Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome

Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS) and associated with higher inter- and intra-muscular adipose tissue (IMAT). We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS). A non-classical body mass index (BMI) threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m²). Measurements included plasma 25-hydroxyvitamin D (25OHD), insulin resistance (glucose infusion rate (GIR; mg/m²/min), fasting glucose and insulin, and glycated haemoglobin), visceral fat, mid-thigh IMAT (computed tomography) and total body fat (dual-energy X-ray absorptiometry). Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05). Higher IMAT was associated with lower 25OHD (B = -3.95; 95% CI -6.86, -1.05) and GIR (B = -21.3; 95% CI -37.16, -5.44) in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044), but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women

A Single Dose of Prednisolone as a Modulator of Undercarboxylated Osteocalcin and Insulin Sensitivity Post-Exercise in Healthy Young Men: A Study Protocol

Background: Undercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice.Objectives: A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise.Methods: Healthy young men (n=12) aged 18 to 40 years will be recruited. Initial assessments will include analysis of fasting blood, body composition, aerobic power (VO2peak), and peak heart rate. Participants will then be randomly allocated, double-blind, to a single dose of 20 mg of prednisolone or placebo. The two experimental trials will involve 30 minutes of interval exercise (90%-95% peak heart rate), followed by 3 hours of recovery and 2 hours of euglycaemic- hyperinsulinaemic clamp (insulin clamp). Seven muscle biopsies and blood samples will be obtained at rest, following exercise and post-insulin clamps.Results: The study is funded by the National Heart Foundation of Australia and Victoria University. Enrollment has already commenced and data collection will be completed in 2016.Conclusion: If the hypothesis is confirmed, the study will provide novel insights into the potential role of ucOC in insulin sensitivity in human subjects and will elucidate pathways involved in exercise-induced insulin sensitivity

Glucose-loading reduces bone remodeling in women and osteoblast function in vitro

Aging is associated with a reduction in osteoblast life span and the volume of bone formed by each basic multicellular unit. Each time bone is resorbed, less is deposited producing microstructural deterioration. Aging is also associated with insulin resistance and hyperglycemia, either of which may cause, or be the result of, a decline in undercarboxylated osteocalcin (ucOC), a protein produced by osteoblasts that increases insulin sensitivity. We examined whether glucose-loading reduces bone remodeling and ucOC in&nbsp;vivo and osteoblast function in&nbsp;vitro, and so compromises bone formation. We administered an oral glucose tolerance test (OGTT) to 18 pre and postmenopausal, nondiabetic women at rest and following exercise and measured serum levels of bone remodeling markers (BRMs) and ucOC. We also assessed whether increasing glucose concentrations with or without insulin reduced survival and activity of cultured human osteoblasts. Glucose-loading at rest and following exercise reduced BRMs in pre and postmenopausal women and reduced ucOC in postmenopausal women. Higher glucose correlated negatively, whereas insulin correlated positively, with baseline BRMs and ucOC. The increase in serum glucose following resting OGTT was associated with the reduction in bone formation markers. D-glucose (&gt;10&nbsp;mmol&nbsp;L-1) increased osteoblast apoptosis, reduced cell activity and osteocalcin expression compared with 5&nbsp;mmol&nbsp;L-1. Insulin had a protective effect on these parameters. Collagen expression in&nbsp;vitro was not affected in this time course. In conclusion, glucose exposure reduces BRMs in women and exercise failed to attenuate this suppression effect. The suppressive effect of glucose on BRMs may be due to impaired osteoblast work and longevity. Whether glucose influences material composition and microstructure remains to be determined

Circulating 25-hydroxyvitamin D concentration and cause-specific mortality in the Melbourne Collaborative Cohort Study.

Vitamin D deficiency is associated with higher all-cause mortality, but associations with specific causes of death are unclear. We investigated the association between circulating 25-hydroxyvitamin D (25(OH)D) concentration and cause-specific mortality using a case-cohort study within the Melbourne Collaborative Cohort Study (MCCS). Eligibility for the case-cohort study was restricted to participants with baseline dried blood spot samples and no pre-baseline diagnosis of cancer. These analyses included participants who died (n = 2307) during a mean follow-up of 14 years and a sex-stratified random sample of eligible cohort participants ('subcohort', n = 2923). Concentration of 25(OH)D was measured using liquid chromatography-tandem mass spectrometry. Cox regression, with Barlow weights and robust standard errors to account for the case-cohort design, was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for cause-specific mortality in relation to 25(OH)D concentration with adjustment for confounders. Circulating 25(OH)D concentration was inversely associated with risk of death due to cancer (HR per 25 nmol/L increment = 0.88, 95 % CI 0.78-0.99), particularly colorectal cancer (HR = 0.75, 95 % CI 0.57-0.99). Higher 25(OH)D concentrations were also associated with a lower risk of death due to diseases of the respiratory system (HR = 0.62, 95 % CI 0.43-0.88), particularly chronic obstructive pulmonary disease (HR = 0.53, 95 % CI 0.30-0.94), and diseases of the digestive system (HR = 0.44, 95 % CI 0.26-0.76). Estimates for diabetes mortality (HR = 0.64, 95 % CI 0.33-1.26) and cardiovascular disease mortality (HR = 0.90, 95 % CI 0.76-1.07) lacked precision. The findings suggest that vitamin D might be important for preventing death due to some cancers, respiratory diseases, and digestive diseases

Harmonization of Osteoporosis Guidelines: Paving the Way for Disrupting the Status Quo in Osteoporosis Management in the Asia Pacific.

In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia-Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically diverse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country-specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer-to-peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can also be utilized in other parts of the world that have similar socioeconomic diversity and heterogeneity of healthcare resources. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Osteo-cise: Strong Bones for Life: protocol for a community-based randomised controlled trial of a multi-modal exercise and osteoporosis education program for older adults at risk of falls and fractures

Background : Osteoporosis affects over 220 million people worldwide, and currently there is no \u27cure\u27 for the disease. Thus, there is a need to develop evidence-based, safe and acceptable prevention strategies at the population level that target multiple risk factors for fragility fractures to reduce the health and economic burden of the condition. Methods : The \u27Osteo-cise: Strong Bones for Life\u27 study will investigate the effectiveness and feasibility of a multi-component targeted exercise, osteoporosis education/awareness and behavioural change program for improving bone health and muscle function, and reducing falls risk in community-dwelling older adults at an increased risk of fracture. Men and women aged 60 years or above will participate in an 18-month randomised controlled trial comprising a 12-month structured and supervised community-based program and a 6-month \u27research to practise\u27 translational phase. Participants will be randomly assigned to either the \u27Osteo-cise\u27 intervention or a self-management control group. The intervention will comprise a multi-modal exercise program incorporating high velocity progressive resistance training, moderate impact weight-bearing exercise and high challenging balance exercises performed three times weekly at local community-based fitness centres. A behavioural change program will be used to enhance exercise adoption and adherence to the program. Community-based osteoporosis education seminars will be conducted to improve participant knowledge and understanding of the risk factors and preventative measures for osteoporosis, falls and fractures. The primary outcomes measures, to be collected at baseline, 6, 12, and 18 months, will include DXA-derived hip and spine bone mineral density measurements and functional muscle power (timed stair-climb test). Secondary outcomes measures include: MRI-assessed distal femur and proximal tibia trabecular bone micro-architecture, lower limb and back maximal muscle strength, balance and function (four square step test, functional reach test, timed up-and-go test and 30-second sit-to-stand), falls incidence and health-related quality of life. Cost-effectiveness will also be assessed. Discussion : The findings from the Osteo-cise: Strong Bones for Life study will provide new information on the efficacy of a targeted multi-modal community-based exercise program incorporating high velocity resistance training, together with an osteoporosis education and behavioural change program for improving multiple risk factors for falls and fracture in older adults at risk of fragility fracture.<br /

Associations of body mass index, body fat percentage and sarcopenia components with bone health estimated by second-generation high-resolution peripheral quantitative computed tomography in older adults with obesity.

PURPOSE: To investigate associations between body mass index (BMI), body fat percentage, and components of sarcopenia (muscle mass and muscle strength/power), with bone microarchitecture measured by high-resolution peripheral computed tomography (HR-pQCT) in older adults with obesity. METHODS: Seventy-four adults aged ≥ 55 years with body fat percentage ≥ 30 % (men) or ≥40 % (women) were included. Fat mass, lean mass and total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry. Appendicular lean mass (ALM) was calculated as the sum of lean mass in the upper- and lower-limbs. BMI was calculated and participants completed physical function assessments including stair climb power test. Distal tibial bone microarchitecture was assessed using HR-pQCT. Linear regression (β-coefficients and 95 % confidence intervals) analyses were performed with adjustment for confounders including age, sex, smoking status, vitamin D and self-reported moderate to vigorous physical activity. RESULTS: BMI and ALM/height2 were both positively associated with total hip, femoral neck and lumbar spine aBMD and trabecular bone volume fraction after adjusting for confounders (all p < 0.05). Body fat percentage was not associated with aBMD or any trabecular bone parameters but was negatively associated with cortical area (p < 0.05). Stair climb power (indicating better performance) was positively associated with cortical area and negatively associated with bone failure load (both p < 0.05). CONCLUSION: Higher BMI, ALM/height2 and muscle power were associated with more favourable bone microarchitecture, but higher body fat percentage was negatively associated with cortical bone area. These findings suggest that high BMI may be protective for fractures and that this might be attributable to higher muscle mass and/or forces, while higher relative body fat is not associated with better bone health in older adults with obesity

Associations of Serum 25-Hydroxyvitamin D with Physical Performance and Bone Health in Overweight and Obese Older Adults

Low vitamin D status commonly accompanies obesity, and both vitamin D deficiency and obesity have been associated with falls and fracture risk in older adults. We aimed to determine the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with physical performance and bone health in community-dwelling, overweight and obese older men and women. Serum 25(OH)D concentrations were measured in 84 participants with body mass index ≥25 kg/m² (mean ± SD age 62.4 ± 7.9 years; 55% women). Physical function was determined by short physical performance battery, hand grip and quadriceps strength, and stair climb power tests. Body composition and bone structure were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Mean ± SD 25(OH)D was 49.6 ± 17.7 nmol/L, and 50% of participants had low 25(OH)D ( 0.05). Lower 25(OH)D concentrations are associated with poorer quadricep strength and muscle power in overweight and obese older women but not men