Risk Of Osteoporosis In Later Life Research Articles

Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition

IntroductionThe growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear. ObjectivesThis study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied. MethodsData on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis. ResultsIndividuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: −0.51, −0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements. ConclusionsOur findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

Factors influencing peak bone mass gain.

Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.

MAVIDOS Maternal Vitamin D Osteoporosis Study: study protocol for a randomized controlled trial. The MAVIDOS Study Group

MAVIDOS is a randomised, double-blind, placebo-controlled trial (ISRCTN82927713, registered 2008 Apr 11), funded by Arthritis Research UK, MRC, Bupa Foundation and NIHR.BackgroundOsteoporosis is a major public health problem as a result of associated fragility fractures. Skeletal strength increases from birth to a peak in early adulthood. This peak predicts osteoporosis risk in later life. Vitamin D insufficiency in pregnancy is common (31% in a recent Southampton cohort) and predicts reduced bone mass in the offspring. In this study we aim to test whether offspring of mothers supplemented with vitamin D in pregnancy have higher bone mass at birth than those whose mothers were not supplemented.Methods/DesignWomen have their vitamin D status assessed after ultrasound scanning in the twelfth week of pregnancy at 3 trial centres (Southampton, Sheffield, Oxford). Women with circulating 25(OH)-vitamin D levels 25-100 nmol/l are randomised in a double-blind design to either oral vitamin D supplement (1000 IU cholecalciferol/day, n = 477) or placebo at 14 weeks (n = 477). Questionnaire data include parity, sunlight exposure, dietary information, and cigarette and alcohol consumption. At 19 and 34 weeks maternal anthropometry is assessed and blood samples taken to measure 25(OH)-vitamin D, PTH and biochemistry. At delivery venous umbilical cord blood is collected, together with umbilical cord and placental tissue. The babies undergo DXA assessment of bone mass within the first 14 days after birth, with the primary outcome being whole body bone mineral content adjusted for gestational age and age. Children are then followed up with yearly assessment of health, diet, physical activity and anthropometric measures, with repeat assessment of bone mass by DXA at age 4 years.DiscussionAs far as we are aware, this randomised trial is one of the first ever tests of the early life origins hypothesis in human participants and has the potential to inform public health policy regarding vitamin D supplementation in pregnancy. It will also provide a valuable resource in which to study the influence of maternal vitamin D status on other childhood outcomes such as glucose tolerance, blood pressure, cardiovascular function, IQ and immunology.

Maternal Diet, Behaviour and Offspring Skeletal Health

Osteoporotic fracture has a major impact upon health, both in terms of acute and long term disability and economic cost. Peak bone mass, achieved in early adulthood, is a major determinant of osteoporosis risk in later life. Poor early growth predicts reduced bone mass, and so risk of fracture in later life. Maternal lifestyle, body build and 25(OH) vitamin D status predict offspring bone mass. Recent work has suggested epigenetic mechanisms as key to these observations. This review will explore the role of the early environment in determining later osteoporotic fracture risk.

Maternal nutrition and bone health in the offspring

Osteoporosis is a major public health issue as well as a considerable socioeconomic burden owing to its association with fragility fractures. Bone mass (a composite of bone size and mineral density) increases through life, from conception to a peak in early adulthood. The magnitude of this peak bone mass is a major determinant of osteoporosis risk in later life. Over the last couple of decades, evidence has accrued that factors in utero and in early life may have persisting influences on later health and disease. Thus, low birthweight is associated with reduced bone density at peak and in older age, and poor infant growth predicts increased risk of hip fracture in later life. Maternal lifestyle, physical activity, body build and, in particular, vitamin D status, appear to be important determinants of intrauterine bone mineral accrual, with a persisting negative influence of maternal vitamin D insufficiency demonstrated at 9 years of age in the offspring. This review examines the impact of maternal nutriti...

Vitamin D and estrogen receptor-α genotype and indices of bone mass and bone turnover in Danish girls

Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERalpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERalpha genotypes were associated (P < 0.05) with reduced levels of urinary pyridinium cross-links, whereas serum osteocalcin was similar among genotypes. These findings suggest that the rate of bone resorption was influenced by ERalpha genotypes, even though these biochemical differences were not evident in bone mass indices.

Oral Communication Abstracts

Aims: Evidence suggests that intrauterine bone mineral accrual predicts osteoporosis risk in later life, and that maternal 25(OH)- vitamin D status in pregnancy is a determinant of neonatal bone mass. We aimed to explore the relationship between intrauterine bone mineral accrual in the offspring, and 1) maternal 25(OH)- vitamin D status during late pregnancy, and 2) expression of calcium transporters in the placenta. Methods: Pregnancies were recruited from the Southampton Women’s Survey, a unique, ongoing, well established cohort of women, aged 20–34 years, assessed before and during pregnancy. Maternal 25(OH)-vitamin D status was measured by radioimmunoassay in late pregnancy (34 weeks); the healthy, term, neonates underwent whole body (WB) DXA within 20 days of birth, using a Lunar DPX instrument. Placental samples, snap frozen in liquid nitrogen within 30 minutes of birth, were available for 70 of the pregnancies. A quantitative real time polymerase chain reaction was used to measure the mRNA expression of PMCA isoforms 1, 3 and 4 in the placenta, using beta-actin as a control gene. Results: 556 (286 males) neonates were studied. Offspring of mothers who were deficient ( late pregnancy had lower bone mass than those of replete mothers. Thus the mean WB bone area (BA) of the female offspring of 25(OH)-vitamin D deficient mothers was 110cm2 vs 119cm2 in offspring of replete mothers (p=0.04). The mean WB bone mineral content (BMC) for offspring of deficient vs replete mothers was 58g vs 63g (p=0.04), respectively. The relationships in the boys did not reach statistical significance. There was no association with maternal alkaline phosphatase. After controlling for beta-actin expression, PMCA3 mRNA expression predicted neonatal WB BA (r=0.28,p=0.02), WB BMC (r=0.25,p=0.04), placental weight (r=0.26,p=0.03), and birth weight (r=0.33,p=0.006). Conclusions: These data are consistent with previous findings that mothers deficient in 25(OH)-vitamin D in pregnancy have children with reduced bone mass. The mechanism underlying this process may be explained, in part, by the demonstrated association between expression of the placental calcium transporter PMCA3 and neonatal whole body bone mineral content. Further elucidation of this process may allow development of novel therapeutic strategies to optimise childhood bone mineral accrual and thus reduce osteoporotic fractures in future generations.

The Effect of Nutrient Intake on Bone Mineral Status in Young Adults: The Northern Ireland Young Hearts Project

Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.