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BACKGROUND: This project examined the ability of the popular DUI/DWI offender assessment instrument, the Driver Risk Inventory (DRI; Behavior Data Systems, Ltd., 1985), to identify short-term DUI recidivists in a sample of Floridian DUI offenders who were charged with DUI between January 1st, 2008 and December 31st, 2009. The DRI provides a number of behavioral risk scales, DSM-IV substance abuse and dependence classifications, as well as measurement of demographic and criminal history characteristics. METHODS: Cox proportional hazards models were used to identify the demographic, criminal history, and behavioral characteristics most closely associated with the risk of rapid DUI recidivism. Follow-up analyses including ROC curves were used to further examine the ability of the DRI to identify short-term DUI recidivists. RESULTS: In the final model controlling for all variables, the DRI driver risk scale was the single strongest predictor of rapid DUI recidivism. The DSM-IV substance abuse and dependence classifications were also significant predictors of DUI recidivism. A number of the DRI risk scales and the DSM-IV classifications exhibited significant predictive validity and exhibited sensitivity in identifying recidivists similar to other popular DUI offender assessment instruments. CONCLUSIONS: The DRI provides useful identification of DUI recidivists in a sample able to capture only the most rapid DUI recidivists. The results of this research warrant further examination of the DRI's ability to identify DUI recidivists using longer intervals of time between DUI arrests. [ABSTRACT FROM AUTHOR]

Bone disease with persistent reduced bone mineralisation is common in premature infants. To test the hypothesis that enhancement of nutritional intake after discharge from hospital improves bone mineralisation, 31 formula fed preterm infants were randomly assigned to receive standard or multinutrient enriched milk from the time of discharge. The calcium and phosphorus contents of the enriched milk were 70 and 35 mg/100 ml v 35 and 29 mg/100 ml for the standard formula. Bone mineral content was measured before discharge from hospital in 21 of the infants; there was no difference in the bone mineral content between the groups at that time (35 mg/cm for the two groups). There was a significant increase in bone mineral content for those infants receiving the enriched v standard formula at 3 and 9 months corrected postnatal age: at 3 months the bone mineral content was 83 v 63 mg/cm and at 9 months 115 v 95 mg/cm. The difference between the groups was thus maintained although not increased at a corrected age of 9 months, when the bone mineral content of infants fed the enriched but not the standard formula was no longer significantly different from that of normal infants after adjusting for body size. The difference was not explained by the larger body size in infants fed the enriched formula. The results suggest that the use of a special nutrient enriched postdischarge formula has a significant positive effect on bone growth and mineralisation during a period of rapid skeletal development. [ABSTRACT FROM AUTHOR]

Vitamin D is essential for the health of pregnant women and their infants. Vitamin D insufficiency and deficiency during pregnancy are reflected in lower maternal weight gain and biochemical evidence of disturbed skeletal homeostasis in the infant, with, in extreme situations, reduced bone mineralization, radiologically evident rickets, and fractures. Populations at risk for vitamin D deficiency are those for which, for environmental, cultural, or medical reasons, exposure to sunlight is poor and the dietary intake of vitamin D is low. The infants born in such populations have low vitamin D stores and may receive little additional vitamin D if they are breast-fed without supplements for long periods. In the short term, lack of vitamin D supplementation in infancy leads to biochemical disturbances, reduced bone mineralization, slower growth, and eventual alterations in bone shape and increased risk of fracture, the hallmarks of rickets. In the longer term, lack of vitamin D supplementation may result in reduced bone size and mass during childhood and an increased risk of type 1 diabetes mellitus. Clear recommendations are needed regarding the intake of vitamin D during pregnancy and infancy. Such recommendations should be based on functional outcomes, rather than biochemical measurements, so that the medical problems resulting from the lack of this essential nutrient can be overcome. Copyright © 2004 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Background: Findings from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial demonstrated a positive effect of gestational cholecalciferol supplementation on offspring bone mineral density (BMD) at age 4 y. Demonstrating the persistence of this effect is important to understanding whether maternal vitamin D supplementation could be a useful public health strategy to improving bone health., Objectives: We investigated whether gestational vitamin D supplementation increases offspring BMD at ages 6-7 y in an exploratory post-hoc analysis of an existing trial., Methods: In the MAVIDOS randomized controlled trial, pregnant females <14 wk' gestation with a singleton pregnancy and serum 25-hydroxyvitamin D 25-100nmol/l at 3 United Kingdom hospitals (Southampton, Sheffield, and Oxford) were randomly assigned to either 1000 IU/d cholecalciferol or placebo from 14 to 17-wk gestation until delivery. Offspring born at term to participants recruited in Southampton were invited to the childhood follow-up at ages 4 and 6-7 y. The children had a dual-energy X-ray absorptiometry (DXA, Hologic discovery) scan of whole-body-less-head (WBLH) and lumbar spine, from which bone area, bone mineral content (BMC), BMD, and bone mineral apparent density (BMAD) were derived. Linear regression was used to compare the 2 groups adjusting for age, sex, height, weight, duration of consumption of human milk, and vitamin D use at 6-7 y., Results: A total of 454 children were followed up at ages 6-7 y, of whom 447 had a usable DXA scan. Gestational cholecalciferol supplementation resulted in higher WBLH BMC [0.15 SD, 95% confidence interval (CI): 0.04, 0.26], BMD (0.18 SD, 95% CI: 0.06, 0.31), BMAD (0.18 SD, 95% CI: 0.04, 0.32), and lean mass (0.09 SD, 95% CI: 0.00, 0.17) compared with placebo. The effect of pregnancy cholecalciferol on bone outcomes was similar at ages 4 and 6-7 y., Conclusions: Supplementation with cholecalciferol 1000 IU/d during pregnancy resulted in greater offspring BMD and lean mass in mid-childhood compared with placebo in this exploratory post-hoc analysis. These findings suggest that pregnancy vitamin D supplementation may be an important population health strategy to improve bone health., Trial Registration Number: This trial was registered at the ISRCTN (https://doi.org/10.1186/ISRCTN82927713) as 82927713 and EUDRACT (https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001716-23/results) as 2007-001716-23., Competing Interests: Conflict of interest RJM has received travel bursaries from Kyowa Kirin unrelated to this work. EMC has received travel bursaries or lecture fees from Eli Lilly, Pfizer, Thornton and Ross, and UCB, unrelated to this work. KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd., and Danone, outside the submitted work. MKJ reports consultancy and speaker fees from UCB, Amgen, and Kyowa Kirin. CC reports personal fees from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, and Takeda, outside the submitted work. NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Theramex, Shire, Consilient Healthcare, Kyowa Kirin, and Internis Pharma, outside the submitted work. KAW received Honoraria from Abbott Nutrition unrelated to this work. IS, SRC, and SD declare no conflicts of interest related to the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Person-centered approaches to measuring severity of multimorbidity (≥ 2 chronic conditions) can help clinicians assess the individual experience of multimorbidity and inform effective caregiving and intervention strategies. We examine how limitations in everyday activities attributable to specific chronic conditions act independently and in tandem to influence individual perceptions of multimorbidity severity., Methods: Data from the Panel Study of Income Dynamics (2005-2021) were used to investigate self-reported limitations in normal daily activities resulting from nine chronic conditions (hypertension, arthritis, diabetes, heart condition [heart disease/heart attack], cancer, lung disease, stroke, depression, and memory loss) in 4 318 adults aged 55-95 (18 878 person-wave observations). We used descriptive and inferential analyses to estimate limitations resulting from specific conditions, limitations attributable to condition combinations, and the contribution of comorbid conditions to condition-specific and overall severity. Follow-up analyses addressed mortality selection using inverse probability weighting and examined cancer type and cancer status/treatment modality among respondents reporting cancer diagnosis., Results: Of the more prevalent conditions, arthritis was associated with the most severe limitations to normal activities. Memory loss was the least frequent condition reported but resulted in the most severe limitations, and as a comorbid condition, increased limitations reported for most conditions. Inverse probability weighting adjusted models revealed heterogeneity in estimates for some conditions including cancer and cancer survivors tended to report less lethal cancers that were cured or in remission., Conclusions: Our results suggest that efforts to prevent and treat arthritis and support cognitive function may reduce the severity of multimorbidity experienced by the individual., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Excessive production of Transforming Growth Factor β (TGFβ) is commonly associated with dominant and recessive forms of OI. Previous reports have indicated that administration of TGFβ-targeted antibodies maybe of potential therapeutic benefit to OI patients. However, direct targeting of TGFβ is likely to cause multiple adverse effects including simulation of autoimmunity. In the current study we use patient-derived normal and OI fibroblasts, osteoblasts and OIM mouse models to determine the effects of Losartan, an angiotensin II receptor type 1 (AT1) antagonist, on TGFβ signalling and bone morphology in OI. In OIM mice bred on a mixed background administration of 0.6 g/L losartan for 4 weeks was associated with a significant reduction in TGFβ from 79.2 g/L in the control to 60.0 ng/ml following losartan ( p  < 0.05), reduced osteoclast activity as measured by CTX from 275.9 ng/ml in the control to 157.2 ng/ml following 0.6 g/L of losartan (p < 0.05) and increased cortical bone thickness ( P  < 0.001). Furthermore in OIM mice bred on a C57BL/6 background 0.6 g/L losartan increased trabecular bone volume in the tibiae ( P  < 0.05) and the vertebrae ( P  < 0.01), increased cortical bone thickness ( P  < 0.001) reduced the trabecular pattern factor ( P  < 0.01 and P < 0.001 for the tibiae and vertebrae respectively), reduced osteoclast ( P  < 0.05) and osteoblast (P < 0.01) numbers as well as reducing the area of bone covered by these cell types. Interestingly, losartan did not affect immune cells infiltrating into bone, nor did this drug alter TGFβ signalling in normal or OI fibroblasts. Instead, losartan reduced SMAD2 phosphorylation in osteoblasts, inhibiting their ability to differentiate. Our data suggest that losartan may be an effective treatment for the bone-associated dysmorphia displayed in OI whilst minimising potential adverse immune cell-related effects., Competing Interests: NJB is global chief investigator of the Ultragenyx-funded studies (ORBIT, COSMIC) of setrusumab in children and young adults with OI and has consulted with Alexion, Mereo and Rampart and has been DMEC chair for a Pfizer study (recifercept in achondroplasia). No other authors have relevant conflicts of interest to declare., (© 2024 The Authors.)

Background: The rapidly growing field of multimorbidity research demonstrates that changes in multimorbidity in mid- and late-life have far reaching effects on important person-centered outcomes, such as health-related quality of life. However, there are few organizing frameworks and comparatively little work weighing the merits and limitations of various quantitative methods applied to the longitudinal study of multimorbidity., Methods: We identify and discuss methods aligned to specific research objectives with the goals of (i) establishing a common language for assessing longitudinal changes in multimorbidity, (ii) illuminating gaps in our knowledge regarding multimorbidity progression and critical periods of change, and (iii) informing research to identify groups that experience different rates and divergent etiological pathways of disease progression linked to deterioration in important health-related outcomes., Results: We review practical issues in the measurement of multimorbidity, longitudinal analysis of health-related data, operationalizing change over time, and discuss methods that align with 4 general typologies for research objectives in the longitudinal study of multimorbidity: (i) examine individual change in multimorbidity, (ii) identify subgroups that follow similar trajectories of multimorbidity progression, (iii) understand when, how, and why individuals or groups shift to more advanced stages of multimorbidity, and (iv) examine the coprogression of multimorbidity with key health domains., Conclusions: This work encourages a systematic approach to the quantitative study of change in multimorbidity and provides a valuable resource for researchers working to measure and minimize the deleterious effects of multimorbidity on aging populations., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Existing research suggests that children who experience poverty and hospitalization in early childhood are at risk of developing behavior problems. We examined whether the association between early childhood hospitalization and children's internalizing and externalizing behaviors were moderated by family poverty status and child sex. Participants included 224 children from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development. There was no direct association between hospitalization and problematic behaviors. Poverty status during early childhood, but not child sex, significantly moderated the association between hospitalization and externalizing problems. Findings support the need for community programs that promote an integrative approach to healthcare for families experiencing poverty., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Observational studies relating maternal 25-hydroxyvitamin D status to timing and mode of delivery have reported inconsistent results. We assessed the effect of antenatal cholecalciferol supplementation on the incidence of preterm birth, delivery mode and post-partum haemorrhage (PPH)., Methods: MAVIDOS was a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks' gestation until delivery. Gestational age, mode of delivery [categorized as spontaneous vaginal delivery (SVD), instrumental (including forceps and vacuum extraction) or Caesarean section] and PPH (>500 ml estimated blood loss) were determined from medical records., Results: A total of 965 women participated in the study until delivery. Gestation at birth and incidence of preterm birth (cholecalciferol 5.7%, placebo 4.5%, P = 0.43) were similar between the two treatment groups. SVD (versus instrumental or Caesarean delivery) was more likely in women randomized to cholecalciferol [Relative Risk (RR) 1.13, 95% confidence interval (CI) 1.02,1.25] due to lower instrumental (RR 0.68, 95%CI 0.51,0.91) but similar risk of Caesarean delivery (RR 0.94, 95%CI 0.74,1.19). PPH was less common in women randomized to cholecalciferol [32.1% compared with placebo (38.1%, P = 0.054) overall], but similar when stratified by delivery mode., Conclusions: Antenatal cholecalciferol supplementation did not alter timing of birth or prevalence of preterm birth but demonstrated a possible effect on the likelihood of SVD., (© The Author(s) 2022. Published by Oxford University Press on behalf of Faculty of Public Health.)

Objectives: Multimorbidity, also referred to as multiple chronic conditions (MCCs), is the concurrent presence of 2 or more chronic health conditions. Increasing multimorbidity represents a substantial threat to the health of aging populations. Recent trends suggest greater risk of poor health and mortality among later-born cohorts, yet we are unaware of work examining cohort differences in multimorbidity among aging U.S. adults., Methods: We examine intercohort variation in MCC burden in adults aged 51 years and older using 20 years (n = 33,598; 1998-2018) of repeated assessment drawn from the Health and Retirement Study. The index of MCCs included 9 chronic conditions (heart disease, hypertension, stroke, diabetes, arthritis, lung disease, cancer excluding skin cancer, high depressive symptoms, and cognitive impairment). We used linear mixed models with various approaches to estimate age/period/cohort effects to model intercohort patterns in MCC burden. We also explored variation in the specific conditions driving cohort differences in multimorbidity., Results: More recent cohorts had greater MCC burden and developed multimorbidity at earlier ages than those born to prior generations. The burden of chronic conditions was patterned by life-course sociodemographic factors and childhood health for all cohorts. Among adults with multimorbidity, arthritis and hypertension were the most prevalent conditions for all cohorts, and there was evidence that high depressive symptoms and diabetes contributed to the observed cohort differences in multimorbidity risk., Discussion: Our results suggest increasing multimorbidity burden among more recently born cohorts of aging U.S. adults and should inform policy to address diminishing health in aging populations., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Biochemical and haematological testing is recommended in the United Kingdom when inflicted injury is suspected. We examined the associations of test results with radiologically-confirmed fracture(s), and between test results, in a large retrospective observational cohort., Methods: Infants up to age two years presenting with suspected inflicted injury, without clinically or radiologically apparent bone disease, and where a skeletal survey was undertaken during the period 1st August 2013 to 31st December 2020, were included. Biochemical parameters: corrected calcium (cCa); phosphate (P); alkaline phosphatase (ALP); parathyroid hormone (PTH); 25-hydroxyvitamin D (25D); and haematological parameters: haemoglobin (Hb); mean corpuscular haemoglobin (MCH); mean corpuscular haemoglobin content (MCHC); mean corpuscular volume (MCV); platelet count were collated together with the results of the radiological assessments., Findings: Of 332 eligible infants (190 male), 142 (84 male) had fracture(s) and/or intracranial injury. Mean PTH in the non-fracture group (n measured 50/190) was 27.3 ng/l; in those with intracranial injury alone (n measured 9/23) was 39.4 ng/l; in those with fracture alone (n measured 62/84) was 45.0 ng/l; and in those with fracture and intracranial injury (n measured 20/35) 51.8 ng/l. F-test of multiple means = 0.0369. There was no difference in 25D between the groups., Interpretation: PTH was raised in infants who had fracture(s), intracranial injury or both. A single raised PTH may not necessarily be an indicator of prior disturbed skeletal health in these circumstances. The relevance of vitamin D status and interpretation of data from biochemical testing should be informed by the overall presentation in suspected inflicted injury cases. A single raised PTH may be a consequence of the child's injuries rather than prior disturbed bone health., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Secreted protein, acidic, cysteine rich ( SPARC )-related osteogenesis imperfecta (OI), also referred to as OI type XVII, was first described in 2015, since then there has been only one further report of this form of OI. SPARC is located on chromosome 5 between bands q31 and q33. The encoded protein is necessary for calcification of the collagen in bone, synthesis of extracellular matrix and the promotion of changes to cell shape., Methods: We describe a further two patients with previously unreported homozygous SPARC variants with OI: one splice site; one nonsense pathogenic variant. We present detailed information on the clinical and radiological phenotype and correlate this with their genotype. There are only two previous reports by Mendozo-Londono et al and Hayat et al with clinical descriptions of patients with SPARC variants., Results: From the data we have obtained, common clinical features in individuals with OI type XVII caused by SPARC variants include scoliosis (5/5), vertebral compression fractures (5/5), multiple long bone fractures (5/5) and delayed motor development (3/3). Interestingly, 2/4 patients also had abnormal brain MRI, including high subcortical white matter changes, abnormal fluid-attenuated inversion in the para-atrial white matter and a large spinal canal from T10 to L1. Of significance, both patients reported here presented with significant neuromuscular weakness prompting early workup., Conclusion: Common phenotypic expressions include delayed motor development with neuromuscular weakness, scoliosis and multiple fractures. The data presented here broaden the phenotypic spectrum establishing similar patterns of neuromuscular presentation with a presumed diagnosis of 'myopathy'., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The current study aimed to investigate the association between grandparenting and cognitive function over time in noncustodial grandparents in China and the United States. Lagged dependent variable (LDV) approach and linear regression models were applied to analyze a sample of 1,411 Chinese and 6,579 American adults aged 65 and above from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2013) and the U.S. Health and Retirement Study (HRS, 2012-2014). Grandparenting involvement was associated with less decline in episodic memory for grandparents and greater level of grandparenting had no negative effect on mental status and global cognitive function in noncustodial grandparents in China and the United States. The impact of grandparenting on cognitive function was conditioned on caregiving intensity, gender, urban/rural residence, and nation. Findings of the study suggest that greater attention on grandparenting facilitation might yield improved research, social support, policy, and interventions on cognitive health for the general older population.

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008-2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013-2018). Anthropometry and dual-energy X-ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm 2 ; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm 2 , p  = 0.048). Associations were consistent for BMC and lean mass, and in age- and sex-adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: EMC reports honoraria/travel support from Eli Lilly, Pfizer, and UCB outside the submitted work. NJB reports remuneration from Internis Pharmaceuticals Ltd, outside the submitted work. ATP reports grants from Versus Arthritis, Medical Research Council, National Institute for Health Research, Bupa Foundation, BBSRC, and EU outside the submitted work. KMG reports reimbursement for speaking at Nestle Nutrition Institute conferences, grants from Abbott Nutrition & Nestec, outside the submitted work; in addition, KMG has a patent Phenotype Prediction pending, a patent Predictive Use of CpG Methylation pending, and a patent Maternal Nutrition Composition pending, not directly related to this work. MKJ reports personal fees from Stirling Anglia, Consilient Health and Internis, outside the submitted work. RE reports grants from Amgen, grants and personal fees from IDS, grants from Alexion, grants and personal fees from Roche, personal fees from GSK Nutrition, personal fees from Mereo, personal fees from Sandoz, grants and personal fees from Nittobo, personal fees from AbbVie, personal fees from Samsung, personal fees from Haoma Medica, personal fees from Elsevier, personal fees from CL Bio, personal fees from FNIH, personal fees from Viking, personal fees from UCSF, personal fees from Biocon, from Lyramid, outside the submitted work. CC reports personal fees from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier and Takeda, outside the submitted work. NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Consilient Healthcare, Kyowa Kirin and Internis Pharma, outside the submitted work. RJM, SD, SRC, JSGK, SHK, RF, SVG, IS, AP, and HMI have nothing to disclose. Of the MAVIDOS group: N. Arden has received honoraria, held advisory board positions (which involved receipt of fees), and received consortium research grants, respectively, from: Merck, grants from Roche, personal fees from Smith & Nephew, Nicox, Flexion, grants from Bioiberica, Novartis, and personal fees from Bioventus and Freshfields, outside the submitted work. M.Z. Mughal has received lecture fees from Abbott Nutrition & Thornton & Ross, outside the submitted work. A. Carr, M. Clynes, E. Dennison, D. Reid, and S. Woolford have nothing to disclose., (© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Objectives: In the context of a lack of national consensus on the benefits of skull base imaging in children with osteogenesis imperfecta (OI), this study aims to analyse and correlate the clinical symptoms and radiological images of children with severe OI., Methods: A retrospective case notes and image analysis was carried out on children with complex OI between 2012 and 2018 at a specialist tertiary centre. Data were collected on patient demographic factors, clinical data, imaging findings (presence of Wormian bones, platybasia, basilar impression (McGregor's technique) and basilar invagination (McRae's technique)), and clinical features at the time of imaging., Results: Of the 127 patients in the OI database, 94 were included. A total of 321 radiographs, 21 CT scans and 39 MRI scans were analysed. Average frequency of radiographs was 8 per 10 years. Of the 94 patients, 58 (62%), 10 (11%), 1 (1%) demonstrated platybasia, basilar impression, and basilar invagination, respectively. Of the radiographs analysed, platybasia, basilar impression, basilar invagination, and the presence of Wormian bones, could not be evaluated in 71 (22.3%), 48 (15.2%), 61 (19.5%) and 28 (9.4%) radiographs respectively (due to poor positioning, anatomical abnormalities, and poor image quality). Of the 140 radiographs with platybasia, 17 (12%) also demonstrated basilar impression compared to only 3 (2.9%) out of the 99 without platybasia (p = 0.03). No significant associations were seen between the presence of Wormian bones and basilar impression. Of the 39 MRIs, additional information on CSF flow rate, spinal cord signal and cerebellar morphology was reported in 14 (36%). There was a lack of concordance between MRI and matched radiographs in 7.1% (1/14) and 36% (5/14) for platybasia and basilar impression respectively, with full concordance for basilar invagination. Fewer than 5% had positive clinical symptoms/signs at the time of imaging; 2% (7/321) had macrocephaly, 0.6% (2/321) headache, all other neurological features were absent). Clinical features were not documented in >85% of patients., Conclusion: The apparent low prevalence of clinical symptoms and signs and of radiologically identified cranio-cervical abnormalities, suggests that current levels of serial imaging may be excessive. Until larger prospective studies clarify these issues, we suggest a clinical pathway for base of skull imaging which proposes a risk stratification approach to radiographic frequency and suggests parameters for proceeding to MRI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

eHealth literacy is a critical factor that influences caregivers' well-being. The purpose of this study is to examine the association between eHealth literacy, education, and caregiver burden among Chinese caregivers of older adults with cognitive impairment. Data came from structured interviews with 300 primary family caregiver-care recipient dyads in Wuhan, China. We used logistic regression to examine the association between eHealth literacy, education, and caregiver burden. An interaction effect between eHealth literacy and education on caregiver burden was identified. eHealth literacy was positively associated with caregiver burden among caregivers with less than a high school education, but not among those with a high school education or above. eHealth literacy is salient in the burden experienced by caregivers with low education. eHealth literacy needs to be enhanced with health information verification from health professionals and programs to support caregiving efficacy to realize its positive impact on caregivers' mental health.

To identify potentially modifiable risk-factors in the age-related disablement process, we examined the association between change in mobility limitations and multimorbidity and how dietary quality moderates this association. Information from 3320 adults aged 65 and older in 2012 was drawn from the Health and Retirement Study and the Health Care and Nutrition Study. Mobility limitations reported in 2012 and change in mobility limitations from 2012 to 2014 were regressed on multimorbidity measured as number of chronic conditions in 2012, dietary quality measured in 2013 using the Alternative Healthy Eating Index-2010 (AHEI-2010), and their interaction term using Poisson regression. Respondents reported an average of 2.9 (SD, 2.9) mobility limitations in 2012 and 3.1 (SD, 3.0) mobility limitations in 2014, an average of 2.64 (SD, 1.4) chronic conditions in 2012, and mean AHEI-2010 score in 2013 of 57.1 (SD, 10.9). Greater AHEI-2010 scores were associated with fewer mobility limitations at baseline (p < .001) and slower progression of mobility limitations over the two-year observational window (p < .001). For those with AHEI-2010 scores ≥48.4, dietary quality appeared to moderate the association between multimorbidity and change in mobility limitations. These results suggest that improving dietary quality may be an effective means of reducing the progression of mobility limitations among older adults and that dietary quality may modify the effect of multimorbidity on progressive disablement. Our work adds to research supporting dietary quality as a potentially intervenable factor in the reduction of disablement in aging populations., (Copyright © 2021. Published by Elsevier Inc.)

Background: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized., Objectives: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices., Methods: MAVIDOS (the Maternal Vitamin D Osteoporosis Study) is a randomized, double-blind, placebo-controlled trial of 1000 IU cholecalciferol/d compared with placebo from 14 weeks of gestation to birth. Maternal second-void urinary α- and β-CTX were measured (ELISA) at 14 and 34 weeks of gestation; DXA was performed within 2 wk postpartum. The Mann-Whitney Rank Sum test, Spearman's rank correlation, and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes., Results: In total, 372 women had CTX and 25-hydroxyvitamin D [25(OH)D] measured in early and late pregnancy. CTX at 14 and 34 weeks of gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX increased from 14 to 34 weeks of gestation in both groups (n = 372 total) [placebo (n = 188): from 223.6 to 449.7 μg/mmol creatinine; cholecalciferol (n = 184): from 222.3 to 419.3 μg/mmol creatinine; P = 0.03 for placebo compared with cholecalciferol difference in CTX at 34 weeks of gestation]. The conditional mean ± SD increase in CTX [z-score (SD)] from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) (placebo: 0.16 ± 0.92; cholecalciferol: -0.16 ± 1.06; P-difference < 0.01). Higher CTX at 34 weeks of gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content and bone mineral density (BMD) (e.g., lumbar spine BMD: β = -0.02 g · cm-2 · SD-1 increase in CTX; 95% CI: -0.027, -0.002 g · cm-2 · SD-1; P = 0.02, n = 283)., Conclusions: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, although to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass postpartum.This trial was registered at www.isrctn.com as ISRCTN 82927713 and eudract.ema.europa.eu as EudraCT 2007-001716-23., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: Osteogenesis Imperfecta (OI) is a heterogeneous condition mainly characterised by bone fragility; extra-skeletal features in OI include blue sclerae, dentinogenesis imperfecta, skin laxity and joint hyper-extensibility. Most patients with OI are thought to have a low bone mass but contrary to expectations there are certain forms of OI with high bone mass which this study explores in further detail., Method: A cohort of n = 6 individuals with pathogenic variants in BMP1 and the C-propeptide cleavage variants in COL1A1 were included in this study. Detailed clinical and radiological phenotyping was done and correlated with genotype to identify patterns of clinical presentation and fracture history in this cohort of patients. This data was compared to previously reported literature in this group., Results: 2 patients with BMP1 and 4 patients with pathogenic variants in C-propeptide region in COL1A1 were deep-phenotyped as part of this study and 1 patient with C-propeptide variant in COL1A1 , showed low bone mineral density. In those with an elevated bone mineral density, this became even more apparent on bisphosphonate therapy. Patients in this cohort had variable clinical presentation ranging from antenatal presentation to more of an insidious course resulting in later confirmation of genetic diagnosis up to 19 years of age., Conclusions: Patients with pathogenic variants in the C-propeptide region of COL1A1/A2 and BMP1 appear to have a high bone mass phenotype with increased sensitivity to bisphosphonate therapy. It is important to closely monitor patients with these genotypes to assess their response to therapy and tailor their treatment regime accordingly., Competing Interests: The authors declare that they have no known competing financialinterestsor personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Objective: Existing research suggests walnut intake may be associated with better cognitive function in older adults, yet few studies utilise longitudinal data from observational studies of ageing populations. Our objective was to estimate the association between whole walnut intake and cognitive change in a representative sample of older Americans., Design: Secondary analysis of the Health and Retirement Study and Health Care and Nutrition Study. Walnut consumption was defined as a categorical measure (none, low intake (0·01-0·08 1 oz. servings per day) and moderate intake (>0·08 1 oz. servings per day)) and cognitive function was measured using the Telephone Interview for Cognitive Status. Latent growth modelling estimated the association between walnut consumption and trajectories of cognitive status over a 4-year observational period. Sensitivity analyses assessing non-random dropout and Monte Carlo power analyses were conducted to contextualise results., Setting: The USA., Participants: A sample of 3632 US adults aged 65 years and older., Results: Those reporting any walnut consumption had greater cognitive scores at baseline than those not consuming walnuts (low walnut consumption, b = 1·53, se = 0·21, P < 0·001; moderate walnut consumption, b = 2·22, se = 0·27, P < 0·001), but walnut consumption was not associated with cognitive change. Walnut consumption was positively associated with socioeconomic status and health behaviours as well as intake of nutrients identified to have neuroprotective benefits., Conclusions: We identified an association between walnut consumption and cognitive function in older adults, although we did not find that walnut consumption was protective against age-related cognitive decline.

Objective: The purpose of the study was to examine the association between dietary lutein and zeaxanthin (L + Z) intake and immediate word recall (IWR) and delayed word recall (DWR), and to identify the major contributors to dietary L + Z intake in a recent and representative sample of the older US population., Design: In this cross-sectional analysis, multivariate path analytic models estimated the association between L + Z consumption and cognitive performance while adjusting for covariates., Setting: Observations were drawn from the 2014 Health and Retirement Study, a nationally representative panel study of older US adults, and the 2013 Health Care and Nutrition Study, which assessed dietary intake via FFQ in a subsample of respondents., Participants: The analytic sample included 6390 respondents aged ≥50 years., Results: L + Z intake was 2·44 ± 2·32 mg/d on average, and L + Z intake differed significantly across quartiles (P < 0·001). For example, average L + Z intake in Q1 was 0·74 ± 0·23 mg/d and in Q4 was 5·46 ± 2·88 mg/d. In covariate adjusted models, older adults in the highest quartiles of L + Z intake had significantly greater IWR and DWR scores than those in the lowest quartile. Leafy vegetables, cruciferous vegetables, dark yellow vegetables, fish and seafood, legumes, eggs and fruit were significant and meaningful predictors of dietary L + Z intake., Conclusion: A high consumption of vegetables, fish and seafood, legumes, eggs and fruit is associated with a higher intake of L + Z and greater word recall among older adults.

Bone health in children with osteogenesis imperfecta is monitored using radiographs and dual-energy X-ray absorptiometry, which have limitations. High-resolution peripheral quantitative CT can non-invasively derive bone microarchitectural data. Children with severe osteogenesis imperfecta have fragile deformed bones, and positioning for this scan can be difficult. We assessed the feasibility of high-resolution peripheral quantitative CT in nine children aged 9-15 years with osteogenesis imperfecta and compared results with dual-energy X-ray absorptiometry and with healthy controls. All nine recruited children were successfully scanned and showed no preference for either modality. It therefore appears feasible to perform high-resolution peripheral quantitative CT in children with osteogenesis imperfecta aged 9 years and older. Future studies should focus on understanding the clinical implications of the technology in this patient cohort.

This article provides an overview of the current knowledge on hypophosphatasia-a rare genetic disease of very variable presentation and severity-with a special focus on adolescents and adults. It summarizes the available information on the many known mutations of tissue-nonspecific alkaline phosphatase (TNSALP), the epidemiology and clinical presentation of the disease in adolescents and adults, and the essential diagnostic clues. The last section reviews the therapeutic approaches, including recent reports on enzyme replacement therapy (EnzRT).

Objective: To estimate latent dietary profiles in a community-dwelling sample of older Americans and identify associations between dietary profile membership and individual demographic, socio-economic and health characteristics., Design: Secondary analysis of the 2012 Health and Retirement Study (HRS) and linked 2013 Health Care and Nutrition Study (HCNS). Latent profile analysis identified mutually exclusive subgroups of dietary intake and bivariate analyses examined associations between dietary profile membership, participant characteristics and nutrient intakes., Setting: USA., Participants: An analytic sample of 3558 adults aged 65 years or older., Results: Four dietary profiles were identified with 15·5 % of the sample having a 'Healthy' diet, 42·0 % consuming a 'Western' diet, 29·7 % having a diet consisting of high intake of all food groups and 12·7 % reporting relatively low intake of all food groups. Members of the 'Healthy' profile reported the greatest socio-economic resources and health, and members of the 'Low Intake' profile had the fewest resources and worst health outcomes. Macronutrient and micronutrient intakes varied across profile although inadequate and excessive intakes of selected nutrients were observed for all profiles., Conclusions: We identified dietary patterns among older Americans typified by either selective intake of foods or overall quantity of foods consumed, with those described as 'Low Intake' reporting the fewest socio-economic resources, greatest risk of food insecurity and the worst health outcomes. Limitations including the presence of measurement error in dietary questionnaires are discussed. The causes and consequences of limited dietary intake among older Americans require further study and can be facilitated by the HRS and HCNS.

Background and Objectives: The purpose of the present study is to examine the socioeconomic correlates of adherence to minimum mineral intake recommended by the Chinese Dietary Guidelines during each trimester of pregnancy among Chinese women., Methods and Study Design: A total of 567 pregnant women with foetal age of 6 - 12 weeks were recruited from nine community health centres and three hospitals. Cross-sectional survey data were collected using structured interviews and questionnaires. Mineral intake was calculated from food consumption reported on 24-hour dietary reviews using the Chinese Food Composition Metrics. Logistic regression models were estimated to assess the relationship between sociodemographic factors and adherence to mineral intake recommendations for each trimester., Results: Significant predictors of adherence to mineral intake recommendations include: (1) age (zinc: OR=1.09, p<0.05; copper: OR=1.11, p<0.05), having bachelor's degree (copper: OR=2.23, p<0.05; phosphorus: OR=2.23, p<0.01), and household income ≥5,000RMB (potassium: OR=2.51, p<0.001; phosphorus: OR=1.91, p<0.05) during the first trimester, (2) being employed (zinc: OR=0.54, p<0.001; selenium: OR=0.53, p<0.05) and household income ≥5,000 RMB (zinc: OR=1.86, p<0.05) during the second trimester, and (3) husband/partner with associate degree or vocational school education (selenium: OR=3.26, p<0.01) and household income of 3,000-4,999 RMB (potassium: OR=1.71, p<0.05; zinc: OR=1.48, p<0.05) during the third trimester., Conclusions: To our knowledge, this is the first study that examines the relationship between socioeconomic factors and mineral intake among Chinese pregnant women at three trimesters. Findings highlight the importance of considering individuals' socioeconomic status to develop personalized interventions to prevent undernutrition among this population.

Objective: Existing research supports a positive relationship between egg intake and cognitive function in older populations, although the impact of whole egg consumption on multi-domain cognitive function and cognitive decline in representative samples of older adults has not been described. We examined the association between egg consumption, cognitive performance, and cognitive change in a representative sample of U.S. adults aged 65 and older. Methods: We drew observations from the 2012 and 2014 Health and Retirement Study and the recently released 2013 Health Care and Nutrition Study. The analytic sample contained 3835 respondents, representing a weighted population of 37,806,082 community-dwelling adults aged 65 and older in 2013. Multivariate path analytic models were used to estimate the association between egg consumption groups (none, ≤ 1 serving per week, 2-6 servings per week, ≥ 7 servings per week) and cognitive performance across domains of working memory, executive function, and global mental status. First-order autoregressive models were used to estimate cognitive change over the 2-year observational period. Follow-up analyses examined associations between egg consumption group, dietary patterns, and nutrient intake. Results: On average, older adults consumed 0.34 eggs per day ( SD  = 0.36). Although bivariate analyses suggested that moderate egg consumers had the best cognitive performance at baseline assessment, egg consumption was not associated with cognitive performance or cognitive change when adjusting models for covariates known to have a robust association with cognitive health. Conclusions: Our results suggest that egg consumption does not benefit, nor is detrimental to, the cognitive health of older adults. Further studies of whole egg consumption and cognitive performance would benefit from controlled experimental settings, longer follow-up periods to measure cognitive change, and assessment of both community-dwelling and institutionalized older adults.

We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. In this study, we used an existing randomized trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicenter, double-blind, randomized, placebo-controlled trial of 1000 IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at -80°C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significantly lower in the umbilical cord from offspring of cholecalciferol-supplemented mothers, reaching statistical significance at four CpG sites, represented by CpG5: mean difference in % methylation between the supplemented and placebo groups was -1.98% (95% CI, -3.65 to -0.32, p = 0.02). ENCODE (Encyclopedia of DNA Elements) evidence supports the functionality of this locus with strong DNase hypersensitivity and enhancer chromatin within biologically relevant cell types including osteoblasts. Enrichment of the enhancer-related H3K4me1 histone mark is also seen in this region, as are binding sites for a range of transcription factors with roles in cell proliferation, response to stress, and growth factors. Our findings are consistent with previous observational results and provide new evidence that maternal gestational supplementation with cholecalciferol leads to altered perinatal epigenetic marking, informing mechanistic understanding of early life mechanisms related to maternal vitamin D status, epigenetic marks, and bone development. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc., (© 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.)

Objectives: It is well established that UK Asians typically have lower vitamin D levels than Caucasians. It is also known that vitamin D binding protein (DBP) is lower in some races than Caucasians. To investigate how ethnicity, skin colour and genetic variation affect the response to vitamin D (15000 IU) administered to young Asian and Caucasian men., Design: Prospective, single-centre clinical trial., Participants: Sixty young men (18-25 year) of Asian (n = 30) and Caucasian (n = 30) origin., Measurements: We measured serum calcium, phosphate, magnesium, alkaline phosphatase, albumin, parathyroid hormone; total 25 hydroxyvitamin D (25OHD); calculated and directly measured free 25OHD; DBP at baseline and 4 weeks; DBP genotype, skin colour (Fitzpatrick scale), dietary vitamin D and calcium intake at baseline; and urine calcium:creatinine ratio at baseline, 1 and 4 weeks., Results: At baseline, Asians had lower serum total 25OHD (26.4 [13.7] vs 34.1 [12.3] nmol/L P = 0.0272) and DBP (6.7 [3.4] vs 9.6 [4.4] nmol/L; P = 0.0065) but similar free 25OHD (16.7 [10.4] vs 17.8 [7.5] pmol/L P = 0.6530). After dosing, total 25OHD rose similarly in each group (≈56 nmol/L), but measured free 25OHD rose more in Asians (18.1 [9.4] vs 12.2 [13.3] pmol/L P = 0.0464). Lower DBP at baseline, possibly reflecting genotype differences, was associated with a greater change in measured free 25OHD in Caucasians, but not in Asians., Conclusions: Asian compared with Caucasian males had a larger increment in measured free 25OHD following 150 000 units vitamin D3, possibly reflecting differences in DBP affinity for 25OHD. Ethnicity should be considered when devising guidelines for the treatment of vitamin D deficiency., (© 2018 John Wiley & Sons Ltd.)

Bone disease in the neonatal period has often been regarded as an issue affecting premature infants, or a collection of rare and ultra-rare disorders that most neonatologists will see only once or twice each year, or possibly each decade. The emergence of targeted therapies for some of these rare disorders means that neonatologists may be faced with diagnostic dilemmas that need a rapid solution in order to access management options that did not previously exist. The diagnostic modalities available to the neonatologist have not changed a great deal in recent years; blood tests and radiographs still form the mainstays with other techniques usually reserved for research studies, but rapid access to genomic testing is emergent. This paper provides an update around diagnosis and management of bone problems likely to present to the neonatologist., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Both food insecurity and comorbidity have been identified as precursors to functional limitation in older adults, yet whether food insecurity modifies the progression from chronic disease to disability has not been assessed. We examined 5986 respondents age 50 and older drawn from the 2012-2014 Health and Retirement Study (HRS) and 2013 Health Care and Nutrition Study (HCNS). Mobility limitations reported in 2014 and change in mobility limitations from 2012 to 2014 were regressed on measures of food insecurity, number of chronic conditions, and their interaction terms using Poisson regression. Around 17.3% of the sample was identified as food insecure. In 2012, respondents reported an average of 1.9 (SD = 1.5) chronic conditions and 2.4 mobility limitations (SD = 3.0). In 2014, individuals reported an average of 2.5 (SD = 3.1) mobility limitations. Food insecurity was associated with a greater number of mobility limitations (IRR = 1.20, 95% CI: 1.11-1.29, p < .001) and more rapid increase in mobility limitations over the two-year observational period (IRR = 1.06, 95% CI: 1.00-1.11, p = .047). Food security status also modified the association between comorbidity and both mobility limitation outcomes, with the food secure exhibiting a stronger positive association between chronic conditions and mobility limitations than the food insecure. The food insecure tended to have more mobility limitations than the food secure when few chronic conditions were reported. Our results suggest that food insecurity is associated with prevalence and change in mobility limitations among older adults., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Idiopathic Juvenile Osteoporosis (IJO) refers to significantly lower than expected bone mass manifesting in childhood with no identifiable aetiology. IJO classically presents in early pubertal period with multiple fractures including metaphyseal and vertebral crush fractures, and low bone-mass., Methods: Here we describe two patients and provide information on their clinical phenotype, genotype and bone material analysis in one of the patients., Results: Patient 1: 40-year old adult male diagnosed with IJO in childhood who re-presented with a hip fracture as an adult. Genetic analysis identified a pathogenic PLS3 hemizygous variant, c.1765del in exon 16. Patient 2: 15-year old boy with multiple vertebral fractures and bone biopsy findings suggestive of IJO who also has a diagnosis of autism spectrum disorder. Genetic analysis identified a maternally inherited PLS3 pathogenic c.1295T>A variant in exon 12. Analyses of the transiliac bone sample revealed severe reduction of trabecular volume and bone turnover indices and elevated bone matrix mineralisation., Discussion: We propose that genetic testing for PLS3 should be undertaken in patients presenting with a current or previous history of IJO as this has implications for genetic counselling and cascade screening. The extensive evaluation of the transiliac biopsy sample of Patient 2 revealed a novel bone phenotype., Conclusion: This report includes a review of IJO and genetic causes of osteoporosis, and suggests that existing cases of IJO should be screened for PLS3. Through analysis of bone material properties in Patient 2, we can conclude that PLS3 does have a role in bone mineralisation., (© 2018 Wiley Periodicals, Inc.)