Gestational vitamin D and offspring fracture risk: do associations persist into mid adolescence?

BACKGROUND: Previous studies report that maternal vitamin D exposure during pregnancy is associated with offspring later-life bone health. A study in the Vitamin D in Pregnancy (VIP) cohort reported sexually dimorphic effects of maternal 25-hydroxyvitamin-D (25(OH)D) and offspring fracture profiles at 10 years of age. We, therefore, aimed to determine associations between maternal 25(OH)D status and offspring fracture risk at 16 years of age in this cohort. METHODS: In total, 475 mother-child pairs were recruited to the VIP study in southeastern Australia. Maternal serum samples were obtained at recruitment (<16 weeks' gestation) and/or 28-32 weeks' gestation and analysed for 25(OH)D. Radiologically-confirmed incident fractures in children were ascertained from date of birth (2002-2004) until July 16, 2019. Cox proportional hazard models were used to determine associations between maternal 25(OH)D and childhood fracture risk, and final models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of 25(OH)D sample. RESULTS: Data were available for 400 children (mean age 16.1 years). There were 122 (30.5%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was associated with a decreased fracture risk in boys (HR 0.87; 95% CI: 0.77, 0.99); the pattern was reversed in girls (HR 1.10; 95% CI 1.00, 1.22). At late gestation, higher maternal 25(OH)D was associated with an increased fracture risk in girls (HR 1.14; 95% CI: 1.04, 1.24). CONCLUSIONS: While our findings must be interpreted within the constraints of our limitations, we report that the contradictory risk profiles observed at early childhood in this cohort remain in adolescence.

Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.

As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low.

Transition to Adulthood for Extremely Preterm Survivors.

OBJECTIVE: To compare transition into adulthood of survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) in the postsurfactant era with term-born controls. METHODS: Prospective longitudinal cohort study of all EP/ELBW survivors born in the State of Victoria, Australia between January 1, 1991 and December 31, 1992 and matched term-born controls. Outcomes include educational attainment, employment, financial status, romantic partnering, living arrangements, parenthood, physical health and mental health, risk-taking behaviors, life satisfaction, and interpersonal relationships at 25 years. RESULTS: Data were available from 165 EP/ELBW and 127 control participants. Overall, there was little evidence for differences between the EP/ELBW and control groups on most comparisons after adjustment for social risk and multiple births. However, compared with controls, the EP/ELBW group was more likely to have their main source of income from government (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.21-5.13; P = .01) and to have never moved out of the parental home (aOR 2.13, 95% CI 1.27-3.58; P = .01), and fewer had ever engaged in smoking (aOR 0.52, 95% CI 0.28-0.98; P = .04), binge drinking (aOR 0.41, 95% CI 0.18-0.93; P = .03), or street drugs (aOR 0.56, 95% CI 0.32-0.98; P = .04). CONCLUSIONS: Aside from clinically important differences in main income source, leaving the parental home, and reduced risk-taking behavior, survivors born EP/ELBW in the era since surfactant was introduced are transitioning into adulthood similarly to term-born controls in some areas assessed but not all.

Actualisation 2023 des lignes directrices de pratique clinique pour la prise en charge de l'ostéoporose et la prévention des fractures au Canada.

CONTEXTE: Au Canada, plus de 2 millions de personnes vivent avec l'ostéoporose, une maladie qui accroît le risque de fracture, ce qui fait augmenter la morbidité et la mortalité, et entraîne une perte de qualité de vie et d'autonomie. La présente actualisation des lignes directrices vise à accompagner les professionnelles et professionnels de la santé au Canada dans la prestation de soins visant à optimiser la santé osseuse et à prévenir les fractures chez les femmes ménopausées et les hommes de 50 ans et plus. MÉTHODES: Le présent document fournit une actualisation des lignes directrices de pratique clinique de 2010 d'Ostéoporose Canada sur le diagnostic et la prise en charge de l'ostéoporose au pays. Nous avons utilisé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation) et effectué l'assurance de la qualité conformément aux normes de qualité et de présentation des rapports de la grille AGREE II (Appraisal of Guidelines for Research & Evaluation). Les médecins de premier recours et les patientes et patients partenaires ont été représentés à tous les niveaux des comités et des groupes ayant participé à l'élaboration des lignes directrices, et ont participé à toutes les étapes du processus pour garantir la pertinence des informations pour les futurs utilisateurs et utilisatrices. Le processus de gestion des intérêts concurrents a été entamé avant l'élaboration des lignes directrices et s'est poursuivi sur toute sa durée, selon les principes du Réseau international en matière de lignes directrices. Dans la formulation des recommandations, nous avons tenu compte des avantages et des risques, des valeurs et préférences de la patientèle, des ressources, de l'équité, de l'acceptabilité et de la faisabilité; la force de chacune des recommandations a été déterminée en fonction du cadre GRADE. RECOMMANDATIONS: Les 25 recommandations et les 10 énoncés de bonne pratique sont répartis en sections : activité physique, alimentation, évaluation du risque de fracture, instauration du traitement, interventions pharmacologiques, durée et séquence du traitement, et monitorage. La prise en charge de l'ostéoporose devrait se fonder sur le risque de fracture, établi au moyen d'une évaluation clinique réalisée avec un outil d'évaluation du risque de fracture validé. L'activité physique, l'alimentation et la pharmacothérapie sont des éléments essentiels à la stratégie de prévention des fractures, qui devraient être personnalisés. INTERPRÉTATION: Les présentes lignes directrices ont pour but d'outiller les professionnelles et professionnels de la santé et la patientèle afin qu'ensemble ils puissent parler de l'importance de la santé osseuse et du risque de fracture tout au long de la vie adulte avancée. La détection et la prise en charge efficace de la fragilité osseuse peuvent contribuer à réduire les fractures et à préserver la mobilité, l'autonomie et la qualité de vie.

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Quantifying Bone Strength Deficits in Young Adults Born Extremely Preterm or Extremely Low Birth Weight.

The long-term bone health of young adults born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g birth weight) in the post-surfactant era (since the early 1990s) is unclear. This study investigated their bone structure and estimated bone strength using peripheral quantitative computed tomography (pQCT)-based finite element modeling (pQCT-FEM). Results using this technique have been associated with bone fragility in several clinical settings. Participants comprised 161 EP/ELBW survivors (46.0% male) and 122 contemporaneous term-born (44.3% male), normal birth weight controls born in Victoria, Australia, during 1991-1992. At age 25 years, participants underwent pQCT at 4% and 66% of tibia and radius length, which was analyzed using pQCT-FEM. Groups were compared using linear regression and adjusted for height and weight. An interaction term between group and sex was added to assess group differences between sexes. Parameters measured included compressive stiffness (kcomp ), torsional stiffness (ktorsion ), and bending stiffness (kbend ). EP/ELBW survivors were shorter than the controls, but their weights were similar. Several unadjusted tibial pQCT-FEM parameters were lower in the EP/ELBW group. Height- and weight-adjusted ktorsion at 66% tibia remained lower in EP/ELBW (mean difference [95% confidence interval] -180 [-352, -8] Nm/deg). The evidence for group differences in ktorsion and kbend at 66% tibia was stronger among males than females (pinteractions <0.05). There was little evidence for group differences in adjusted radial models. Lower height- and weight-adjusted pQCT-FEM measures in EP/ELBW compared with controls suggest a clinically relevant increase in predicted long-term fracture risk in EP/ELBW survivors, particularly males. Future pQCT-FEM studies should utilize the tibial pQCT images because of the greater variability in the radius possibly related to lower measurement precision. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

WHAM-A Prospective Study of Weight and Body Composition After Risk-Reducing Bilateral Salpingo-oophorectomy.

CONTEXT: Body weight and composition may change over the natural menopause transition. Whether surgical menopause has similar effects, and the impact of hormone replacement therapy (HRT), are unknown. Understanding the metabolic effects of surgical menopause will inform clinical care. OBJECTIVE: To prospectively measure weight and body composition over 24 months following surgical menopause compared with a similar comparison group who retained their ovaries. METHODS: Prospective observational study of weight change from baseline to 24 months in 95 premenopausal women at elevated risk of ovarian cancer planning risk-reducing salpingo-oophorectomy (RRSO) and 99 comparators who retained their ovaries. Change in body composition from baseline to 24 months was also assessed by dual-energy x-ray absorptiometry in a subgroup of 54 women who underwent RRSO and 81 comparators who retained their ovaries. In the subgroup, weight, fat mass, lean mass, and abdominal fat measures were compared between groups. RESULTS: At 24 months both groups had gained weight (RRSO 2760 ± 4860 g vs comparators 1620 ± 4540 g) with no difference between groups (mean difference 730 g; 95% CI 920 g to 2380 g; P = .383). In the body composition subgroup, there was no difference in weight between groups at 24 months (mean difference 944 g; 95% CI -1120 g to 2614 g; P = .431). RRSO women may have gained slightly more abdominal visceral adipose tissue (mean difference 99.0 g; 95% CI 8.8 g to 189.2 g; P = .032) but there were no other differences in body composition. There were also no differences in weight or body composition between HRT users and nonusers at 24 months. CONCLUSION: 24 months after RRSO, there was no difference in body weight compared with women who retained their ovaries. RRSO women gained more abdominal visceral adipose tissue than comparators, but there were no other differences in body composition. Use of HRT following RRSO had no effect on these outcomes.

Growth from infancy to adulthood and associations with cardiometabolic health in individuals born extremely preterm.

Background: Few studies have tracked growth in children born extremely preterm (EP, <28 weeks' gestation) beyond late adolescence. The relationships between growth parameters (including weight and BMI) through childhood and adolescence with later cardiometabolic health, are unclear in those born EP. We aimed to (i) compare growth from 2 to 25 years between EP and controls; and in the EP group (ii) determine the associations of growth parameters with cardiometabolic health. Methods: Prospective state-wide cohort of all EP livebirths in Victoria, Australia, in 1991-1992 and contemporaneous term-born controls. Z-scores for weight (z-weight), height (z-height) and BMI (z-BMI) at 2, 5, 8, 18 and 25 years, and cardiometabolic health at 25 years (body composition, glucose tolerance, lipid profiles, blood pressure, exercise capacity) were measured. Growth trajectories were compared between groups using mixed models. The relationships between z-BMI changes/year, and being overweight at different ages, with cardiometabolic health were explored using linear regression. Findings: Z-weight and z-BMI were lower in EP than controls, but the gap decreased with age due to a more rapid rate of rise in z-weight and a decrease in z-height in the EP group compared with controls. Greater increases in z-BMI/year in the EP group were associated with poorer cardiometabolic health [coefficient (95% CI) per 0.1 z-BMI increase/year: visceral fat volume (cm3) 217.8 (160.9, 274.7), triglycerides (mmol/L) 0.45 (0.20, 0.71), systolic blood pressure (mmHg) 8.9 (5.8, 12.0), and exercise capacity (BEEP test maximum level -1.2 (-1.7, -0.7)), all p < 0.001]. The association between being overweight with poorer cardiometabolic health strengthened with age. Interpretation: The catch-up in weight and BMI by young adulthood in survivors born EP may not be desirable as it is associated with poorer cardiometabolic health. The associations of being overweight from mid-childhood with poorer cardiometabolic health may provide a window for intervention. Funding: National Health and Medical Research Council of Australia.

Health-related quality of life in adults born extremely preterm or with extremely low birth weight in the postsurfactant era: a longitudinal cohort study.

OBJECTIVES: To compare health-related quality of life (HRQoL) at 25 and 18 years in individuals born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW, birth weight <1000 g) with term-born (≥37 weeks) controls. Within the EP/ELBW cohort, to determine whether HRQoL differed between those with lower and higher IQs. METHODS: HRQoL was self-reported using the Health Utilities Index Mark 3 (HUI3) at 18 and 25 years by 297 EP/ELBW and 251 controls born in 1991-1992 in Victoria, Australia. Median differences (MDs) between groups were estimated using multiple imputation to handle missing data. RESULTS: Adults born EP/ELBW had lower HRQoL (median utility 0.89) at 25 years than controls (median utility 0.93, MD -0.040), but with substantial uncertainty in the estimate (95% CI -0.088 to 0.008) and a smaller reduction at 18 years (MD -0.016, 95% CI -0.061 to 0.029). On individual HUI3 items, there was suboptimal performance on speech (OR 9.28, 95% CI 3.09 to 27.93) and dexterity (OR 5.44, 95% CI 1.04 to 28.45) in the EP/ELBW cohort. Within the EP/ELBW cohort, individuals with lower IQ had lower HRQoL compared with those with higher IQ at 25 (MD -0.031, 95% CI -0.126 to 0.064) and 18 years (MD -0.034, 95% CI -0.107 to 0.040), but again with substantial uncertainty in the estimates. CONCLUSIONS: Compared with term-born controls, young adults born EP/ELBW reported poorer HRQoL, as did those with lower IQ compared with those with higher IQ in the EP/ELBW cohort. Given the uncertainties, our findings need corroboration.

The effects of Pilates on health-related outcomes in individuals with increased risk of fracture: a systematic review.

This systematic review examined the effect of Pilates on health-related outcomes in individuals with increased fracture risk to inform the 2021 Clinical Practice Guidelines for Management of Osteoporosis and Fracture Prevention in Canada. Seven electronic databases were searched to December 2020. Studies of Pilates in men and postmenopausal women aged ≥50 years with low bone mineral density (BMD), history of fragility fracture, or moderate-high risk of fragility fracture were included. Two reviewers independently screened studies and performed risk of bias assessment. Of 7286 records and 504 full-text articles, 5 studies were included, encompassing data from 143 participants (99% female). Data were insufficient for meta-analyses. There is low-certainty evidence that Pilates improved physical functioning and health-related quality of life. The effect of Pilates on falls and BMD is uncertain. No evidence was available for the effect of Pilates on mortality, fractures, or adverse events. Overall, Pilates may improve physical functioning and quality of life. Evidence of benefits relative to harms of Pilates in people with increased fracture risk, particularly males, is limited. PROSPERO registration: CRD42019122685. Novelty: Pilates may improve physical functioning and quality of life in women with osteoporosis. Evidence of the effect of Pilates on BMD, falls, fractures, or adverse events is limited.

Exploring the Association between Pain and Fracture Characteristics in Women with Osteoporotic Vertebral Fractures.

Purpose: The purpose of this study was to estimate the association between pain and the number, severity, and location of fractures in women with osteoporotic vertebral fractures. Method: We used an 11-point numeric pain rating scale to assess pain during movement in the preceding week and lateral spinal radiographs to confirm number, location, and severity of vertebral fractures. In model 1, we assessed the association between pain during movement and the number, severity, and location of fractures. We adjusted model 2 for pain medication use and age. Results: The mean age of participants was 76.4 (SD 6.9) years. We found no statistically significant associations between pain and fracture number (estimated ß = 0.23, 95% CI: -0.27, 0.68), fracture severity (estimated ß = -0.46, 95% CI: -1.38, 0.49), or fracture location at T4-T8 (estimated ß = 0.06, 95% CI: -1.26, 1.34), T9-L1 (estimated ß = 0.35, 95% CI: -1.17, 1.74), or L2-L4 (estimated ß = 0.40, 95% CI: -1.01, 1.75). Age and pain medication use were not significantly associated with pain. Model 1 accounted for 4.7% and model 2 for 7.2% of the variance in self-reported pain. Conclusion: The number, location, and severity of fractures do not appear to be the primary explanation for pain in women with vertebral fractures. Clinicians must consider other factors contributing to pain.

Objectif : estimer le lien entre la douleur et le nombre, la gravité et le foyer des fractures chez les femmes atteintes de fractures vertébrales ostéoporotiques. Méthodologie : utilisation d'une échelle d'évaluation numérique de la douleur en 11 points pour établir la douleur pendant le mouvement au cours de la semaine précédente et de radiographies vertébrales latérales pour confirmer le nombre, le foyer et la gravité des fractures vertébrales. Dans le modèle 1, les chercheurs ont évalué l'association entre la douleur pendant le mouvement et le nombre, la gravité et le foyer des fractures. Ils ont rajusté le modèle 2 pour tenir compte de la médication contre la douleur et de l'âge. Résultats : les participants avaient un âge moyen de 76,4 ans (ÉT 6,9). Les chercheurs n'ont pas trouvé d'associations importantes entre la douleur et le nombre de fractures (ß estimatif = 0,23, IC à 95 % : ­0,27, 0,68), la gravité des fractures (ß estimatif = ­0,46, IC à 95 % : ­1,38, 0,49) ou le foyer des fractures aux vertèbres T4 à T8 (ß estimatif = 0,06, IC à 95 % : ­1,26, 1,34), aux vertèbres T9 à L1 (b estimatif = 0,35, IC à 95 % : ­1,17, 1,74) ou aux vertèbres L2 à L4 (ß estimatif = 0,40, IC à 95 % : ­1,01, 1,75). L'âge et l'utilisation d'analgésiques n'étaient pas associés à la douleur de manière significative. Le modèle 1 représentait 4,7 % et le modèle 2, 7,2 % des écarts en matière de douleur autodéclarée. Conclusion : Le nombre, le foyer et la gravité des fractures ne semblaient pas être l'explication primaire de la douleur chez les femmes atteintes de fractures vertébrales. Les cliniciens doivent envisager d'autres facteurs qui contribuent à la douleur.

Effect of yoga on health-related outcomes in people at risk of fractures: a systematic review.

We summarized the effects of yoga on health-related outcomes and adverse events in men and postmenopausal women ≥50 years-old at increased risk of fracture, to inform the updated Osteoporosis Canada clinical practice guidelines. Six databases were searched for observational studies, randomized controlled trials and case series. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation handbook. Nine studies were included and reported using narrative syntheses due to the limited available evidence. Overall, the available evidence was of very low certainty. There was no effect of yoga on health-related quality of life in randomized trials. Effects on other health-related outcomes were mixed or not available in the literature. Five studies reported no adverse events directly related to the study intervention, and 2 studies did not report whether adverse events occurred. However, 2 case series reported vertebral fractures related to yoga participation, possibly due to excessive spinal flexion. Due to the limited and very low certainty evidence, guideline developers will need to draw indirect evidence from yoga studies among middle aged or older adults that are not at fracture risk. PROSPERO: CRD42019124898. Novelty: Evidence in general was of very low certainty. Yoga had no effect on health-related quality of life in randomized trials. Evidence was mixed or unavailable for other outcomes. Case studies reported yoga poses involving spinal flexion coincided with incidents of vertebral compression fracture among older adults with increased fracture risk.

Maternal vitamin D and offspring fracture risk: the Vitamin D in Pregnancy study.

Vitamin D is important for bone health and strength. Previous studies report 25-hydroxyvitamin D (25(OH)D) exposure during pregnancy may impact offspring bone health later in life. In this study, maternal 25(OH)D at recruitment was associated with a lower fracture risk in boys and an increased fracture risk in girls at 28-32 weeks gestation. PURPOSE: Maternal 25-hydroxyvitamin D (25(OH)D) in pregnancy has been shown to be associated with offspring bone measures in some studies, but few have examined fracture risk. We aimed to determine associations between maternal vitamin D status and offspring fracture risk. METHODS: In total, 475 mother-child pairs participating in the Vitamin D in Pregnancy study in southeastern Australia were recruited. Maternal serum samples were taken at recruitment (< 16 weeks gestation) and/or 28-32 weeks gestation and analysed for 25(OH)D. Incident fractures in children were ascertained from date of birth (2002-2004) until December 31, 2012. Cox proportional hazard models included maternal age at recruitment, offspring sex, birth weight, gestation length and season of vitamin D sample. RESULTS: Complete follow-up data were available for 400 children (median age = 9.5 years). There were 68 (17.0%) children who sustained at least one fracture. Higher maternal 25(OH)D (per 10 nmol/L) in early gestation was weakly associated with a decreased fracture risk in boys (HR 0.82; 95% CI 0.68, 0.99; p = 0.048) but not girls (HR 1.10; 95% CI 0.98, 1.25; p = 0.11). At late gestation, higher maternal 25(OH)D was associated with increased fracture risk in girls (HR 1.11; 95% CI 1.01, 1.23; p = 0.038) but not boys (HR 0.94; 95% CI 0.80, 1.10; p = 0.42). No statistically significant relationships were detected in analyses investigating 25(OH)D as a categorical variable. CONCLUSION: There is some evidence that higher maternal 25(OH)D at recruitment was associated with lower fracture risk in boys, while higher maternal 25(OH)D at 28-32 weeks gestation was associated with an increased fracture risk in girls.

Detection of Vitamin D Metabolites in Breast Milk: Perspectives and challenges for measurement by Liquid Chromatography Tandem-Mass Spectrometry.

Breast milk is an emerging matrix for vitamin D assessment of breastfed infants and their mothers. It is considered a more reliable indicator of infant intake than the assessment of maternal circulating vitamin D. With the improved sensitivity of mass spectrometry-based technologies, this method principle has been the recent mainstay for the quantitation of various vitamin D metabolites in breast milk for population-based clinical trials. There are still several areas across the total testing process (pre-analytical, analytical and post-analytical) to be defined and harmonised to translate breast milk vitamin D measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from population-based research to routine clinical use and public health applications. Pre-analytically, the determination of the best form of vitamin D to measure in breast milk requires more evidence. Analytically, standardisation of the methods to allow for comparability of results is required. Post analytically, breast milk vitamin D decision limits are needed to turn the individual numerical outputs into clinically meaningful results. This review aims to synthesise the current evidence and utility of measurement of breast milk vitamin D by LC-MS/MS and to lead a future discussion on best practices to allow for its clinical utility beyond its current research-based use.

What Happens After Menopause? (WHAM): A prospective controlled study of cardiovascular and metabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: To prospectively measure cardiometabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared to a similar age comparison group, and the effects of Hormone Therapy (HT) on cardiometabolic risk. METHODS: Prospective observational study of 95 premenopausal women planning RRBSO and 99 comparisons who retained their ovaries. At baseline and 12 months, blood pressure (BP), Body Mass Index (BMI), waist and hip circumference, fasting total, HDL and LDL cholesterol, triglycerides, high-sensitivity C-reactive protein, glucose and insulin were measured and HOMA-IR was calculated. Chi-square tests, t-tests and adjusted logistic regression models were used to compare groups. RESULTS: Baseline cardiometabolic phenotypes were similar between groups but more RRBSO participants were overweight/obese with higher waist/hip ratios. By 12 months, BP and cardiometabolic phenotypes were largely unchanged. Paired t-tests showed statistically significant increases in BMI (p = 0.037) and weight (p = 0.042) and larger increases in waist circumference (p < 0.001) and waist-hip ratio (p = 0.009) after RRBSO vs comparisons. However, these were not significant when adjusted for baseline values. After RRBSO 60% initiated Hormone Therapy (HT). Paired t-tests demonstrated that non-HT users had a significantly greater mean increase in waist circumference of 4.3 cm (95% CI 2.0-6.5) compared to 1.3 cm in HT users (95% CI -0.2-2.7, p < 0.001), which remained significant when adjusted for baseline values (p = 0.02). At 12 months, mean waist circumference was 2.94 cm greater in non-HT users compared to HT users. CONCLUSIONS: Cardiometabolic risk markers are largely unchanged 12 months after RRBSO. Hormone Therapy after RRBSO may prevent against an increase in waist circumference.

Risk of Fractures and Other Injuries in Children Treated with Antiseizure Medications for Epilepsy.

This study aimed to investigate the prevalence of fractures and non-fracture injuries, including associated risk factors, in children with epilepsy prescribed antiseizure medications (ASM). A controlled, cross-sectional study was conducted in a hospital outpatient setting, comparing children with epilepsy prescribed ASMs with their non-epileptic siblings. Information was collected by questionnaire included history of fractures, non-fracture injuries and epilepsy, comorbidities and ASM use. 261 participants completed the questionnaire, 133 children with epilepsy (aged 10.7 ± 3.5 years, mean ± SD) and 128 siblings (10.1 ± 3.7 years). There were 49 non-seizure-related fractures in 34 ASM patients while prescribed ASMs, compared with 21 lifetime fractures in 15 controls, giving a 2.7 (95% CI 1.3-5.3, p = 0.007) times greater fracture prevalence in children treated with ASMs compared to healthy siblings. The rates of non-fracture injuries were similar across groups, except that concussion was more common in children taking ASMs (9.0% vs 1.6%, p = 0.026). Duration of ASM use and generalized tonic-clonic seizures (GTCS) were independent predictors of fractures (OR 1.55; 95% CI 1.03-2.31, p = 0.03; OR 2.50; 95% CI 1.05-5.94, p = 0.04, respectively). Fewer than 20% of participants and/or their families were aware that ASM use was related to bone health. Children with epilepsy treated with ASMs had a higher fracture prevalence than their sibling controls. Duration of ASM treatment and GTCS were associated with fracture risk. Longitudinal prospective studies are required to further explore risk and the direct impact of epilepsy on bone health.

The Effect of Impact Exercise (Alone or Multicomponent Intervention) on Health-Related Outcomes in Individuals at Risk of Fractures: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Exercise is commonly recommended to prevent and manage osteoporosis. High magnitude strains at rapid rate and short bouts should theoretically elicit an osteogenic response; however, the effects of different levels of impact exercises on several outcomes in people at risk of fracture are still unknown. OBJECTIVE: To report the effect of impact exercise on falls, fractures, adverse events, mortality, bone mineral density (BMD), physical functioning, and health-related quality of life (QoL). METHODS: We included randomized controlled trials testing the effect of impact exercise compared with a non-exercise control on outcomes in adults ≥ 50 years with low BMD or fragility fractures. Two reviewers selected studies and extracted data. Where possible, we pooled outcomes using mean difference (MD) with a fixed-effects model and 95% confidence interval (CI). We reported risk of bias using Cochrane and certainty of evidence using GRADE. RESULTS: We included 29 trials; 19 studies evaluated impact exercise alone, and the remaining trials combined impact with resistance or balance training. Impact exercise alone or combined with resistance training improved Timed Up-and-Go values (MD - 0.95 s, 95% CI - 1.09 to - 0.81, low certainty evidence) and lumbar spine (MD 0.04 g/cm2, 95% CI 0.02-0.06, low certainty evidence) and femoral neck BMD (MD 0.04 g/cm2, 95% CI 0.02-0.07, low certainty evidence). Impact exercise did not improve health-related QoL assessed with QUALEFFO-41 (MD 0.06, 95% CI - 2.18 to 2.30, moderate certainty evidence). The effects of impact exercise on falls, fractures, and mortality are uncertain due to insufficient data. Many trials had a high risk of bias for two or more items. CONCLUSIONS: There is low certainty evidence that impact exercise may improve physical function and BMD in people at risk of fracture. The effect of impact exercises on falls, fractures, and mortality remains unclear. Our findings should be interpreted with caution due to risk of bias and small sample sizes. TRIAL REGISTRATION: Registered in Prospero (CRD42018115579) on January 30, 2019.

Wildfire smoke exposure and respiratory health outcomes in young adults born extremely preterm or extremely low birthweight.

OBJECTIVE: Adults born either extremely preterm (EP, <28 weeks gestation) or extremely low birthweight (ELBW, <1000 g birthweight) have more obstructive airflow than controls of normal birthweight (>2499 g). We compared self-reported adverse respiratory health outcomes in young adults born EP/ELBW with controls following smoke exposure from the 2019/2020 wildfires in the Australian state of Victoria, and explored if any effects were mediated by airway obstruction, reflected in the forced expiratory volume in 1 second (FEV1). METHODS: EP/ELBW participants were derived from all survivors born in the state of Victoria in 1991-92. Contemporaneous controls of normal birthweight (>2499 g) were recruited in the newborn period and matched for sociodemographic variables. Both groups had been assessed at intervals through childhood and into adulthood. Those who participated in the most recent follow-up assessment at 25 years of age, when FEV1 had been measured, were sent a survey when they were approximately 28 years of age asking about respiratory health related outcomes (respiratory symptoms, health services usage, medication uptake) following wildfire smoke exposure over the southern hemisphere summer of 2019-20. RESULTS: A total of 296 participants (166 EP/ELBW; 130 controls) were sent the survey; 44% of the EP/ELBW group and 47% of the control group responded. Compared with controls, EP/ELBW respondents reported more overall respiratory problems (30%vs 20%) and specific respiratory symptoms (breathlessness, wheezing, cough and chest tightness) following wildfire smoke exposure, as well as higher health services usage (e.g. local health clinic, hospital emergency department) and medication uptake for respiratory-related problems. Higher FEV1 values were associated with lower odds of most self-reported respiratory symptoms; adjusting for FEV1 attenuated the differences between EP/ELW and control groups. CONCLUSION: Survivors born EP/ELBW may be at an increased risk of adverse respiratory health outcomes following wildfire smoke exposure in early adulthood, in part related to worse expiratory airflows.

The Effects of Walking or Nordic Walking in Adults 50 Years and Older at Elevated Risk of Fractures: A Systematic Review and Meta-Analysis.

Walking is a common activity among older adults. However, the effects of walking on health-related outcomes in people with low bone mineral density (BMD) are unknown. The authors included randomized controlled trials comparing walking to control in individuals aged ≥50 years with low BMD and at risk of fractures. The authors identified 13 randomized controlled trials: nine multicomponent interventions including walking, one that was walking only, and three Nordic walking trials. Most studies had a high risk of bias. Nordic walking may improve the Timed Up-and-Go values (1.39 s, 95% CI [1.00, 1.78], very low certainty). Multicomponent interventions including walking improved the 6-min walk test (39.37 m, 95% CI [21.83, 56.91], very low certainty) and lumbar spine BMD (0.01 g/cm2, 95% CI [0.00, 0.03], low certainty evidence). The effects on quality of life or femoral neck BMD were not significant. There were insufficient data on fractures, falls, or mortality. Nordic walking may improve physical functioning. The effects on other outcomes are less certain; one may need to combine walking with other exercises to be of benefit.

Progressive Resistance Training for Improving Health-Related Outcomes in People at Risk of Fracture: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Osteoporosis clinical practice guidelines recommend exercise to prevent fractures, but the efficacy of exercise depends on the exercise types, population studied, or outcomes of interest. The purpose of this systematic review was to assess the effects of progressive resistance training (PRT) on health-related outcomes in people at risk of fracture. METHODS: Multiple databases were searched in October 2019. Eligible articles were randomized controlled trials of PRT interventions in men and women ≥50 years with low bone mineral density (BMD) or fracture history. Descriptive information and mean difference (MD) and SD were directly extracted for included trials. A total of 53 studies were included. RESULTS: The effects of PRT on the total number of falls (incidence rate ratio [IRR] = 1.05; 95% CI = 0.91 - 1.21; 7 studies) and on the risk of falling (risk ratio [RR] = 1.23; 95% CI = 1.00 - 1.51; 5 studies) are uncertain. PRT improved performance on the Timed "Up and Go" test (MD = -0.89 seconds; 95% CI = -1.01 to -0.78; 13 studies) and health-related quality of life (standardized MD = 0.32; 95% CI = 0.22-0.42; 20 studies). PRT may increase femoral neck (MD = 0.02 g/cm2; 95% CI = 0.01-0.03; 521 participants, 5 studies) but not lumbar spine BMD (MD = 0.02 g/cm2; 95% CI = -0.01-0.05; 4 studies), whereas the effects on total hip BMD are uncertain (MD = 0.00 g/cm2; 95% CI = 0.00-0.01; 435 participants, 4 studies). PRT reduced pain (standardized MD = -0.26; 95% CI = -0.37 to -0.16; 17 studies). Sensitivity analyses, including PRT-only studies, confirmed these findings. CONCLUSION: Individuals at risk of fractures should be encouraged to perform PRT, as it may improve femoral neck BMD, health-related quality of life, and physical functioning. PRT also reduced pain; however, whether PRT increases or decreases the risk of falls, the number of people experiencing a fall, or the risk of fall-related injuries is uncertain. IMPACT: Individuals at risk of fractures should be encouraged to perform PRT, as it may have positive effects on femoral neck BMD, health-related quality of life, physical functioning, and pain, and adverse events are rare. LAY SUMMARY: Exercise is recommended for people at risk of osteoporotic fractures. Our study showed that progressive resistance training improves physical functioning, quality of life, and reduces pain. The effects of progressive resistance training on the risk of falling are unclear. Adverse events are rare, and often minor (eg, soreness, pain, musculoskeletal injury). Considering the benefits and safety, people at risk of fractures should engage in progressive resistance training interventions.