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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: knowledge on the natural history of rare diseases is necessary to improve outcomes. Disease registries may play a key role in covering these unmet needs in the rare bone and mineral community., Objective: to map existing bone and mineral conditions registries in Europe and their characteristics., Methods: online survey about the use of registries/databases and their characteristics. This survey was disseminated among members of the European Reference Network on Rare Bone Diseases (ERN BOND) and non-ERN experts in the field of bone and mineral conditions as well as patient organisations., Results: sixty-three responses from health care providers (HCPs) and 10 responses from patient groups (PGs) were collected. The response rate for ERN BOND members was 55%. Of 63 HCPs, 37 declared using a registry. Osteogenesis imperfecta (OI) was the most registered condition. We mapped 3 international registries, all were disease-specific., Conclusions: There is a need for developing a common high-quality platform for registering rare bone and mineral conditions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

N-heterocyclic carbene (NHC) adducts have shown remarkable biological potential for numerous medical applications. With an aim to improve biological potential of benzimidazolium salts, newer analogues of benzimidazole and their silver complexes were synthesized and characterized. Synthesized salts (L 1 -L 2 ) and silver complexes (C 1 -C 2 ) were confirmed through elemental analysis, UV-visible spectroscopy, FTIR, 1 H NMR & 13 C NMR spectroscopy. The compounds C1 & C2 were found stable in solution form for studied time period when examined spectroscopically and showed optimum lipophilicity when measured for their partition coefficient through flask shake method. Synthesized compounds showed good antimicrobial potential against gram positive bacterial strain S. Aureus with IC 50 2.02±0.12 and 2.11±0.13 µM respectively while 2.11±0.1 and 2.28±0.17 µM against gram negative bacterial strain E. Coli for C1 and C2 respectively. The interaction study of the related compounds with DNA was predicted by molecular docking study, which confirmed that the studied compound C1 (-8.04 kcal/mol) has a higher binding energy than compound C2 (-4.23 kcal/mol); Also, the compound C1 exhibits a better affinity against to DNA than Ethidium bromide (-7.68 kcal/mol) and cisplatin (-6.21 kcal/mol).The claim was practically assured through spectroscopic and viscometeric method which confirmed that compounds have good affinity for DNA with binding constant kb, 5.78×10 4 M -1 and 6.84×10 4 M -1 for C1 and C2 respectively., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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.)

Background: Multiple myeloma (MM) is associated with high healthcare resource utilisation and increasing hospitalisation rates. The aim of this study was to characterise the hospital use by patients with MM in the English National Health Service (NHS)., Methods: Routinely-collected aggregate data about all NHS-funded hospital admissions of patients with MM were analysed. Data were obtained from the English Hospital Episodes Statistics on admissions between 1 April 2014 and 31 March 2018., Results: A total of 754,345 admissions were reported over four years, equivalent to a mean of 188,586 admissions per year. Of the 41,845 patients admitted during this period, 42% were women and 58% men. From the total admissions, 90% were elective and 10% unplanned. Mean annual estimated costs over the period were £46 million for elective and £56 million for unplanned admissions. The number of elective admissions increased by 4.5% with costs increasing 1.5% per year; for unplanned admissions, these figures were 4.1% and 9.0%, respectively., Conclusions: MM is associated with a significant number of hospital admissions and NHS costs. The majority of the hospital admissions are elective, but the highest burden in terms of costs relates to unplanned admissions, with numbers increasing over time.

Aims: To provide a case history of the service model, commissioning, implementation and delivery of an interface secondary fracture prevention service., Background: Fracture Prevention has been identified as key to reducing the burden on the NHS from an ageing population. The need to have a systematic process for identifying, assessing and ensuring treatment adherence is vital., Rationale: Delivering the service to identify patients at risk and initiate treatment is important as is the use of a database for patient tracking and the need to ensure that patients remain on treatment to ensure maximum fracture prevention benefit, and cost savings are seen. The process for implementing a Fracture Prevention service can be challenging but identifying the components and working closely with local commissioners can provide the evidence and release the resource required., Summary: The key components of a Fracture Prevention Service should include robust case-finding, assessment, treatment initiation, patient education and monitoring., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The evidence linking body mass index (BMI) to severe OA shows a strong association in the knee. There are limited data exploring the effect of BMI on the risk of joint arthroplasty in a healthy population with long periods of follow up. We compared the self-reported BMI at age 20, measured BMI at baseline, year 5 and year 10 with the year 19 risk of total knee arthroplasty (TKA) in a well-described, population based cohort of healthy women. A total of 733 women attended the 19th year visit, of whom 31 underwent TKA and 676 were used as a control group after 26 were removed for having hip arthoplasty. Using logistic regression, an increase in 1 unit of BMI at baseline was associated with a 10.5% increased risk of TKA (p=0.017) and at year 5 the increased risk is 8.6% (p=0.042). When adjusted for baseline age and smoking, baseline BMI was the only significant predictor of TKA at 10.0% with p=0.024. There was no significant association at 10 years or for change in BMI over time. In this prospective, population based study, BMI predicted the risk of TKA for OA. The risk was greatest at baseline when the patients were in middle age suggesting that this is the most important time to target weight reduction interventions., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Vitamin D insufficiency is common in women of childbearing age and increasing evidence suggests that the risk of osteoporotic fracture in adulthood could be determined partly by environmental factors during intrauterine and early postnatal life. We investigated the effect of maternal vitamin D status during pregnancy on childhood skeletal growth., Methods: In a longitudinal study, we studied 198 children born in 1991-92 in a hospital in Southampton, UK; the body build, nutrition, and vitamin D status of their mothers had been characterised during pregnancy. The children were followed up at age 9 years to relate these maternal characteristics to their body size and bone mass., Findings: 49 (31%) mothers had insufficient and 28 (18%) had deficient circulating concentrations of 25(OH)-vitamin D during late pregnancy. Reduced concentration of 25(OH)-vitamin D in mothers during late pregnancy was associated with reduced whole-body (r=0.21, p=0.0088) and lumbar-spine (r=0.17, p=0.03) bone-mineral content in children at age 9 years. Both the estimated exposure to ultraviolet B radiation during late pregnancy and the maternal use of vitamin D supplements predicted maternal 25(OH)-vitamin D concentration (p<0.0001 and p=0.0110, respectively) and childhood bone mass (p=0.0267). Reduced concentration of umbilical-venous calcium also predicted reduced childhood bone mass (p=0.0286)., Interpretation: Maternal vitamin D insufficiency is common during pregnancy and is associated with reduced bone-mineral accrual in the offspring during childhood; this association is mediated partly through the concentration of umbilical venous calcium. Vitamin D supplementation of pregnant women, especially during winter months, could lead to longlasting reductions in the risk of osteoporotic fracture in their offspring.

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 characterized 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, in both genders there is a dissociation between the peak velocities for height gain and bone mineral accrual. 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. Measures for maximizing bone mineral acquisition, particularly through encouraging physical activity and adequate dietary calcium intake, are likely to affect the risk of fracture in later generations. In addition to these modifiable factors during childhood, evidence has also accrued that the risk of fracture 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 - pitutiary - adrenal (HPA) and growth hormone/insulin-like growth factor I (GH/IGF-I) axes. Maternal smoking, diet and physical activity levels 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 optimization of maternal nutrition and intrauterine growth should also be included within preventive strategies against osteoporotic fracture, albeit for future generations., (Copyright 2002 Elsevier Science Ltd.)

The high rate of osteoporotic fracture in Western populations has resulted in a significant burden in terms of morbidity, mortality and health care costs. The use of DXA has made the diagnosis of osteoporosis easier and identified a subgroup of individuals who are at a higher risk of fracture. It is a useful tool in determining therapy in those at greatest risk of fracture. However, widespread use of such treatments is low and greater uptake remains an elusive goal. There are now many different treatments that reduce fracture rate, and can accompany lifestyle measures such as smoking cessation, diet and exercise. Dietary supplementation with calcium has been shown to reduce the risk of vertebral fracture, and the combination of calcium with vitamin D has been shown to reduce fracture at non-vertebral sites, including the hip. Although ERT, SERMs and tibolone all retard bone loss, prospective fracture prevention has only been shown for SERMs and then only at the spine. Bisphosphonates represent a class of potent anti-resorptive agents, which have been shown to reduce fracture rate at vertebral and non-vertebral sites. Other agents such as calcitonin, PTH and fluoride are of less certain benefit in preventing fracture., (Copyright 2001 Harcourt Publishers Ltd.)