS: 32% of men and 46% of women had at least some limitation in PF scale items. Poor SF-36 PF scores (lowest fifth of the gender-specific distribution) were related to: lower grip strength; longer timed-up-and-go, 3m walk, and chair rises test times in men and women; and lower quadriceps peak torque in women but not men. HSE normative data showed that median PF scores declined with increasing age in men and women. CONCLUSION: Our results are consistent with the SF-36 PF score being a valid measure of mobility disability in epidemiological studies. This approach might be a first step towards enabling simple comparisons of prevalence of mobility disability between different studies of older people. The SF-36 PF score could usefully complement existing detailed schemes for classification of disability and it now requires validation against them.

Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study.

BACKGROUND: Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data relate bone density, lipid profile and anthropometric measures. AIM: To investigate these relationships in a large, well-characterized cohort of men and women (The Hertfordshire Cohort Study). METHODS: Men (n = 465) and women (n = 448) from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur. RESULTS: BMD at the lumbar spine (males r = 0.15, p = 0.001; females r = 0.14, p = 0.003) and total femoral region (males r = 0.18, p = 0.0001; females r = 0.16, p = 0.0008) was related to serum triglyceride level, even after adjustment for waist-hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r = -0.15, p = 0.001) and total femoral BMD in both sexes (males r = -0.15, p = 0.002; females r = -0.23, p < 0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist-hip ratio. No relationships were seen between total or LDL cholesterol with BMD. DISCUSSION: In this cohort, relationships between lipid profile and BMD were robust to adjustment for one measure of central obesity (waist-hip ratio), but not total body fat. This broadly supports the idea that adiposity may confound the relationship between lipids and bone mass.

Relationships between SF-36 health profile and bone mineral density: the Hertfordshire Cohort Study.

We utilised the Hertfordshire Cohort Study (HCS) to relate bone mineral density (BMD) to SF-36 health-related quality of life scores. We studied 737 men and 675 women who had completed a home interview and clinic. Four hundred and ninety-eight men and 468 women subsequently attended for bone densitometry [dual-energy X-ray absorptiometry (DXA)]. SF-36 questionnaire responses were mapped to eight domains: physical function (PF), role physical (RP), role emotional (RE), social functioning (SF), mental health (MH), vitality (VT), bodily pain (BP) and general health perception (GH). Subjects with scores in the lowest gender-specific fifth of the distribution were classified as having "poor" status for each domain. Odds ratios (OR) for poor status for each domain were calculated per unit increase in lumbar spine or total femoral BMD t score. Among men after adjustment for age, BMI, social class, lifestyle (including physical activity) and known comorbidity, higher total femoral t score was associated with decreased prevalence of poor SF-36 scores for PF [OR 0.72 (95%CI 0.53, 0.97), p=0.03], SF [OR 0.70 (95%CI 0.53, 0.94), p=0.02] or GH domains [OR 0.74 (95%CI 0.56, 0.99), p=0.05], but no relationships were apparent between SF-36 scores and lumbar spine t score. Among women, the adjusted relationship between higher total femoral t score and decreased prevalence of poor PF was consistent [OR 0.71 (95%CI 0.50, 1.00), p=0.05], but no other relationships were significant. Poorer functioning (assessed by SF-36 questionnaire) is associated with lower total femoral BMD in older men (but less so in women) after adjustment for lifestyle factors and comorbidity.

Is hand-held dynamometry useful for the measurement of quadriceps strength in older people? A comparison with the gold standard Bodex dynamometry.

BACKGROUND: The lower limb muscle strength is an important determinant of physical function in older people. However, measurement in clinical and epidemiological settings has been limited because of the requirement for large-scale equipment. A protocol using a novel, versatile hand-held dynamometer (HHD) has been developed to measure the quadriceps strength in a supine position. OBJECTIVE: The objective of this study was to assess the validity of this new methodology for measuring the lower limb muscle strength compared to the gold standard Biodex dynamometer. METHODS: The supine quadriceps strength was measured twice with each of the Biodex and the HHD in 20 men and women, aged 61-81 years, on their non-dominant leg. The agreement between the peak torques obtained by Biodex and HHD was analyzed. RESULTS: The mean peak Biodex and HHD results were 83.4 +/- (SD) 28.0 Nm and 68.9 +/- 19.6 Nm, respectively. The HHD undermeasured the quadriceps strength by an average of 14.5 Nm (95% CI 8.5, 20.6) compared to the Biodex, and this effect was most marked in the strongest participants. Nevertheless, there was a good correlation between the measures (r = 0.91, p < 0.0001). Classification of individuals into tertiles of muscle strength showed good agreement between the two methods (Kappa = 0.69, p < 0.0001). CONCLUSIONS: Our findings suggest that the HHD using a supine positioning offers a feasible, inexpensive, and portable test of quadriceps muscle strength for use in healthy older people. It underestimates the absolute quadriceps strength compared to the Biodex particularly in stronger people, but is a useful tool for ranking muscle strength of older people in epidemiological studies. It may also be of value for quick and objective assessment of physical function in the clinical setting.

Type 2 diabetes mellitus is associated with increased axial bone density in men and women from the Hertfordshire Cohort Study: evidence for an indirect effect of insulin resistance?

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: Our findings suggest that hyperinsulinaemia may affect bone mineral density through indirect effects, e.g. body weight.

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

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