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.

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.

Gestational Vitamin D and Offspring Bone Measures: Is the Association Independent of Maternal Bone Quality?

Previously we have reported an association between maternal vitamin D and offspring bone as measured by dual-energy X-ray absorptiometry. It is plausible that shared genetics might confound associations between maternal vitamin D in pregnancy and offspring bone measures. We aimed to determine whether such associations are independent of maternal bone quality. Data for this analysis were derived from 168 mother-child pairs who returned at the 11-year follow-up of the vitamin D in pregnancy study. Gestational 25-hydroxyvitamin D [25(OH)D] was assessed by radioimmunoassay in early pregnancy at recruitment (before 16 weeks gestation) and later in pregnancy (28-32 weeks gestation). Bone quality was assessed for mothers and children at the calcaneus using quantitative ultrasound (Achilles InSight, GE). Speed of Sound (SOS), Broadband Ultrasound Attenuation (BUA) and Stiffness Index (SI) were the outcomes of interest. Maternal 25(OH)D in early pregnancy was associated with offspring SOS (ß 1.46 m/s 95% CI 0.12, 2.8). When separated by sex, there was no association between maternal 25(OH)D at recruitment and offspring SI (r = - 0.05, p = 0.68), SOS (r = 0.11, p = 0.34) or BUA (- 0.09, p = 0.43) in girls. In boys, maternal 25(OH)D at recruitment was associated with SI (r = 0.21, p = 0.048), and SOS (r = 0.24, p = 0.03) but not BUA (r = 0.10, p = 0.37). Adjustment for the offspring factors and respective maternal QUS parameter did not attenuate associations between maternal 25(OH)D in early pregnancy with offspring SOS, nor SI. There was no association with BUA. Furthermore, there was no association between maternal 25(OH)D in late pregnancy with any offspring QUS parameter. These prospective data support existing evidence of a positive relationship between maternal 25(OH)D levels during early pregnancy and measures of bone health of offspring in childhood, independent of maternal bone phenotype.

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.

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.

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.

Bone Measures by Dual-Energy X-Ray Absorptiometry and Peripheral Quantitative Computed Tomography in Young Women With Type 1 Diabetes Mellitus.

Understanding bone fragility in young adult females with type 1 diabetes mellitus (T1DM) is of great clinical importance since the high fracture risk in this population remains unexplained. This study aimed to investigate bone health in young adult T1DM females by comparing relevant variables determined by dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) at the tibia and pQCT-based finite element analysis (pQCT-FEA) between T1DM subjects (n = 21) and age-, height- and weight-matched controls (n = 63). Tibial trabecular density (lower by 7.1%; 228.8 ± 33.6 vs 246.4 ± 31.8 mg/cm3, p = 0.02) and cortical thickness (lower by 7.3%; 3.8 ± 0.5 vs 4.1 ± 0.5 cm, p = 0.03) by pQCT were significantly lower in T1DM subjects than in controls. Tibial shear stiffness by pQCT-FEA was also lower in T1DM subjects than in controls at both the 4% site (by 17.1%; 337.4 ± 75.5 vs 407.1 ± 75.4 kN/mm, p < 0.01) and 66% site (by 7.9%; 1113.0 ± 158.6 vs 1208.8 ± 161.8 kN/mm, p = 0.03). These differences remained statistically significant after adjustment for confounding factors. No difference between groups was observed in DXA-determined variables (all p ≥ 0.08), although there was a trend towards lower aBMD at the lumbar spine in T1DM subjects than in controls after adjustment for confounders (p = 0.053). These novel findings elicited using pQCT and pQCT-FEA suggest a clinically significant impact of T1DM on bone strength in young adult females with T1DM. Peripheral QCT and pQCT-FEA may provide more information than DXA alone on bone fragility in this population. Further longitudinal studies with a larger sample size are warranted to understand the evolution and causes of bone fragility in young T1DM females.

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.

Exploring Fear of Falling and Exercise Self-Efficacy in Older Women With Vertebral Fractures.

Fear of falling is a common issue among older adults, which decreases quality of life and leads to an avoidance of activities they are still able to do. The goal of this secondary data analysis was to explore the relationship between fear of falling and exercise self-efficacy in 141 women with at least one nontraumatic Genant Grade 2 vertebral fracture. Fear of falling, exercise self-efficacy, history of falling, the number of falls, the use of assisting devices, and pain at rest or during movement were obtained using medical history and health status questionnaires. There was a negative association between fear of falling and exercise self-efficacy (pseudo R2 = .253; p = .004), which persisted when the analysis was adjusted for history and number of falls, use of assistive devices, and pain at rest (pseudo R2 = .329; p < .0001) or during movement (pseudo R2 = .321; p < .0001). Fear of falling may be negatively associated with exercise self-efficacy in older women with vertebral fracture.

The Association Between Muscle Mass and Strength in Relation to Bone Measures in a Paediatric Population: Sex-Specific Effects.

Post-puberty, bone mass displays clear sex-specific patterns. However, research has suggested that a sexual dimorphism in bone mass is evident in younger children and is likely attributable to differences in lean mass. Thus, we aimed to determine whether the association with both overall muscle mass and/or muscle strength was different between the sexes in a paediatric population. Participants were recruited as part of the Vitamin D in Pregnancy Study, Australia. There were 209/402 (52.3%) children at the 11-year follow-up, and 172 had complete data. Children were assessed for bone mineral content (BMC), bone mineral density (BMD) and lean mass by DXA (Lunar). Handgrip strength (kg) was measured using a dynamometer (JAMAR). Linear regression models were adjusted for height, weight, age and pubertal stage. In adjusted models, including both muscle strength and lean mass, the observed association differed between boys and girls. At the spine in boys, BMC and BMD were associated with muscle strength (ß 0.34 [95%CI 0.09-0.59] and 0.008 [95%CI 0.003-0.014]; respectively) but not total muscle mass. However, muscle mass was associated with BMC and BMD at the total body (less head). In girls, spine BMC and BMD were associated with total lean mass (ß 0.95 [95%CI 0.61-1.3] and ß 0.01 [95%CI 0.005-0.02], respectively), with a similar pattern of association with total body (less head) measures. Muscle mass and strength appear to have sexually dimorphic effects on bone mass in school-aged children. These findings should be replicated in longitudinal studies.

Quadrivalent human papillomavirus vaccination successfully reduces the prevalence of vaccine-targeted genotypes in a young, vaccine-eligible-age sample of Australian females.

Background The prevalence of genital tract vaccine-type human papillomavirus (HPV) is on the decline due to high vaccine uptake through the national HPV immunisation program in Australia. The aim of this study was to investigate HPV vaccine coverage and factors associated with HPV in a vaccine-eligible sample of young Australian females. METHODS: Females aged 16-25 years were recruited into the Young Female Health Initiative study, a young women's health study, via Facebook advertising from 2012 to 2017. Sexually active participants were asked to provide a self-collected vaginal swab for the detection of HPV DNA; positive samples were genotyped. Self-reported HPV vaccination status was confirmed by the National HPV Vaccination Program Register. Outcomes of the study were HPV acquisition and genotype, HPV vaccination status and factors associated with HPV. RESULTS: Overall, 22.8% of samples (95% confidence interval (CI) 17.8-27.8%; n = 62/272) were positive for any HPV DNA, of which 19.1% (95% CI 14.4-23.8%; n = 52/272) were oncogenic types. HPV 16 was detected in three samples (1.1%; 95% CI -0.1%, 2.3%; two not HPV vaccinated and one vaccinated after sexual debut). Early sexual debut (<16 years) and multiple sexual partners were independently associated with an increased risk of any HPV. CONCLUSIONS: In a community sample of vaccine-eligible-age females with a high vaccine uptake, the prevalence of vaccine-related HPV genotypes is extremely low. Early sexual debut and multiple sexual partners are positively associated with HPV, underscoring the importance of vaccination at the routinely recommended age of 12-13 years for best vaccine impact.

Quantifying Use of a Health Virtual Community of Practice for General Practitioners' Continuing Professional Development: A Novel Methodology and Pilot Evaluation.

BACKGROUND: Health care practitioners (HPs), in particular general practitioners (GPs), are increasingly adopting Web-based social media platforms for continuing professional development (CPD). As GPs are restricted by time, distance, and demanding workloads, a health virtual community of practice (HVCoP) is an ideal solution to replace face-to-face CPD with Web-based CPD. However, barriers such as time and work schedules may limit participation in an HVCoP. Furthermore, it is difficult to gauge whether GPs engage actively or passively in HVCoP knowledge-acquisition for Web-based CPD, as GPs' competencies are usually measured with pre- and posttests. OBJECTIVE: This study investigated a method for measuring the engagement features needed for an HVCoP (the Community Fracture Capture [CFC] Learning Hub) for learning and knowledge sharing among GPs for their CPD activity. METHODS: A prototype CFC Learning Hub was developed using an Igloo Web-based social media software platform and involved a convenience sample of GPs interested in bone health topics. This Hub, a secure Web-based community site, included 2 key components: an online discussion forum and a knowledge repository (the Knowledge Hub). The discussion forum contained anonymized case studies (contributed by GP participants) and topical discussions (topics that were not case studies). Using 2 complementary tools (Google Analytics and Igloo Statistical Tool), we characterized individual participating GPs' engagement with the Hub. We measured the GP participants' behavior by quantifying the number of online sessions of the participants, activities undertaken within these online sessions, written posts made per learning topic, and their time spent per topic. We calculated time spent in both active and passive engagement for each topic. RESULTS: Seven GPs participated in the CFC Learning Hub HVCoP from September to November 2017. The complementary tools successfully captured the GP participants' engagement in the Hub. GPs were more active in topics in the discussion forum that had direct clinical application as opposed to didactic, evidence-based discussion topics (ie, topical discussions). From our knowledge hub, About Osteoporosis and Prevention were the most engaging topics, whereas shared decision making was the least active topic. CONCLUSIONS: We showcased a novel complementary analysis method that allowed us to quantify the CFC Learning Hub's usage data into (1) sessions, (2) activities, (3) active or passive time spent, and (4) posts made to evaluate the potential engagement features needed for an HVCoP focused on GP participants' CPD process. Our design and evaluation methods for ongoing use and engagement in this Hub may be useful to evaluate future learning and knowledge-sharing projects for GPs and may allow for extension to other HPs' environments. However, owing to the limited number of GP participants in this study, we suggest that further research with a larger cohort should be performed to validate and extend these findings.

Maternal stress does not exacerbate long-term bone deficits in female rats born growth restricted, with differential effects on offspring bone health.

Females born growth restricted have poor adult bone health. Stress exposure during pregnancy increases risk of pregnancy complications. We determined whether maternal stress exposure in growth-restricted females exacerbates long-term maternal and offspring bone phenotypes. On gestational day 18, bilateral uterine vessel ligation (restricted) or sham (control) surgery was performed on Wistar-Kyoto rats. At 4 mo, control and restricted females were mated and allocated to unstressed or stressed pregnancies. Stressed pregnancies had physiological measurements performed; unstressed females were not handled. After birth, mothers were aged to 13 mo. Second-generation (F2) offspring generated four experimental groups: control unstressed, restricted unstressed, control stressed and restricted stressed. F2 offspring were studied at postnatal day 35 (PN35), 6, 12, and 16 mo. Peripheral quantitative computed tomography was performed on maternal and F2 offspring femurs. Restricted females, irrespective of stress during pregnancy, had decreased endosteal circumference, bending strength, and increased osteocalcin concentrations after pregnancy at 13 mo. F2 offspring of stressed mothers were born lighter. F2 male offspring from stressed pregnancies had decreased trabecular content at 6 mo and decreased endosteal circumference at 16 mo. F2 female offspring from growth-restricted mothers had reduced cortical thickness at PN35 and reduced endosteal circumference at 6 mo. At 12 mo, females from unstressed restricted and stressed control mothers had decreased trabecular content. Low birth weight females had long-term bone changes, highlighting programming effects on bone health. Stress during pregnancy did not exacerbate these programmed effects. Male and female offspring responded differently to maternal growth restriction and stress, indicating gender-specific programming effects.

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.

Peripheral Quantitative Computed Tomography (pQCT) Measures Contribute to the Understanding of Bone Fragility in Older Patients With Low-trauma Fracture.

Dual-energy X-ray absorptiometry (DXA) as currently used has limitations in identifying patients with osteoporosis and predicting occurrence of fracture. We aimed to express peripheral quantitative computed tomography (pQCT) variables of patients with low-trauma fracture as T-scores by using T-score scales obtained from healthy young women, and to evaluate the potential clinical utility of pQCT for the assessment of bone fragility. Fracture patients were recruited from a fracture liaison service at the Royal Melbourne Hospital. Reference pQCT data were obtained from studies on women's health conducted by our group. A study visit was arranged with fracture patients, during which DXA and pQCT were applied to measure their bone strength. A total of 59 fracture patients were recruited, and reference data were obtained from 78 healthy young females. All DXA variables and most pQCT variables were significantly different between healthy young females and fracture patients (p < 0.05), except polar stress-strain index (p = 0.34) and cortical bone density (p = 0.19). Fracture patients were divided into osteoporosis and non-osteoporosis groups according to their DXA T-scores. Significant differences were observed in most pQCT variables (p < 0.05), except trabecular area and cortical density (p > 0.9 and p = 0.5, respectively). By applying pQCT T-scores, 11 (27%) of patients who were classified as having low or medium risk of osteoporosis on DXA T-scores alone were reclassified as high risk. Results of logistic regression suggested trabecular bone density as an independent predictor of osteoporosis status. More patients can be identified with osteoporosis by applying pQCT T-score variables in older people with low-trauma fracture. Peripheral QCT T-scores contribute to the understanding of bone fragility in this population.

Polycystic ovarian syndrome: Prevalence and impact on the wellbeing of Australian women aged 16-29 years.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common condition among reproductive-aged women. However, its exact prevalence is unknown. AIMS: To determine the prevalence of PCOS in Australian women aged 16-29 years using the National Institutes of Health (NIH) criteria compared to self-reported PCOS, to compare co-morbidities between the groups and to determine the most distressing aspect of a diagnosis of PCOS for these young women. MATERIALS AND METHODS: Participants were recruited from the Young Female Health Initiative (YFHI) and Safe-D studies. Participants completed questionnaires, physical examinations and blood tests from 2012 to 2016. In March 2016, two supplementary questionnaires were distributed: the first, comprising questions on reproductive health and impact of diagnosis, was sent to participants who self-reported having PCOS in the original studies. The second, comprising general reproductive health questions, was sent to the remainder. RESULTS: The prevalence of PCOS, according to the NIH criteria, was 12% (31/254), while the prevalence of self-reported PCOS was 8% (23/300). Only 35% (8/23) of those with self-reported PCOS actually fulfilled the NIH criteria for PCOS. Comorbidities were relatively similar among groups. Finally, approximately 65% (15/23) were unhappy or worried about their initial PCOS diagnosis, with 72% (13/18) stating fertility concerns were the most distressing aspect of their diagnosis. CONCLUSIONS: The lack of consistent and accurate diagnosis of PCOS in young women potentially leads to over-diagnosis. This creates unnecessary fears of health complications, particularly infertility. Therefore, we recommend the development of standardised criteria with set parameters that allow for better diagnosis of PCOS.

Maternal Dietary Nutrient Intake During Pregnancy and Offspring Linear Growth and Bone: The Vitamin D in Pregnancy Cohort Study.

Magnesium, phosphorus, zinc, calcium, potassium and protein all play integral roles in maintaining bone health in adults; however, less is known about the importance of these minerals in utero. We aimed to determine associations between maternal dietary consumption of these nutrients during gestation and birth measures in offspring. Of 475 pregnant women recruited from a single antenatal clinic before 16-week gestation (2002-2003) as part of the vitamin D in pregnancy study, 346 with recorded maternal dietary intakes at 28- to 32-week gestation and offspring measures at birth were included. At birth, trained personnel measured the infant's weight, knee-heel length, crown-heel length and head circumference. At age 11, returning offspring underwent assessment of bone mass by dual-energy X-ray absorptiometry (n = 171). Crown-heel length was positively and weakly correlated with maternal intakes of all measured nutrients except calcium, fat and carbohydrate (r = 0.15-0.17; all p ≤ 0.05). The associations with protein, phosphorus and potassium were not attenuated after adjustment for maternal and offspring characteristics. No sustained associations were seen with other birth measures. Further, associations with some nutrients persisted with offspring height at age 11 years. Offspring bone area was associated with maternal diet, but no other measure of bone mass at age 11. After adjustment for height, associations were not significant. These data highlight that whilst some nutritional factors during pregnancy are associated with offspring linear growth in utero and childhood, this does not necessarily translate into an effect on offspring bone measures in childhood.

Impaired bone and muscle development in young people treated with antiepileptic drugs.

OBJECTIVE: Antiepileptic drugs (AEDs) are associated with reduced bone density, balance impairment, and increased fracture risk in adults. However, pediatric data are limited. Therefore, we aimed to examine bone, muscle, and balance outcomes in young patients taking AEDs. METHODS: We undertook a case-control study utilizing an AED exposure-discordant matched-pair approach. Subjects were aged 5-18 years with at least 12 months of AED exposure. Pairs were twins, nontwin siblings and first cousins, sex- and age-matched (to within 2 years), allowing for greater power than with unrelated control subjects. Dual energy x-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and muscle force/balance were tested, with questionnaires were administered for bone health and epilepsy details. RESULTS: Twenty-three pairs were recruited, (median age 12.9 years [subjects] and 13.5 years [controls])-7 twin, 14 sibling, and 2 cousin pairs. Those taking AEDs had an increased prevalence of fractures (15 fractures in 8 subjects, compared with 4 fractures in 3 controls, p < 0.01). Trabecular volumetric bone mineral density (vBMD) measured by pQCT at the 4% site (tibia) was reduced by 14% (p = 0.03) in subjects. Subjects exerted a decreased maximum force compared to body weight (Fmax total/g) at the tibia. There were no differences seen in either bone mineral parameters measured by DXA or balance measures. SIGNIFICANCE: Young people taking AEDs reported more fractures and had reductions in tibial vBMD and lower limb muscle force compared to their matched controls. These findings suggest that further exploration of bone health issues of young patients on AED therapy is required. Longitudinal studies are required to confirm these changes in the muscle-bone unit and to further explore the clinical outcomes.

Predictors and correlates of serum 25-hydroxyvitamin D concentrations in young women: results from the Safe-D study.

Vitamin D deficiency is a global public health concern. Studies of serum 25-hydroxyvitamin D (25(OH)D) determinants in young women are limited and few include objective covariates. Our aims were to define the prevalence of vitamin D deficiency and examine serum 25(OH)D correlates in an exploratory study of women aged 16-25 years. We studied 348 healthy females living in Victoria, Australia, recruited through Facebook. Data collected included serum 25(OH)D assayed by liquid chromatography-tandem MS, relevant serum biochemistry, soft tissue composition by dual-energy X-ray absorptiometry, skin melanin density, Fitzpatrick skin type, sun exposure using UV dosimeters and lifestyle factors. Mean serum 25(OH)D was 68 (sd 27) nmol/l and 26 % were vitamin D deficient (25(OH)D 2 h in the sun in summer daily, holidaying in the most recent summer period, serum Fe levels, height and multivitamin use were positively associated with 25(OH)D. Fat mass and a blood draw in any season except summer was inversely associated with 25(OH)D. Vitamin D deficiency is common in young women. Factors such as hormonal contraception, sun exposure and sun-related attitudes, as well as dietary supplement use are essential to consider when assessing vitamin D status. Further investigation into methods to safely optimise vitamin D status and to improve understanding of the impact of vitamin D status on long-term health outcomes is required.

Genetic and Environmental Factors in Invasive Cervical Cancer: Design and Methods of a Classical Twin Study.

BACKGROUND: Persistent high-risk human papillomavirus (HPV) infection is a necessary prerequisite for development of cervical cancer and its precursor lesion, high-grade squamous intraepithelial lesion (HSIL). However, HPV infection is not sufficient to drive this process, and genetic and environmental factors may also play a role. METHODS/DESIGN: The Cervical Cancer, Genetics and Environment Twin Study was established to investigate the environmental and genetic influences on variation in susceptibility to cervical pre-cancer in 25- to 69-year-old monozygotic (MZ) and dizygotic (DZ) twins recruited through the Australian Twin Registry. Reviews of Papanicolaou (Pap) screening histories were undertaken to identify individual women with a history of an abnormal Pap test. This was followed by detection of HPV in archival Pap smears of selected twin pairs to determine HPV persistence. Selected twin pairs also completed a detailed questionnaire on socio-demographic characteristics, sexual behavior, and HPV knowledge. In future analyses, under the assumptions of the classical twin design, case-wise concordance for persistent HPV infection and HSIL will be calculated for MZ and DZ twin pairs, and twin pairs (both MZ and DZ) who are discordant for the above outcomes will be used to assess the contributions of measured environmental risk factors. DISCUSSION: The study examines factors related to HPV persistence and development of HSIL among female MZ and DZ twins. The results will contribute to our understanding of the natural history of cervical HPV infection and the relative contributions of genetic and environmental factors in disease progression.