Feitong Wu

Effects of Individualized Bone Density Feedback and Educational Interventions on Osteoporosis Knowledge and Self-Efficacy: A 12-Yr Prospective Study

This is 12-yr follow-up of a randomized controlled trial aimed to evaluate the long-term effects of bone density feedback and osteoporosis education on osteoporosis knowledge and self-efficacy. We examined the effects of feedback of bone density-defined fracture risk (high [T-score <0] vs normal [T-score ≥0] risk) and 2 different educational interventions (the group-based Osteoporosis Prevention and Self-Management Course [OPSMC] vs an osteoporosis leaflet) on osteoporosis knowledge and self-efficacy in women aged 25-44. Seventy-four percent (N = 347) of 470 participants at baseline participated at 12 yr. Overall, the scores were higher for osteoporosis knowledge but lower for self-efficacy at 12 yr. However, neither intervention had an effect on the change in knowledge (T-score, β = 0.4, 95% confidence interval [CI] = -0.3 to 1.1; OPSMC, β = 0.2, 95% CI = -0.5 to 0.9) or self-efficacy (T-score, β = -1.1, 95% CI = -2.5 to 0.4; OPSMC, β = -0.2, 95% CI = -1.6 to 1.3). Women in households with an unemployed main financial provider had a decrease in knowledge at 12 yr compared with those in households with an employed main financial provider in whom knowledge increased (β = -1.95, 95% CI = -3.40 to -0.50), but there were no other predictors of change identified for knowledge or self-efficacy. In conclusion, beneficial effects of both OPSMC and feedback of high fracture risk on osteoporosis knowledge seen previously at 2 yr were not sustained after 12 yr although overall knowledge was still significantly higher than at baseline. Neither intervention improved osteoporosis self-efficacy. More frequent osteoporosis education and bone density feedback may be required to maintain knowledge, and other approaches to improve self-efficacy are necessary.

Moderate-to-vigorous physical activity but not sedentary time is associated with musculoskeletal health outcomes in a cohort of Australian middle-aged women†

Associations between physical activity and time spent sedentary and musculoskeletal outcomes remain unclear in middle‐aged adults. This study aimed to describe associations between objectively‐measured physical activity and sedentary time and musculoskeletal health outcomes in middle‐aged women. This cross‐sectional study from a population‐based sample of 309 women (age 36 to 57 years) examined associations of total physical activity (accelerometer counts/min of wear time), and time spent sedentary, in light physical activities and moderate‐to‐vigorous physical activities (MVPA) (by Actigraph GT1M accelerometer) with lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) (by dual‐energy X‐ray absorptiometry), lower limb muscle strength (LMS), and functional mobility and balance tests (timed up and go test [TUG], functional reach test [FRT], lateral reach test [LRT], and step test [ST]) using linear regression. Total physical activity was beneficially associated with FN BMD (values are β; 95% CI) (0.011 g/cm2; 95% CI, 0.003 to 0.019 g/cm2), LMS (2.13 kg; 95% CI, 0.21 to 4.06 kg), and TUG (–0.080 s; 95% CI, –0.129 to –0.030 s), after adjustment for confounders. MVPA was also beneficially associated with FN BMD (0.0050 g/cm2; 95% CI, 0.0007 to 0.0094 g/cm2), LMS (1.48 kg; 95% CI, 0.45 to 2.52 kg), ST (0.12 steps; 95% CI, 0.02 to 0.23 steps), and TUG (–0.043 s; 95% CI, –0.070 to –0.016 s). Associations between MVPA and LMS, TUG and ST persisted after further adjustment for sedentary time. Only TUG was associated with sedentary time, with a detrimental effect (0.075 s; 95% CI, 0.013 to 0.137 s) and this did not persist after further adjustment for MVPA. Light physical activity was not associated with any outcome. MVPA appears more important than light physical activity or sedentary time for many musculoskeletal outcomes in middle‐aged women. This needs to be considered when developing interventions to improve habitual physical activity that aim to improve musculoskeletal health.

Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis.

Background: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). Objective: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. Methods: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size (Neff) = 5555) and a large MS GWAS (Neff = 15,231). Results: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 (p = 4.11 × 10−9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP (p = 3.32 × 10−20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance (p < 5 × 10−8). Conclusions: Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.

Both youth and long-term vitamin D status is associated with risk of type 2 diabetes mellitus in adulthood: a cohort study

Abstract Objectives: To determine whether vitamin D status in childhood and adolescence (herein collectively referred to as youth) and the long-term status from youth to adulthood is associated with risk of developing type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) in adulthood. Materials and methods: This was a 31-year follow-up study of 2300 participants aged 3–18 years. Multinomial logistic regression was used to assess the association of both (a) baseline 25-hydroxyvitamin D (25OHD) levels and (b) the mean of baseline and the latest follow-up 25OHD levels (continuous variable and quartiles) with incident T2DM and IFG (cut-off = 5.6 mmol/L) in adult life. Results: High serum 25OHD levels in youth and also mean values from youth to adulthood were associated with reduced risk of developing T2DM in adulthood (odds ratio, 95% confidence interval= 0.73, 0.57–0.95 and 0.65, 0.51–0.84, respectively, for each SD increment in 25OHD). Compared to Q1, a dose-dependent negative association was observed across other quartiles of youth 25OHD, while the strongest association was found in the Q3 for the mean 25OHD levels. Neither youth nor the mean 25OHD was associated with IFG. Conclusions: High serum 25OHD levels in youth, and from child to adult life, were associated with a reduced risk of developing T2DM in adulthood. Key Messages High serum 25OHD levels in youth, and between youth and adulthood, were associated with a lower risk of T2DM in adulthood. Each SD (15.2 nmol/L) increment in youth serum 25OHD levels was associated with a 26% reduction in odds for T2DM, which was independent of a number of confounding variables and other risk factors for T2DM. A similar magnitude of association was observed for the long-term 25OHD levels between youth and adulthood. These findings suggest a potentially simple and cost-effective strategy for reducing adulthood risk of T2DM starting in an earlier stage of life – improving and maintaining vitamin D status throughout youth and early adulthood.

Threshold Effects of Vitamin D Status on Bone Health in Chinese Adolescents With Low Calcium Intake

CONTEXT There is no consensus on the definition of vitamin D deficiency for bone health based on serum 25-hydroxyvitamin D (25OHD) levels. OBJECTIVE Our objective was to determine whether thresholds exist for associations between 25OHD levels and bone outcomes and if low 25OHD levels have adverse effects on bone health. DESIGN This is a cross-sectional study. PARTICIPANTS This study included secondary school students in Beijing, China, aged 12-15 years. MEASURES We measured serum 25OHD; bone mineral density (BMD) of total body, hip, and lumbar spine (LS); serum PTH; bone alkaline phosphatase (BAP); and tartrate-resistant acid phosphatase 5b (TRAP5b) in 222 healthy adolescents (111 girls, 111 boys). RESULTS The prevalence of low 25OHD was 61% (<30 nmol/liter) and 97% (<50 nmol/liter) (mean 25OHD, 30 nmol/liter). Dietary calcium intake was low (294 and 307 mg/d for boys and girls, respectively). In girls, break-points for 25OHD (nmol/liter) were: total body BMD 20 (95% confidence interval [CI], 14-27), hip BMD 25 (17-34), LS BMD 22 (14-30), TRAP5b 37 (22-52), and PTH 31 (23-38). In boys, break-points were: total body BMD 39 (24-55), TRAP5b 33 (20-45), and PTH 35 (27-43); no break-points were identified for hip and LS BMD. No break-points were identified for BAP in either gender. Below these break-points, higher 25OHD is associated with increased total body BMD, reduced PTH, and TRAP5b, whereas above these break-points, no such relationship exists. CONCLUSIONS Vitamin D deficiency and insufficiency is common in healthy Chinese adolescents. Attaining serum 25OHD levels of more than 20-37 nmol/liter in girls and 33-39 nmol/liter in boys had positive influences on BMD and bone remodelling markers. However, estimates may be affected by low calcium intake and low serum 25OHD levels, with 97% of adolescents having levels below 50 nmol/liter.

Tracking of areal bone mineral density from age eight to young adulthood and factors associated with deviation from tracking: A 17-year prospective cohort study

We have previously shown that bone mineral density (BMD) tracks strongly from age 8 to 16 years. This study aimed to describe whether this strong tracking continued to age 25 years and describe factors associated with deviation from tracking. Ninety‐nine participants were followed from age 8 to 25 years and 197 participants from age 16 to 25 years. Outcomes measured were BMD at the spine, hip, and total body (by dual‐energy X‐ray absorptiometry [DXA]). Other factors measured were anthropometrics, inhaled corticosteroids (ICS) use, history of being breastfed, sports participation, fitness (by physical work capacity [PWC170]), lean mass (LM), and fat mass (FM) (by DXA). There was moderate to strong tracking of BMD from age 8 to 25 years (correlation coefficients: males, 0.59 to 0.65; females, 0.70 to 0.82) and strong tracking from age 16 to 25 years (males, 0.81 to 0.83; females, 0.84 to 0.88) after adjustment for change in body size. From age 8 to 25 years, 54% to 56% of participants kept their BMD tertile position. PWC170 at age 8 years, relative and absolute change in LM, and sports participation at age 25 years predicted males would improve their tertile position or remain in the highest tertile of spine or hip BMD. However, relative and absolute change in FM had the opposite association in males while absolute change in FM predicted positive deviation in females. From age 16 to 25 years, LM, PWC170, sports participation at age 16 years, and change in LM, PWC170, and sports participation at age 25 years predicted positive deviation in males. LM at age 16 years was positively associated and PWC170 negatively associated with positive deviation in females. BMD tracks from childhood to early adulthood in both males and females. There appears to be greater capacity to alter tracking before age 16 years. Increasing LM in both sexes and improving fitness and sports participation in males during growth might be effective strategies to improve BMD in early adulthood.

Familial resemblance in trabecular and cortical volumetric bone mineral density and bone microarchitecture as measured by HRpQCT

To estimate the heritability of bone geometry, volumetric bone mineral density (vBMD) and microarchitecture of trabecular (Tb) and cortical (Ct) bone measured by high resolution peripheral quantitative computerised tomography (HRpQCT) at the distal radius and tibia and to investigate the genetic correlations of these measures. Participants were 177 mother-offspring pairs from 162 families (mothers, mean age (SD) = 52.1 (4.7) years; offspring, 25.6 (0.73) years). Trabecular and cortical bone measures were obtained by HRpQCT. Multivariable linear regression was used to analyse the association of bone measures between mother and offspring. Sequential Oligogenic Linkage Analysis Routines (SOLAR) software was utilised to conduct quantitative genetic analyses. All maternal bone measures were independently associated with the corresponding bone measures in the offspring before and after adjustment for age, sex, weight and height. Heritability estimates ranged from 24% to 67% at the radius and from 42% to 74% at the tibia. The relationship for most bone geometry measures was significantly stronger in mother-son pairs (n = 107) compared with mother-daughter pairs (n = 70) (p < 0.05). In contrast, the heritability for most vBMD and microarchitecture measures were higher in mother-daughter pairs. Bivariate analyses found moderate to strong genetic correlations across all measures between radius and tibia (Rg = 0.49 to 0.93). Genetic factors have an important role in the development of bone geometry, vBMD and microarchitecture. These factors are strongly shared for the radius and tibia but vary by sex implying a role for imprinting.

Both baseline and change in lower limb muscle strength in younger women are independent predictors of balance in middle age: A 12-Year population-based prospective study

Poor balance is a risk factor for falls and fracture in older adults, but little is known about modifiable factors affecting balance in younger women. This study aimed to examine whether lower limb muscle strength (LMS) in young women and changes in LMS are independent predictors of balance in middle age. This was an observational 10‐year follow‐up of 470 women aged 25 to 44 years at baseline who had previously participated in a 2‐year population‐based randomized controlled trial of osteoporosis education interventions. Linear regression was used to examine the association between baseline LMS (by dynamometer) and change in LMS over 12 years with balance at 12 years (timed up and go test [TUG], step test [ST], functional reach test [FRT], and lateral reach test [LRT]). LMS declined by a mean of 17.3 kg over 12 years. After adjustment for potential confounders, baseline and change in LMS were independently beneficially associated with TUG (β = –0.008 sec/kg, 95% confidence interval [CI] –0.01 to –0.006, and β = –0.006 sec/kg, 95% CI –0.009 to –0.003 for baseline and change, respectively), FRT (β = 0.057 cm/kg, 95% CI 0.030 to 0.084, and β = 0.071 cm/kg, 95% CI 0.042 to 0.101, respectively), and LRT (β = 0.030 cm/kg, 95% CI 0.012 to 0.049, and β = 0.022 cm/kg, 95% CI 0.002 to 0.043, respectively) 12 years later. There was an association between baseline LMS and ST (β = 0.044 steps/kg, 95% CI 0.022 to 0.067) but not between change in LMS and ST. Among young women, greater LMS at baseline and slower decline over time are both associated with better balance in midlife. Analogous to the contributions of peak bone mass and bone loss to fracture risk in older adults, this suggests that both improvement of muscle strength in younger age and prevention of age‐related loss of muscle strength could be potentially useful strategies to improve balance and reduce falls in later life.

Association of Youth Triponderal Mass Index vs Body Mass Index With Obesity-Related Outcomes in Adulthood

Debate continues on the limitations of using body mass index (BMI) to assign youth overweight/obesity status. Calculated as weight in kilograms divided by height in meters squared, BMI might not be applicable in youth during periods of rapid growth. Although recent evidence has indicated that triponderal mass index (TMI, calculated as weight in kilograms divided by height in meters cubed) might have better accuracy in estimating youth body fat levels than BMI, its clinical importance in estimating adulthood outcomes has not been examined. Therefore, we assessed whether youth TMI and its combination with BMI or subscapular skin fold thickness (SST), compared with BMI alone, have better utility in estimating adult obesity-related outcomes.

Predictive utility of childhood anthropometric measures on adult glucose homeostasis measures: a 20-year cohort study

Background/objectivesChildhood body mass index (BMI) predicts adult glucose homeostasis measures and type 2 diabetes mellitus, but little is known about the predictive utility of other anthropometric measures in childhood. We aimed to identify the anthropometric measure in childhood that best predicts adult glucose homeostasis measures and examine if the combination of additional anthropometric measures further improves predictive utility.MethodsA 20-year follow-up of children participating in the Childhood Determinants of Adult Health Study (n = 2345, aged 7–15 years at baseline). Baseline anthropometric measures were waist circumference (WC), WC adjusted for height, weight adjusted for height, hip circumference, waist-hip-ratio, waist-height-ratio, BMI, conicity index, abdominal volume index (AVI), body adiposity index, and a body shape index. Fasting glucose and insulin levels measured at follow-up were used to define insulin resistance (HOMA2-IR), low beta-cell function (HOMA2-β), high fasting insulin, and impaired fasting glucose (IFG).ResultsAll child anthropometric measures were significantly associated with HOMA2-IR, HOMA2-β, and high fasting insulin (relative risk = 1.12–1.55), but not IFG. AVI had the largest area under receiver-operating curve (AUC) in predicting adult HOMA2-IR (AUC, 95% confidence interval: 0.610, 0.584–0.637), HOMA2-β (0.615, 0.588–0.642) and high fasting insulin (0.613, 0.587–0.639). Combining each additional anthropometric measure with AVI did not appreciably increase predictive utility (an increase of 0.001–0.002 in AUC, p > 0.05 for all).ConclusionsAnthropometric measures from a single time-point in childhood are associated with insulin-related outcomes 20-year later in adulthood. However, overall predictive utility was low and was not substantially enhanced by combining multiple different child anthropometric measures.