[Show abstract][Hide abstract] ABSTRACT: Objective: Vitamin D is an important component of calcium and phosphate metabolism, ensuring, with PTH and FGF23, adequate serum concentrations of these two analytes for optimal cell function and bone mineralisation. Despite a surge of interest in vitamin D physiology over the last decade, a single threshold for deficiency remains uncertain in functional terms, and it is clear that correlation between serum concentration of 25(OH)-vitamin D and disease outcomes is very poor at the level of the individual. In this review, we describe the physiology of vitamin D, its potential associations with disease, and relate, in detail, the epidemiology of vitamin D status across populations worldwide. Design: Through a comprehensive literature review, we identified relevant studies from Europe, the Middle East, Africa, Asia, North America, Latin America, and Oceania. Results: Although rickets and osteomalacia are established potential consequences of vitamin D deficiency, evidence for low levels of vitamin D as a cause of the multitude of other health outcomes with which they have been linked is lacking. We observed geographical differences in serum 25(OH)-vitamin D concentrations, which may be partly, but not wholly, explained by factors such as sunlight exposure, skin pigmentation, skin coverage, dietary choices, supplements, adiposity, malabsorption, disease, demographics and lifestyle. Conclusion: We conclude that low serum concentrations of 25(OH)-vitamin D appear common across the globe; the relevance of this observation to human health remains to be elucidated.
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved.
[Show abstract][Hide abstract] ABSTRACT: Background:
We investigated relationships between early growth and proximal femoral geometry at age 6 y in a prospective population-based cohort, the Southampton Women's Survey.
In 493 mother-offspring pairs, we assessed linear size using high-resolution ultrasound at 11, 19, and 34 wk gestation (femur length) and at birth and 1, 2, 3, 4, and 6 y (crown-heel length/height). SD scores were created and conditional regression modeling generated mutually independent growth variables. Children underwent hip dual-energy X-ray absorptiometry (DXA) at 6 y; hip structure analysis software yielded measures of geometry and strength.
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 y, with the strongest relationships observed for femur growth from 19 to 34 wk gestation (β = 0.26 cm(3)/SD, P < 0.0001), and for height growth from birth to 1 y (β = 0.25 cm(3)/SD, P < 0.0001) and 1 to 2 y (β = 0.33 cm(3)/SD, P < 0.0001), with progressively weaker relationships over years 3 (β = 0.23 cm(3)/SD, P = 0.0002) and 4 (β = 0.10 cm(3)/SD, P = 0.18).
These results demonstrate that growth before age 3 y predicts proximal femoral geometry at 6 y old. These data suggest critical periods in which there is capacity for long-term influence on the later skeletal growth trajectory.
Pediatric Research 07/2013; 74(4). DOI:10.1038/pr.2013.119 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Harvey NC, Mahon PA, Kim M, Cole ZA, Robinson SM, Javaid K, Inskip HM, Godfrey KM, Dennison EM, Cooper C, the SWS Study Group. Intrauterine growth and postnatal skeletal development: findings from the Southampton Women's Survey. Paediatric and Perinatal Epidemiology 2012; 26: 34–44.
We have previously demonstrated associations between fetal growth in late pregnancy and postnatal bone mass. However, the relationships between the intrauterine and early postnatal skeletal growth trajectory remain unknown. We addressed this in a large population-based mother–offspring cohort study. A total of 628 mother–offspring pairs were recruited from the Southampton Women's Survey. Fetal abdominal circumference was measured at 11, 19 and 34 weeks gestation using high-resolution ultrasound with femur length assessed at 19 and 34 weeks. Bone mineral content was measured postnatally in the offspring using dual-energy X-ray absorptiometry at birth and 4 years; postnatal linear growth was assessed at birth, 6, 12, 24, 36 and 48 months. Late pregnancy abdominal circumference growth (19–34 weeks) was strongly (P < 0.01) related to bone mass at birth, but less robustly associated with bone mass at 4 years. Early pregnancy growth (11–19 weeks) was more strongly related to bone mass at 4 years than at birth. Postnatal relationships between growth and skeletal indices at 4 years were stronger for the first and second postnatal years, than the period aged 2–4 years. The proportion of children changing their place in the distribution of growth velocities progressively reduced with each year of postnatal life. The late intrauterine growth trajectory is a better predictor of skeletal growth and mineralisation at birth, while the early intrauterine growth trajectory is a more powerful determinant of skeletal status at age 4 years. The perturbations in this trajectory which influence childhood bone mass warrant further research.
[Show abstract][Hide abstract] ABSTRACT: In a free-living cohort of 4-year old children, mean daily time in moderate-vigorous physical activity and daily calcium intake at 3 years, were positively related to hip bone size and density. Relationships between physical activity and bone indices were stronger when calcium intake was above compared with below median (966 mg/day).
We examined the cross-sectional relationships between childhood physical activity, dietary calcium intake and bone size and density.
Children aged 4 years were recruited from the Southampton Women's Survey. They underwent measurement of bone mass by DXA (Hologic Discovery). Physical activity was assessed by accelerometry (Actiheart, Cambridge Neurotechnology Ltd, Cambridge, UK) for seven continuous days.
Four hundred twenty-two children (212 boys) participated. In a cross-sectional analysis, after adjusting for gender, daily mean time(minutes per day) spent in moderate to very vigorous activity (MVPA) was positively related to hip BA (R(2) = 3%, p < 0.001), BMC (R(2) = 4%, p < 0.001), aBMD (R (2) = 3%, p = 0.001) and estimated vBMD (R(2) = 2%, p = 0.01), but not height (r (s) = 0.04, p = 0.42) or weight (r(s) = 0.01, p = 0.76). Mean daily calcium intake (assessed at 3 years old) positively predicted bone indices in those with a calcium intake below the median (966 mg/day), but there was a much attenuated relationship in those above this. These associations persisted after inclusion of total energy, protein and phosphorus in multivariate models. The relationships between MVPA and bone indices were stronger in children with calcium intakes above the median. Thus, for aBMD, the variance explained by MVPA when daily calcium intake was below the median was 2% (p = 0.1) and above median was 6% (p = 0.001).
These results support the notion that adequate calcium intake may be required for optimal action of physical activity on bone development and that improving levels of physical activity and calcium intake in childhood may help to optimise accrual of bone mass.
Osteoporosis International 05/2011; 23(1):121-30. DOI:10.1007/s00198-011-1641-y · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have shown that obesity is associated with an increased risk of fracture in both adults and children. It has been suggested that, despite greater bone size, obese individuals may have reduced true volumetric density; however this is difficult to assess using two dimensional techniques such as DXA. We evaluated the relationship between fat mass, and bone size and density, in a population cohort of children in whom DXA and pQCT measurements had been acquired. We recruited 530 children at 6 years old from the Southampton Women's Survey. The children underwent measurement of bone mass at the whole body, lumbar spine and hip, together with body composition, by DXA (Hologic Discovery, Hologic Inc., Bedford, MA, USA). In addition 132 of these children underwent pQCT measurements at the tibia (Stratec XCT2000, Stratec Biomedical Systems, Birkenfeld, Germany). Significant positive associations were observed between total fat mass and both bone area (BA) and bone mineral content (BMC) at the whole body minus head, lumbar spine and hip sites (all p<0.0001). When true volumetric density was assessed using pQCT data from the tibia, fat mass (adjusted for lean mass) was negatively associated with both trabecular and cortical density (β=-14.6 mg/mm(3) per sd, p=0.003; β=-7.7 mg/mm(3) per sd, p=0.02 respectively). These results suggest that fat mass is negatively associated with volumetric bone density at 6 years old, independent of lean mass, despite positive associations with bone size.
Bone 05/2011; 50(2):562-7. DOI:10.1016/j.bone.2011.05.005 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis constitutes a major public health problem through its association with age-related fractures, most notably those of the proximal femur. Substantial geographic variation has been noted in the incidence of hip fracture throughout the world, and estimates of recent incidence trends have varied widely. Studies in the published literature have reported an increase, plateau, and decrease in age-adjusted incidence rates for hip fracture among both men and women. Accurate characterisation of these temporal trends is important in predicting the health care burden attributable to hip fracture in future decades. We therefore conducted a review of studies worldwide, addressing secular trends in the incidence of hip and other fractures. Studies in western populations, whether in North America, Europe or Oceania, have generally reported increases in hip fracture incidence through the second half of the last century, but those continuing to follow trends over the last two decades have found that rates stabilise with age-adjusted decreases being observed in certain centres. In contrast, some studies suggest that the rate is rising in Asia. This synthesis of temporal trends in the published literature will provide an important resource for preventing fractures. Understanding the reasons for the recent declines in rates of hip fracture may help understand ways to reduce rates of hip fracture worldwide.
Osteoporosis International 04/2011; 22(5):1277-88. DOI:10.1007/s00198-011-1601-6 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is a skeletal disorder characterized by low bone mass and micro-architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture. Evidence is now accumulating from human studies that programming of bone growth might be an important contributor to the later risk of osteoporotic fracture. Body weight in infancy is a determinant of adult bone mineral content, as well as of the basal levels of activity of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) and hypothalamo-pituitary-adrenal (HPA) axes, and recent work has suggested a central role for vitamin D. Epidemiological studies have shown that maternal smoking and nutrition during pregnancy influence intrauterine skeletal mineralization. Childhood growth rates have been directly linked to the risk of hip fracture many decades later, and now evidence is emerging from experimental animal studies that support these observational data. Recent studies have also highlighted epigenetic phenomena as potential mechanisms underlying the findings from epidemiological studies.
[Show abstract][Hide abstract] ABSTRACT: Intrauterine life may be a critical period for the programming of later obesity, but there is conflicting evidence about whether pregnancy weight gain is an important determinant of offspring adiposity.
The purpose of this study was to examine the relation of pregnancy weight gain with neonatal and childhood body composition.
The participants (n = 948) were children born to women in the Southampton Women's Survey who had dual-energy X-ray absorptiometry measurements of body composition at birth, 4 y, or 6 y. Pregnancy weight gain was derived from the mothers' measured weights before pregnancy and at 34 wk gestation and analyzed by using 2009 Institute of Medicine categories (inadequate, adequate, or excessive) and as a continuous measure.
Almost one-half (49%) of the children were born to women who gained excessive weight in pregnancy. In comparison with children born to women with adequate weight gain, they had a greater fat mass in the neonatal period (SD: 0.17; 95% CI: 0.02, 0.32; P = 0.03), at 4 y (SD: 0.17; 95% CI: 0.00, 0.34; P = 0.05), and at 6 y (SD: 0.30; 95% CI: 0.11, 0.49; P = 0.002). Greater pregnancy weight gain, as a continuous measure, was associated with greater neonatal fat mass (SD: 0.10 per 5-kg weight gain; 95% CI: 0.04, 0.15; P = 0.0004) and was weakly associated with fat mass at 6 y (SD: 0.07 per 5-kg weight gain; 95% CI: 0.00, 0.14; P = 0.05) but not at 4 y (SD: 0.02 per 5-kg weight gain; 95% CI: -0.04, 0.08; P = 0.55).
Appropriate pregnancy weight gain, as defined by 2009 Institute of Medicine recommendations, is linked to lower levels of adiposity in the offspring.
American Journal of Clinical Nutrition 04/2010; 91(6):1745-51. DOI:10.3945/ajcn.2009.29128 · 6.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mother's diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.
Proceedings of The Nutrition Society 12/2009; 69(1):25-33. DOI:10.1017/S0029665109991765 · 5.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of variations in current infant feeding practice on bone mineral accrual is not known. We examined the associations between duration of breast-feeding and compliance with infant dietary guidelines and later bone size and density at age 4 years. At total of 599 (318 boys) mother-child pairs were recruited from the Southampton Women's Survey. Duration of breast-feeding was recorded and infant diet was assessed at 6 and 12 months using FFQ. At 6 and 12 months the most important dietary pattern, defined by principal component analysis, was characterised by high consumption of vegetables, fruits and home-prepared foods. As this was consistent with infant feeding recommendations, it was denoted the 'infant guidelines' pattern. At age 4 years, children underwent assessment of whole-body bone size and density using a Hologic Discovery dual-energy X-ray absorptiometry instrument. Correlation methods were used to explore the relationships between infant dietary variables and bone mineral. There was no association between duration of breast-feeding in the first year of life and 4-year bone size or density. 'Infant guidelines' pattern scores at 6 and 12 months were also unrelated to bone mass at age 4 years. We observed wide variations in current infant feeding practice, but these variations were not associated with differences in childhood bone mass at age 4 years.
The British journal of nutrition 05/2009; 102(6):915-20. DOI:10.1017/S0007114509317420 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Maternal nutrition is a potentially important determinant of intrauterine skeletal development. Previous studies have examined the effects of individual nutrients, but the pattern of food consumption may be of greater relevance. We therefore examined the relationship between maternal dietary pattern during pregnancy and bone mass of the offspring at 9 yr of age. We studied 198 pregnant women 17–43 yr of age and their offspring at 9 yr of age. Dietary pattern was assessed using principal component analysis from a validated food frequency questionnaire. The offspring underwent measurements of bone mass using DXA at 9 yr of age. A high prudent diet score was characterized by elevated intakes of fruit, vegetables, and wholemeal bread, rice, and pasta and low intakes of processed foods. Higher prudent diet score in late pregnancy was associated with greater (p < 0.001) whole body and lumbar spine BMC and areal BMD in the offspring, after adjustment for sex, socioeconomic status, height, arm circumference, maternal smoking, and vitamin D status. Associations with prudent diet score in early pregnancy were weaker and nonsignificant. We conclude that dietary patterns consistent with current advice for healthy eating during pregnancy are associated with greater bone size and BMD in the offspring at 9 yr of age.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2009; 24(4):663 - 668. DOI:10.1359/jbmr.081212 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis constitutes a major public health problem through its association with age related fractures. Fracture rates are generally higher in caucasian women than in other populations. Important determinants include estrogen deficiency in women, low body mass index, cigarette smoking, alcohol consumption, poor dietary calcium intake, physical inactivity, certain drugs and illnesses. Thus, modification of physical activity and dietary calcium/vitamin D nutrition should complement high risk approaches. In addition, the recently developed WHO algorithm for evaluation of 10-year absolute risk of fracture provides a means whereby various therapies can be targeted cost-effectively to those at risk. Risk factors, together with bone mineral density (BMD) and biochemical indices of bone turnover, can be utilised to derive absolute risks of fracture and cost-utility thresholds at which treatment is justified. These data will provide the basis for translation into coherent public health strategies aiming to prevent osteoporosis both in individuals and in the general population.
Salud publica de Mexico 02/2009; 51 Suppl 1:S38-45. DOI:10.1590/S0036-36342009000700007 · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis is a major cause of morbidity and mortality through its association with age-related fractures. Although most effort in fracture prevention has been directed at retarding the rate of age-related bone loss, and reducing the frequency and severity of trauma among elderly people, evidence is growing that peak bone mass is an important contributor to bone strength during later life. The normal patterns of skeletal growth have been well characterised in cross-sectional and longitudinal studies. It has been confirmed that boys have higher bone mineral content, but not volumetric bone density, than girls. Furthermore, there is a dissociation between the peak velocities for height gain and bone mineral accrual in both genders. Puberty is the period during which volumetric density appears to increase in both axial and appendicular sites. Many factors influence the accumulation of bone mineral during childhood and adolescence, including heredity, gender, diet, physical activity, endocrine status, and sporadic risk factors such as cigarette smoking. In addition to these modifiable factors during childhood, evidence has also accrued that fracture risk might be programmed during intrauterine life. Epidemiological studies have demonstrated a relationship between birthweight, weight in infancy, and adult bone mass. This appears to be mediated through modulation of the set-point for basal activity of pituitary-dependent endocrine systems such as the hypothalamic-pituitary-adrenal (HPA) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. Maternal smoking, diet (particularly vitamin D deficiency) and physical activity also appear to modulate bone mineral acquisition during intrauterine life; furthermore, both low birth size and poor childhood growth, are directly linked to the later risk of hip fracture. The optimisation of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations.
Advances in Experimental Medicine and Biology 02/2009; 646:31-9. DOI:10.1007/978-1-4020-9173-5_3 · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis remains a major public health problem through its association with fragility fractures. Despite the availability of preventative therapeutic agents, the incidence and its associated costs continue to rise globally. Understanding osteoporosis epidemiology is essential to developing strategies to reduce the burden of osteoporotic fracture in the population. This article reviews the epidemiology of osteoporosis globally, highlighting recent advances. It describes the burden of common osteoporotic fractures, the associated morbidity and mortality, the clustering of fractures in individuals, and the identification of at-risk groups. It also highlights the development of new algorithms to identify individuals at high risk of fracture, enabling the implementation of appropriate treatment strategies.
Current Rheumatology Reports 05/2008; 10(2):92-6. DOI:10.1007/s11926-008-0017-6 · 2.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Osteoporosis has a huge impact on public health, through the increased morbidity, mortality and economic costs associated with resultant fractures. The goal is to evaluate and identify those that are at risk of osteoporotic fracture in order to start preventative and therapeutic measures to reduce their risk of fracture.
This article reviews the data from randomized controlled trials for the current therapeutic agents available in the UK. It also reviews new trial data for promising osteoporosis therapies, in particular Denosumab, a monoclonal antibody against RANK ligand.
Bisphosphonates are the current recommended first-line treatments for patients with osteoporosis. AREAS OF CONTROVERSY/GROWING POINTS: There are a number of patients where bisphosphonates are contraindicated. Under these circumstances, it is important that clinicians have access to alternative treatments. The long-awaited National Institute for Health and Clinical Excellence (NICE) technology appraisals for both primary and secondary prevention and the clinical guidelines will clarify this. Treatment decisions should be based on risk factors and pharmaceutical intervention given to those with the highest risks.
Future studies are required to look at these agents in combination to see whether anti-fracture efficacy can be improved.
British Medical Bulletin 02/2008; 86(1):129-43. DOI:10.1093/bmb/ldn017 · 3.66 Impact Factor